Folic Acid
15 benefits mapped to clinical evidence across supplements.
Dose per serving from products
16,813 products in our catalogue print how much Folic Acid a serving holds.
Most common: 250 mcg to 500 mcg, 38% of 16,813 products.
| Dose per serving | Products |
|---|---|
| 50 mcg or less | 707 |
| 50 mcg to 100 mcg | 834 |
| 100 mcg to 250 mcg | 2,522 |
| 250 mcg to 500 mcg | 6,381 |
| 500 mcg to 1 mg | 4,774 |
| 1 mg to 2.5 mg | 939 |
| over 2.5 mg | 656 |
Dose per serving from research
1,135 study groups in 700 studies say how much Folic Acid participants took a day.
These are the doses the studies gave. They are not a recommendation.
Most common: 250 mcg to 500 mcg, 38% of 1,135 study groups.
| Daily dose | Study groups |
|---|---|
| 100 mcg or less | 52 |
| 100 mcg to 250 mcg | 93 |
| 250 mcg to 500 mcg | 430 |
| 500 mcg to 1 mg | 212 |
| 1 mg to 2.5 mg | 69 |
| 2.5 mg to 5 mg | 200 |
| 5 mg to 10 mg | 28 |
| over 10 mg | 51 |
Commonly used together
635 of 1,131 study groups took Folic Acid with something else. Shown: what 3 or more different studies gave. The 10 most common of 40.
What was given together, not what works together.
| Taken with | Study groups |
|---|---|
| Iron | 284 |
| Vitamin B12 | 252 |
| Vitamin B6 | 162 |
| Zinc | 67 |
| Vitamin C | 51 |
| Vitamin A | 41 |
| Vitamin E | 41 |
| Inositol | 33 |
| Vitamin D | 32 |
| Riboflavin | 29 |
Benefit Evidence
Immune/infection ↓, +5‑fold folate
Inflammation ↓, homocysteine −22%
Neutropenia ↓, WBC +
Immune/infection ↓, +5‑fold folate
Inflammation ↓, homocysteine −22%
Neutropenia ↓, WBC +
Research sources
Blood circulation (195)
- [Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid]
PubMed ID: 15847747
Folic acid supplementation reduced elevated homocysteine in patients on AEDs — homocysteine reduction is circulation-relevant.
- Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans
PubMed ID: 15928685
Folic acid‑fortified milk raised folate and modestly lowered homocysteine in healthy adults — supports vascular risk reduction.
- Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype
PubMed ID: 16002796
5 mg/day folic acid reduced pulse pressure and large-artery stiffness over 3 weeks — direct arterial stiffness and BP benefits.
- Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation: randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype
PubMed ID: 15895286
1 mg/day produced large, genotype-dependent tHcy reductions — directly relevant to circulation risk modulation.
- [Treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients with vitamin B]
PubMed ID: 16083628
B‑vitamin therapy including folate lowered tHcy and improved endothelial function in renal transplant patients.
- Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, Vitamins B6 and B12
PubMed ID: 15939064
B‑vitamin combination reduced homocysteine and slightly decreased carotid IMT over 1 year — structural vascular improvement supporting circulation.
- Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus
PubMed ID: 16818571
High‑dose folic acid (5 mg/day) produced rapid, large improvements in endothelial function (FMD) in children with type 1 diabetes — strong direct evidence for vascular function.
- Methylenetetrahydrofolate reductase polymorphisms and homocysteine-lowering effect of vitamin therapy in Singaporean stroke patients
PubMed ID: 16397167
One-year folic-acid–containing therapy lowered homocysteine substantially in stroke patients, a relevant vascular risk marker.
- Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects
PubMed ID: 16491109
Folic acid improved insulin sensitivity and lowered inflammatory markers—metabolic/inflammatory changes relevant to vascular health.
- Effect of folic acid on endothelial function following acute myocardial infarction
PubMed ID: 17293188
High-dose folic acid (10 mg/day) improved flow-mediated dilation after MI, a direct measure of endothelial/vascular function.
- Effect of short-term folate and vitamin B supplementation on blood homocysteine level and carotid artery wall thickness in chronic hemodialysis patients
PubMed ID: 17048428
B‑vitamin treatment including folic acid lowered homocysteine in hemodialysis patients, though IMT did not change over 6 months.
- Effects of folic acid before and after vitamin B12 on plasma homocysteine concentrations in hemodialysis patients with known MTHFR genotypes
PubMed ID: 16391331
In dialysis patients folic acid robustly reduced homocysteine, particularly in MTHFR TT genotype—biomarker evidence relevant to circulation.
- No effect of homocysteine-lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease
PubMed ID: 16634837
B‑vitamin/folic acid therapy cut homocysteine by ~33% in peripheral arterial disease, a vascular biomarker improvement.
- Homocysteine-lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease
PubMed ID: 17645592
B‑vitamin therapy substantially lowered homocysteine in CAD patients though inflammatory markers unchanged.
- Lowering homocysteine with B vitamins has no effect on blood pressure in older adults
PubMed ID: 17449579
Daily B‑vitamin (including folate) robustly lowered homocysteine in older adults (biomarker relevant to vascular health) though BP unchanged.
- [Efficacy and safety of Enalapril-Folate acid tablets in lowering blood pressure and plasma homocysteine]
PubMed ID: 18087553
Adding folic acid to enalapril improved homocysteine lowering and increased proportion achieving joint BP/Hcy reduction—supportive for circulation.
- Effects of folic acid and N-acetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease
PubMed ID: 18214123
Randomized trial: folic acid 5 mg/day markedly lowered homocysteine and improved endothelium-dependent dilation (direct vascular function improvement).
- Long-term effect of folic acid therapy in heart transplant recipients: follow-up analysis of a randomized study
PubMed ID: 18431235
Post‑transplant folate therapy linked to lower cardiovascular deaths and improved survival — circulation/vascular relevance.
- Dietary intervention with Okinawan vegetables increased circulating endothelial progenitor cells in healthy young women
PubMed ID: 19013573
Diet raising folate lowered homocysteine and increased endothelial progenitor cells (EPCs) — direct vascular biomarker improvements.
- Effects of plasma homocysteine levels on serum HTase/PON activity in patients with type 2 diabetes
PubMed ID: 18781288
Folic acid reduced homocysteine and increased HTase/PON activity in diabetics — favorable vascular enzyme changes.
- Dietary intervention with emphasis on folate intake reduces serum lipids but not plasma homocysteine levels in hyperlipidemic patients
PubMed ID: 19083486
Diet emphasizing folate increased folate and produced large lipid improvements — indirect benefit for circulation.
- Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery
PubMed ID: 18400808
Postoperative homocysteine rises (N2O effect) associated with major complications—links folate pathway to perioperative vascular risks.
- Treatment of hyperhomocysteinemia and endothelial dysfunction in renal transplant recipients with B vitamins in the Chinese population
PubMed ID: 18206175
B‑vitamin treatment including folic acid markedly lowered homocysteine and improved endothelium‑dependent vasodilation.
- Increasing the number of SNP loci does not necessarily improve prediction power at least in the comparison of MTHFR SNP and haplotypes
PubMed ID: 19075497
1 mg/day folic acid in healthy men produced robust homocysteine reductions (vascular risk marker).
- [The effect of baseline homocysteine level on the efficacy of enalapril maleate and folic acid tablet in lowering blood pressure and plasma homocysteine]
PubMed ID: 19080072
Adding folic acid to enalapril improved BP control and lowered homocysteine in hypertensive patients (large RCT).
- The effect of folic acid supplementation on carotid intima-media thickness in patients with cardiovascular risk: a randomized, placebo-controlled trial
PubMed ID: 19201496
Randomized 5 mg folic acid for 18 months lowered homocysteine and produced a small but significant carotid IMT reduction.
- Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine - a six-year follow-up study
PubMed ID: 19917166
Observational RA cohort: folic acid users had lower homocysteine; high Hcy predicted atherothrombotic events.
- Effect of Sclerovit on endothelial dysfunction, hemorheological parameters, platelet aggregation, plasma concentration of homocysteine and progression of atherosclerosis in patients with vascular diseases
PubMed ID: 19363237
Small multivitamin (incl. folate) RCT improved FMD and lowered homocysteine.
- Plasma Abeta, homocysteine, and cognition: the Vitamin Intervention for Stroke Prevention (VISP) trial
PubMed ID: 19153374
B‑vitamin therapy in stroke patients lowered homocysteine (biochemical vascular effect) though clinical benefit on cognition absent.
- Effect of folate supplementation on serum homocysteine and plasma total antioxidant capacity in hypercholesterolemic adults under lovastatin treatment: a double-blind randomized controlled clinical trial
PubMed ID: 19766902
5 mg folic acid in hypercholesterolemic adults lowered homocysteine and increased antioxidant capacity, relevant to vascular health.
- Randomized clinical trial of folate supplementation in patients with peripheral arterial disease
PubMed ID: 19672935
Randomized trial in PAD patients: folate/5‑MTHF lowered homocysteine and produced small but significant improvements in ABPI and PWV.
- Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial
PubMed ID: 19228852
Large trial showed homocysteine‑lowering vitamins including folic acid reduced stroke incidence—circulatory benefit at population level.
- Role of folic acid in atherosclerosis after kidney transplant: a double-blind, randomized, placebo-controlled clinical trial
PubMed ID: 19364310
Post‑kidney transplant trial: 5 mg/day folic acid lowered homocysteine and slightly reduced carotid IMT.
- Ethnicity does not affect the homocysteine-lowering effect of B-vitamin therapy in Singaporean stroke patients
PubMed ID: 19372453
B‑vitamin treatment consistently lowered homocysteine in stroke patients—favors vascular risk reduction.
- Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina
PubMed ID: 19491420
High‑dose folic acid (5 mg) markedly reduced homocysteine and improved endothelial flow‑mediated dilation in unstable angina.
- [Efficacy of enalapril combined with folic acid in lowering blood pressure and plasma homocysteine level]
PubMed ID: 20058594
Adding folic acid to enalapril lowered homocysteine and increased the proportion achieving combined BP+Hcy reduction (cardiovascular‑risk biomarkers/clinical BP endpoint).
- Effect of physiological doses of oral vitamin B12 on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India
PubMed ID: 20216560
In rural cohort folic acid (200 µg) reduced homocysteine by ~4.8 µmol/L over 12 months (improves vascular risk biomarker).
- Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke: a possible linkage to homocysteine
PubMed ID: 20092401
Folate+B12 in stroke patients lowered tHcy and reduced CF6 (a pro‑atherogenic marker) over 2 months (direct vascular marker changes).
- Folic Acid and vitamin B12 supplementation improves coronary flow reserve in elderly subjects with vitamin B12 deficiency
PubMed ID: 20851295
In elderly B12‑deficient patients, folate+B12 improved coronary flow reserve and lowered homocysteine (objective measure of coronary microvascular function).
- Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults
PubMed ID: 20727555
High‑dose folic acid in older adults produced large tHcy reductions (−47.7%), a marker associated with vascular risk.
- Do novel risk biomarkers reflect the severity of peripheral arterial disease?
PubMed ID: 20834026
Cross-sectional study found higher homocysteine and lower RBC folate independently associated with greater peripheral arterial disease severity.
- A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy
PubMed ID: 20980493
Dose-ranging folic acid trials clearly lowered homocysteine and raised serum folate, a biochemical pathway linked to vascular risk.
- Adiponectin relates to smooth muscle function and folate in obese children
PubMed ID: 19606374
In obese children folic acid lowered homocysteine and raised folate though endothelial/vascular biomarkers did not change in this small study.
- Folic acid treatment normalizes NOS-dependence of vascular tone in the metabolic syndrome
PubMed ID: 20864946
Randomized crossover in metabolic-syndrome patients: 4 weeks of folic acid improved vascular NO-dependence and oxidative-stress markers, indicating vascular benefit.
- Coronary blood flow in patients with stable coronary artery disease treated long term with folic acid and vitamin B12
PubMed ID: 21389855
Small RCT: folic acid + B12 improved resting and maximal coronary blood flow over 2 years — direct microvascular circulation benefit.
- MTHFR 677C->T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation
PubMed ID: 21508090
Large supplementation trial: folic acid raised folate and lowered homocysteine — biochemically relevant to vascular health, genotype-modified response.
- Effect of different doses of folic acid on serum homocysteine level in patients on hemodialysis
PubMed ID: 21368386
Folic acid markedly lowered homocysteine in hemodialysis patients — homocysteine reduction is mechanistically linked to vascular health (biochemical evidence).
- Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial
PubMed ID: 22554931
Large B‑vitamin (including folic acid) trial modestly reduced vascular events overall and more in those not on antiplatelets — clinical-circulatory outcome signal.
- MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults
PubMed ID: 22230384
0.8 mg folic acid produced greater homocysteine lowering in MTHFR TT hypertensives — supports dose/genotype effects on a vascular risk biomarker.
- The effects of folic acid on markers of endothelial function in patients with type 1 diabetes mellitus
PubMed ID: 22482335
High‑dose folic acid (5 mg) reduced endothelial dysfunction markers in young type‑1 diabetics — direct vascular/circulatory biomarker improvement.
- Assessment of the efficacy of combination therapy with folic acid and tadalafil for the management of erectile dysfunction in men with type 2 diabetes mellitus
PubMed ID: 23347176
Adding 5 mg/day folic acid to tadalafil improved erectile function (vascular benefit proxy) significantly vs tadalafil alone.
- Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia
PubMed ID: 23698160
Dietary or low‑dose folate supplements produced ~20% reductions in plasma homocysteine—mechanistically relevant to circulation.
- The effects of folate supplementation on inflammatory factors and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial
PubMed ID: 24628390
High‑dose folate in PCOS lowered Hcy and hs‑CRP (inflammation), both relevant to vascular health.
- Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly
PubMed ID: 24916013
Low‑dose B‑vitamin (including folic acid) increased HDL and modestly reduced calculated 10‑yr CVD risk in elderly cohort.
- Metabolic response to folate supplementation in overweight women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial
PubMed ID: 24828019
5 mg folic acid in obese PCOS women lowered homocysteine and improved LDL/ratios—favorable for circulation risk profile.
- Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial
PubMed ID: 25771069
High‑quality RCT: enalapril+folic acid significantly reduced first stroke, ischemic stroke and composite CVD events.
- Neuroprotective impact of a vitamin trace element composition - a randomized, double blind, placebo controlled clinical trial with healthy volunteers
PubMed ID: 25789594
Multivitamin (including folic acid) increased folate and decreased homocysteine in healthy adults (favorable for circulation).
- Effects of 2-year vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly on arterial stiffness and cardiovascular outcomes within the B-PROOF trial
PubMed ID: 26147383
Folate+B12 produced clear lowering of plasma homocysteine (tHcy), a biomarker linked to vascular risk (biochemical benefit).
- B vitamin treatments modify the risk of myocardial infarction associated with a MTHFD1 polymorphism in patients with stable angina pectoris
PubMed ID: 26803590
MTHFD1 genotype modified AMI risk depending on B‑vitamin (including folic acid) treatment, implicating folate metabolism in vascular risk (genetic/interventional interaction).
- Folic acid supplementation reduces plasma homocysteine in postmenopausal women
PubMed ID: 26758937
Folic acid lowered homocysteine in postmenopausal women; homocysteine is linked to vascular risk, supporting circulation relevance.
- The Effects of Folate Supplementation on Carotid Intima-Media Thickness and Metabolic Status in Patients with Metabolic Syndrome
PubMed ID: 27450552
5 mg folate improved carotid intima‑media thickness and glucose/insulin markers in metabolic‑syndrome patients—strong vascular/ circulation biomarker benefits.
- Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients
PubMed ID: 27729579
Addition of 0.8 mg folic acid to enalapril reduced first‑stroke risk in a subgroup, indicating circulatory/vascular benefit.
- Homocysteine and Stroke Risk: Modifying Effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention
PubMed ID: 28360116
Large RCT: 0.8 mg folic acid reduced stroke risk in hypertensive patients (MTHFR-genotype/homocysteine-dependent), directly supporting vascular/circulatory benefit.
- Effects of folic acid combined with vitamin B12 on DVT in patients with homocysteine cerebral infarction
PubMed ID: 28617530
In hyperhomocysteinemic stroke patients, folic acid+B12 substantially lowered Hcy and was associated with much lower DVT recurrence—relevant to thrombotic/circulatory outcomes.
- Association between percent decline in serum total homocysteine and risk of first stroke
PubMed ID: 29030456
Post‑hoc analysis: greater reductions in homocysteine (often via folic acid) were linked to modestly lower first-stroke risk in hypertensive adults, supporting circulation benefits from tHcy lowering.
- Effects of Folic Acid Therapy on the New-Onset Proteinuria in Chinese Hypertensive Patients: A Post Hoc Analysis of the Renal Substudy of CSPPT (China Stroke Primary Prevention Trial)
PubMed ID: 28607125
Large hypertensive trial: adding folic acid reduced new proteinuria and slowed eGFR decline in diabetics—indirect evidence of improved vascular/kidney microcirculation in that subgroup.
- Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke
PubMed ID: 29747834
CSPPT subgroup: folic acid markedly reduced first‑stroke risk in high tHcy/low‑platelet subgroup (circulatory event).
- The modifying effect of the MTHFR genotype on the association between folic acid supplementation and pulse wave velocity: Findings from the CSPPT
PubMed ID: 30372582
Raising folate reduced arterial stiffness (ba-PWV) in hypertensive adults, especially MTHFR CC genotype.
- MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment
PubMed ID: 29371246
Large trial showed folic acid lowers homocysteine (~11%), a key vascular risk biomarker.
- Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men
PubMed ID: 29273594
Folic acid linked to reduced first-stroke risk in certain subgroups, implying vascular benefit.
- Estimated Stroke-Free Survival of Folic Acid Therapy for Hypertensive Adults: Projection Based on the CSPPT
PubMed ID: 31865785
CSPPT modeling (enalapril+folic acid) showed reduced first stroke risk and increased stroke‑free survival—strong vascular relevance.
- Interaction of serum vitamin B(12) and folate with MTHFR genotypes on risk of ischemic stroke
PubMed ID: 31932513
Large RCT: folic acid added to enalapril reduced first ischemic stroke notably in low folate/B12 subgroups—strong circulatory benefit.
- Interaction of neutrophil counts and folic acid treatment on new-onset proteinuria in hypertensive patients
PubMed ID: 33308359
Folic acid + enalapril halved incident proteinuria in high‑neutrophil hypertensive subgroup—supports vascular/kidney endpoints linked to circulation.
- A Randomized Trial of Short-term Treatment with Folic Acid to Reduce the Oxidative Stress of Patients with Chronic Kidney Disease
PubMed ID: 34895119
5 mg/day folic acid lowered homocysteine and oxidative stress markers in CKD—mechanistically supports vascular health.
- Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension
PubMed ID: 36280851
CSPPT: adding folic acid to enalapril produced ~21% reduction in first stroke—strong evidence for improved vascular outcomes.
- Effects of folate supplementation on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2/3 in overweight and obese women: a randomized double-blind placebo-controlled trial
PubMed ID: 35383339
Folate supplementation lowered homocysteine and some metabolic/inflammatory markers—supports circulation via reduced vascular risk factors.
- Effects of individualized administration of folic acid on prothrombotic state and vascular endothelial function with H-type hypertension: A double-blinded, randomized clinical cohort study
PubMed ID: 35060542
Genotype‑guided folic acid with antihypertensive therapy lowered homocysteine and improved endothelial/prothrombotic markers—direct vascular benefits.
- Combined use of amlodipine and folic acid are significantly more efficacious than amlodipine alone in lowering plasma homocysteine and blood pressure among hypertensive patients with hyperhomocysteinemia and intolerance to ACEI: A multicenter, randomized, double-blind, parallel-controlled clinical trial
PubMed ID: 37433173
Randomized trial adding folic acid to amlodipine lowered homocysteine substantially and improved combined BP + homocysteine control—direct evidence for vascular risk‑marker improvement.
- A micronutrient supplement modulates homocysteine levels regardless of vitamin B biostatus in elderly subjects
PubMed ID: 36715360
Elderly RCT (FA+B12) lowered homocysteine and improved folate/B12 biomarkers—supports improved vascular risk profile.
- Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)
PubMed ID: 38478042
High‑quality dose–response RCT showing robust homocysteine reductions with folic acid (biomarker strongly linked to vascular health).
- Vitamin B12 decreases, but does not normalize, homocysteine and methylmalonic acid in end-stage renal disease: a link with glycine metabolism and possible explanation of hyperhomocysteinemia in end-stage renal disease
PubMed ID: 12601627
Folic acid reduced homocysteine in dialysis patients — relevant to vascular risk/homocysteine.
- Niacin treatment increases plasma homocyst(e)ine levels
PubMed ID: 10577438
Niacin raised homocysteine markedly and authors explicitly note folic acid lowers homocysteine — mechanistic/clinical relevance to vascular risk and circulation.
- Homocysteine in patients with rheumatoid arthritis in relation to inflammation and B-vitamin treatment
PubMed ID: 14626626
B‑vitamin supplement (B6, B12, folic acid) significantly lowered total homocysteine — direct vascular risk biomarker relevant to circulation.
- Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins
PubMed ID: 15780109
Multivitamin including 1 mg folic acid substantially reduced elevated homocysteine, a biomarker linked to vascular risk (direct biochemical effect).
- A single-center, double-blinded, randomized controlled study to evaluate the relative efficacy of sublingual and oral vitamin B-complex administration in reducing total serum homocysteine levels
PubMed ID: 17109579
B‑complex including 400 µg folic acid significantly lowered homocysteine, a biomarker linked to vascular risk.
- Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients
PubMed ID: 18206891
B‑vitamin (including folate) therapy decreased homocysteine and improved small‑artery elasticity over 4 months—direct vascular outcome, though combined vitamins used.
- B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial
PubMed ID: 20688574
B‑vitamin supplementation including folic acid lowered total homocysteine and produced a small, borderline reduction in major vascular events after stroke/TIA.
- Kidney function and risk of cardiovascular disease and mortality in kidney transplant recipients: the FAVORIT trial
PubMed ID: 22594581
FAVORIT randomized trial directly tested high‑dose folic acid (with B‑vitamins) in kidney transplant recipients for CVD outcomes — highly relevant (trial was neutral for benefit).
- Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis
PubMed ID: 23765945
Large RCT in patients with prior stroke/TIA: folic acid+B‑vitamins clearly lowered homocysteine (biomarker linked to vascular risk) though clinical vascular/cognitive benefits were not shown.
- Short-term folinic acid supplementation improves vascular reactivity in HIV-infected individuals: a randomized trial
PubMed ID: 23660169
Randomized trial: folinic acid improved endothelium‑dependent vasoreactivity vs placebo in HIV patients (direct vascular effect).
- Folate administration decreases oxidative status and blood pressure in postmenopausal women
PubMed ID: 24906471
15 mg 5‑MTHF lowered night blood pressure and homocysteine in randomized trial—direct circulation benefit.
- ESSENS dyslipidemia: A placebo-controlled, randomized study of a nutritional supplement containing red yeast rice in subjects with newly diagnosed dyslipidemia
PubMed ID: 27143594
Randomized trial of a nutraceutical (contains folic acid) showed large LDL and non‑HDL reductions — relevant to circulation/vascular risk, though folic acid was one of several active components.
- A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes in Healthy Humans and Their Effects on Homocysteine, Oxidative Stress, and Antioxidant Levels
PubMed ID: 31915511
Synthetic B‑complex (including folic acid) produced sustained serum folate increases and reduced total homocysteine — a direct biochemical marker linked to vascular health.
- Association between serum 5-methyltetrahydrofolate and homocysteine in Chinese hypertensive participants with different MTHFR C677T polymorphisms: a cross-sectional study
PubMed ID: 35562805
Strong association: higher 5‑MeTHF linked to substantially lower homocysteine (a cardiovascular risk marker), supporting a plausible benefit for circulation.
- Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways(TM)) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial
PubMed ID: 38892484
Randomized RCT: methylfolate+B6+B12 produced a large (~30%) homocysteine reduction and modest LDL‑C change—direct, strong circulation/vascular relevance.
- Posttreatment Blood Pressure as a Key Predictor in a 5-Year Stroke Prediction Model
PubMed ID: 39821957
CSPPT-derived analysis: folic-acid supplementation independently reduced 5‑year stroke risk (HR 0.79), a direct circulation/vascular outcome.
- Efficacy of L-methylfolate and methylcobalamin in treating resistant hypertension associated with elevated serum homocysteine in hemodialysis patients
PubMed ID: 41580678
L‑methylfolate + methylcobalamin significantly reduced pre-dialysis systolic BP and homocysteine—direct cardiovascular/circulatory benefits.
- Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease
PubMed ID: 14985687
Folic acid + B12 produced a clear ~32% lowering of plasma homocysteine in coronary artery disease patients — strong biochemical support for circulation-related benefit.
- Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects
PubMed ID: 16391577
800 µg/day folic acid raised serum folate and lowered homocysteine in healthy men — supports improved circulation-related biomarker profile.
- Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamin supplementation
PubMed ID: 14699020
B‑vitamin supplementation (including folic acid) attenuated betaine–homocysteine relationship relevant to vascular risk.
- Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations
PubMed ID: 15941890
Folic acid dose‑dependently lowered homocysteine and raised betaine — homocysteine reduction linked to vascular health.
- Effect of Folic Acid, Betaine, Vitamin B₆, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine
PubMed ID: 26771632
Randomized folic acid arm produced a clear reduction in fasting homocysteine—mechanistically linked to vascular health.
- Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults
PubMed ID: 32918135
Folic acid supplementation lowered homocysteine and improved arsenic methylation in an RCT—homocysteine reduction is relevant to vascular health.
- 5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial
PubMed ID: 37482222
Randomized trial: adding 5‑MTHF to propranolol significantly lowered portal pressure and improved NO‑related biomarkers—direct vascular effect of active folate.
- Randomized controlled trial of the effect of short-term coadministration of methylcobalamin and folate on serum ADMA concentration in patients receiving long-term hemodialysis
PubMed ID: 20430500
High‑dose folate plus IV methylcobalamin normalized homocysteine and produced larger ADMA and arterial stiffness improvements vs folate alone in HD patients.
- [Impact of adding folic acid, vitamin B(12) and probucol to standard antihypertensive medication on plasma homocysteine and asymmetric dimethylarginine levels of essential hypertension patients]
PubMed ID: 23363713
Folic acid 5 mg/day + B12 significantly lowered homocysteine and increased serum NO/eNOS markers in hypertensive patients—supportive for vascular function.
- Nitrate-Rich Beetroot Juice Reduces Blood Pressure in Tanzanian Adults with Elevated Blood Pressure: A Double-Blind Randomized Controlled Feasibility Trial
PubMed ID: 32729923
Folic acid (5 mg) increased folate and lowered homocysteine but did not clearly enhance nitrate BP lowering; relevant to circulation via homocysteine reduction.
- Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial
PubMed ID: 9583842
B‑vitamin supplement including folic acid produced ~28% homocysteine reduction—a biomarker tied to vascular health.
- Antioxidants, but not B-group vitamins increase the resistance of low-density lipoprotein to oxidation: a randomized, factorial design, placebo-controlled trial
PubMed ID: 10407503
B‑vitamins (with folic acid) lowered homocysteine (circulatory risk marker) though no antioxidant effect on LDL.
- A mixed fruit and vegetable concentrate increases plasma antioxidant vitamins and folate and lowers plasma homocysteine in men
PubMed ID: 12840177
Supplement raised folate and modestly lowered homocysteine—supports circulation via homocysteine pathway.
- Multivitamin supplementation of HIV-positive women during pregnancy reduces hypertension
PubMed ID: 15987864
Multivitamins including folic acid reduced pregnancy hypertension risk in HIV+ women, a circulatory outcome in pregnancy.
- Four week supplementation with mixed fruit and vegetable juice concentrates increased protective serum antioxidants and folate and decreased plasma homocysteine in Japanese subjects
PubMed ID: 17704021
Folate rose and plasma homocysteine fell ~20%—biochemical changes tied to vascular risk reduction.
- Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers
PubMed ID: 18270369
Large cohort: higher dietary folate associated with ~20% lower ischemic stroke risk in male smokers.
- Effect of homocysteine-lowering treatment with folic Acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial
PubMed ID: 19491213
Folate + B6/B12 lowered homocysteine significantly in RCT, a biomarker for vascular risk (clinical vascular outcome not shown).
- High- but not low-dose folic acid improves endothelial function in coronary artery disease
PubMed ID: 17087779
High‑dose folic acid (5 mg) improved flow‑mediated dilatation in coronary disease patients—direct functional vascular benefit.
- Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial
PubMed ID: 27655522
Combined methyl‑donor supplement (including folate) produced large homocysteine reductions in hypertensive patients — homocysteine linked to vascular risk.
- l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women
PubMed ID: 29878267
l‑5‑MTHF raised blood folate and (with folic acid) lowered homocysteine; improved folate status ties to vascular health.
- A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia
PubMed ID: 31408467
Bespoke drink with betaine/B‑vitamins reduced homocysteine more than standard multivitamin in women — beneficial for circulation.
- Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial
PubMed ID: 36717385
Low‑dose folic acid with B vitamins and betaine significantly lowered homocysteine in hyperhomocysteinemic adults (improves vascular risk profile).
- Plasma homocysteine concentration is decreased by dietary intervention
PubMed ID: 12696562
High‑folate diet increased folate status and lowered homocysteine in healthy women.
- Effect of folic acid on fenofibrate-induced elevation of homocysteine and cysteine
PubMed ID: 12851616
Folic acid reduced fenofibrate‑induced tHcy rise and attenuated creatinine increase, supporting vascular/organ protection.
- Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12
PubMed ID: 11981075
High‑dose folinic or oral folic acid (with B6/B12) produced large (~42–46%) homocysteine reductions in haemodialysis patients — strong CVD biomarker effect.
- Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women
PubMed ID: 14749760
Folic acid‑fortified mineral water markedly raised folate and lowered plasma homocysteine in free‑living adults — direct vascular biomarker benefit.
- High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial
PubMed ID: 19118243
B‑vitamin regimen lowered homocysteine; subgroup showed less CIMT progression — biochemical and limited clinical vascular signals.
- Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium-dependent vasodilation in patients with cardiovascular disease
PubMed ID: 21884007
Short‑term B‑vitamin supplementation (including folic acid) improved flow‑mediated dilation and lowered homocysteine — direct vascular function evidence.
- Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers
PubMed ID: 30401001
Large RCT: long‑term low‑dose folic acid produced clear, clinically meaningful reductions in plasma total homocysteine, a circulation/vascular risk biomarker.
- Interaction of serum calcium and folic acid treatment on first stroke in hypertensive males
PubMed ID: 33148481
CSPPT subgroup: adding folic acid to enalapril halved first‑stroke risk in a large hypertensive subgroup—strong direct evidence for circulation/stroke risk reduction in this context.
- B-vitamin Treatment Modifies the Mortality Risk Associated with Calcium Channel Blockers in Patients with Suspected Stable Angina Pectoris: A Prospective Cohort Study
PubMed ID: 37121550
B‑vitamin treatment (including folic acid) attenuated higher mortality associated with calcium‑channel‑blocker use—suggests cardiovascular/circulatory benefit as part of B‑vitamin therapy.
- Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial
PubMed ID: 26311810
Folic acid (400 μg/d) lowered plasma total homocysteine by ~23% in an RCT — homocysteine is a vascular biomarker.
- Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial
PubMed ID: 32019154
Higher-folate diet decreased homocysteine in MTHFR TT individuals—directly relevant to circulatory risk modulation.
- Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease
PubMed ID: 15930443
Multi-nutrient drink including folic acid improved walking distance in PAD and lowered homocysteine and cholesterol—clinically relevant circulation benefit (multi-nutrient).
- Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program
PubMed ID: 17237316
Fortified dairy (incl. folic acid) in men post-MI lowered LDL/total cholesterol and hs-CRP—supports cardiovascular/circulatory risk reduction (combined nutrients).
- Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 does not affect the proportion of (n-3) long chain polyunsaturated fatty acids in plasma phosphatidylcholine
PubMed ID: 18287365
Large RCT: folate+B12+B6 lowered homocysteine—strong mechanistic marker for vascular health/circulation.
- Milk enriched with "healthy fatty acids" improves cardiovascular risk markers and nutritional status in human volunteers
PubMed ID: 19084376
Enriched milk including folic acid improved lipid profile over 1 year—favorable for circulation (multi-component supplement).
- A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease
PubMed ID: 11401123
High‑dose folic acid lowered homocysteine and trended toward better endothelium‑dependent dilation in coronary patients (non‑significant).
- Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide?
PubMed ID: 11451751
Folic acid increased serum folate, lowered homocysteine and produced a significant improvement in flow‑mediated dilation and reduced intracellular superoxide.
- Global improvement of vascular function and redox state with low-dose folic acid: implications for folate therapy in patients with coronary artery disease
PubMed ID: 17420345
Low‑dose folic acid (400 µg/day) improved NO‑mediated endothelial function and reduced vascular superoxide; mechanistic vascular benefit.
- Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia
PubMed ID: 8416664
Folate-containing therapy normalized elevated homocysteine, a circulatory risk marker.
- Vitamin requirements for the treatment of hyperhomocysteinemia in humans
PubMed ID: 7931701
Low‑dose folic acid produced a large (~42%) reduction in plasma homocysteine in men — a strong biomarker change relevant to vascular health and circulation.
- Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid
PubMed ID: 7714461
In acute MI patients, oral folic acid substantially lowered post‑MI homocysteine (~27%) — relevant to post‑MI circulatory biomarker modulation.
- Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers
PubMed ID: 9514403
Large trial: high-dose folic acid (with B-vitamins) produced substantial, rapid homocysteine lowering — homocysteine is a circulation risk marker.
- Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women
PubMed ID: 9808229
400 µg folic acid lowered homocysteine in young women; co‑supplementing B12 enhanced reductions.
- Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease
PubMed ID: 9535664
Dose-dependent folic-acid fortification raised plasma folate and significantly lowered homocysteine in people with coronary disease.
- The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study
PubMed ID: 9683392
Dietary folic acid increased serum/red cell folate and reduced plasma homocysteine in healthy adults.
- Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial
PubMed ID: 9925130
Low‑dose folic acid (250–500 µg) significantly reduced plasma homocysteine in young women.
- Low-dose folic acid supplementation does not influence plasma methionine concentrations in young non-pregnant women
PubMed ID: 10743479
Randomized trial showing homocysteine lowering with low‑dose folic acid.
- Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients
PubMed ID: 10591669
Dose‑dependent homocysteine reductions in renal transplant recipients (higher folate gave greater lowering).
- A pilot study with simvastatin and folic acid/vitamin B12 in preparation for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH)
PubMed ID: 11079257
Folate+B12 substantially lowered homocysteine in trial; plausible circulation benefit.
- Dietary strategies for lowering homocysteine concentrations
PubMed ID: 10837284
Supplements/fortified cereal raised folate and substantially lowered homocysteine vs diet alone.
- Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine
PubMed ID: 11076820
High‑dose folic acid + B12 reduced free homocysteine (~30%) and improved flow‑mediated dilatation in CAD patients.
- Plasmatic homocysteine response to vitamin supplementation in elderly people
PubMed ID: 11152929
Folate‑rich diet lowered homocysteine in elderly, supporting vascular benefit potential.
- Hyperhomocysteinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins
PubMed ID: 10916110
B‑vitamin (including folate) supplementation substantially reduced very high tHcy in hemodialysis patients.
- Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study
PubMed ID: 10820175
High‑dose folate (15–60 mg) produced marked tHcy reductions in dialysis patients.
- Folate status of elderly women following moderate folate depletion responds only to a higher folate intake
PubMed ID: 10827214
Dose-dependent repletion in elderly normalized folate and reversed homocysteine rise—relevant to vascular health.
- Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease
PubMed ID: 10987596
In coronary disease patients folic acid markedly raised folate and improved endothelial function (FMD) — strong direct vascular benefit.
- Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial
PubMed ID: 10683000
Folic acid + B6 halved fasting homocysteine and was associated with fewer abnormal exercise ECGs—supportive of vascular/cardiac function.
- Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women
PubMed ID: 11035344
500 µg/day in postmenopausal women substantially lowered homocysteine — biomarker supporting vascular health.
- Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial
PubMed ID: 11339442
Low-dose folic acid in young women raised folate and lowered homocysteine dose-dependently—supports vascular risk marker improvement.
- Randomized trial of folic acid supplementation and serum homocysteine levels
PubMed ID: 11231701
Ischemic heart disease trial: ~0.8 mg/day folic acid raised folate and lowered homocysteine by ~23%—relevant to circulation/vascular risk markers.
- Folate supplementation in peritoneal dialysis patients with normal erythrocyte folate: effect on plasma homocysteine
PubMed ID: 11598393
5 mg/day folic acid normalized folate pools and greatly lowered homocysteine in PD patients — relevant to circulation via biomarker change.
- Decreased rate of coronary restenosis after lowering of plasma homocysteine levels
PubMed ID: 11757505
Folate-containing B-vitamin regimen substantially lowered homocysteine and halved restenosis after angioplasty — strong circulatory benefit.
- Homocyst(e)ine metabolism in hemodialysis patients treated with vitamins B6, B12 and folate
PubMed ID: 11426667
IV folate+vitamins markedly cut homocysteine in HD patients — meaningful biochemical vascular marker improvement.
- Long-term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year, randomized, placebo-controlled trial
PubMed ID: 11742887
Two-year high-dose folate+B6 slightly lowered systolic/diastolic BP — modest circulatory benefit.
- Homocysteine--a treatable risk factor for allograft vascular disease after heart transplantation?
PubMed ID: 11448801
5 mg folic acid reduced plasma homocysteine by ~23% in heart transplant patients — beneficial for circulating risk markers.
- Randomized trial of methylcobalamin and folate effects on homocysteine in hemodialysis patients
PubMed ID: 12021520
High-dose folic acid (10 mg/day) produced large reductions in fasting homocysteine in dialysis patients — relevant to vascular risk markers.
- Fiber-multivitamin combination therapy: a beneficial influence on low-density lipoprotein and homocysteine
PubMed ID: 12200762
Combination product (includes folate) lowered LDL and modestly lowered homocysteine — circulation-relevant but confounded.
- Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors
PubMed ID: 12048127
5 mg/day folic acid in smokers raised folate and lowered homocysteine — circulation/vascular biomarker improvements.
- Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial
PubMed ID: 12190367
Post-angioplasty patients on homocysteine‑lowering B-vitamins (incl. folic acid) had fewer repeat procedures — improved vascular outcomes (combination therapy).
- Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial
PubMed ID: 12122551
Low-dose fortified cereal folic acid increased serum folate and reduced homocysteine within 4 weeks.
- Hyperhomocysteinemia in Japanese patients with convalescent stage ischemic stroke: effect of combined therapy with folic acid and mecobalamine
PubMed ID: 12220694
In stroke patients folic acid + mecobalamin produced large homocysteine reductions — relevant to vascular/recurrence risk.
- Decreasing plasma endothelin-1 and unchanged plasma neopterin during folate supplementation in hyperhomocysteinemia
PubMed ID: 12110777
Folate supplementation markedly lowered homocysteine and reduced endothelial activation markers in vascular patients.
- The effect of folic acid supplementation on plasma homocysteine in an elderly population
PubMed ID: 11834770
Elderly RCT showing dose threshold (≥400 µg) to lower homocysteine—supports vascular risk biomarker improvement.
- Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease
PubMed ID: 12395803
Dose‑dependent homocysteine reductions in CHD patients—biomarker improvement relevant to circulation.
- Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering
PubMed ID: 11772871
Acute high‑dose folic acid improved endothelial flow‑mediated dilatation rapidly—direct evidence for improved vascular function.
- Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial
PubMed ID: 14576756
Combined B‑vitamin trial in elderly lowered homocysteine—relevant to vascular health biomarkers.
- Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients
PubMed ID: 12792513
B‑vitamin therapy including folic acid markedly reduced homocysteine and produced large regression in carotid intima‑media thickness.
- Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study
PubMed ID: 12600857
L‑MTHF/folic acid increased plasma/RBC folate and lowered homocysteine—beneficial for circulation biomarkers.
- Homocysteine-lowering treatment with folic acid plus vitamin B6 lowers urinary albumin excretion but not plasma markers of endothelial function or C-reactive protein: further analysis of secondary end-points of a randomized clinical trial
PubMed ID: 12641538
Folic acid+B6 halved homocysteine and reduced albuminuria (~20%), clear vascular-biomarker and endothelial/kidney benefit signal.
- Weekly high-dose folic Acid supplementation is effective in lowering serum homocysteine concentrations in women
PubMed ID: 12652055
Weekly high-dose folic acid lowered homocysteine and increased erythrocyte folate in healthy women (biomarker relevant to circulation).
- Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study
PubMed ID: 12716688
Dose-response RCT showing ~22% homocysteine lowering at ~400 µg/day, relevant to circulation/vascular risk.
- Short-term high-dose folic acid does not alter markers of endothelial cell damage in patients with coronary heart disease
PubMed ID: 15093982
High-dose folic acid improved nitric-oxide–mediated endothelial function in coronary patients (objective vascular function improvement).
- Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial
PubMed ID: 15113718
Fortified cereal including folic acid lowered homocysteine in older adults, supporting vascular biomarker improvement.
- Effect of homocysteine-lowering treatment with folic acid plus vitamin B on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo-controlled, randomized trial
PubMed ID: 15086356
B‑vitamin therapy produced large homocysteine reductions; imaging outcomes trended favorably though not significant.
- No effect of folic acid on markers of endothelial dysfunction or inflammation in patients with type 2 diabetes mellitus and mild hyperhomocysteinaemia
PubMed ID: 15554600
High-dose folic acid lowered homocysteine ~29% in type 2 diabetes, relevant to vascular risk markers despite no change in inflammation markers.
- Oral folic acid enhances endothelial function in patients with hypercholesterolaemia receiving statins
PubMed ID: 15616416
Randomized trial: 5 mg folic acid for 4 weeks improved flow‑mediated dilation (endothelial function), a direct circulation endpoint.
- Folic acid improves endothelial function in children and adolescents with type 1 diabetes
PubMed ID: 15069400
8 weeks of 5 mg folic acid improved flow‑mediated dilation in adolescents with type 1 diabetes (strong endothelial effect).
- Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention
PubMed ID: 15321804
Folic acid + B12 produced large homocysteine reductions, a recognized vascular risk mediator.
- Determining bioavailability of food folates in a controlled intervention study
PubMed ID: 15447898
Folic acid raised serum folate and lowered homocysteine more than food folates—relevant to vascular risk modulation.
- Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia
PubMed ID: 15476449
Folic acid + B12 lowered homocysteine and substantially improved post‑ischemic hyperemic vasodilation in metabolic syndrome.
- Comparative study of response to treatment with supraphysiologic doses of B-vitamins in hyperhomocysteinemic hemodialysis patients
PubMed ID: 15115259
Very high‑dose folic acid + B‑vitamins produced large Hcy reductions in hemodialysis patients (biochemical cardiovascular relevance).
- Cardiovascular effects of oral Supplementation of vitamin C, E and folic acid in young healthy males
PubMed ID: 15580811
Study combining vitamins C/E with folate showed a significant systolic BP reduction, a circulation/pressure endpoint (combination intervention).
- Sustained homocysteine-lowering effect over time of folic acid-based multivitamin therapy in stroke patients despite increasing folate status in the population
PubMed ID: 15608435
Folic‑acid–based multivitamins lowered homocysteine by ~3–4 µmol/L in stroke/TIA patients (biochemical vascular effect).
- Folic acid and vitamin E supplementation effects on homocysteinemia, endothelial function and plasma antioxidant capacity in young myocardial-infarction patients
PubMed ID: 14597156
Randomized trial in young MI patients: folic acid reduced homocysteine ~41% and improved endothelial vasodilation — direct positive vascular effects.
- Aleurone flour increases red-cell folate and lowers plasma homocyst(e)ine substantially in man
PubMed ID: 15877875
Dietary folate intervention raised folate and reduced homocysteine (~25%), a biomarker linked to vascular risk.
- Efficacy of B vitamins in lowering homocysteine in older men: maximal effects for those with B12 deficiency and hyperhomocysteinemia
PubMed ID: 16373648
B‑vitamin tablets (incl. folate) substantially lowered homocysteine in older men, supporting vascular health.
Pregnancy support (158)
- Improving women's preconceptional health: findings from a randomized trial of the Strong Healthy Women intervention in the Central Pennsylvania women's health study
PubMed ID: 19059553
Intervention increased preconception multivitamin (with folic acid) use—direct behavioral relevance for healthy pregnancy preparation.
- Trial of zinc supplements in relation to pregnancy outcomes, hematologic indicators, and T cell counts among HIV-1-infected women in Tanzania
PubMed ID: 15640476
Study context is prenatal iron+folic acid supplementation—folic acid is standard for pregnancy health; although trial tested zinc, folic acid was a core component of prenatal care.
- A prospective, partially randomized study of pregnancy outcomes and hematologic responses to oral and intramuscular iron treatment in moderately anemic pregnant women
PubMed ID: 14684407
Pregnant participants received folic acid alongside iron; study demonstrates hematologic improvements relevant to pregnancy; folic acid is standard prenatal support though study confounds iron effect.
- The (ir)relevance of framing nutrition education messages
PubMed ID: 12803277
Trial directly studied messaging to increase folic acid supplement use before/during pregnancy — directly relevant to pregnancy support (behavioral domain).
- Effect of multivitamin and vitamin A supplements on weight gain during pregnancy among HIV-1-infected women
PubMed ID: 12399282
Daily multivitamin including folic acid modestly increased third‑trimester maternal weight gain in HIV-positive pregnant women — relevant to pregnancy nutrition though effect not isolated to folic acid.
- Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation
PubMed ID: 8882400
Randomized double‑blind trial found periconceptional multivitamin with 0.8 mg folic acid halved major congenital anomaly rates (RR ~0.54), direct high‑certainty evidence.
- The higher rate of multiple births after periconceptional multivitamin supplementation: an analysis of causes
PubMed ID: 8588492
Same trial reported increased multiple births in multivitamin (folic acid) group (pregnancy outcome effect).
- Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report
PubMed ID: 7979565
Randomized periconceptional multivitamin with 0.8 mg folic acid significantly reduced occurrence/recurrence of neural‑tube defects (direct, high-quality evidence).
- Prevention of congenital abnormalities by periconceptional multivitamin supplementation
PubMed ID: 8324432
Periconceptional folic acid in a large randomized trial produced a clear reduction in neural tube defects and other major congenital abnormalities (direct high‑quality evidence).
- Impact of anaemia prophylaxis in pregnancy on maternal haemoglobin, serum ferritin & birth weight
PubMed ID: 1959958
Large trial in pregnancy: daily iron + 500 µg folic acid significantly improved maternal Hb/ferritin and increased mean birth weight / reduced low‑birth‑weight incidence—direct pregnancy benefit.
- The effect of facility-based nutrition education and counseling on dietary intake and supplemental iron folic acid use among pregnant women: a cluster randomised controlled trial
PubMed ID: 41178447
Intervention raised iron‑folic acid (IFA) use and dietary diversity in pregnant women — direct programmatic pregnancy relevance.
- Effects of quintuply-fortified salt on the micronutrient status of females of reproductive age in Punjab, India: a randomized, community-based trial
PubMed ID: 40610127
Quintuply‑fortified salt markedly reduced folate insufficiency in women, supporting improved pregnancy folate status at population level.
- Maternal serum unmetabolized folic acid concentration following multivitamin and mineral supplementation with or without folic acid after 12 weeks gestation: A randomized controlled trial
PubMed ID: 38783413
RCT showing stopping folic acid after 12 weeks lowered UMFA and reduced serum/RBC folate late in pregnancy—direct evidence on maternal folate exposure during pregnancy.
- Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)
PubMed ID: 38478042
Precision dose–response RCT defines doses at which homocysteine falls and serum folate rises—supports establishing adequate dosing for NTD prevention (biomarker basis, not direct NTD outcome).
- Cognitive benefits of folic acid supplementation during pregnancy track with epigenetic changes at an imprint regulator
PubMed ID: 39681839
Maternal folic acid in later pregnancy increased cord folate and ZFP57 methylation and preserved infant processing speed in a subgroup—RCT evidence linking maternal folate to fetal/neonatal outcomes.
- Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms
PubMed ID: 35578268
Randomized continuation of folic acid in later pregnancy increased maternal/foetal folate, altered newborn DNA methylation and associated with improved child cognition—evidence of benefit when continued beyond early pregnancy.
- Effects of individualized administration of folic acid on prothrombotic state and vascular endothelial function with H-type hypertension: A double-blinded, randomized clinical cohort study
PubMed ID: 35060542
Genotype‑guided folic acid improved endothelial and prothrombotic markers in H‑type hypertension—mechanistically relevant to placental perfusion and function.
- Effectiveness of Health Information Package Program on Knowledge and Compliance among Pregnant Women with Anemia: A Randomized Controlled Trial
PubMed ID: 35270420
Education intervention in anemic pregnant women improved IFA compliance and hemoglobin—supports healthier pregnancy course.
- Effect of Picture-based health education and counselling on knowledge and adherence to preconception Iron-folic acid supplementation among women planning to be pregnant in Eastern Ethiopia: a randomized controlled trial
PubMed ID: 35912303
Marked increases in preconception IFA use support appropriate folate status entering pregnancy (key to healthy pregnancy and NTD prevention).
- Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: Secondary analysis of a double-blind randomized controlled trial
PubMed ID: 33594802
Early prenatal MMN (including folic acid) started before 12 weeks reduced pregnancy‑induced hypertension—important pregnancy health benefit.
- Efficacy of 4.0 mg versus 0.4 mg Folic Acid Supplementation on the Reproductive Outcomes: A Randomized Controlled Trial
PubMed ID: 34959975
Randomized trial: 4.0 mg/day periconceptional folic acid associated with fewer spontaneous abortions, SGA infants and preterm deliveries—direct pregnancy outcome benefits.
- The effect of folic acid throughout pregnancy among pregnant women at high risk of pre-eclampsia: A randomized clinical trial
PubMed ID: 31987769
Large RCT: high‑dose folic acid from preconception/early pregnancy reduced recurrent pre‑eclampsia—strong pregnancy benefit.
- [Bioavailability of natural versus synthetic B vitamins and their effects on metabolic processes]
PubMed ID: 32189314
B‑vitamin complex (synthetic) raised folate substantially—supports adequate folate status important for NTD risk reduction though not an outcomes trial.
- Weekly iron-folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia
PubMed ID: 33272946
High‑quality randomized trial: 2.8 mg weekly folic acid produced RBC folate concentrations and % >748 nmol/L strongly associated with low NTD risk—direct evidence for lowering NTD risk.
- Nutrient supplementation during the first 1000 days and growth of infants born to pregnant adolescents
PubMed ID: 31378980
Prenatal LNS (contains folate) reduced newborn stunting and small head circumference in adolescents—fetal growth outcomes improved though multi‑nutrient.
- Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation
PubMed ID: 31005964
Randomized folic acid dosing study derived plasma/RBC folate thresholds linked to optimal neural tube defect prevention—direct biomarker basis for reduced NTD risk.
- Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial)
PubMed ID: 31672132
Continuation of 400 µg/day folic acid after first trimester increased maternal and cord folate and improved child verbal cognition.
- Effectiveness of a Pediatric Primary Care Intervention to Increase Maternal Folate Use: Results from a Cluster Randomized Controlled Trial
PubMed ID: 29246348
Clinic intervention doubled odds of maternal daily folate use—practical pregnancy benefit by increasing supplementation uptake.
- Effects of lipid-based nutrient supplements or multiple micronutrient supplements compared with iron and folic acid supplements during pregnancy on maternal haemoglobin and iron status
PubMed ID: 30047245
Pregnancy trial: standard IFA (60 mg Fe + folic acid) improved haemoglobin and iron markers vs lower iron MMN/LNS—clinical pregnancy benefit.
- Response of Red Blood Cell Folate to Supplementation in Nonpregnant Women is Predictable: A Proposal for Personalized Supplementation
PubMed ID: 29143484
Quantitative RBC‑folate response data enable personalized dosing to achieve levels associated with reduced NTD risk.
- The effectiveness of daily supplementation with 400 or 800 µg/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial
PubMed ID: 28447203
800 µg/day produced higher RBC‑folate and a greater proportion reached RBC thresholds associated with lower neural tube defect risk.
- Lipid-based nutrient supplementation in the first 1000 d improves child growth in Bangladesh: a cluster-randomized effectiveness trial
PubMed ID: 28275125
Maternal LNS (includes folic acid) across pregnancy and early childhood resulted in small but significant improvements in child length and head circumference at 24 months.
- mRNA Levels of Placental Iron and Zinc Transporter Genes Are Upregulated in Gambian Women with Low Iron and Zinc Status
PubMed ID: 28515164
Gambian pregnancy study (supplements including folic acid) changed placental iron‑uptake gene expression (TfR1 increased) and maternal iron markers—shows supplement‑driven placental molecular changes where folic acid was a component.
- Effects of Prenatal Micronutrient Supplementation on Spontaneous Preterm Birth: A Double-Blind Randomized Controlled Trial in China
PubMed ID: 28472219
Very large RCT: starting folate‑containing supplements before 12 weeks substantially reduced spontaneous preterm birth—strong evidence for early pregnancy benefit.
- Randomized control trial comparing effectiveness of weekly versus daily antenatal oral iron supplementation in preventing anemia during pregnancy
PubMed ID: 29271022
Weekly iron+folic acid was non‑inferior to daily for preventing third‑trimester anemia in non‑anemic pregnant women and had fewer side effects—relevant to maternal health in pregnancy.
- A Village-Based Intervention: Promoting Folic Acid Use among Rural Chinese Women
PubMed ID: 28230798
Intervention greatly increased preconception folic acid uptake—by improving uptake it supports healthy pregnancy outcomes indirectly.
- Preconception Micronutrient Supplementation with Iron and Folic Acid Compared with Folic Acid Alone Affects Linear Growth and Fine Motor Development at 2 Years of Age: A Randomized Controlled Trial in Vietnam
PubMed ID: 28615372
Preconception weekly iron+folic acid produced modest but significant improvements in child linear growth and reduced stunting at 24 months—directly supports fetal/early-child growth effects from preconception folate programs.
- The effects of high and low doses of folic acid on oxidation of protein levels during pregnancy: a randomized double-blind clinical trial
PubMed ID: 28866652
Small pregnancy RCT showed folic acid (both low and high dose) reduced maternal homocysteine and protein oxidation—biomarkers relevant to pregnancy health.
- Folic acid fortified milk increases blood folate to concentrations associated with a very low risk of neural tube defects in Singaporean women of childbearing age
PubMed ID: 26965763
400 μg folic‑acid‑fortified milk raised red‑cell folate and plasma folate to levels linked with very low neural‑tube‑defect risk — strong surrogate evidence for lowered NTD risk.
- Evidence from a Randomized Trial That Exposure to Supplemental Folic Acid at Recommended Levels during Pregnancy Does Not Lead to Increased Unmetabolized Folic Acid Concentrations in Maternal or Cord Blood
PubMed ID: 26817717
Randomized continuation of 400 μg folic acid after trimester 1 increased cord blood folate without raising unmetabolized folic acid, indicating fetal folate benefit in pregnancy.
- The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial
PubMed ID: 27166794
Randomized trial comparing 5 mg vs 0.5 mg folic acid in pregnancy showed marked homocysteine lowering, modestly heavier babies and fewer early abortions — direct, high‑relevance evidence for pregnancy outcomes.
- Cost-effectiveness of invitation to food supplementation early in pregnancy combined with multiple micronutrients on infant survival: analysis of data from MINIMat randomized trial, Bangladesh
PubMed ID: 26018633
Early prenatal food supplementation combined with MMS (including folic acid) greatly lowered infant mortality vs later food+IFA—strong combined‑intervention pregnancy benefit (folic acid part of MMS).
- Lipid-based nutrient supplement increases the birth size of infants of primiparous women in Ghana
PubMed ID: 25833980
LNS (contains folic acid among many nutrients) increased birth weight/length/head circumference in primiparous women—evidence for improved fetal growth in that subgroup.
- Multivitamin and iron supplementation to prevent periconceptional anemia in rural tanzanian women: a randomized, controlled trial
PubMed ID: 25905863
Preconception iron+folate reduced hypochromic microcytic anemia—improving maternal status pre-pregnancy and reducing a pregnancy risk factor.
- Pregnancy-induced changes in the long-term pharmacokinetics of 1.1 mg vs. 5 mg folic acid: a randomized clinical trial
PubMed ID: 25167960
Pregnancy PK study: 5 mg/day raised RBC folate earlier and to higher levels than 1.1 mg—directly relevant to pregnancy folate sufficiency.
- Equity in adherence to and effect of prenatal food and micronutrient supplementation on child mortality: results from the MINIMat randomized trial, Bangladesh
PubMed ID: 24393610
Early prenatal food + MMS (includes folic acid) reduced under‑5 mortality and improved outcomes—benefit for fetal/infant growth in combined intervention.
- Effect of daily milk supplementation on serum and umbilical cord blood folic acid concentrations in pregnant Han and Mongolian women and birth characteristics in China
PubMed ID: 25516314
Daily milk intake associated with higher maternal/cord folate and slightly larger newborns (direct association with fetal growth).
- Impact of continuing folic acid after the first trimester of pregnancy: findings of a randomized trial of Folic Acid Supplementation in the Second and Third Trimesters
PubMed ID: 23719554
Randomized continuation of 400 μg/day folic acid after 12 weeks raised maternal and cord RBC folate and prevented homocysteine rise—strong pregnancy‑relevant biochemical effect.
- Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women
PubMed ID: 22932279
Prenatal folic acid‑containing supplement produced high maternal blood folate and increased breast‑milk folic acid—directly relevant to pregnancy nutrition.
- Effects of prenatal micronutrient and early food supplementation on maternal hemoglobin, birth weight, and infant mortality among children in Bangladesh: the MINIMat randomized trial
PubMed ID: 22665104
Prenatal early food + MMS (including folic acid) markedly reduced infant and under‑5 mortality in MINIMat — supports benefit of comprehensive prenatal nutrition including folate.
- Rationale, design, methodology and sample characteristics for the Vietnam pre-conceptual micronutrient supplementation trial (PRECONCEPT): a randomized controlled study
PubMed ID: 23092451
PRECONCEPT trial protocol (weekly preconception folic acid vs alternatives) is directly designed to assess effects on birth outcomes — highly relevant though no outcomes reported here.
- Oral cleft prevention program (OCPP)
PubMed ID: 23181832
Large RCT protocol comparing 4 mg vs 0.4 mg preconception folic acid to reduce recurrence of orofacial clefts — directly targets birth‑defect prevention (protocol only).
- Folate status of reproductive age women and neural tube defect risk: the effect of long-term folic acid supplementation at doses of 140 µg and 400 µg per day
PubMed ID: 22254076
Randomized folic acid (140 vs 400 μg) raised RBC folate and reduced prevalence below the 906 nmol/L RBC folate threshold associated with lower neural-tube-defect risk—strong biomarker evidence.
- Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population
PubMed ID: 20412605
Pregnant women taking a multivitamin including folic acid had small hemoglobin/folate increases and fewer small-for-gestational-age infants among compliant users.
- A combination of iron and retinol supplementation benefits iron status, IL-2 level and lymphocyte proliferation in anemic pregnant women
PubMed ID: 21147712
In anemic pregnant women, iron+retinol+folic acid improved iron and some immune markers vs iron alone; folate included in interventions improving maternal status.
- Effects of maternal micronutrient supplementation on fetal loss and under-2-years child mortality: long-term follow-up of a randomised controlled trial from Guinea-Bissau
PubMed ID: 21243915
Antenatal multiple‑micronutrient supplement including folate modestly reduced fetal loss vs iron‑folate (large trial) — direct pregnancy outcome improvement.
- Supplementation of iron alone and combined with vitamins improves haematological status, erythrocyte membrane fluidity and oxidative stress in anaemic pregnant women
PubMed ID: 20615267
Iron+folic acid improved hemoglobin in anemic pregnant women—important for maternal pregnancy health.
- From the Field: Improving Fetal and Infant Growth in Vulnerable Populations
PubMed ID: 29734823
SQ-LNS prenatal/postnatal supplementation improved birth weight and 18-month length vs IFA/MMN — direct evidence for improved fetal/infant growth (multinutrient context).
- Prenatal supplementation with Corn Soya Blend Plus reduces the risk of maternal anemia in late gestation and lowers the rate of preterm birth but does not significantly improve maternal weight gain and birth anthropometric measurements in rural Cambodian women: a randomized trial
PubMed ID: 26739037
CSB Plus (on background iron‑folic acid) lowered preterm birth and late‑gestation anemia — clinically relevant pregnancy benefits, though folic acid was provided to all.
- Small-quantity, lipid-based nutrient supplements provided to women during pregnancy and 6 mo postpartum and to their infants from 6 mo of age increase the mean attained length of 18-mo-old children in semi-urban Ghana: a randomized controlled trial
PubMed ID: 27534634
LNS recipients (product contained folic acid) had modestly greater length and lower stunting at 18 months — supports improved early growth outcomes though folic acid not isolated.
- Impact evaluation of a population-based 'Screen and Treat for Anaemia Reduction (STAR)' strategy: a cluster randomised trial in rural Telangana, India
PubMed ID: 41448804
Large community IFA screen-and-treat targeted adolescent girls and women of reproductive age and significantly improved hemoglobin and reduced anemia—directly relevant to pregnancy health.
- Antenatal micronutrient supplementation and third trimester cortisol and erythropoietin concentrations
PubMed ID: 25059838
Randomized antenatal micronutrient arms (including folic acid in some) altered maternal biomarkers related to pregnancy outcomes (moderate evidence, folate not isolated).
- The effect of intermittent antenatal iron supplementation on maternal and infant outcomes in rural Viet Nam: a cluster randomised trial
PubMed ID: 23853552
This randomized antenatal trial directly studied iron–folic acid regimens in pregnancy; although folic acid was not isolated, the trial context is directly about folic-acid–containing prenatal supplementation and maternal/infant endpoints.
- Once a week (200 mg) elemental iron: an effective option for prophylaxis in non-anaemic pregnant women
PubMed ID: 22480099
Pregnant‑women trial of weekly vs daily iron+folic acid showed hemoglobin increases and better tolerability — direct evidence of folic acid as part of pregnancy supplementation regimens.
- Modifying effect of maternal nutritional status on the impact of maternal multiple micronutrient supplementation on birthweight in Indonesia
PubMed ID: 21673719
Large trial in ~14,000 births compared MMN vs iron+folic acid; showed improved birthweight/LBW outcomes in better‑nourished women — folic acid was the comparator and directly relevant to pregnancy nutrition.
- Dietary diversity as a modifier of the effect of supplementation with multiple micronutrients during pregnancy on low birth weight in a randomized controlled trial in Bangladesh
PubMed ID: 40653272
Directly compares multiple micronutrient supplements vs iron‑folic acid (IFA) in pregnant women; IFA (contains folic acid) was comparator and results relate directly to birthweight outcomes and folic acid policy.
- A cluster randomized controlled trial of a community-based initiative to reduce stunting in rural Indonesia
PubMed ID: 38041533
Large community RCT increased iron–folic‑acid tablet consumption during pregnancy—direct programmatic evidence supporting pregnancy‑targeted folic acid delivery (though no reduction in stunting outcome).
- Multivitamin Supplementation Is Associated with Greater Adequacy of Gestational Weight Gain among Pregnant Women in Tanzania
PubMed ID: 34964890
Daily multivitamin (including folic acid) in pregnant women modestly improved adequacy of gestational weight gain—direct pregnancy outcome relevance though not folic acid–only.
- Factors influencing quality nutrition service provision at antenatal care contacts: Findings from a public health facility-based observational study in 21 districts of Bangladesh
PubMed ID: 35085319
Directly reports on antenatal iron–folic acid (IFA) provision in public ANC services; highly relevant to folic acid's role in pregnancy care delivery.
- Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial
PubMed ID: 35276810
In iron‑deficient pregnant women, adding folinic acid to iron supplementation improved Hb, iron stores and slightly increased newborn weight—direct, clinically relevant maternal/pregnancy outcomes.
- The effect of Lactiplantibacillus plantarum 299v together with a low dose of iron on iron status in healthy pregnant women: A randomized clinical trial
PubMed ID: 33880752
Pregnant women receiving probiotic+low‑dose iron+folic acid had better iron status and Hb trajectories — supports maternal health in pregnancy when folic acid included.
- Preconception micronutrient supplementation positively affects child intellectual functioning at 6 y of age: A randomized controlled trial in Vietnam
PubMed ID: 33668050
Large RCT in preconception setting used folic acid control — provides direct context for periconception folic acid use (standard of care) though this trial compared broader MM vs FA alone.
- Promoting fertility awareness and preconception health using a chatbot: a randomized controlled trial
PubMed ID: 33039321
Fertility‑education intervention increased intentions to take folic acid preconception — directly relevant to pregnancy preparation.
- Using reproductive life plan-based information in a primary health care center increased Iranian women's knowledge of fertility, but not their future fertility plan: A randomized, controlled trial
PubMed ID: 30267937
RLP counseling markedly increased preconception folic-acid intake (behavioral prep for pregnancy) — strong for pregnancy preparation though outcomes not measured.
- Effects of prenatal food and micronutrient supplementation on child growth from birth to 54 months of age: a randomized trial in Bangladesh
PubMed ID: 22152147
Large randomized prenatal nutrition trial where folate (400 μg) was included in randomized micronutrient supplements — directly relevant to pregnancy outcomes (stunting/HAZ) and maternal supplementation practices.
- Multiple micronutrient supplementation during early childhood increases child size at 2 y of age only among high compliers
PubMed ID: 19225121
High‑compliance maternal multiple‑micronutrient supplementation (including folic acid) was associated with modestly increased child length at 24 months—supports fetal/early growth signal.
- Micronutrient supplementation affects maternal-infant feeding interactions and maternal distress in Bangladesh
PubMed ID: 19439457
Pregnancy trial arms all contained 400 µg folic acid as part of micronutrient regimens; study addressed maternal outcomes and postpartum distress.
- Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial
PubMed ID: 18996930
Large rural China trial used folic acid as the control arm; comparisons with iron–folic acid and multiple micronutrients showed meaningful effects on birth weight, gestation, and early neonatal mortality—direct antenatal relevance.
- Supplementation with a multivitamin containing 800 microg of folic acid shortens the time to reach the preventive red blood cell folate concentration in healthy women
PubMed ID: 20108207
800 µg folic acid raised RBC folate above the protective threshold for neural tube defects rapidly—strong direct evidence for reducing NTD risk.
- Comparison study on the effect of prenatal administration of high dose and low dose folic acid
PubMed ID: 19139780
Higher prenatal folic acid dose markedly lowered maternal homocysteine (dose‑dependent) during pregnancy—relevant to maternal metabolic health.
- Periconceptional iron supplementation does not reduce anemia or improve iron status among pregnant women in rural Bangladesh
PubMed ID: 19793860
Preconception IFA improved iron status in nonpregnant women, supporting better prepregnancy health when started early and adhered to.
- Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural Nepal
PubMed ID: 19368922
Large RCT in rural Nepal: prenatal folic acid+iron reduced postpartum hemorrhage and puerperal sepsis—clear pregnancy benefit.
- Providing iron/folic acid tablets free of charge improves compliance in pregnant women in Senegal
PubMed ID: 19203773
Free iron+folic acid program markedly increased uptake and halved anemia in pregnant women—strong programmatic pregnancy benefit.
- A comparative evaluation of multiple micronutrient and iron-folic acid supplementation during pregnancy in Pakistan: impact on pregnancy outcomes
PubMed ID: 20120791
Multiple micronutrients vs iron‑folic acid increased mean birthweight by ~70 g (multinutrient context limits attribution to folic acid alone).
- Programmatic effects of a large-scale multiple-micronutrient supplementation trial in Indonesia: using community facilitators as intermediaries for behavior change
PubMed ID: 20496613
Programmatic supplementation (including folic acid) plus community facilitation reduced early infant deaths—relevant to pregnancy/newborn outcomes.
- Steady state folate concentrations achieved with 5 compared with 1.1 mg folic acid supplementation among women of childbearing age
PubMed ID: 19158211
Higher/faster attainment of RBC folate with 5 mg folic acid supports prevention of neural‑tube defects (biomarker strongly linked to lower NTD risk).
- Preventing low birthweight through maternal multiple micronutrient supplementation: a cluster-randomized, controlled trial in Indramayu, West Java
PubMed ID: 20120790
Cluster RCT: MM (which includes folic acid) yielded fewer adverse perinatal outcomes among high‑adherence women compared with IFA.
- Antenatal and postnatal iron supplementation and childhood mortality in rural Nepal: a prospective follow-up in a randomized, controlled community trial
PubMed ID: 19778983
Large randomized community trial: maternal iron–folic acid supplementation associated with ~31% reduction in offspring mortality through age 7—strong pregnancy/neonatal benefit.
- Prenatal multiple micronutrient supplementation impact on biochemical indicators during pregnancy and postpartum
PubMed ID: 19668928
Prenatal MM modestly improved postpartum folate deficiency rates vs iron‑only, supporting maternal folate status.
- Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial
PubMed ID: 18207017
MM vs IFA reduced low birthweight and early infant mortality in undernourished/anaemic subgroups; folic acid was part of baseline IFA regimen.
- Effect of different dosage and administration schedules of folic acid on blood folate levels in a population of Honduran women of reproductive age
PubMed ID: 18426639
Demonstrated faster attainment of protective folate levels with daily dosing—important for periconceptional pregnancy protection.
- Effects of antenatal multiple micronutrient supplementation on children's weight and size at 2 years of age in Nepal: follow-up of a double-blind randomised controlled trial
PubMed ID: 18262041
Maternal multiple‑vitamin use associated with slightly higher infant weight and head circumference at 2.5 years.
- Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring
PubMed ID: 8585581
Periconceptional multivitamin use that included folic acid was associated with substantially lower risks of certain heart and limb birth defects — direct, strong pregnancy benefit.
- Improving preventive service delivery at adult complete health check-ups: the Preventive health Evidence-based Recommendation Form (PERFORM) cluster randomized controlled trial
PubMed ID: 16836761
Primary‑care checklist substantially increased folic acid counseling — improves pregnancy preventive care delivery.
- The effect of preconception counselling on lifestyle and other behaviour before and during pregnancy
PubMed ID: 19059545
Preconception counseling greatly increased folic acid initiation before pregnancy — strong implementation evidence supporting healthy pregnancy.
- An intervention in contraceptive counseling increased the knowledge about fertility and awareness of preconception health-a randomized controlled trial
PubMed ID: 31495254
Counseling markedly raised knowledge that folic acid should be taken before pregnancy—direct behavioral evidence supporting healthy pregnancy preparation.
- First effective mHealth nutrition and lifestyle coaching program for subfertile couples undergoing in vitro fertilization treatment: a single-blinded multicenter randomized controlled trial
PubMed ID: 32741619
mHealth coaching increased folic acid supplement use in couples undergoing IVF/ICSI—relevant to improving pregnancy preconception care.
- Smartphone-based lifestyle coaching modifies behaviours in women with subfertility or recurrent miscarriage: a randomized controlled trial
PubMed ID: 34053852
App‑based coaching increased folic acid intake and was associated with higher pregnancy odds—links folic acid uptake to pregnancy outcomes via behavior.
- Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on cognitive development of children at 6.5 y of age
PubMed ID: 21849596
Direct prenatal trial of 5‑MTHF during pregnancy — addresses folate use in pregnancy even though no child cognitive benefit was observed.
- Effects of a combined micronutrient supplementation on maternal biological status and newborn anthropometrics measurements: a randomized double-blind, placebo-controlled trial in apparently healthy pregnant women
PubMed ID: 14679367
Micronutrient supplementation including folic acid raised maternal folate and resulted in higher birth weight and fewer low‑weight infants—strong pregnancy benefit.
- Multivitamin supplementation of HIV-positive women during pregnancy reduces hypertension
PubMed ID: 15987864
Multivitamin (0.8 mg folic acid) during pregnancy reduced pregnancy hypertension risk in HIV+ women—important pregnancy outcome.
- Vitamin supplementation of HIV-infected women improves postnatal child growth
PubMed ID: 15817867
Maternal multivitamins including folic acid improved child attained weight and growth z-scores at 24 months.
- Improving women's diet quality preconceptionally and during gestation: effects on birth weight and prevalence of low birth weight--a randomized controlled efficacy trial in India (Mumbai Maternal Nutrition Project)
PubMed ID: 25332324
Per‑protocol analysis showed increased newborn weight and fewer low‑birthweight infants with a supplement that increased folate intake.
- Maternal B-vitamin and vitamin D status before, during, and after pregnancy and the influence of supplementation preconception and during pregnancy: Prespecified secondary analysis of the NiPPeR double-blind randomized controlled trial
PubMed ID: 38051700
Preconception‑to‑delivery trial showed folate/other B‑vitamin status improved and baseline folic acid raised folate in early pregnancy—direct relevance to pregnancy health.
- l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women
PubMed ID: 29878267
l‑5‑MTHF raised RBC folate more than folic acid — higher folate status is important for pregnant women.
- Functionality of endogenous folates from rye and orange juice using human in vivo model
PubMed ID: 12474071
Food folates and fortified folic acid raised serum/RBC folate — increased folate status is directly relevant to pregnancy health.
- Multicentric study of efficacy of periconceptional folic acid containing vitamin supplementation in prevention of open neural tube defects from India
PubMed ID: 11247198
Periconceptional multivitamin containing 4 mg folic acid substantially reduced recurrence of open neural tube defects — direct pregnancy benefit.
- Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status
PubMed ID: 17065044
Multi‑antioxidant (including folic acid) in pregnant women was associated with fewer preeclampsia cases and better perinatal outcomes in a small trial.
- Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women
PubMed ID: 17302515
Randomized double‑blind folic acid fortification in pregnant women robustly raised serum/erythrocyte folate and lowered homocysteine.
- Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women
PubMed ID: 23616513
Randomized fortification raised erythrocyte and plasma folate—strong surrogate evidence because adequate maternal folate is the established preventive factor for NTDs.
- Integrating Nutrition Interventions into an Existing Maternal, Neonatal, and Child Health Program Increased Maternal Dietary Diversity, Micronutrient Intake, and Exclusive Breastfeeding Practices in Bangladesh: Results of a Cluster-Randomized Program Evaluation
PubMed ID: 29021370
Program evaluation showed large increases in iron–folic‑acid uptake and other pregnancy‑relevant behaviors—direct programmatic support for healthy pregnancy.
- Maternal nutrition intervention and maternal complications in 4 districts of Bangladesh: A nested cross-sectional study
PubMed ID: 31584939
Areas with integrated maternal nutrition (including IFA) had fewer postpartum complications and lower PPH—beneficial pregnancy outcomes linked to maternal supplementation.
- Integrating Calcium Into Antenatal Iron-Folic Acid Supplementation in Ethiopia: Women's Experiences, Perceptions of Acceptability, and Strategies to Support Calcium Supplement Adherence
PubMed ID: 33008855
Household trials in rural Ethiopia showed acceptability/adherence patterns for antenatal calcium coadministered with IFA (contains folic acid)—programmatic relevance to pregnancy folate delivery.
- Strengthening Nutrition Interventions in Antenatal Care Services Affects Dietary Intake, Micronutrient Intake, Gestational Weight Gain, and Breastfeeding in Uttar Pradesh, India: Results of a Cluster-Randomized Program Evaluation
PubMed ID: 34038529
Large cluster program evaluation increased IFA (including folic acid) receipt and consumption in pregnant women—strong programmatic evidence for improving pregnancy folate exposure.
- Longitudinal Nutritional Intakes in Italian Pregnant Women in Comparison with National Nutritional Guidelines
PubMed ID: 35565911
Dietary assessment in pregnant women revealed insufficient folate intake—underscores the need for supplementation in pregnancy (supporting the benefit by deficit evidence).
- Serum Concentrations of Folate Forms Following Supplementation of Multimicronutrients with 400 µg or 800 µg Mix of (6S)-5-Methyltetrahydrofolate and Folic Acid (1:1) in Women of Childbearing Age
PubMed ID: 39466653
Supplementation with (6S)‑5‑MTHF/folic acid in women of childbearing age raised circulating active folate in a dose‑dependent fashion—directly relevant to pregnancy folate status and prevention strategies.
- Efficacy of a Personalized mHealth App in Improving Micronutrient Supplement Use Among Pregnant Women in Karachi, Pakistan: Parallel-Group Randomized Controlled Trial
PubMed ID: 40203301
mHealth intervention substantially increased pregnant women's uptake of folic acid and improved supplement adherence—directly relevant to pregnancy folate coverage.
- Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation
PubMed ID: 1307234
High‑quality randomized evidence that periconceptional multivitamin including 0.8 mg folic acid markedly reduced first‑occurrence neural‑tube defects.
- [Prevention of the first occurrence of anencephaly and spina bifida with periconceptional multivitamin supplementation (conclusion)]
PubMed ID: 7970646
Randomized trial where multivitamin containing 0.8 mg folic acid prevented neural‑tube defects (clear, large clinical effect).
- The effect of docosahexaenoic acid and folic acid supplementation on placental apoptosis and proliferation
PubMed ID: 16870008
DHA + 5‑MTHF increased placental PCNA (proliferation marker) in late pregnancy—direct placental effect where folate was part of the intervention.
- Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial
PubMed ID: 17490978
Factorial trial showed MTHF associated with higher maternal DHA proportions—positive pregnancy nutritional interaction (combined trial).
- Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group
PubMed ID: 1677062
Large randomized trial showed ~72% reduction in recurrent neural tube defects with periconceptional folic acid — direct, high‑certainty evidence.
- A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group
PubMed ID: 1489222
Randomized evidence showing no NTD recurrences in folic acid arms; supportive clinical data.
- Maternal erythropoietin in singleton pregnancies: a randomized trial on the effect of oral hematinic supplementation
PubMed ID: 8141223
Iron+folic acid supplementation increased maternal iron stores and slightly higher hemoglobin late in pregnancy — supportive of maternal hematologic health (folate was co‑administered).
- Postpartum folic acid supplementation of adolescents: impact on maternal folate and zinc status and milk composition
PubMed ID: 7625346
Postpartum folic acid prevented RBC folate decline in adolescent mothers — important for maternal folate status around pregnancy/lactation.
- Blood folic acid and vitamin B12 in relation to neural tube defects
PubMed ID: 8605127
Case–control observations show lower folate/B12 in pregnancies affected by NTDs — consistent evidence linking folate status to NTD risk.
- Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects
PubMed ID: 8596381
Randomized interventions raising red‑cell folate via supplements/fortified foods support approaches that reduce NTD risk by increasing tissue folate.
- Minimum effective dose of folic acid for food fortification to prevent neural-tube defects
PubMed ID: 9400511
Dose‑dependent increases in red‑cell folate with 200–400 µg/day achieved levels associated with lower neural‑tube defect risk — strong mechanistic and biomarker support.
- Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women
PubMed ID: 9808229
400 µg folic acid lowered homocysteine in women of childbearing age — relevant to periconceptional folate status.
- Maternal folate status during extended lactation and the effect of supplemental folic acid
PubMed ID: 9989694
Supplementing breastfeeding mothers with 1 mg folic acid increased maternal and milk folate and stabilized homocysteine — supports peripartum folate adequacy.
- The influence of folic acid supplement on the outcome of pregnancies in the county of Funen in Denmark. Part I
PubMed ID: 10597955
Community folic acid (1.0–2.5 mg) associated with modest increases in birthweight and reduced preterm/low birth weight when started preconceptionally.
- Changes in iron status during pregnancy in peruvian women receiving prenatal iron and folic acid supplements with or without zinc
PubMed ID: 10731503
Iron+folic acid improved iron stores overall in pregnancy though folic acid effect not isolated—some pregnancy hematologic benefit.
- Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial
PubMed ID: 11339442
Low-dose folic acid raised folate biomarkers in young women of reproductive age—a proxy for reduced neural-tube defect risk though trial did not measure birth defects.
- Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone)
PubMed ID: 11355560
Daily iron with folic acid substantially reduced typical Hb decline in pregnancy—protects maternal hematologic status.
- Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid
PubMed ID: 12421850
Low-dose folic acid substantially increased plasma and RBC folate in women of childbearing age — strong relevance to pregnancy prep.
- Iron plus folate is more effective than iron alone in the treatment of iron deficiency anaemia in pregnancy: a randomised, double blind clinical trial
PubMed ID: 12269674
Pregnant women with iron-deficiency anemia had larger Hb rises when given iron+folinic acid — direct pregnancy cohort benefit.
- Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women
PubMed ID: 12495257
Iron–folate supplementation raised haemoglobin in anaemic pregnant women — clear pregnancy health relevance.
- 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women
PubMed ID: 11815318
400 µg/day in young women raised folate and lowered homocysteine—supports preconception folate sufficiency.
- Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age
PubMed ID: 12391385
Folic acid in women of childbearing age raised folate stores and lowered homocysteine—preparation for healthy pregnancy.
- Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal
PubMed ID: 14668283
Maternal folic acid reduced early deaths in preterm infants—important pregnancy/neonatal outcome improvement.
- [Changes in plasma zinc and folic acid concentrations in pregnant adolescents submitted to different supplementation regimens]
PubMed ID: 12700794
Supplementation in pregnant adolescents markedly increased folate status—direct pregnancy nutritional benefit.
- A micronutrient-fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women
PubMed ID: 12730420
Multimicronutrient beverage containing folate halved anemia risk in pregnant women, supporting pregnancy health though folate-specific contribution uncertain.
- Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe
PubMed ID: 15213046
Multimicronutrient supplementation (on background iron+folic acid) was associated with increased birth size—pregnancy growth effect though folate not isolated.
- Intermittent iron supplementation regimens are able to maintain safe maternal hemoglobin concentrations during pregnancy in Venezuela
PubMed ID: 15113952
Intermittent iron regimens that included folic acid generally maintained safe maternal hemoglobin—relevant to healthy pregnancy outcomes.
- Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities
PubMed ID: 15523663
Clear large‑scale evidence: periconceptional folic‑acid–containing multivitamins greatly reduced neural tube defects and some congenital heart defects.
- Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women
PubMed ID: 14985695
RCT in nonpregnant women: daily 400 µg folic acid raised RBC folate more than weekly dosing and a greater proportion reached the target associated with lower NTD risk — strong preconception evidence.
- Effect of time of initiation and dose of prenatal iron and folic acid supplementation on iron and folate nutriture of Korean women during pregnancy
PubMed ID: 16210715
Starting prenatal iron+folic acid earlier preserved maternal folate/iron status better than later start — practical pregnancy nutrition evidence.
- Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age
PubMed ID: 15927936
Large randomized trial in women of childbearing age produced marked RBC/plasma folate increases — directly relevant to periconception folate sufficiency.
- Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women
PubMed ID: 16740440
Nonanemic pregnant women: daily iron+folic acid prevented anemia better than weekly dosing, but increased hemoconcentration risk and adverse birth outcomes — strong effect on pregnancy hematology but safety tradeoffs.
- Milk folate secretion is not impaired during iron deficiency in humans
PubMed ID: 16988136
Folic acid supplementation in breastfeeding women preserved maternal and milk folate concentrations — supports peripartum maternal folate status relevant to pregnancy/postpartum nutrition.
- Lack of inhibition of the anti-malarial action of sulfadoxine-pyrimethamine by folic acid supplementation when used for intermittent preventive treatment in Gambian primigravidae
PubMed ID: 16760504
Adding folic acid to iron during pregnancy did not impair antimalarial efficacy and slightly increased hemoglobin—supporting safe use in pregnancy with some hematologic benefit.
- [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation
PubMed ID: 16600937
In lactating women [6S]-5‑methylTHF maintained higher RBC folate than placebo and slightly more than folic acid, supporting peripartum folate status.
- Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age
PubMed ID: 16825690
5‑MTHF raised RBC folate more than folic acid in women of childbearing age—strong biomarker evidence relevant to pregnancy folate status.
- A randomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy
PubMed ID: 17915799
Iron formulations given with folic acid/B12 raised hemoglobin in pregnant women with anemia — supports maternal hematologic health during pregnancy (combination therapy).
- Computerized counseling for folate knowledge and use: a randomized controlled trial
PubMed ID: 19000845
Study directly increased women's knowledge and uptake of folate supplements known to lower neural tube defect risk — strong behavioral linkage.
- Effects of prenatal food and micronutrient supplementation on infant development: a randomized trial from the Maternal and Infant Nutrition Interventions, Matlab (MINIMat) study
PubMed ID: 18326610
Early food + multiple micronutrients (including folate) produced modest developmental/size gains in infants of undernourished mothers.
- Effect of Nutritional Interventions on Micronutrient Status in Pregnant Malawian Women with Moderate Malnutrition: A Randomized, Controlled Trial
PubMed ID: 29986492
In pregnant, moderately malnourished women, higher maternal folate (from supplementation) associated with modest increases in infant birth length → direct evidence of impact on fetal growth.
- The effects of a household conditional cash transfer programme on coverage and quality of antenatal care: a secondary analysis of Indonesia's pilot programme
PubMed ID: 29061598
Policy intervention increased coverage and receipt of iron–folic acid supplements during pregnancy — strong implementation evidence that pregnant women are more likely to get folic acid, supporting healthier pregnancies indirectly.
Heart health (115)
- High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial
PubMed ID: 19118243
High‑dose B‑vitamin supplementation (including folic acid) markedly lowered homocysteine but did not reduce atherosclerosis overall; some subgroup benefit.
- Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers
PubMed ID: 30401001
Largest RCT evidence for tHcy lowering with folic acid—tHcy reduction is mechanistically linked to cardiovascular risk reduction strategies.
- Interaction of serum calcium and folic acid treatment on first stroke in hypertensive males
PubMed ID: 33148481
Large RCT subgroup showing folic acid added to antihypertensive therapy substantially reduced first‑stroke risk—a major cardiovascular outcome related to heart/vascular health.
- B-vitamin Treatment Modifies the Mortality Risk Associated with Calcium Channel Blockers in Patients with Suspected Stable Angina Pectoris: A Prospective Cohort Study
PubMed ID: 37121550
B‑vitamin treatment (including folic acid) modified the increased mortality risk seen with CCBs—implies cardiovascular benefit in this context.
- Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease
PubMed ID: 15930443
PAD patients improved walking distance and reduced cholesterol/homocysteine with a supplement containing folic acid—cardiovascular benefit (multi-nutrient).
- Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program
PubMed ID: 17237316
Post-MI men given fortified milk including folic acid had reductions in LDL/total cholesterol and hs-CRP—favorable for heart health (multi-nutrient).
- Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 does not affect the proportion of (n-3) long chain polyunsaturated fatty acids in plasma phosphatidylcholine
PubMed ID: 18287365
Homocysteine lowering by B‑vitamins including folate has plausible heart-protective implications, though outcome benefits were not consistently shown.
- Milk enriched with "healthy fatty acids" improves cardiovascular risk markers and nutritional status in human volunteers
PubMed ID: 19084376
Year-long enriched milk improved lipids and folate status—supports heart-risk-factor improvement (combined intervention).
- Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide?
PubMed ID: 11451751
Improved FMD and reduced intracellular oxidative stress after folic acid suggests cardioprotective endothelial effects.
- Global improvement of vascular function and redox state with low-dose folic acid: implications for folate therapy in patients with coronary artery disease
PubMed ID: 17420345
Low‑dose folic acid improved vascular NO bioavailability and reduced oxidative stress—mechanisms relevant to heart health.
- Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia
PubMed ID: 8416664
Normalization of homocysteine by folate/B‑vitamin therapy is plausibly cardioprotective though no clinical events were measured.
- Vitamin requirements for the treatment of hyperhomocysteinemia in humans
PubMed ID: 7931701
Marked homocysteine lowering with folic acid supports a mechanism tied to cardiovascular risk reduction (biomarker evidence).
- Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid
PubMed ID: 7714461
Folic acid reduced homocysteine in acute MI patients — clinically relevant biomarker change for heart disease contexts.
- Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers
PubMed ID: 9514403
High-dose folic acid produced robust homocysteine reductions — commonly considered relevant to heart disease risk.
- Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease
PubMed ID: 9535664
Folic-acid–fortified cereal lowered homocysteine in coronary disease patients — directly relevant to cardiac risk markers.
- The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study
PubMed ID: 9683392
Dietary folic acid reduced homocysteine in healthy adults — mechanistic support for cardiovascular risk factor modification.
- Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease
PubMed ID: 10539749
Dietary folate raising lowered homocysteine in at‑risk subjects, relevant to cardiovascular risk.
- Dietary strategies for lowering homocysteine concentrations
PubMed ID: 10837284
Supplements/fortified cereals produced substantial homocysteine reductions vs dietary change alone.
- Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine
PubMed ID: 11076820
In men with heart disease folate+B12 improved endothelial function and markedly reduced free homocysteine.
- Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease
PubMed ID: 10987596
Improved endothelial function (FMD) in CAD patients after folic acid—clinically relevant heart health effect.
- Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial
PubMed ID: 10683000
Folic acid + B6 reduced homocysteine and was associated with fewer abnormal exercise ECGs—supports cardiac endpoints.
- Randomized trial of folic acid supplementation and serum homocysteine levels
PubMed ID: 11231701
Ischemic heart disease patients had substantial homocysteine lowering with folic acid—relevant to cardiac risk management.
- Decreased rate of coronary restenosis after lowering of plasma homocysteine levels
PubMed ID: 11757505
B-vitamin (including folate) regimen reduced restenosis and need for revascularization after angioplasty — strong heart-specific clinical benefit.
- Homocysteine--a treatable risk factor for allograft vascular disease after heart transplantation?
PubMed ID: 11448801
Folate significantly lowered homocysteine in heart transplant recipients — favorable biomarker change for cardiac risk.
- Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial
PubMed ID: 12190367
Large RCT after angioplasty showed fewer major cardiac events with B‑vitamin regimen including folic acid (combination therapy).
- Decreasing plasma endothelin-1 and unchanged plasma neopterin during folate supplementation in hyperhomocysteinemia
PubMed ID: 12110777
Marked homocysteine lowering with folate accompanied by declines in vascular activation markers — heart-relevant biomarkers.
- The effect of folic acid supplementation on plasma homocysteine in an elderly population
PubMed ID: 11834770
Elderly trial showing required dose to lower homocysteine—relevant to heart disease risk factors.
- Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease
PubMed ID: 12395803
Dose‑dependent homocysteine lowering in CHD patients—supports cardiac risk biomarker improvement.
- Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering
PubMed ID: 11772871
Acute improvement in endothelial function supports cardiac vascular health mechanisms.
- Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial
PubMed ID: 14576756
B‑vitamin combo lowered homocysteine and MMA in elderly—supportive biochemical effects for heart health.
- Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients
PubMed ID: 12792513
Marked homocysteine reduction and cIMT regression—strong surrogate support for heart/vascular health.
- Homocysteine-lowering treatment with folic acid plus vitamin B6 lowers urinary albumin excretion but not plasma markers of endothelial function or C-reactive protein: further analysis of secondary end-points of a randomized clinical trial
PubMed ID: 12641538
Large homocysteine reduction and reduced albuminuria suggest vascular/kidney improvements that may support heart health.
- Weekly high-dose folic Acid supplementation is effective in lowering serum homocysteine concentrations in women
PubMed ID: 12652055
Homocysteine lowering and erythrocyte folate increases are favorable biomarkers for cardiovascular risk.
- Short-term high-dose folic acid does not alter markers of endothelial cell damage in patients with coronary heart disease
PubMed ID: 15093982
Improved endothelial (NO-mediated) function in coronary disease patients after high-dose folic acid, directly relevant to heart vascular function.
- Oral folic acid enhances endothelial function in patients with hypercholesterolaemia receiving statins
PubMed ID: 15616416
Improved endothelial function with folic acid supports myocardial/vascular health mechanisms.
- Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention
PubMed ID: 15321804
Large homocysteine lowering with folic acid + B12, homocysteine being a cardiac risk biomarker.
- Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia
PubMed ID: 15476449
Folic acid + B12 improved endothelial function and insulin resistance—favorable for heart risk profile.
- Sustained homocysteine-lowering effect over time of folic acid-based multivitamin therapy in stroke patients despite increasing folate status in the population
PubMed ID: 15608435
Folic‑acid–based multivitamins lowered homocysteine in stroke/TIA patients (biomarker improvement though clinical benefit unproven).
- Folic acid and vitamin E supplementation effects on homocysteinemia, endothelial function and plasma antioxidant capacity in young myocardial-infarction patients
PubMed ID: 14597156
Homocysteine reduction and improved endothelial function in young MI patients indicate potential heart‑related benefit (small study).
- Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype
PubMed ID: 16002796
Reduced pulse pressure and large-artery stiffness are heart-relevant hemodynamic improvements.
- [Treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients with vitamin B]
PubMed ID: 16083628
B‑vitamin regimen (incl. folate) lowered homocysteine and improved endothelial function in renal transplant patients, relevant for cardiac vascular health.
- Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus
PubMed ID: 16818571
Marked improvement in endothelial function (FMD) in children with type 1 diabetes implies improved cardiovascular risk physiology.
- Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
PubMed ID: 16755160
In hemodialysis patients, folate‑based B‑vitamin therapy associated with lower homocysteine and fewer cardiovascular events — moderate supportive evidence (single‑center/limited design).
- Methylenetetrahydrofolate reductase polymorphisms and homocysteine-lowering effect of vitamin therapy in Singaporean stroke patients
PubMed ID: 16397167
Sustained homocysteine lowering in stroke patients could translate to cardiovascular benefit (biomarker evidence).
- Effect of folic acid on endothelial function following acute myocardial infarction
PubMed ID: 17293188
Post-MI endothelial function improved with high-dose folic acid, directly relevant to cardiac vascular health.
- [Efficacy and safety of Enalapril-Folate acid tablets in lowering blood pressure and plasma homocysteine]
PubMed ID: 18087553
Adjunct folic acid improved combined BP and homocysteine reductions with enalapril—clinically relevant to heart health risk factors.
- Effects of folic acid and N-acetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease
PubMed ID: 18214123
Improved endothelial function and marked homocysteine lowering in CAD patients supports heart/cardiovascular health biomarkers.
- Long-term effect of folic acid therapy in heart transplant recipients: follow-up analysis of a randomized study
PubMed ID: 18431235
Randomized post‑transplant folate therapy associated with markedly better 7‑year survival and fewer cardiovascular deaths.
- Effects of plasma homocysteine levels on serum HTase/PON activity in patients with type 2 diabetes
PubMed ID: 18781288
Folic acid (±B12) reduced homocysteine and raised protective HTase/PON activity — cardioprotective enzyme changes.
- Treatment of hyperhomocysteinemia and endothelial dysfunction in renal transplant recipients with B vitamins in the Chinese population
PubMed ID: 18206175
Improved endothelial function and reduced homocysteine with B‑vitamin therapy including folic acid supports cardiac vascular health.
- Increasing the number of SNP loci does not necessarily improve prediction power at least in the comparison of MTHFR SNP and haplotypes
PubMed ID: 19075497
Homocysteine reductions in healthy men support lower cardiovascular risk markers.
- [The effect of baseline homocysteine level on the efficacy of enalapril maleate and folic acid tablet in lowering blood pressure and plasma homocysteine]
PubMed ID: 19080072
Folic acid added to ACE inhibitor improved BP control in hypertensive patients (cardiovascular risk reduction implication).
- The effect of folic acid supplementation on carotid intima-media thickness in patients with cardiovascular risk: a randomized, placebo-controlled trial
PubMed ID: 19201496
Carotid IMT regression with high‑dose folic acid indicates reduced atherosclerotic burden—relevant to heart health.
- Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine - a six-year follow-up study
PubMed ID: 19917166
High baseline homocysteine predicted thrombotic events in RA; folic acid linked to lower Hcy (observational).
- Effect of folate supplementation on serum homocysteine and plasma total antioxidant capacity in hypercholesterolemic adults under lovastatin treatment: a double-blind randomized controlled clinical trial
PubMed ID: 19766902
Marked homocysteine lowering and increased antioxidant capacity in hypercholesterolemic adults suggest cardioprotective biochemical effects.
- Randomized clinical trial of folate supplementation in patients with peripheral arterial disease
PubMed ID: 19672935
PAD study showed improved peripheral arterial measures and lowered homocysteine—supportive for cardiovascular health.
- Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial
PubMed ID: 19228852
Large randomized trial in CVD patients found folic acid/B6/B12 modestly reduced stroke incidence over ~5 years.
- Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina
PubMed ID: 19491420
5 mg folic acid reduced Hcy and improved endothelial function in unstable angina—cardiac vascular benefit.
- [Efficacy of enalapril combined with folic acid in lowering blood pressure and plasma homocysteine level]
PubMed ID: 20058594
Folic acid added to antihypertensive therapy improved homocysteine and combined BP+Hcy endpoints relevant to cardiac risk.
- Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke: a possible linkage to homocysteine
PubMed ID: 20092401
Lowering homocysteine and CF6 in stroke patients suggests potential cardiovascular benefit (small trial).
- Folic Acid and vitamin B12 supplementation improves coronary flow reserve in elderly subjects with vitamin B12 deficiency
PubMed ID: 20851295
Folate+B12 improved coronary flow reserve in elderly B12‑deficient subjects—functional cardiac benefit.
- Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults
PubMed ID: 20727555
Large reductions in tHcy with high‑dose folic acid are biologically linked to heart risk modulation (biomarker evidence).
- Folic acid treatment normalizes NOS-dependence of vascular tone in the metabolic syndrome
PubMed ID: 20864946
Improvements in vascular function and oxidative stress in metabolic-syndrome subjects suggest mechanisms beneficial to heart health.
- Coronary blood flow in patients with stable coronary artery disease treated long term with folic acid and vitamin B12
PubMed ID: 21389855
Improved coronary microvascular flow with folic acid + B12 suggests a cardioprotective microvascular effect (small study).
- Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial
PubMed ID: 22554931
B‑vitamin regimen including folic acid showed modest reduction in major vascular events (subgroup effect) — clinical support for cardiovascular benefit in some patients.
- The effects of folic acid on markers of endothelial function in patients with type 1 diabetes mellitus
PubMed ID: 22482335
Improved endothelial markers with high‑dose folic acid indicate potential mechanistic benefit for heart/vascular health (small trial).
- Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly
PubMed ID: 24916013
B‑vitamin regimen including folic acid raised HDL and modestly lowered calculated CVD risk score in older adults.
- Metabolic response to folate supplementation in overweight women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial
PubMed ID: 24828019
High‑dose folic acid improved LDL and total/HDL ratio and reduced homocysteine in PCOS women—beneficial cardiometabolic signals.
- Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial
PubMed ID: 25771069
Large RCT showed clear reductions in stroke and composite cardiovascular events when folic acid (0.8 mg) was added to antihypertensive therapy.
- B vitamin treatments modify the risk of myocardial infarction associated with a MTHFD1 polymorphism in patients with stable angina pectoris
PubMed ID: 26803590
Genetic trial data show folate‑related treatment modifies AMI risk in specific genotypes, suggesting a potential heart‑health role in some contexts.
- The Effects of Folate Supplementation on Carotid Intima-Media Thickness and Metabolic Status in Patients with Metabolic Syndrome
PubMed ID: 27450552
5 mg folate improved carotid IMT and metabolic markers, supporting heart/vascular risk reduction.
- Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients
PubMed ID: 27729579
Enalapril+0.8 mg folic acid reduced first‑stroke risk by ~31% in the high‑cholesterol subgroup — meaningful cardiovascular benefit.
- Homocysteine and Stroke Risk: Modifying Effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention
PubMed ID: 28360116
Folic acid reduced stroke risk in a large RCT subgroup—supports some cardiovascular protection, especially in hyperhomocysteinemic/MTHFR contexts.
- Association between percent decline in serum total homocysteine and risk of first stroke
PubMed ID: 29030456
Greater homocysteine reduction associated with lower first-stroke risk, supporting downstream heart/vascular benefit from folate-mediated tHcy lowering.
- Effects of Folic Acid Therapy on the New-Onset Proteinuria in Chinese Hypertensive Patients: A Post Hoc Analysis of the Renal Substudy of CSPPT (China Stroke Primary Prevention Trial)
PubMed ID: 28607125
Folic acid plus enalapril reduced proteinuria and slowed renal decline in diabetics, an outcome associated with lower cardiovascular risk in that subgroup.
- Folic acid therapy reduces the risk of mortality associated with heavy proteinuria among hypertensive patients
PubMed ID: 28441699
In hypertensives with heavy proteinuria, adding folic acid halved mortality—important cardiovascular/overall mortality signal in a subgroup.
- Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke
PubMed ID: 29747834
Strong CSPPT subgroup stroke reduction with 0.8 mg/day folic acid—clinically important cerebrovascular benefit (cardio/brain vascular).
- The modifying effect of the MTHFR genotype on the association between folic acid supplementation and pulse wave velocity: Findings from the CSPPT
PubMed ID: 30372582
Reduced arterial stiffness with increased folate supports improved vascular/heart health metrics.
- MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment
PubMed ID: 29371246
Large RCT demonstrated homocysteine lowering which is linked to cardiovascular risk reduction potential.
- Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men
PubMed ID: 29273594
Folic acid supplementation associated with lower first-stroke risk in prespecified subgroups, a major cardiovascular outcome.
- Estimated Stroke-Free Survival of Folic Acid Therapy for Hypertensive Adults: Projection Based on the CSPPT
PubMed ID: 31865785
CSPPT RCT data/modeling: adding folic acid to enalapril reduced first stroke incidence by ~21%—strong cardiovascular benefit evidence.
- Efficacy of L-methylfolate and methylcobalamin in treating resistant hypertension associated with elevated serum homocysteine in hemodialysis patients
PubMed ID: 41580678
L‑methylfolate lowered BP and homocysteine in hemodialysis patients—both are heart risk factors.
- Posttreatment Blood Pressure as a Key Predictor in a 5-Year Stroke Prediction Model
PubMed ID: 39821957
Folic-acid supplementation reduced stroke risk in hypertensive patients—strong cardiovascular-relevant evidence.
- Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways(TM)) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial
PubMed ID: 38892484
RCT showed substantial homocysteine lowering and modest LDL reduction—biologically plausible benefit for cardiovascular risk markers.
- ESSENS dyslipidemia: A placebo-controlled, randomized study of a nutritional supplement containing red yeast rice in subjects with newly diagnosed dyslipidemia
PubMed ID: 27143594
Large LDL reductions in a supplement trial that included folic acid — plausibly supportive of heart health though effect cannot be attributed to folic acid alone.
- Folate administration decreases oxidative status and blood pressure in postmenopausal women
PubMed ID: 24906471
5‑MTHF lowered nocturnal BP and homocysteine, both relevant to cardiovascular risk reduction.
- Short-term folinic acid supplementation improves vascular reactivity in HIV-infected individuals: a randomized trial
PubMed ID: 23660169
Improved endothelial function with folinic acid suggests potential heart/vascular benefit.
- Kidney function and risk of cardiovascular disease and mortality in kidney transplant recipients: the FAVORIT trial
PubMed ID: 22594581
Direct RCT of folic acid (high dose) in kidney transplant recipients assessing cardiovascular events and mortality — directly relevant even though no benefit was found.
- Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients
PubMed ID: 18206891
Improvement in small‑artery elasticity and homocysteine reduction with a B‑vitamin regimen including folate suggests possible heart/cardiovascular benefit (combination product).
- Homocysteine in patients with rheumatoid arthritis in relation to inflammation and B-vitamin treatment
PubMed ID: 14626626
Folic acid included in B‑vitamin combo that lowered homocysteine, a cardiovascular risk marker; folic acid likely contributed though not isolated.
- Niacin treatment increases plasma homocyst(e)ine levels
PubMed ID: 10577438
By lowering homocysteine (not directly tested here but cited), folic acid is plausibly beneficial to heart/vascular risk — moderate indirect support from this study.
- Vitamin B12 decreases, but does not normalize, homocysteine and methylmalonic acid in end-stage renal disease: a link with glycine metabolism and possible explanation of hyperhomocysteinemia in end-stage renal disease
PubMed ID: 12601627
tHcy reduction with folic acid in dialysis patients — homocysteine is a CV risk marker.
- Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)
PubMed ID: 38478042
Dose–response homocysteine reductions (well‑conducted RCT) provide the strongest biomarker evidence linking folic acid to potential heart risk reduction.
- Effects of individualized administration of folic acid on prothrombotic state and vascular endothelial function with H-type hypertension: A double-blinded, randomized clinical cohort study
PubMed ID: 35060542
Genotype‑guided folic acid improved endothelial function and reduced prothrombotic markers in H‑type hypertension—direct heart/vascular relevance.
- Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension
PubMed ID: 36280851
Large randomized trial showed folic acid added to enalapril reduced first stroke risk—robust cardiovascular benefit.
- A Randomized Trial of Short-term Treatment with Folic Acid to Reduce the Oxidative Stress of Patients with Chronic Kidney Disease
PubMed ID: 34895119
Homocysteine lowering and reduced oxidative stress with folic acid in CKD supports cardiovascular risk reduction.
- Interaction of serum vitamin B(12) and folate with MTHFR genotypes on risk of ischemic stroke
PubMed ID: 31932513
Reduced first ischemic stroke in a large trial implies cardiovascular/vascular benefit relevant to heart health.
- Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease
PubMed ID: 14985687
Homocysteine lowering with folic acid + B12 in CAD patients supports a plausible heart‑health mechanism (biochemical evidence).
- Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects
PubMed ID: 16391577
Rapid lowering of homocysteine after folic acid supplementation in healthy men supports a heart-risk biomarker benefit.
- Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations
PubMed ID: 15941890
Clear, dose‑dependent homocysteine lowering with folic acid, a mechanism tied to cardiovascular risk reduction.
- The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people
PubMed ID: 17537289
Combined B12+folic acid reduced homocysteine substantially — supports cardiac risk pathways.
- Effect of Folic Acid, Betaine, Vitamin B₆, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine
PubMed ID: 26771632
Well‑controlled RCT showed folic acid substantially lowered homocysteine, a recognized cardiovascular risk marker.
- Randomized controlled trial of the effect of short-term coadministration of methylcobalamin and folate on serum ADMA concentration in patients receiving long-term hemodialysis
PubMed ID: 20430500
Combination folate+methylcobalamin improved ADMA and arterial stiffness in HD patients, markers of cardiovascular risk.
- [Impact of adding folic acid, vitamin B(12) and probucol to standard antihypertensive medication on plasma homocysteine and asymmetric dimethylarginine levels of essential hypertension patients]
PubMed ID: 23363713
Folic acid 5 mg/day + B12 substantially lowered homocysteine and increased NO/eNOS markers in hypertensive patients—mechanistic support for cardiovascular health.
- Nitrate-Rich Beetroot Juice Reduces Blood Pressure in Tanzanian Adults with Elevated Blood Pressure: A Double-Blind Randomized Controlled Feasibility Trial
PubMed ID: 32729923
Folic acid increased folate and lowered homocysteine in hypertensive adults; BP effects modest—some cardiovascular relevance.
- Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial
PubMed ID: 9583842
Strong RCT evidence that folic-acid-containing B‑vitamins substantially lower homocysteine, a cardiovascular risk biomarker.
- Antioxidants, but not B-group vitamins increase the resistance of low-density lipoprotein to oxidation: a randomized, factorial design, placebo-controlled trial
PubMed ID: 10407503
B‑vitamins lowered homocysteine in a factorial RCT—relevant to heart disease risk markers.
- Four week supplementation with mixed fruit and vegetable juice concentrates increased protective serum antioxidants and folate and decreased plasma homocysteine in Japanese subjects
PubMed ID: 17704021
Significant homocysteine lowering and folate increase—biochemical changes linked to heart/vascular risk.
- Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers
PubMed ID: 18270369
Dietary folate associated with lower ischemic stroke risk, supporting cardiovascular benefit epidemiologically.
- High- but not low-dose folic acid improves endothelial function in coronary artery disease
PubMed ID: 17087779
High‑dose folic acid improved endothelial function independent of Hcy lowering—mechanistic support for heart health.
- Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial
PubMed ID: 27655522
Large homocysteine reductions with methyl‑donor supplement in hypertensive patients — relevant to heart disease risk factors.
- A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia
PubMed ID: 31408467
Tailored drink reduced homocysteine more than standard multivitamin — may lower cardiovascular risk.
- Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial
PubMed ID: 36717385
Folic acid‑containing supplement lowered homocysteine significantly in hyperhomocysteinemic adults.
- Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12
PubMed ID: 11981075
Large homocysteine reductions with folate/folinate in dialysis patients — homocysteine is a heart disease biomarker.
- Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women
PubMed ID: 14749760
Folic acid fortification lowered homocysteine in adults — supports a heart‑health biomarker pathway.
Nutrient uptake (175)
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PubMed ID: 22811376
Multivitamin with folic acid lowered homocysteine and hsCRP — evidence of metabolic/biomarker improvement.
- Prevention of congenital abnormalities by periconceptional multivitamin supplementation
PubMed ID: 8324432
Periconceptional folic acid trial demonstrates practical benefit of supplementing folate during periconception (shows effective nutrient use in preventing defects).
- Niacin treatment increases plasma homocyst(e)ine levels
PubMed ID: 10577438
Study documents homocysteine rise with niacin and mentions folic acid reduces homocysteine — implies improved methylation/nutrient (one-carbon) utilization with folate.
- Study of the effect of a liquid nutrition supplement on the nutritional status of psycho-geriatric nursing home patients
PubMed ID: 11960300
Multinutrient liquid including folic acid produced clear increases in plasma folate and decreases in homocysteine — direct evidence of improved folate status/nutrient handling.
- Effect of iron supplementation on serum zinc status of lactating women in Addis Ababa, Ethiopia
PubMed ID: 16167707
Trial directly showed interaction: iron+folic acid supplementation lowered serum zinc and increased zinc deficiency, indicating folic‑containing regimens affect micronutrient status (clear nutrient‑use effect).
- A single-center, double-blinded, randomized controlled study to evaluate the relative efficacy of sublingual and oral vitamin B-complex administration in reducing total serum homocysteine levels
PubMed ID: 17109579
B‑complex including folic acid lowered homocysteine, demonstrating improved B‑vitamin metabolism.
- Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients
PubMed ID: 18206891
B‑vitamin therapy (including folate) produced a marked homocysteine decline—evidence of improved one‑carbon metabolism/nutrient handling (combination product).
- Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study
PubMed ID: 19628319
High‑dose folic acid+B6/B12 produced large, sustained reductions in total homocysteine — direct evidence of altered one‑carbon metabolism/nutrient use.
- The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability
PubMed ID: 19384265
Folic acid with B6/B12 greatly lowered homocysteine in migraine RCT, indicating improved methylation/metabolite handling.
- The effects of iron and/or zinc supplementation on maternal reports of sleep in infants from Nepal and Zanzibar
PubMed ID: 19322104
Iron–folic acid supplementation produced behavioral/sleep changes in infants and represents improved micronutrient status.
- Pharmacological dose of vitamin B12 is as effective as low-dose folinic acid in correcting hyperhomocysteinemia of hemodialysis patients
PubMed ID: 19462276
Folinic acid (folate form) lowered plasma tHcy vs B12 alone in dialysis patients — clear biochemical effect on folate‑dependent metabolism.
- B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: results of a randomized controlled trial
PubMed ID: 20231532
High‑dose folic acid with B vitamins produced marked homocysteine lowering in dialysis patients (biochemical nutrient effect).
- B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial
PubMed ID: 20688574
Large RCT showed clear tHcy lowering with B‑vitamin (including folic acid) supplementation.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
B‑vitamin treatment (including folic acid) substantially raised plasma folate/B12 and lowered homocysteine in MCI patients—clear nutrient status changes.
- [Dietary efficacy of a micronutrient combination in patients with recurrent upper respiratory tract infections. Results of a placebo-controlled double-blind study]
PubMed ID: 22184801
Micronutrient supplement increased serum folic acid levels compared with placebo, showing improved folate status when folic acid was included in the mix.
- Effects of exercise and B vitamins on homocysteine and glutathione in Parkinson's disease: a randomized trial
PubMed ID: 22261439
Direct small RCT showing B6/B12/folic acid lowered homocysteine — clear evidence of improved one‑carbon metabolism/nutrient use.
- Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: results of a randomized placebo-controlled trial
PubMed ID: 22474057
Large randomized trial of folic acid+B6+B12 — substantial direct evidence that supplemental folate alters relevant metabolic biomarkers (homocysteine), supporting 'better nutrient use'.
- Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis
PubMed ID: 23765945
B‑vitamin (including folic acid) RCT produced a clear biochemical effect: substantial lowering of total homocysteine — direct evidence of improved one‑carbon/folate metabolism.
- Folate administration decreases oxidative status and blood pressure in postmenopausal women
PubMed ID: 24906471
5‑MTHF lowered homocysteine and improved HOMA‑IR—evidence of improved one‑carbon/metabolic handling of nutrients.
- Acceptability of multiple micronutrient powders and iron syrup in Bihar, India
PubMed ID: 29210507
Direct study of an iron+folic acid syrup showing very high acceptability/adherence — strong evidence about delivery/use of folic acid product.
- Prenatal and Postnatal Supplementation with Lipid-Based Nutrient Supplements Reduces Anemia and Iron Deficiency in 18-Month-Old Bangladeshi Children: A Cluster-Randomized Effectiveness Trial
PubMed ID: 29901736
Home fortification with LNS/MNP (containing folic acid) produced strong, direct improvements in child iron status and anemia → good evidence for improved nutrient outcomes where folic acid was included.
- Relationship between folate concentration and expression of folate-associated genes in tissue and plasma after intraoperative administration of leucovorin in patients with colorectal cancer
PubMed ID: 30269276
Intraoperative leucovorin dose-dependently raised tissue and plasma folate and altered folate-pathway gene expression — direct mechanistic evidence of increased folate uptake/use (folinic acid context).
- A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes in Healthy Humans and Their Effects on Homocysteine, Oxidative Stress, and Antioxidant Levels
PubMed ID: 31915511
Directly showed serum folate increases and total homocysteine reduction with B‑complex containing folic acid — clear evidence of improved folate status and one‑carbon metabolism markers.
- Optimizing Vitamin and Trace Element Profiles in Blood after Gastrointestinal Tract Surgery by a New Parenteral Nutrition Formula
PubMed ID: 30799392
Revised parenteral nutrition with higher folic acid produced higher blood folate concentrations postoperatively—direct evidence of improved folate status with formulation change.
- Higher baseline global leukocyte DNA methylation is associated with MTX non-response in early RA patients
PubMed ID: 31242943
Study links folate/one‑carbon metabolism (DNA methylation) to MTX response while folic acid was given — relevant to cellular nutrient (folate) handling.
- The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT
PubMed ID: 31776782
Optimized multivitamin produced higher serum folate and lower anemia vs standard MVS—direct evidence of improved micronutrient status/use.
- Effects of standard v. very long Roux limb Roux-en-Y gastric bypass on nutrient status: a 1-year follow-up report from the Dutch Common Channel Trial (DUCATI) Study
PubMed ID: 32077402
Direct measurement: differing Roux limb length resulted in significantly different folate (folic acid) levels at 1 year → direct evidence for altered nutrient handling.
- Effect of Fortification with Multiple Micronutrient Powder on the Prevention and Treatment of Iron Deficiency and Anaemia in Brazilian Children: A Randomized Clinical Trial
PubMed ID: 34201821
MNP and Fe+folic acid both greatly reduced anaemia and iron deficiency — evidence of effective nutrient use/impact.
- Fortified Balanced Energy-Protein Supplements Increase Nutrient Adequacy without Displacing Food Intake in Pregnant Women in Rural Burkina Faso
PubMed ID: 34494113
Fortified BEP supplement significantly increased folate intake (≈+399 μg/day) and overall nutrient adequacy during pregnancy.
- Improving Micronutrient Status of Children and Women in Rural Communities in India Using Crystal Salt Enriched with Multiple Micronutrients
PubMed ID: 33952731
Fortified salt containing folic acid (with other micronutrients) improved hemoglobin, ferritin and iron status—evidence of improved nutrient status with folic‑acid–containing vehicle (though multi‑nutrient).
- Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial
PubMed ID: 35276810
Folinic acid combined with ferrous bisglycinate resulted in superior iron absorption and iron marker improvements vs ferrous fumarate—strong evidence of improved nutrient utilization with a folate form.
- Association between serum 5-methyltetrahydrofolate and homocysteine in Chinese hypertensive participants with different MTHFR C677T polymorphisms: a cross-sectional study
PubMed ID: 35562805
Direct biochemical evidence: higher circulating 5‑MeTHF strongly associated with lower homocysteine, demonstrating improved folate-mediated one‑carbon metabolism and nutrient utilization.
- A cluster randomized controlled trial of a community-based initiative to reduce stunting in rural Indonesia
PubMed ID: 38041533
Program increased iron–folic‑acid tablet consumption substantially—direct evidence of improved uptake/use of IFA in the community intervention.
- Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways(TM)) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial
PubMed ID: 38892484
Direct RCT of methylfolate+B6+B12 produced meaningful homocysteine reductions—evidence of improved one‑carbon metabolism/nutrient utilization.
- Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial
PubMed ID: 15113718
Fortified cereal substantially increased B-vitamin levels including folate, showing improved nutrient status with fortification.
- Effect of cow milk on food folate bioavailability in young women
PubMed ID: 15585769
Cow-milk inclusion in a low-folate diet helped maintain erythrocyte folate and prevented tHcy rise, showing dietary factors affect folate utilization.
- Determining bioavailability of food folates in a controlled intervention study
PubMed ID: 15447898
Controlled trial showing folic acid raises serum folate and lowers homocysteine much more than natural food folates—strong evidence of superior bioavailability/use.
- Effect of folic Acid supplementation on the folate status of buccal mucosa and lymphocytes
PubMed ID: 15247137
1.2 mg/day raised lymphocyte folate demonstrating tissue uptake and distribution (nutrient utilization).
- Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults
PubMed ID: 14985217
Older adults: monoglutamyl folic acid raised serum/erythrocyte folate more than polyglutamyl dietary folates (bioavailability evidence).
- Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene
PubMed ID: 15321811
Dietary polyglutamyl folate is substantially (~64–70%) less bioavailable than monoglutamyl folic acid — clear data on differences in folate bioavailability.
- Efficacy of B vitamins in lowering homocysteine in older men: maximal effects for those with B12 deficiency and hyperhomocysteinemia
PubMed ID: 16373648
B‑vitamin supplementation markedly reduced tHcy, reflecting improved B‑vitamin metabolic function.
- Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma
PubMed ID: 15831910
400 μg folic acid increased leukocyte DNA methylation and lowered homocysteine — shows improved one‑carbon metabolism and nutrient utilization.
- Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age
PubMed ID: 15927936
Large increases in RBC and plasma folate demonstrate effective dietary folate utilization in women of childbearing age.
- Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation: randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype
PubMed ID: 15895286
Clear genotype‑dependent homocysteine reductions with folic acid indicate improved folate-mediated one‑carbon metabolism.
- Responsiveness of homocysteine concentrations to food and supplemental folate intakes in smokers and never-smokers enrolled in a diet intervention trial
PubMed ID: 16497600
Supplemental folic acid in breast cancer trial participants increased serum folate and lowered homocysteine over 12 months — clear nutrient status change.
- Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers
PubMed ID: 16736000
Folic acid supplementation increased SAM and lowered homocysteine and uracil misincorporation — demonstrates improved one‑carbon metabolism and nutrient utilization.
- [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation
PubMed ID: 16600937
In lactation, 5‑methylfolate maintained RBC folate at least as well as folic acid, indicating better active-form utilization in some settings.
- Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age
PubMed ID: 16825690
5‑MTHF raised RBC folate more than folic acid in women of childbearing age—clear evidence about form-specific bioefficacy.
- Effect of folate supplementation on N-terminal pro-brain natriuretic peptide
PubMed ID: 17052779
Dose-dependent serum folate rises with folic acid in healthy adults demonstrate predictable nutrient uptake/response.
- Bioavailability of food folates is 80% of that of folic acid
PubMed ID: 17284745
Isotope tracer study: food folates are ~80% as bioavailable as synthetic folic acid — directly informs nutrient bioavailability/use.
- Responses of biomarkers of folate and riboflavin status to folate and riboflavin supplementation in healthy and colorectal polyp patients (the FAB2 Study)
PubMed ID: 17932361
Randomized supplementation raised plasma/RBC and colorectal mucosal folate in dose‑response fashion — clear evidence of nutrient uptake.
- [Hyperhomocysteinemia and alternate vitamin supplementation]
PubMed ID: 17342693
Alternate folic acid/B12 therapy altered homocysteine with genotype effects—evidence for folate metabolism/nutrient utilization dynamics.
- How well do blood folate concentrations predict dietary folate intakes in a sample of Canadian lactating women exposed to high levels of folate? An observational study
PubMed ID: 17961229
Folate supplementation in lactating women raised plasma and RBC folate substantially—direct biomarker evidence of improved folate status.
- The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study
PubMed ID: 17522618
L‑5‑MTHF (active folate) significantly lowered homocysteine where folic acid did not—important evidence on form‑dependent nutrient utilization.
- Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial
PubMed ID: 18689382
Large RCT showing dose‑dependent, large increases in plasma/RBC folate and corresponding homocysteine changes—direct evidence of folate bioavailability/effect.
- Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial
PubMed ID: 18689370
Bread fortification with folic acid + B12 produced big rises in folate/B12 and lowered homocysteine—strong evidence of improved nutrient status.
- Gender and body size affect the response of erythrocyte folate to folic acid treatment
PubMed ID: 18641191
Demonstrated sex differences in erythrocyte folate response to folic acid — important for dosing and nutrient handling.
- Weekly may be as efficacious as daily folic acid supplementation in improving folate status and lowering serum homocysteine concentrations in Guatemalan women
PubMed ID: 18641196
Weekly or daily folic acid clearly raised serum folate and lowered homocysteine in reproductive‑age women — direct nutrient‑status improvement.
- Effect of different dosage and administration schedules of folic acid on blood folate levels in a population of Honduran women of reproductive age
PubMed ID: 18426639
Randomized trial clearly showed dose‑dependent increases in serum and RBC folate with daily regimens, demonstrating improved folate status and nutrient availability.
- Steady state folate concentrations achieved with 5 compared with 1.1 mg folic acid supplementation among women of childbearing age
PubMed ID: 19158211
Dose‑dependent PK trial: 5 mg led to faster/higher steady‑state RBC folate than 1.1 mg—relevant to dosing/uptake.
- Effect of 2 pieces of nutritional advice on folate status in Swedish women: a randomized controlled trial
PubMed ID: 19190070
Folate‑rich breakfast increased erythrocyte folate and lowered homocysteine—dietary delivery improved tissue folate use.
- Supplementation with a multivitamin containing 800 microg of folic acid shortens the time to reach the preventive red blood cell folate concentration in healthy women
PubMed ID: 20108207
800 µg folic acid raised RBC folate above protective threshold and quickly—evidence of efficient folate repletion.
- Comparison of (6 S)-5-methyltetrahydrofolic acid v. folic acid as the reference folate in longer-term human dietary intervention studies assessing the relative bioavailability of natural food folates: comparative changes in folate status following a 16-week placebo-controlled study in healthy adults
PubMed ID: 19852872
16‑week feeding studies show how supplemental folic acid vs 5‑MTHF affects plasma and RBC folate changes—directly informs nutrient bioavailability and use.
- Impact of a stage-tailored, web-based intervention on folic acid-containing multivitamin use by college women
PubMed ID: 20594096
Behavioral RCT increased multivitamin (folic acid) uptake — improves population nutrient use/adherence (implementation evidence).
- Community-level micronutrient fortification of school lunch meals improved vitamin A, folate, and iron status of schoolchildren in Himalayan villages of India
PubMed ID: 20410083
School-meal fortification including folic acid improved folate biomarkers at the population level—improved nutrient status/use in children.
- Folate status of reproductive age women and neural tube defect risk: the effect of long-term folic acid supplementation at doses of 140 µg and 400 µg per day
PubMed ID: 22254076
Controlled folic acid dosing (140 vs 400 μg) produced large, dose-dependent increases in plasma and RBC folate and reduced prevalence of RBC folate below the NTD threshold—clear nutrient-use effect.
- MTHFR 677C->T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation
PubMed ID: 21508090
Folic acid supplementation raised plasma/RBC folate and lowered homocysteine; response was modified by MTHFR genotype — important for nutrient utilization.
- Long-term effect of low-dose folic acid intake: potential effect of mandatory fortification on the prevention of neural tube defects
PubMed ID: 21593499
Dosing RCT showed clear dose-dependent kinetics of RBC folate and long time to steady state — directly about folate status and nutrient handling.
- Effect of different doses of folic acid on serum homocysteine level in patients on hemodialysis
PubMed ID: 21368386
Folic acid doses (2–15 mg) lowered homocysteine in dialysis patients with a flat dose‑response beyond 2 mg — evidence on biochemical utilization and ceiling effects.
- Effects of a multivitamin, mineral and herbal supplement on cognition and blood biomarkers in older men: a randomised, placebo-controlled trial
PubMed ID: 22711385
Multivitamin raised folate and B12 and lowered homocysteine, showing improved one‑carbon nutrient status and interaction in older men.
- Differences in erythrocyte folate concentrations in older adults reached steady-state within one year in a two-year, controlled, 1 mg/d folate supplementation trial
PubMed ID: 22810981
Controlled 2‑year trial showed sustained increases in erythrocyte/plasma folate with 1 mg/day—direct evidence of improved folate status (nutrient use).
- Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C677T genotype: results from a crossover trial
PubMed ID: 23456769
Well‑controlled crossover trial showing clear, dose‑dependent increases in serum and RBC folate — strong biochemical evidence of improved folate status.
- Effects of supplement therapy on sperm parameters, protamine content and acrosomal integrity of varicocelectomized subjects
PubMed ID: 23435530
Folate‑fortified oral contraceptive markedly increased dietary folate equivalents and plasma/RBC folate — clear improvement in nutrient intake and status.
- Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism
PubMed ID: 23740686
Oral folic acid lowered plasma homocysteine significantly (plasma surrogate of improved one‑carbon metabolism), though intracellular effects were limited.
- Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia
PubMed ID: 23698160
Folate‑rich diet or low‑dose folic/5‑MTHF comparably lowered homocysteine (~20%) and raised RBC folate — good evidence of improved one‑carbon nutrient handling.
- Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly
PubMed ID: 24916013
Daily B‑vitamin regimen including 400 µg folic acid substantially increased plasma folate and B12—direct nutrient repletion evidence.
- Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The "RISTOMED project": Randomized controlled trial in healthy older people
PubMed ID: 25453395
Addition of probiotic to diet increased plasma folate/B12 and lowered homocysteine—shows modifiable folate status in intervention.
- Optimization of vitamin suppletion after Roux-en-Y gastric bypass surgery can lower postoperative deficiencies: a randomized controlled trial
PubMed ID: 25437032
Optimized post‑RYGB multivitamin with higher folic acid produced higher serum folate and fewer deficiencies than standard MVS.
- Results of 2-year vitamin B treatment on cognitive performance: secondary data from an RCT
PubMed ID: 25391305
Folic acid+B12 markedly lowered homocysteine in older adults—clear biochemical effect on folate‑dependent metabolism.
- Effect of folic acid supplementation on plasma homocysteine in obese children: a randomized, double-blind, placebo-controlled trial
PubMed ID: 25391194
5 mg folic acid in obese children significantly lowered homocysteine and raised serum folate—evidence of improved one‑carbon nutrient status.
- Pregnancy-induced changes in the long-term pharmacokinetics of 1.1 mg vs. 5 mg folic acid: a randomized clinical trial
PubMed ID: 25167960
Dose‑dependent RBC folate kinetics in pregnancy (5 mg > 1.1 mg) demonstrate superior folate repletion with higher dose.
- Effect of supplementation with a lipid-based nutrient supplement on the micronutrient status of children aged 6-18 months living in the rural region of Intibucá, Honduras
PubMed ID: 24628577
Infant LNS raised plasma folate and B12 concentrations vs control—indicative of improved nutrient status.
- Effect of folic acid on bone metabolism: a randomized double blind clinical trial in postmenopausal osteoporotic women
PubMed ID: 25223378
1 mg folic acid produced modest homocysteine reduction and preserved B12 in postmenopausal women—nutrient status benefit.
- Influence of dialysis techniques and alternate vitamin supplementation on homocysteine levels in patients with known MTHFR genotypes
PubMed ID: 24652221
In dialysis patients, alternating folic acid and B12 lowered homocysteine while on treatment—demonstrates improved metabolic handling.
- Neuroprotective impact of a vitamin trace element composition - a randomized, double blind, placebo controlled clinical trial with healthy volunteers
PubMed ID: 25789594
Multinutrient supplement (including folic acid) significantly increased folate and decreased homocysteine—the clearest evidence of improved one‑carbon nutrient status/utilization.
- Impact of weekly iron folic acid supplementation with and without vitamin B12 on anaemic adolescent girls: a randomised clinical trial
PubMed ID: 26695724
Weekly IFA with added B12 improved B12 status and decreased ferritin deficiency vs IFA alone—shows improved micronutrient status when folic acid included in regimens.
- Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial
PubMed ID: 25943647
Direct RCT: folic acid (400 µg) raised active folate and increased prevalence of unmetabolized folic acid, and lowered homocysteine—clear biomarker improvement in folate status.
- Whey protein isolate improves vitamin B(12) and folate status in elderly Australians with subclinical deficiency of vitamin B(12)
PubMed ID: 27981743
Whey protein intervention increased serum folate and prevented rises in homocysteine/MMA versus soy in older adults—evidence of improved folate/B12 status and nutrient bioavailability.
- Response of Red Blood Cell Folate to Supplementation in Nonpregnant Women is Predictable: A Proposal for Personalized Supplementation
PubMed ID: 29143484
Well‑powered study showing predictable, dose‑ and time‑dependent RBC‑folate increases—helps personalized nutrient dosing.
- Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial
PubMed ID: 31425504
Active folate formula (L-5-MTHF) produced higher red-cell folate and less unmetabolized folic acid—improved folate utilization biomarker.
- Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation
PubMed ID: 31005964
Randomized folic acid dosing study defined plasma–RBC folate relationships and biomarker thresholds—directly informs folate kinetics and nutrient use.
- Weekly iron-folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia
PubMed ID: 33272946
Randomized weekly folic acid doses produced dose‑dependent, large increases in RBC/plasma folate and proportion reaching RBC folate NTD‑low threshold—strong evidence for folate repletion and use.
- [Bioavailability of natural versus synthetic B vitamins and their effects on metabolic processes]
PubMed ID: 32189314
Crossover study showed synthetic B‑vitamin complex (incl. folate) raised serum folate substantially and lowered homocysteine—evidence for bioavailability and metabolic use.
- Newborn micronutrient status biomarkers in a cluster-randomized trial of antenatal multiple micronutrient compared with iron folic acid supplementation in rural Bangladesh
PubMed ID: 32844185
Maternal MMN (including folic acid) increased newborn cord ferritin, 25(OH)D and zinc vs IFA, indicating improved nutrient delivery to neonate.
- A community-based randomized controlled trial providing weekly iron-folic acid supplementation increased serum- ferritin, -folate and hemoglobin concentration of adolescent girls in southern Ethiopia
PubMed ID: 33958657
Weekly IFA increased serum folate along with hemoglobin and ferritin—improved folate and iron biomarkers indicate better nutrient status.
- Plasma Methylmalonic Acid Concentration in Folic Acid-Supplemented Depressed Patients with Low or Marginal Vitamin B-12: A Randomized Trial
PubMed ID: 34510193
High‑dose folic acid (5 mg/d) markedly increased serum and RBC folate in depressed patients—clear effect on folate status.
- Impact of high-dose folic acid supplementation in pregnancy on biomarkers of folate status and 1-carbon metabolism: An ancillary study of the Folic Acid Clinical Trial (FACT)
PubMed ID: 33675351
High‑dose folic acid in pregnancy clearly raised serum folate and unmetabolized folic acid—demonstrates altered folate status/nutrient exposure.
- Iron and folic acid consumption and changing social norms: cluster randomized field trial, Odisha, India
PubMed ID: 34737470
Cluster RCT showed norms‑based intervention greatly increased self‑reported iron‑folic acid consumption—direct evidence of improved nutrient uptake.
- Improving iron folic acid consumption through interpersonal communication: Findings from the Reduction in Anemia through Normative Innovations (RANI) project
PubMed ID: 33980397
Interpersonal‑communication trial substantially increased self‑reported IFA use and related behaviors—strong programmatic improvement in nutrient use.
- How does a social norms-based intervention affect behaviour change? Interim findings from a cluster randomised controlled trial in Odisha, India
PubMed ID: 35803626
Social‑norms RCT produced large increases in IFA uptake (self‑report)—clear evidence of better use of folic‑acid‑containing supplements.
- Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B(12) status among young Laotian children: a randomized controlled trial
PubMed ID: 35534778
Daily MNP for 9 months greatly reduced folate deficiency in children—demonstrates effective folate delivery/uptake.
- The effect of blister packaging Iron and Folate on adherence to medication and hemoglobin levels among pregnant women at National Referral Hospital antenatal clinics in a low to middle income country: a Randomised Controlled Trial (The IFAd Trial)
PubMed ID: 35241006
Packaging (blister) slightly increased hemoglobin despite no adherence difference—some operational impact on effective nutrient use.
- Effect of Picture-based health education and counselling on knowledge and adherence to preconception Iron-folic acid supplementation among women planning to be pregnant in Eastern Ethiopia: a randomized controlled trial
PubMed ID: 35912303
Picture‑based preconception education produced very large increases in IFA use and knowledge—direct improvement in preconception nutrient use.
- Effectiveness of Health Information Package Program on Knowledge and Compliance among Pregnant Women with Anemia: A Randomized Controlled Trial
PubMed ID: 35270420
Education+reminders markedly increased IFA tablet adherence—practical improvement in nutrient use and compliance.
- Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6-7 Years: A Follow-Up of a Randomized Controlled Trial
PubMed ID: 36889645
Early‑life folic acid ± B12 produced lower homocysteine 6–7 years later, showing sustained improvement in one‑carbon nutrient status and utilization.
- Effects of quintuply-fortified salt on the micronutrient status of females of reproductive age in Punjab, India: a randomized, community-based trial
PubMed ID: 40610127
Quintuply‑fortified salt markedly improved folate (and B12) status—strong implementation evidence that folic acid in fortified foods improves nutrient status.
- Vitamin Profile of the Patients with Chronic Kidney Disease Receiving a Novel Total Parenteral Nutrition Formula: Multicenter Randomized Controlled Phase III Trial
PubMed ID: 40906605
TPN kit raised folate blood levels vs control — direct improvement in nutrient delivery/levels.
- Feasibility of a randomized clinical trial comparing 5-methyltetrahydrofolate and folic acid prenatal multivitamins in couples with recurrent pregnancy loss
PubMed ID: 41544303
5‑MTHF reduced unmetabolized folic acid vs folic acid — direct metabolic/processing advantage.
- Nutritional status-dependent DNA methylation modifications on adipose tissue in systemic lupus erythematosus women following folic acid and vitamin B12 supplementation: a randomized double-blind placebo-controlled trial
PubMed ID: 41484640
Folate+B12 supplementation raised serum folate/B12 and altered adipose methylation — biochemical nutrient effects.
- Vitamin B12 decreases, but does not normalize, homocysteine and methylmalonic acid in end-stage renal disease: a link with glycine metabolism and possible explanation of hyperhomocysteinemia in end-stage renal disease
PubMed ID: 12601627
Folic acid lowered tHcy in dialysis patients — demonstrates metabolic improvement in one‑carbon cycle.
- [Effects of vitamin A, vitamin A plus iron and multiple micronutrient-fortified seasoning powder on iron metabolic homeostasis]
PubMed ID: 22336361
Multi‑micronutrient powder (including folic acid) improved iron storage/mobilization markers (SF, sTfR, total body iron).
- Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women
PubMed ID: 23616513
Randomized feeding trial: folic acid fortification substantially raised plasma and erythrocyte folate—direct evidence of improved folate status (nutrient use).
- Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine, but not cognitive performance
PubMed ID: 24481688
Three months of B‑vitamin/folic acid raised folate and lowered homocysteine in children—direct biochemical evidence of improved folate handling.
- One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans
PubMed ID: 25283139
One‑year supplementation dramatically increased 5‑methylTHF and lowered tHcy—evidence of sustained folate utilization.
- Serum Concentrations of Folate Forms Following Supplementation of Multimicronutrients with 400 µg or 800 µg Mix of (6S)-5-Methyltetrahydrofolate and Folic Acid (1:1) in Women of Childbearing Age
PubMed ID: 39466653
Direct supplementation trial showing dose‑dependent increases in active folate (6S‑5‑MTHF) and total serum folate—strong biochemical evidence that supplementation effectively raises usable folate.
- Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh
PubMed ID: 17093162
RCT: folic acid increased arsenic methylation (%DMA) and lowered homocysteine—direct evidence folate improves one‑carbon metabolism and methylation capacity.
- Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A Randomized Controlled Trial
PubMed ID: 25978852
Large RCT: 800 μg/day folic acid increased folate biomarkers, improved arsenic methylation and lowered blood arsenic — strong evidence of improved metabolic handling.
- Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh
PubMed ID: 30590411
Large RCT: FA (400–800 µg) clearly sped arsenic methylation and conversion to excretable metabolites — strong evidence FA improves processing of a toxic nutrient/element.
- The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population
PubMed ID: 36976258
Large randomized double‑blind trial showing blood arsenic methylation improved with FA — robust evidence of altered nutrient/toxin handling.
- Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial
PubMed ID: 32019154
Higher-folate diet increased serum folate and lowered homocysteine in MTHFR TT genotype—improved folate utilization and methylation biomarkers.
- Inter-pregnancy folate and iron status of women in an inner-city population
PubMed ID: 11432768
Postpartum supplementation increased erythrocyte folate—demonstrates improved folate stores and likely improved utilization.
- Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 does not affect the proportion of (n-3) long chain polyunsaturated fatty acids in plasma phosphatidylcholine
PubMed ID: 18287365
Clear biochemical effect: folate+B12+B6 lowered homocysteine—strong signal of improved one‑carbon metabolism and nutrient use.
- Multimicronutrient and omega-3 fatty acid supplementation reduces low-grade inflammation in older participants: An exploratory study
PubMed ID: 40644954
Multimicronutrient including folate significantly increased RBC folate and other nutrient biomarkers after 12 weeks.
- Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?
PubMed ID: 10952955
5 mg folic acid daily markedly raised serum folate (~+407%) and lowered homocysteine (~25%), showing improved folate status and utilization.
- Folic acid therapy reduces plasma homocysteine levels and improves plasma antioxidant capacity in hemodialysis patients
PubMed ID: 17321110
Supervised folic acid in haemodialysis normalized homocysteine and increased antioxidant capacity — evidence of metabolic benefit.
- Feasibility and acceptability of a nutritional intervention testing the effects of nitrate-rich beetroot juice and folic acid on blood pressure in Tanzanian adults with elevated blood pressure
PubMed ID: 32522060
Feasibility RCT confirmed folic acid supplementation reliably raised plasma/saliva folate concentrations.
- Vitamin requirements for the treatment of hyperhomocysteinemia in humans
PubMed ID: 7931701
Folic acid substantially lowered homocysteine (a one‑carbon metabolism marker), showing efficient utilization in methylation pathways.
- Postpartum folic acid supplementation of adolescents: impact on maternal folate and zinc status and milk composition
PubMed ID: 7625346
Postpartum 300 µg/day folic acid prevented the normal drop in RBC folate in adolescent mothers — supports folate's role in maintaining nutritional status.
- Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial
PubMed ID: 9925130
Low‑dose folic acid raised plasma and RBC folate dose‑dependently in young women.
- Effect of dietary patterns on serum homocysteine: results of a randomized, controlled feeding study
PubMed ID: 10952952
Dietary changes increasing folate correlated with homocysteine reductions, supporting effective nutrient use.
- Dietary strategies for lowering homocysteine concentrations
PubMed ID: 10837284
Supplements/fortified cereals increased serum folate and lowered homocysteine substantially versus dietary change alone.
- Folate status of elderly women following moderate folate depletion responds only to a higher folate intake
PubMed ID: 10827214
Controlled depletion/repletion in elderly women showed 415 µg/day restored folate biomarkers and reversed homocysteine—clear nutrient-repletion evidence.
- The effect of oral nutritional supplements on habitual dietary quality and quantity in frail elders
PubMed ID: 10828934
Multinutrient supplement raised serum folate in elders—evidence of folate bioavailability from supplementation.
- Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women
PubMed ID: 11035344
Low-dose folic acid substantially lowered homocysteine in postmenopausal women—improved utilization of one‑carbon nutrients.
- Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial
PubMed ID: 11339442
250–500 µg/day raised plasma/RBC folate and dose-dependently lowered homocysteine in young women—strong biomarker evidence of improved folate status.
- Randomized trial of folic acid supplementation and serum homocysteine levels
PubMed ID: 11231701
Dose-related serum folate increases demonstrated across folic acid doses—clear nutrient status improvement.
- Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype
PubMed ID: 11738277
Dietary or 400 µg/day supplementation increased plasma folate and lowered homocysteine—supports better folate nutrient status.
- Folate supplementation in peritoneal dialysis patients with normal erythrocyte folate: effect on plasma homocysteine
PubMed ID: 11598393
5 mg/day folic acid substantially raised serum and erythrocyte folate — direct improvement in folate pools/nutrient status.
- Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial
PubMed ID: 12081832
Folate-rich diet or 400 µg supplement clearly raised plasma folate and reduced homocysteine — direct evidence of improved folate status and utilisation.
- Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors
PubMed ID: 12048127
5 mg/day folic acid significantly raised serum and RBC folate and lowered homocysteine — clear improvement in folate status/use.
- Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial
PubMed ID: 12122551
Fortified cereal with low-dose folic acid produced dose-dependent serum folate increases and tHcy decreases in 4 weeks.
- Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis
PubMed ID: 12048292
Folate (or folinic acid) prevented MTX-related homocysteine rise and normalized levels — shows restored folate-related metabolism.
- Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid
PubMed ID: 12421850
Low-dose folic acid reliably increased plasma and red cell folate over 24 weeks — strong evidence of improved folate status.
- Effect of homocysteine reduction by B-vitamin supplementation on markers of clotting activation
PubMed ID: 12195694
High-dose B‑vitamin supplementation (including 5 mg folic acid) produced large homocysteine reductions — demonstrates metabolic impact.
- Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of L-folinic or folic acid
PubMed ID: 12427152
Folinic vs folic acid produced comparable total folate increases but different circulating forms — relevant to folate metabolism/forms.
- Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study
PubMed ID: 12600857
L‑MTHF lowered homocysteine more than folic acid and raised RBC folate—data on relative efficacy/usage of folate forms.
- A comparison of the effect of advice to eat either '5-a-day' fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine
PubMed ID: 12571666
Dietary advice (fortified or folate-rich foods) raised plasma folate, demonstrating improved folate status/nutrient uptake.
- Weekly high-dose folic Acid supplementation is effective in lowering serum homocysteine concentrations in women
PubMed ID: 12652055
Dosing study showed effective erythrocyte folate increases and homocysteine lowering, indicating efficient folate utilization by body pools.
- Anemia prophylaxis in adolescent school girls by weekly or daily iron-folate supplementation
PubMed ID: 12736400
Iron+folate supplementation raised ferritin and hemoglobin in schoolgirls; folate contributed to improved nutrient status in combination therapy.
- Folate catabolite excretion is responsive to changes in dietary folate intake in elderly women
PubMed ID: 12663292
Depletion/repletion study showed urinary folate catabolites track body folate pools — clear evidence of folate turnover and status responsiveness.
- Ethnicity and race influence the folate status response to controlled folate intakes in young women
PubMed ID: 15226470
Controlled intake study shows ethnicity-related differences in folate-status responses, directly about nutrient handling.
- Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease
PubMed ID: 14985687
Folic acid + B12 sharply reduced homocysteine — indicates improved one-carbon metabolism and nutrient utilization (biochemical evidence).
- Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects
PubMed ID: 16391577
Short-term folic acid raised serum folate and lowered homocysteine, showing improved folate status and related nutrient metabolism.
- Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamin supplementation
PubMed ID: 14699020
B‑vitamin supplementation (including folic acid) modified the betaine–homocysteine response to methionine load — supports nutrient‑use interactions.
- Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations
PubMed ID: 15941890
Folic acid supplementation dose‑dependently raised betaine and folate and was associated with homocysteine changes — strong evidence for improved one‑carbon nutrient handling.
- Sex and menopausal status influence human dietary requirements for the nutrient choline
PubMed ID: 17490963
Folic acid blunted homocysteine increase during choline depletion — evidence of altered nutrient interplay.
- The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people
PubMed ID: 17537289
Cobalamin+folic acid markedly lowered tHcy and increased betaine — shows enhanced one‑carbon nutrient utilization.
- Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults
PubMed ID: 27052531
Direct RCT: folic acid (400/800 µg) caused dose‑independent increases in betaine and prevented choline decline—clear one‑carbon metabolic effects.
- Effect of Folic Acid, Betaine, Vitamin B₆, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine
PubMed ID: 26771632
Folic acid lowered homocysteine in a randomized trial, indicating improved one‑carbon nutrient handling.
- Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults
PubMed ID: 32918135
Large, placebo‑controlled folic acid RCT demonstrated dose‑dependent improvements in arsenic methylation indices and homocysteine—direct evidence of improved one‑carbon nutrient use.
- Traditional Korean diet high in one-carbon nutrients increases global DNA methylation: implication for epigenetic diet
PubMed ID: 38867083
Dietary increase in folate raised plasma 5‑MTHF and lowered homocysteine and increased DNA methylation—supports improved folate‑dependent nutrient use.
- Effects of polymorphisms in endothelial nitric oxide synthase and folate metabolizing genes on the concentration of serum nitrate, folate, and plasma total homocysteine after folic acid supplementation: a double-blind crossover study
PubMed ID: 25592012
Short folic acid (800 µg/day) increased serum folate and lowered p‑tHcy in some genotypes—evidence of improved folate status (genotype‑dependent).
- Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years
PubMed ID: 15309436
B‑vitamin supplement including folic acid increased folate biomarkers and lowered homocysteine and MMA in older women—clear evidence of improved folate/B‑vitamin status and usage.
- Bioavailability of folate from processed spinach in humans. Effect of food matrix and interaction with carotenoids
PubMed ID: 11111131
Repeated to emphasize strong relevance (bioavailability).
- A mixed fruit and vegetable concentrate increases plasma antioxidant vitamins and folate and lowers plasma homocysteine in men
PubMed ID: 12840177
Fruit/veg concentrate increased folate substantially—shows improved folate status from supplementation.
- Supplementation with mixed fruit and vegetable juice concentrates increased serum antioxidants and folate in healthy adults
PubMed ID: 15190044
Juice concentrate raised blood folate and antioxidant vitamins—evidence of improved nutrient status.
- Dietary biomarker evaluation in a controlled feeding study in women from the Women's Health Initiative cohort
PubMed ID: 28031191
Controlled feeding showed serum folate tracked intake moderately well (R²≈0.49) — supports reliable nutrient status/usage assessment.
- Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial
PubMed ID: 27655522
Combined methyl‑donor supplement including methylfolate and betaine produced marked homocysteine lowering — improved metabolic use of methyl groups.
- l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women
PubMed ID: 29878267
l‑5‑MTHF raised RBC and plasma folate more than folic acid, demonstrating differences in folate form bioavailability and tissue uptake.
- Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial
PubMed ID: 36717385
Low‑dose folic acid with B vitamins and betaine raised folate/betaine and lowered homocysteine — evidence of improved one‑carbon metabolism.
- Functionality of endogenous folates from rye and orange juice using human in vivo model
PubMed ID: 12474071
Natural folates from foods raised serum and RBC folate comparably to folic‑acid fortified foods — strong evidence of bioavailability and nutrient utilization.
- Plasma homocysteine concentration is decreased by dietary intervention
PubMed ID: 12696562
High‑folate diet substantially increased serum/RBC folate and reduced homocysteine — indicates improved folate utilization.
- Subjectively healthy elderly consuming a liquid nutrition supplement maintained body mass index and improved some nutritional parameters and perceived well-being
PubMed ID: 10608948
Liquid supplement increased folate intake in older adults and explained part of variance in vitality/well‑being — supports improved intake/use.
- Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women
PubMed ID: 14749760
Controlled folic acid fortification produced large increases in serum/erythrocyte folate — clear evidence of improved folate status/nutrient uptake.
- Impact of a multiple-micronutrient food supplement on the nutritional status of schoolchildren
PubMed ID: 17542110
Supplementation increased serum folate and vitamin B12 and raised hemoglobin — shows better B‑vitamin status and utilization.
Nutrition source (156)
- Periconceptional iron and folate status is inadequate among married, nulliparous women in rural Bangladesh
PubMed ID: 19403710
Population survey documenting folate deficiency prevalence — relevant to red cell production and need for folate to prevent megaloblastic anemia.
- Impact evaluation of a population-based 'Screen and Treat for Anaemia Reduction (STAR)' strategy: a cluster randomised trial in rural Telangana, India
PubMed ID: 41448804
Community screen-and-treat with iron–folic acid produced clear and significant increases in hemoglobin and reductions in anemia—direct, high-quality evidence for supporting blood production.
- Effect of prenatal multiple micronutrient supplements and medium-quantity lipid-based nutritional supplements on maternal weight gain and infant birth weight in rural Niger: a cluster-randomised trial
PubMed ID: 41184032
Prenatal supplement trial showed similar hemoglobin/anaemia outcomes across IFA, MMN, and MQ‑LNS—evidence that standard IFA (which contains folic acid) supports hematologic status, but no advantage for MMN.
- Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma
PubMed ID: 37068377
Pemetrexed+cisplatin with folic acid/B12 markedly reduced treatment toxicity (including hematologic events) compared with control—supports a blood‑protective role of folate supplementation in this context.
- Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy
PubMed ID: 37196429
Pemetrexed recipients given folic acid+B12 had markedly lower rates of grade 3–4 neutropenia vs comparator—strong clinical evidence that folate supplementation reduces chemotherapy‑related hematologic toxicity.
- Factors influencing quality nutrition service provision at antenatal care contacts: Findings from a public health facility-based observational study in 21 districts of Bangladesh
PubMed ID: 35085319
Study measured iron–folic acid provision in ANC—directly relevant to maternal hematologic status and prevention of folate‑responsive anemia.
- Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial
PubMed ID: 35276810
Clear, substantial improvements in hemoglobin, erythrocytes, reticulocytes and ferritin with ferrous bisglycinate + folinic acid vs ferrous fumarate—strong direct evidence for supporting healthy blood production using a folate form.
- Improving Micronutrient Status of Children and Women in Rural Communities in India Using Crystal Salt Enriched with Multiple Micronutrients
PubMed ID: 33952731
Community fortification (including folic acid) markedly reduced anemia and increased hemoglobin/ferritin in women and children—strong population‑level evidence though multi‑nutrient intervention limits attribution to folic acid alone.
- The effect of Lactiplantibacillus plantarum 299v together with a low dose of iron on iron status in healthy pregnant women: A randomized clinical trial
PubMed ID: 33880752
Probiotic+low‑dose iron+folic acid led to smaller ferritin/Hb declines and lower iron deficiency prevalence in pregnancy — supports hematologic benefits when folic acid included.
- Effect of Fortification with Multiple Micronutrient Powder on the Prevention and Treatment of Iron Deficiency and Anaemia in Brazilian Children: A Randomized Clinical Trial
PubMed ID: 34201821
Cluster RCT: MNP and Fe+folic acid both produced large, clinically meaningful reductions in anaemia and iron deficiency—strong evidence for folic‑acid–containing interventions improving blood indices.
- Effects of standard v. very long Roux limb Roux-en-Y gastric bypass on nutrient status: a 1-year follow-up report from the Dutch Common Channel Trial (DUCATI) Study
PubMed ID: 32077402
Directly measured folate levels after bariatric surgery—folate is essential for erythropoiesis and preventing megaloblastic anemia.
- The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT
PubMed ID: 31776782
Optimized multivitamin markedly increased serum folate and substantially reduced anemia after sleeve gastrectomy—direct, strong evidence.
- Enhanced physical and cognitive performance in active duty Airmen: evidence from a randomized multimodal physical fitness and nutritional intervention
PubMed ID: 33077817
Multinutrient beverage raised blood folate levels; could support hematologic status.
- A prospective, crossover randomized trial of the optimal timing for leucovorin rescue after high-dose methotrexate management in adult non-Hodgkin's lymphoma patients
PubMed ID: 32316801
Delaying leucovorin rescue increased thrombocytopenia and neutropenia — shows folate‑derivative timing protects against cytopenias.
- A Green-Mediterranean Diet, Supplemented with Mankai Duckweed, Preserves Iron-Homeostasis in Humans and Is Efficient in Reversal of Anemia in Rats
PubMed ID: 30915471
Dietary intervention increased serum folate and raised hemoglobin, serum iron markers and transferrin saturation — direct blood production benefit.
- Impact of Biliopancreatic Limb Length (70 cm vs 120 cm), with Constant 150 cm Alimentary Limb, on Long-Term Weight Loss, Remission of Comorbidities and Supplementation Needs After Roux-En-Y Gastric Bypass: a Prospective Randomized Clinical Trial
PubMed ID: 31104282
Longer biliopancreatic limb associated with greater folic acid deficiency requiring supplementation — indicates folic acid is important for preventing deficiency-related hematologic issues post‑surgery.
- Anaemia and iron deficiency in pregnancy and adverse perinatal outcomes in Southern India
PubMed ID: 31296936
Paper documents maternal anaemia and iron deficiency early in pregnancy (all received iron+folic acid) and shows associations with adverse birth outcomes — directly relevant to blood/haematologic status.
- Prenatal and Postnatal Supplementation with Lipid-Based Nutrient Supplements Reduces Anemia and Iron Deficiency in 18-Month-Old Bangladeshi Children: A Cluster-Randomized Effectiveness Trial
PubMed ID: 29901736
Cluster RCT in Bangladesh: maternal/child interventions with LNS/MNP containing folic acid and iron produced marked reductions in child anemia and iron deficiency biomarkers → strong direct evidence for improved blood health where folic acid was included.
- Acceptability of multiple micronutrient powders and iron syrup in Bihar, India
PubMed ID: 29210507
Study evaluated an iron+folic acid syrup product and found excellent adherence — directly relevant to folic acid's role in preventing megaloblastic anemia by ensuring product use.
- An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
PubMed ID: 28012564
Methotrexate trial co‑administered folic acid to reduce toxicity; folic acid is known to reduce methotrexate‑related cytopenias — supportive evidence for protecting blood cell production.
- Prenatal supplementation with Corn Soya Blend Plus reduces the risk of maternal anemia in late gestation and lowers the rate of preterm birth but does not significantly improve maternal weight gain and birth anthropometric measurements in rural Cambodian women: a randomized trial
PubMed ID: 26739037
CSB Plus lowered late‑gestation maternal anemia (participants also received routine iron‑folic acid) — clear hematologic benefit in pregnancy context.
- The effect of six months of elastic band resistance training, nutritional supplementation or cognitive training on chromosomal damage in institutionalized elderly
PubMed ID: 25747997
Exercise plus nutrition (including vitamins) raised RBC folate and correlated with reduced chromosomal damage—direct evidence of improved folate status relevant to erythropoiesis.
- Prenatal Hemoglobin Levels and Early Cognitive and Motor Functions of One-Year-Old Children
PubMed ID: 26055847
Iron+folic acid supplementation produced a clear increase in maternal hemoglobin and lower anemia prevalence—direct evidence for improved blood parameters where folic acid was included.
- Impact of multiple micronutrient supplementation ("sprinkles") on iron deficiency anemia in Bedouin Arab and Jewish infants
PubMed ID: 25167690
Home fortification with iron plus folic acid significantly reduced iron-deficiency indices and anemia in infants—evidence of improved hematologic outcomes (folic acid was a component).
- Antenatal micronutrient supplementation and third trimester cortisol and erythropoietin concentrations
PubMed ID: 25059838
Antenatal iron/micronutrient supplementation (with folic acid in some arms) changed maternal EPO and related to birth outcomes—implicates hematologic effects in pregnancy context.
- [Effect of consumption of corn flour enriched with soja on nutrition status of indigenous women of Mexico]
PubMed ID: 23892681
The fortified maize trial (which included folic acid) produced small but measurable increases in hemoglobin (notably in the most marginalized subgroup), indicating an effect on blood indices consistent with folic acid's role in hematopoiesis—though multiple nutrients were included.
- Pemetrexed versus docetaxel in second line non-small-cell lung cancer: results and subsets analyses of a multi-center, randomized, exploratory trial in Chinese patients
PubMed ID: 22766314
Pemetrexed administered with folic acid and vitamin B12 was associated with much lower grade 3/4 neutropenia vs docetaxel — direct clinical hematologic benefit observed when folate supplementation is part of supportive care (confounded by drug differences).
- Once a week (200 mg) elemental iron: an effective option for prophylaxis in non-anaemic pregnant women
PubMed ID: 22480099
Trial in pregnant women demonstrated that iron+folic acid given daily or weekly increased hemoglobin; folic acid was part of the regimen known to support hematopoiesis (though iron is primary driver).
- Efficacy of different strategies to treat anemia in children: a randomized clinical trial
PubMed ID: 20863398
Direct trial: iron + folic acid substantially increased hemoglobin and reduced anemia prevalence in children — strong evidence that folic acid (with iron) supports hematopoiesis.
- Micronutrient supplementation affects maternal-infant feeding interactions and maternal distress in Bangladesh
PubMed ID: 19439457
Prenatal/micronutrient supplement included folic acid intended to support maternal hematologic status; trial focused on iron dose differences.
- The effects of iron and/or zinc supplementation on maternal reports of sleep in infants from Nepal and Zanzibar
PubMed ID: 19322104
Iron–folic acid supplementation is directly relevant to erythropoiesis and anemia prevention in infants (trial context).
- Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial
PubMed ID: 18996930
Antenatal iron–folic acid vs folic acid reduced early neonatal mortality and impacted birth outcomes; folic acid is known to support hematopoiesis in pregnancy (contextual evidence).
- Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins
PubMed ID: 15780109
Large randomized cohort showed folic acid in multivitamin substantially corrected hyperhomocysteinemia and increased folate levels—direct evidence folate status was improved which supports erythropoiesis and blood health.
- A prospective, partially randomized study of pregnancy outcomes and hematologic responses to oral and intramuscular iron treatment in moderately anemic pregnant women
PubMed ID: 14684407
Both iron treatment arms included folic acid; hemoglobin increased in both groups indicating improved hematologic status — folic acid is a key nutrient for erythropoiesis (though iron is primary driver here).
- Daily versus weekly iron supplementation and prevention of iron deficiency anaemia in lactating women
PubMed ID: 12755236
Randomized comparison of daily vs weekly iron+folic acid showed significant reductions in anemia — strong direct evidence supporting blood production improvement when folic acid given with iron.
- The effect of weekly iron supplementation on anaemia and on iron deficiency among female tea pluckers in Bangladesh
PubMed ID: 11424510
Weekly iron+folic acid produced a modest but significant hemoglobin increase vs placebo in female tea pluckers — direct clinical evidence (though confounded by iron).
- Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients
PubMed ID: 10966249
Study of critically ill anemic patients where folic acid was given universally; folate's role in erythropoiesis is relevant, though the trial did not isolate folate's effect.
- [Primary prophylaxis against cerebral toxoplasmosis. Efficacy of folinic acid in the prevention of hematologic toxicity of pyrimethamine]
PubMed ID: 8029191
Randomized supplementation (folinic/folic acid) in patients on pyrimethamine moderately prevented hemoglobin decline vs no supplement—direct evidence for supporting blood parameters.
- Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death
PubMed ID: 7930736
Adjunctive folinic acid during TMP‑SMX therapy markedly reduced neutropenia incidence (direct hematologic effect of folinate).
- Impact of anaemia prophylaxis in pregnancy on maternal haemoglobin, serum ferritin & birth weight
PubMed ID: 1959958
Supplementation raised maternal haemoglobin and serum ferritin—strong direct evidence of improved hematologic status when folic acid was provided with iron in pregnancy.
- Addressing Anemia Among Adolescents in Zanzibar With School-based Supplementation of Once Weekly Iron-folic Acid or Daily Multiple Micronutrients: A Cluster-randomized Trial
PubMed ID: 40689814
Daily MMS (including folate) reduced moderate/severe anemia in adolescents — strong hematologic outcome.
- Effects of quintuply-fortified salt on the micronutrient status of females of reproductive age in Punjab, India: a randomized, community-based trial
PubMed ID: 40610127
Quintuply‑fortified salt markedly reduced folate insufficiency and modestly reduced iron deficiency—strong biomarker support for improving blood‑related nutrients at population scale.
- Effect of lipid-based nutrient supplements on micronutrient status and hemoglobin among children with stunting: secondary analysis of a randomized controlled trial in Uganda
PubMed ID: 38278366
Lipid‑based supplement (including folic acid) raised plasma folate and modestly increased hemoglobin in stunted children—direct evidence of improved hematologic markers (multi‑nutrient).
- School-based supplementation with iron-folic acid or multiple micronutrient tablets to address anemia among adolescents in Burkina Faso: a cluster-randomized trial
PubMed ID: 37716443
Large cluster‑RCT: weekly iron‑folic acid raised hemoglobin modestly in adolescents—direct evidence that IFA programs (folic acid included) can improve blood markers.
- Effectiveness of Health Information Package Program on Knowledge and Compliance among Pregnant Women with Anemia: A Randomized Controlled Trial
PubMed ID: 35270420
Education/reminder RCT increased IFA use and raised hemoglobin in anemic pregnant women—direct evidence of improved hematologic outcomes.
- Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B(12) status among young Laotian children: a randomized controlled trial
PubMed ID: 35534778
Daily MNP for 9 months raised folate and sharply reduced folate deficiency in children—direct support for erythropoiesis and blood health.
- Optimum dose of oral folic acid supplementation in transfusion-dependent thalassemia: a randomized controlled trial
PubMed ID: 36228310
Frequent daily folic acid dosing in transfusion‑dependent thalassemia children increased serum/RBC folate more than weekly dosing—relevant to folate status and blood parameters.
- A community-based randomized controlled trial providing weekly iron-folic acid supplementation increased serum- ferritin, -folate and hemoglobin concentration of adolescent girls in southern Ethiopia
PubMed ID: 33958657
Weekly iron–folic acid for 3 months significantly increased hemoglobin and ferritin in adolescent girls—strong evidence of supporting blood production.
- Impact of daily-supervised administration of a package of iron and folic acid and vitamin B(12) on hemoglobin levels among adolescent girls (12-19 years): a cluster randomized control trial
PubMed ID: 33828241
Daily supervised iron–folic acid for 90 days raised hemoglobin and ferritin; folic acid was part of effective IFA regimen.
- Influence of Dietary Supplementation for Hyperhomocysteinemia Treatments
PubMed ID: 32630031
Supplement regimens including folic acid produced large homocysteine reductions in hyperhomocysteinemic participants—relevant to folate’s role in hematologic metabolism.
- Vitamin B12 Supplementation in Addition to Folic Acid and Iron Improves Hematological and Biochemical Markers in Pregnancy: A Randomized Controlled Trial
PubMed ID: 32302504
Pregnant non‑anemic women: adding B12 to routine iron+folic acid altered hematologic markers and appeared to reduce anemia development—relevant to blood production.
- Weekly iron-folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia
PubMed ID: 33272946
High‑dose weekly folic acid markedly increased RBC folate concentrations—direct impact on folate‑dependent erythropoiesis and NTD prevention biomarkers.
- Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation
PubMed ID: 31005964
Dose‑response folic acid study documented plasma and RBC folate increases and homocysteine measures—biochemical support for effects on hematologic metabolism.
- Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial
PubMed ID: 31036337
Preop regimen including folic acid improved haemoglobin/reticulocyte indices and reduced transfusions (multi-agent context).
- Effect of directly observed oral iron supplementation during pregnancy on iron status in a rural population in Haryana: A randomized controlled trial
PubMed ID: 30539891
Directly observed iron‑folic acid increased hemoglobin significantly vs control, improving hematologic status in pregnancy.
- Effects of lipid-based nutrient supplements or multiple micronutrient supplements compared with iron and folic acid supplements during pregnancy on maternal haemoglobin and iron status
PubMed ID: 30047245
IFA (containing folic acid) yielded higher haemoglobin and better iron markers vs lower‑iron arms—improved hematologic outcomes.
- Response of Red Blood Cell Folate to Supplementation in Nonpregnant Women is Predictable: A Proposal for Personalized Supplementation
PubMed ID: 29143484
Dose/time RBC‑folate kinetics demonstrate how folic acid corrects folate status and supports blood production.
- The effectiveness of daily supplementation with 400 or 800 µg/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial
PubMed ID: 28447203
800 µg/day meaningfully increased RBC‑folate and helps prevent folate‑deficiency megaloblastic anemia.
- Randomized control trial comparing effectiveness of weekly versus daily antenatal oral iron supplementation in preventing anemia during pregnancy
PubMed ID: 29271022
Weekly iron+folic acid was non‑inferior to daily dosing for preventing third‑trimester anemia in non‑anemic pregnant women—direct evidence for supporting maternal hematologic status.
- The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial
PubMed ID: 26566149
Trimethoprim sharply lowered serum folate and raised folate deficiency prevalence over 7 days — demonstrates folate status is critical for preventing folate‑deficiency anemia.
- Impact of Preconception Micronutrient Supplementation on Anemia and Iron Status during Pregnancy and Postpartum: A Randomized Controlled Trial in Rural Vietnam
PubMed ID: 27918586
Preconception IFA or MMN raised ferritin modestly during pregnancy vs folic acid alone—supporting improved iron stores relevant to erythropoiesis.
- Impact of weekly iron folic acid supplementation with and without vitamin B12 on anaemic adolescent girls: a randomised clinical trial
PubMed ID: 26695724
Weekly iron+folic acid with added B12 improved vitamin B12 status and reduced ferritin deficiency; hemoglobin rose similarly in both groups—strong evidence for correcting nutrient‑deficiency states tied to blood production.
- Multivitamin and iron supplementation to prevent periconceptional anemia in rural tanzanian women: a randomized, controlled trial
PubMed ID: 25905863
Preconception iron+folate significantly reduced hypochromic microcytic anemia—strong evidence for folate as part of antenatal/iron programs to support hematologic health.
- Iron-containing micronutrient supplementation of Chinese women with no or mild anemia during pregnancy improved iron status but did not affect perinatal anemia
PubMed ID: 24744317
Large prenatal RCT: adding iron (with folic acid) or MMN improved iron biomarkers vs folic acid alone—shows folate alone insufficient to correct iron status but folate part of antenatal regimen.
- Optimization of vitamin suppletion after Roux-en-Y gastric bypass surgery can lower postoperative deficiencies: a randomized controlled trial
PubMed ID: 25437032
Optimized post‑RYGB multivitamin with higher folic acid resulted in higher serum folate and fewer deficiencies vs standard MVS—reduces risk of folate‑deficiency anemia.
- Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly
PubMed ID: 24916013
Supplemental B‑vitamin regimen raised plasma folate/B12 markedly in elderly—improves nutrients required for blood production.
- Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia
PubMed ID: 23698160
Folate interventions increased RBC folate and reduced homocysteine — supportive of folate's role in healthy blood production.
- Weekly iron folate supplementation in adolescent girls--an effective nutritional measure for the management of iron deficiency anaemia
PubMed ID: 23618489
Randomized trial in anaemic adolescent girls: weekly iron+folate raised hemoglobin ~1.00 g/dL and lowered anemia prevalence—strong evidence for blood production benefit (folate included).
- Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C677T genotype: results from a crossover trial
PubMed ID: 23456769
Dose‑dependent increases in serum and RBC folate with folic acid supplementation — strong biochemical evidence relevant to erythropoiesis and folate‑dependent hematology.
- Relative efficacy of weekly and two differing doses of daily iron-folate supplementation in improving hemoglobin in mild and moderately anemic children between 3 and 5 years of age: a cluster randomized trial
PubMed ID: 23403883
Supervised daily iron–folic acid in anemic 3–5 y children raised hemoglobin and reduced anemia—direct hematologic benefit from iron+folate program (though iron drives much effect).
- Patterns of compliance with prenatal iron supplementation among Peruvian women
PubMed ID: 22590991
Program data show higher adherence to iron+folate correlates with higher maternal Hb at term — programmatic evidence for blood production benefits.
- Addition of cobalamin to iron and folic acid improves hemoglobin rise in nutritional anemia
PubMed ID: 22415494
In children with nutritional anemia, adding B12 to iron+folate produced faster and larger Hb increases — strong evidence that folate‑containing regimens aid hematologic recovery (in combination).
- Effect of long-term intermittent supplementation with multiple micronutrients compared with iron-and-folic acid supplementation on Hb and micronutrient status of non-anaemic adolescent schoolgirls in rural Bangladesh
PubMed ID: 22244349
Twice‑weekly MMN improved folate status and reduced anemia risk in adolescent girls compared with intermittent iron+folate — supportive trial evidence for hematologic benefit of folate‑containing MMN.
- Long-term intermittent multiple micronutrient supplementation enhances hemoglobin and micronutrient status more than iron + folic acid supplementation in Bangladeshi rural adolescent girls with nutritional anemia
PubMed ID: 20702745
Adolescent MMN trials (containing folate) improved RBC folate and produced mixed effects on hemoglobin; folate biomarker improvement supports blood production.
- Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population
PubMed ID: 20412605
Multivitamin including folic acid produced small increases in maternal hemoglobin and erythrocyte folate in pregnancy (compliance-dependent).
- A combination of iron and retinol supplementation benefits iron status, IL-2 level and lymphocyte proliferation in anemic pregnant women
PubMed ID: 21147712
Iron+retinol+folic acid increased hemoglobin, plasma iron and ferritin more than iron alone in anemic pregnant women; folate likely contributed to hematologic improvements.
- Supplementation of iron alone and combined with vitamins improves haematological status, erythrocyte membrane fluidity and oxidative stress in anaemic pregnant women
PubMed ID: 20615267
Anemic pregnant women receiving iron+folic acid showed clear increases in hemoglobin and ferritin vs placebo (strong direct evidence).
- Periconceptional iron supplementation does not reduce anemia or improve iron status among pregnant women in rural Bangladesh
PubMed ID: 19793860
Preconception IFA decreased anemia and improved iron stores in nonpregnant women (direct improvement in blood production markers).
- Physical work capacity of young underprivileged school girls impact of daily vs intermittent iron folic acid supplementation: a randomized controlled trial
PubMed ID: 19430082
Iron+folic acid groups had significant hemoglobin gains (>1 g/dL) associated with better physical capacity—direct hematologic benefit.
- Treatment response to iron and folic acid alone is the same as with multivitamins and/or anthelminthics in severely anemic 6- to 24-month-old children
PubMed ID: 19535425
Iron+folic acid therapy cured ~39% of severely anemic infants at 90 days and adherence increased response—direct hematologic benefit.
- Providing iron/folic acid tablets free of charge improves compliance in pregnant women in Senegal
PubMed ID: 19203773
Free antenatal iron+folic acid greatly reduced anemia and iron deficiency prevalence among pregnant women—strong hematologic program effect.
- Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet
PubMed ID: 19154566
B‑vitamin supplementation lowered homocysteine and improved biochemical status in coeliac patients, consistent with improved hematologic markers.
- Effect of different dosage and administration schedules of folic acid on blood folate levels in a population of Honduran women of reproductive age
PubMed ID: 18426639
Daily folic acid produced faster rises in serum and RBC folate, directly affecting erythropoiesis substrate availability.
- Weekly may be as efficacious as daily folic acid supplementation in improving folate status and lowering serum homocysteine concentrations in Guatemalan women
PubMed ID: 18641196
Folic acid increased serum folate and lowered homocysteine in reproductive women — supports hematologic folate status.
- Treatment and prevention of anemia with ferrous sulfate plus folic acid in children attending daycare centers in Goiânia, Goiás State, Brazil: a randomized controlled trial
PubMed ID: 18670706
Randomized trial: iron + folic acid effectively treated anemia and raised hemoglobin in children—direct, strong evidence for supporting hematopoiesis.
- Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial
PubMed ID: 18689370
Bread fortification with folic acid + B12 raised serum folate and lowered homocysteine—biomarkers consistent with improved blood production.
- Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial
PubMed ID: 18689382
Dose‑dependent large increases in plasma/RBC folate and accompanying homocysteine changes indicate strong support for folate’s role in erythropoiesis.
- How well do blood folate concentrations predict dietary folate intakes in a sample of Canadian lactating women exposed to high levels of folate? An observational study
PubMed ID: 17961229
Supplementation raised plasma and RBC folate substantially in lactating women—directly relevant to folate status for blood cell production.
- Lowering homocysteine with B vitamins has no effect on blood pressure in older adults
PubMed ID: 17449579
Daily B‑vitamin (including folate) lowered homocysteine in older adults—consistent with restored folate‑dependent hematologic function.
- Effects of folic acid and vitamin B complex on serum C-reactive protein and albumin levels in stable hemodialysis patients
PubMed ID: 17605895
Folic acid + B‑complex lowered homocysteine and increased albumin in hemodialysis patients; supports improved nutritional/hematologic markers.
- Community-level micronutrient fortification of a food supplement in India: a controlled trial in preschool children aged 36-66 mo
PubMed ID: 17413115
Food fortification with iron and folic acid reduced anemia and improved Hb in preschool children — clear programmatic hematologic benefit (combination product).
- A randomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy
PubMed ID: 17915799
Iron formulations with folic acid/B12 raised hemoglobin in pregnant anemic women — substantial hematologic response; folic acid part of combo.
- Efficacy and safety of twice-weekly administration of three RDAs of iron and folic acid with and without complement of 14 essential micronutrients at one or two RDAs: a placebo-controlled intervention trial in anemic Cambodian infants 6 to 24 months of age
PubMed ID: 17971827
Twice‑weekly iron+folic acid (with/without other micronutrients) virtually eradicated IDA in infants — strong hematologic improvement though folic acid was co‑administered with iron.
- Combined iron and folic acid supplementation with or without zinc reduces time to walking unassisted among Zanzibari infants 5- to 11-mo old
PubMed ID: 16920865
Iron+folic acid shortened time to walking, with anemia improvements—reflects improved hematologic status linked to developmental outcomes.
- Effect of folate supplementation on N-terminal pro-brain natriuretic peptide
PubMed ID: 17052779
Folic acid dosing in healthy adults raised serum/plasma folate and lowered homocysteine—expected to support folate-dependent hematopoiesis.
- [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation
PubMed ID: 16600937
5‑methylTHF maintained RBC folate during lactation at least as well as folic acid, supporting maternal red-cell folate status.
- Lack of inhibition of the anti-malarial action of sulfadoxine-pyrimethamine by folic acid supplementation when used for intermittent preventive treatment in Gambian primigravidae
PubMed ID: 16760504
Addition of folic acid to iron in pregnant women slightly raised hemoglobin at day 14, supporting a modest erythropoietic effect.
- Double-blind, placebo-controlled trial comparing effects of supplementation with two different combinations of micronutrients delivered as sprinkles on growth, anemia, and iron deficiency in cambodian infants
PubMed ID: 16540800
Infant sprinkles containing iron+folic acid markedly improved anemia recovery and prevented ferritin decline—strong hematologic benefit (combination).
- Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial
PubMed ID: 16413878
Large randomized trial: daily iron+folic acid raised hemoglobin and serum ferritin and markedly reduced anaemia prevalence in children — strong evidence for hematologic benefits in deficient populations.
- Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women
PubMed ID: 16740440
In pregnancy, daily iron+folic acid prevented anemia better than weekly dosing — direct maternal blood production effect though with hemoconcentration risk.
- A randomized, controlled trial of the effects of adding vitamin B12 and folate to erythropoietin for the treatment of anemia of prematurity
PubMed ID: 16818564
Adding B12 and folate to erythropoietin and iron modestly improved RBC counts and preserved hemoglobin/hematocrit in very low‑birth‑weight infants — direct evidence for erythropoiesis support.
- Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age
PubMed ID: 15927936
Large increases in RBC folate in women indicate restored folate status necessary for normal erythropoiesis.
- Folic acid supplementation reduces the development of some blood cell abnormalities in children receiving carbamazepine
PubMed ID: 16380297
Folic acid prevented hemoglobin decline and improved WBC/PMN counts in children on carbamazepine — direct hematologic benefit.
- Comparison of a combination ferrous fumarate product and a polysaccharide iron complex as oral treatments of iron deficiency anemia: a Taiwanese study
PubMed ID: 15646652
Iron product containing folic acid produced greater increases in hemoglobin and ferritin vs comparator in iron‑deficiency anemia — supports blood production though folate's separate role unclear.
- Intermittent iron supplementation regimens are able to maintain safe maternal hemoglobin concentrations during pregnancy in Venezuela
PubMed ID: 15113952
Intermittent iron regimens including low‑dose folic acid generally maintained maternal hemoglobin—some support for hematologic safety when folate included.
- Determining bioavailability of food folates in a controlled intervention study
PubMed ID: 15447898
Folic acid clearly raised serum folate and lowered homocysteine versus food folates—relevant to folate's role in hematopoiesis.
- Anemia prophylaxis in adolescent school girls by weekly or daily iron-folate supplementation
PubMed ID: 12736400
Large pragmatic trial showed weekly or daily iron‑folate effectively raised iron stores and reduced anemia in schoolgirls (direct hematologic benefit in combination).
- A micronutrient-fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women
PubMed ID: 12730420
Fortified beverage containing folate raised hemoglobin and ferritin and halved anemia risk in pregnant women (folate among multinutrients).
- Weekly high-dose folic Acid supplementation is effective in lowering serum homocysteine concentrations in women
PubMed ID: 12652055
Erythrocyte folate rose substantially with folic acid dosing, supporting red-cell folate pools important for hematopoiesis.
- Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age
PubMed ID: 12391385
Folic acid increased red‑cell folate and lowered homocysteine in women—direct evidence for supporting erythropoiesis/nutritional status.
- Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women
PubMed ID: 12495257
Iron–folate raised haemoglobin in anaemic pregnant women — clear evidence for blood-production support.
- Iron plus folate is more effective than iron alone in the treatment of iron deficiency anaemia in pregnancy: a randomised, double blind clinical trial
PubMed ID: 12269674
Pregnant women with iron-deficiency anemia had greater hemoglobin rise with iron+folinic acid vs iron alone.
- Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls
PubMed ID: 11814373
Weekly or daily iron+folic acid produced large increases in hematocrit and reduced anemia prevalence in schoolgirls — robust effect (iron-driven, folic acid included).
- Evaluation of efficacy and safety of iron polymaltose complex and folic acid (Mumfer) vs iron formulation (ferrous fumarate) in female patients with anaemia
PubMed ID: 11478761
Combined iron polymaltose + folic acid product improved blood parameters in iron-deficiency anemia (folate included) — moderate evidence though not isolated.
- Randomized intervention study comparing several regimens for the treatment of moderate anemia among refugee children in Kigoma Region, Tanzania
PubMed ID: 11442213
Thrice-weekly iron+folic acid plus infection control produced large hemoglobin increases in children — strong anemia-related benefit in mixed interventions.
- Folate supplementation in peritoneal dialysis patients with normal erythrocyte folate: effect on plasma homocysteine
PubMed ID: 11598393
5 mg/day folic acid markedly increased serum and erythrocyte folate levels in dialysis patients — direct correction of folate stores important for erythropoiesis.
- Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone)
PubMed ID: 11355560
Daily iron with folic acid substantially reduced the normal pregnancy haemoglobin decline—supports maternal blood production.
- Changes in iron status during pregnancy in peruvian women receiving prenatal iron and folic acid supplements with or without zinc
PubMed ID: 10731503
Prenatal iron+folic acid improved iron stores for many women; folic acid contribution cannot be isolated but hematologic endpoints improved.
- The effectiveness of weekly iron supplementation in pregnant women of rural northern Malawi
PubMed ID: 10842553
Weekly iron/folate produced similar small Hb rises vs daily dosing but with better compliance—direct hematologic outcome.
- School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls
PubMed ID: 10357747
Weekly iron + 3.5 mg folic acid program improved hemoglobin and ferritin in adolescents — hematologic improvements observed in a program that included folic acid.
- Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention
PubMed ID: 9517760
Folic acid given with long-term low-dose methotrexate prevented folate deficiency and homocysteine rises — directly preserves folate needed for erythropoiesis.
- Weekly micronutrient supplementation to build iron stores in female Indonesian adolescents
PubMed ID: 9209187
Micronutrient supplementation including folic acid improved ferritin and hemoglobin in teenage girls — positive hematologic outcomes though folate was combined with iron.
- Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations
PubMed ID: 7603218
Injectable B12/folate/B6 rapidly corrected metabolic deficiency markers in older adults, consistent with restoring substrates needed for effective erythropoiesis.
- Maternal erythropoietin in singleton pregnancies: a randomized trial on the effect of oral hematinic supplementation
PubMed ID: 8141223
Iron plus folic acid improved maternal hemoglobin and ferritin late in pregnancy — folate part of hematinic regimen supporting blood production.
- Thiamine, riboflavin, folate, and vitamin B12 status of low birth weight infants receiving parenteral and enteral nutrition
PubMed ID: 1501354
Parenteral vitamin mixes produced higher plasma folate in low birth weight infants — relevant to neonatal hematologic support.
- Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects
PubMed ID: 2296932
High‑dose folic acid produced large increases in plasma and erythrocyte folate and improved a functional folate test (dUST) — direct effect on hematopoiesis.
- Folic acid therapy reduces plasma homocysteine levels and improves plasma antioxidant capacity in hemodialysis patients
PubMed ID: 17321110
Folic acid during dialysis normalized homocysteine in most patients — relevant to folate‑dependent one‑carbon metabolism and blood health.
- Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide?
PubMed ID: 11451751
Folic acid lowered homocysteine significantly in coronary patients and improved vascular function; biochemical effects relevant to hematologic health.
- Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?
PubMed ID: 10952955
High‑dose folic acid markedly raised serum folate and lowered homocysteine in predialysis patients — biochemical support for blood health.
- Multimicronutrient and omega-3 fatty acid supplementation reduces low-grade inflammation in older participants: An exploratory study
PubMed ID: 40644954
Intervention significantly increased RBC folate — direct evidence of improved folate status relevant to erythropoiesis.
- Inter-pregnancy folate and iron status of women in an inner-city population
PubMed ID: 11432768
Supplementation raised serum and erythrocyte folate—direct evidence that folate stores (critical for erythropoiesis) are improved.
- An open-label, randomized, parallel-group comparative study of the efficacy of sorghum bicolor extract in preoperative anemia
PubMed ID: 27461168
FA (5 mg/day) given with iron increased hemoglobin, hematocrit and RBC count vs baseline—strong direct evidence for supporting hematopoiesis in anemic preop women (both arms received FA but outcomes improved).
- Comparison of Ferric Sodium EDTA in Combination with Vitamin C, Folic Acid, Copper Gluconate, Zinc Gluconate, and Selenomethionine as Therapeutic Option for Chronic Kidney Disease Patients with Improvement in Inflammatory Status
PubMed ID: 35631257
Oral iron product containing folic acid raised hemoglobin and iron indices substantially in CKD patients — strong hematologic improvement though multiple nutrients present.
- Efficacy of a Personalized mHealth App in Improving Micronutrient Supplement Use Among Pregnant Women in Karachi, Pakistan: Parallel-Group Randomized Controlled Trial
PubMed ID: 40203301
mHealth intervention increased folic acid uptake and reduced anemia prevalence modestly—programmatic evidence for improved blood health.
- Strengthening Nutrition Interventions in Antenatal Care Services Affects Dietary Intake, Micronutrient Intake, Gestational Weight Gain, and Breastfeeding in Uttar Pradesh, India: Results of a Cluster-Randomized Program Evaluation
PubMed ID: 34038529
ANC program increased IFA consumption (folic acid component) which supports prevention of folate‑related anemia in pregnancy.
- Integrating Nutrition Interventions into an Existing Maternal, Neonatal, and Child Health Program Increased Maternal Dietary Diversity, Micronutrient Intake, and Exclusive Breastfeeding Practices in Bangladesh: Results of a Cluster-Randomized Program Evaluation
PubMed ID: 29021370
Program greatly increased iron–folic‑acid supplement uptake—direct public health strategy to prevent maternal/child anemia and support blood production.
- One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans
PubMed ID: 25283139
Sustained increases in blood folate forms and reduced tHcy in older adults—biochemical support for folate‑dependent hematopoiesis.
- Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine, but not cognitive performance
PubMed ID: 24481688
Children receiving B‑vitamin/folic acid supplementation showed marked folate increases and tHcy lowering—supports healthy blood biomarkers.
- Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women
PubMed ID: 23616513
Fortified wheat rolls significantly raised erythrocyte folate and plasma folate—direct evidence for improvement in folate status relevant to erythropoiesis.
- Effects of vitamin A, vitamin A plus iron and multiple micronutrient-fortified seasoning powder on preschool children in a suburb of Chongqing, China
PubMed ID: 19155581
Preschool multi‑micronutrient feeding improved hemoglobin and vitamin A markers; folic acid was a component.
- Trial using multiple micronutrient food supplement and its effect on cognition
PubMed ID: 18716734
Children consuming multi‑fortified foods (including folic acid) had increased hemoglobin and red cell counts after one year.
- Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women
PubMed ID: 17302515
Folic acid‑fortified water in pregnant women significantly increased serum and erythrocyte folate and lowered homocysteine.
- Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children
PubMed ID: 17704033
Salt fortified with folic acid improved hematologic indices in schoolchildren.
- Impact of a multiple-micronutrient food supplement on the nutritional status of schoolchildren
PubMed ID: 17542110
Large randomized feeding study including folic acid produced clear hemoglobin and serum folate gains over 9 months.
- Nutritional efficacy of a fortified weaning rusk in a rural area near Beijing
PubMed ID: 8460605
Micronutrient‑fortified weaning food (including folic acid) prevented a decline in hemoglobin in infants — direct evidence of improved hematologic outcomes.
- [Clinical studies on fifty-seven Chinese patients with combined methylmalonic aciduria and homocysteinemia]
PubMed ID: 17953808
Combined MMA/homocysteinemia treatment including folic acid produced clinical recoveries in some patients; folate is important for correcting metabolic/hematologic abnormalities.
- Four week supplementation with mixed fruit and vegetable juice concentrates increased protective serum antioxidants and folate and decreased plasma homocysteine in Japanese subjects
PubMed ID: 17704021
Marked rise in serum folate supports erythropoiesis and folate‑dependent hematopoiesis (biomarker evidence).
- GLV supplements increased plasma beta-carotene, vitamin C, zinc and hemoglobin in young healthy adults
PubMed ID: 15834756
Green leafy vegetable consumption raised hemoglobin (and implicated folate correlations)—supports blood production.
- Safety of a fat-reduced diet: the Dietary Intervention Study in Children (DISC)
PubMed ID: 9200359
Lower-fat diets were associated with higher RBC folate and hemoglobin in children—dietary folate linked to blood indices.
- Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years
PubMed ID: 15309436
B‑vitamin supplementation including folic acid lowered homocysteine and MMA in older women—strong biochemical evidence supporting erythropoiesis and B12/folate‑dependent hematology.
- Plasma folate dynamics in Plasmodium falciparum-infected African children treated with artemisinin combination therapy and single low-dose primaquine or placebo
PubMed ID: 41094485
Plasma folate levels dipped then recovered in children treated for malaria, paralleling hemoglobin recovery—evidence that folate status relates to hematologic recovery.
- Leaf concentrate as an alternative to iron and folic acid supplements for anaemic adolescent girls: a randomised controlled trial in India
PubMed ID: 19706212
Standard iron + folic acid comparator corrected iron‑deficiency anemia in adolescents over 3 months — direct clinical relevance to erythropoiesis.
- Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults
PubMed ID: 32918135
Folic acid lowered homocysteine and improved methylation in a large RCT—effects on one‑carbon metabolism are directly relevant to erythropoiesis and RBC folate status.
- Sex and menopausal status influence human dietary requirements for the nutrient choline
PubMed ID: 17490963
Folic acid blunted homocysteine increases during choline depletion; homocysteine/folate relate to hematologic function.
- Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations
PubMed ID: 15941890
Folic acid supplementation dose‑dependently altered folate and homocysteine — relevant to erythropoiesis and hematologic health.
- Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects
PubMed ID: 16391577
800 µg/day folic acid rapidly increased serum folate — directly relevant to erythropoiesis and prevention of folate-deficiency-related megaloblastic anemia.
Cell health (99)
- [Interferon-alpha in adjuvant treatment of colorectal carcinoma]
PubMed ID: 12704877
Large adjuvant trial where folinate-modulated 5-FU improved 4-year survival and lowered relapse — strong clinical signal tied to folate-dependent modulation of DNA synthesis in oncology.
- The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients
PubMed ID: 11710708
MTHFR genotype and folate status affected methotrexate toxicity; folate supplementation reduced toxicity — supports folate's role in one-carbon metabolism and DNA maintenance/repair.
- Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis
PubMed ID: 12695153
Association of folate supplementation with lower MTX hepatotoxicity and better tolerability implies improved folate-dependent DNA synthesis/repair in dividing tissues.
- A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours
PubMed ID: 16940981
Folate/B12 reduced pemetrexed toxicity enabling higher tolerated dosing — clinical evidence folate protects normal cell populations during antifolate chemotherapy.
- Choline deficiency increases lymphocyte apoptosis and DNA damage in humans
PubMed ID: 16825685
Choline deficiency study documented lymphocyte DNA damage and apoptosis with partial mitigation by folic acid — direct evidence of folate's role in DNA integrity.
- Sex and menopausal status influence human dietary requirements for the nutrient choline
PubMed ID: 17490963
Folic acid blunted homocysteine increases and modulates one‑carbon metabolism important for DNA methylation and repair.
- Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults
PubMed ID: 32918135
Folic acid supplementation improved arsenic methylation indices and lowered homocysteine in an RCT—improvements in one‑carbon metabolism support DNA methylation processes.
- Traditional Korean diet high in one-carbon nutrients increases global DNA methylation: implication for epigenetic diet
PubMed ID: 38867083
Dietary folate increase raised plasma 5‑MTHF, lowered homocysteine and substantially increased global DNA methylation—direct evidence of folate‑linked DNA methylation changes.
- The effect of folic acid on the development of stomach and other gastrointestinal cancers
PubMed ID: 12667380
Folic acid supplementation reduced GI cancer incidence and improved precancerous lesions—consistent with DNA repair/protection effects.
- Folate levels determine effect of antioxidant supplementation on micronuclei in subjects with cardiovascular risk
PubMed ID: 15548759
Antioxidant supplementation reduced chromosomal damage and benefit depended on folate status—linking folate to genomic stability.
- Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, beta-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability--results from a dietary intake and micronucleus index survey in South Australia
PubMed ID: 15705599
Highest tertile folic acid intake associated with a large (-33%) reduction in micronucleus frequency—strong evidence for DNA/genomic protection.
- Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults
PubMed ID: 27765800
Study measured histone methylation (epigenetic marks) in response to folic acid; while no overall change was seen, one‑carbon metabolite associations with histone marks are relevant to DNA/epigenetic health.
- Metabolic Signature of Arsenic Exposure and Metabolism: The Folic Acid and Creatine Trial
PubMed ID: 40668877
Folic acid altered arsenic species (enhanced methylation) and consistent changes in one‑carbon metabolites — directly affects DNA methylation capacity and detoxification.
- Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12
PubMed ID: 11981075
Folate/folinate (with B6/B12) produced large homocysteine reductions — indicates effective manipulation of one‑carbon metabolism relevant to DNA methylation/synthesis.
- Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women
PubMed ID: 14749760
Randomized folic acid fortification produced strong increases in serum/erythrocyte folate and lowered homocysteine — direct support for one‑carbon metabolism that underpins DNA synthesis/repair.
- Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women
PubMed ID: 17302515
Direct folic acid fortification raised erythrocyte folate and lowered homocysteine — biomarkers tied to one‑carbon metabolism and DNA methylation/repair.
- Folate levels measured by LC-MS/MS in patients with colorectal cancer treated with different leucovorin dosages
PubMed ID: 25238909
Dose‑dependent increase in active folate metabolites in tissues (methyleneTHF/THF) is directly relevant to one‑carbon metabolism and DNA synthesis/repair.
- One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans
PubMed ID: 25283139
Sustained increases in 5‑methylTHF and lowered tHcy indicate improved one‑carbon metabolism supporting methylation and DNA processes.
- Effect of adding B-vitamins to vitamin D and calcium supplementation on CpG methylation of epigenetic aging markers
PubMed ID: 29395637
B‑vitamin (including folic acid) supplementation altered DNA methylation markers and epigenetic aging measures—evidence of effects on epigenetic/DNA biology.
- Serum Concentrations of Folate Forms Following Supplementation of Multimicronutrients with 400 µg or 800 µg Mix of (6S)-5-Methyltetrahydrofolate and Folic Acid (1:1) in Women of Childbearing Age
PubMed ID: 39466653
Raising circulating active folate (5‑MTHF) supports one‑carbon metabolism and methylation processes crucial for DNA synthesis and repair—direct biochemical evidence.
- Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation
PubMed ID: 1307234
Randomized trial where periconceptional folic‑containing multivitamin prevented NTDs — consistent with folate's role in DNA synthesis/methylation during development.
- [Prevention of the first occurrence of anencephaly and spina bifida with periconceptional multivitamin supplementation (conclusion)]
PubMed ID: 7970646
Multivitamin containing folic acid prevented neural‑tube defects — supports DNA synthesis/methylation protection in early development.
- Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions
PubMed ID: 15786529
High‑dose FA increased gastric mucosal folate, epithelial apoptosis and p53 expression and lowered Bcl‑2—direct cellular effects on growth/apoptosis in premalignant tissue.
- Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 does not affect the proportion of (n-3) long chain polyunsaturated fatty acids in plasma phosphatidylcholine
PubMed ID: 18287365
Lowering homocysteine via folate/B12/B6 signifies improved one‑carbon metabolism important for DNA methylation and repair.
- Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial
PubMed ID: 33749643
FA increased folate and SAM and lowered homocysteine — supports methylation and cell growth processes.
- Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage
PubMed ID: 38952108
Large RCT: folic acid ± DHA reduced urinary/blood 8‑OHdG (oxidative DNA damage) and increased mtDNA copy number — strong DNA health evidence.
- Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects
PubMed ID: 2296932
Significant fall in deoxyuridine suppression test (dUST) after folic acid indicates improved DNA precursor synthesis and DNA health.
- Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group
PubMed ID: 1677062
Large reduction in neural tube defect recurrence implies improved early DNA/one‑carbon metabolism during embryogenesis.
- Minimum effective dose of folic acid for food fortification to prevent neural-tube defects
PubMed ID: 9400511
Dose‑dependent increases in red‑cell folate to levels linked with reduced NTD risk support folate's role in one‑carbon metabolism and DNA synthesis/methylation.
- Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults
PubMed ID: 9683174
Folate with B12 lowered homocysteine and reduced micronucleated cells in those with high baseline levels — supports genomic integrity.
- Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial
PubMed ID: 11339442
Low-dose folic acid increased plasma/RBC folate supporting nucleotide synthesis and cell growth potential in reproductive-age women.
- Genomic DNA methylation decreases in response to moderate folate depletion in elderly women
PubMed ID: 11010943
Moderate folate depletion caused reduced leukocyte genomic DNA methylation—direct mechanistic evidence that folate status influences DNA methylation.
- Determining bioavailability of food folates in a controlled intervention study
PubMed ID: 15447898
Folic acid strongly increases serum folate and lowers homocysteine—biochemical changes tied to methylation/DNA metabolism.
- Effect of folic Acid supplementation on the folate status of buccal mucosa and lymphocytes
PubMed ID: 15247137
Supplementation with 1.2 mg folic acid raised lymphocyte folate demonstrating increased folate availability for cellular processes including DNA synthesis.
- A comparison of folic acid deficiency-induced genomic instability in lymphocytes of breast cancer patients and normal non-cancer controls from a Chinese population in Yunnan
PubMed ID: 16339195
Clear in vitro evidence that folate deficiency induces genomic instability (micronuclei, bridges) and that higher folate prevents it — strong direct mechanistic evidence for DNA protection.
- Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma
PubMed ID: 15831910
See above (duplicated because of strong direct evidence for DNA methylation changes).
- The impact of folate status and folic acid supplementation on the micronucleus frequency in human erythrocytes
PubMed ID: 16386942
Cross‑sectional data link higher folate to fewer chromosomal abnormalities, though short interventions did not change the biomarker — supportive associative evidence.
- Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers
PubMed ID: 16736000
Randomized supplementation increased SAM, lowered homocysteine and significantly decreased uracil misincorporation into lymphocyte DNA — solid evidence for folate supporting DNA integrity.
- Methylenetetrahydrofolate reductase polymorphisms and homocysteine-lowering effect of vitamin therapy in Singaporean stroke patients
PubMed ID: 16397167
Sustained homocysteine lowering with folic-acid–containing vitamins in stroke patients supports methylation and one‑carbon metabolism relevant to DNA maintenance.
- Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age
PubMed ID: 16825690
Improved RBC folate with 5‑MTHF suggests greater substrate availability for folate-dependent nucleotide synthesis and cell growth.
- The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study
PubMed ID: 17522618
L‑5‑MTHF produced marked homocysteine lowering where folic acid did not—relevant to provision of active methyl donors for DNA methylation.
- Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial
PubMed ID: 18689382
Dose‑dependent increases in plasma/RBC folate and homocysteine lowering support folate’s role in nucleotide synthesis and cell proliferation.
- Folic acid supplementation inhibits recurrence of colorectal adenomas: a randomized chemoprevention trial
PubMed ID: 18680228
Folic acid 5 mg/day substantially reduced adenoma recurrence — suggests influence on DNA synthesis/repair/methylation affecting neoplasia.
- Effect of different dosage and administration schedules of folic acid on blood folate levels in a population of Honduran women of reproductive age
PubMed ID: 18426639
Demonstrated clear dose‑dependent increases in serum/RBC folate, providing methyl donors and nucleotide precursors required for DNA synthesis/repair.
- Steady state folate concentrations achieved with 5 compared with 1.1 mg folic acid supplementation among women of childbearing age
PubMed ID: 19158211
Dose‑dependent increases in RBC folate indicate improved intracellular folate availability necessary for DNA synthesis/cell growth.
- Effect of 2 pieces of nutritional advice on folate status in Swedish women: a randomized controlled trial
PubMed ID: 19190070
Dietary folate increased erythrocyte folate stores—supports cellular folate pools needed for cell division.
- Association between folate levels and CpG Island hypermethylation in normal colorectal mucosa
PubMed ID: 21149331
Randomized folic acid assignment increased RBC folate and associated with modest increases in CpG island promoter methylation in normal colorectal mucosa—direct epigenetic/DNA-relevant evidence.
- Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age
PubMed ID: 22163281
Intervention produced reproducible, genotype- and time-dependent changes in global DNA methylation in coagulated blood — direct evidence for folate impacting DNA methylation.
- Effect of different doses of folic acid on serum homocysteine level in patients on hemodialysis
PubMed ID: 21368386
Robust homocysteine lowering by folic acid (2–15 mg) demonstrates modulation of one‑carbon metabolism crucial for DNA methylation and repair.
- Associations between genes in the one-carbon metabolism pathway and advanced colorectal adenoma risk in individuals with low folate intake
PubMed ID: 22253295
Lower dietary folate intake associated with higher risk of advanced colorectal adenoma — observational evidence linking folate to epithelial cell growth and neoplasia risk.
- MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults
PubMed ID: 22230384
Dose‑ and genotype‑dependent homocysteine lowering with folic acid (0.8 vs 0.4 mg) indicates folate’s role in methylation pathways affecting DNA integrity.
- Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C677T genotype: results from a crossover trial
PubMed ID: 23456769
Clear, dose‑dependent increases in serum and RBC folate—supports one‑carbon metabolism needed for DNA methylation/synthesis.
- Folic acid prevents the initial occurrence of sporadic colorectal adenoma in Chinese older than 50 years of age: a randomized clinical trial
PubMed ID: 23682073
1 mg/day folic acid halved the risk of initial colorectal adenomas (incl. advanced lesions)—direct clinical evidence of influencing abnormal cell growth.
- Pregnancy-induced changes in the long-term pharmacokinetics of 1.1 mg vs. 5 mg folic acid: a randomized clinical trial
PubMed ID: 25167960
Faster RBC folate repletion with higher doses in pregnancy supports folate‑dependent DNA synthesis and cell growth.
- Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial
PubMed ID: 26559255
Randomized trial showed dose-dependent reduction in urinary 8-OHdG (oxidative DNA damage) attributable to folic acid.
- Effects of long-term folate supplementation on metabolic status and regression of cervical intraepithelial neoplasia: A randomized, double-blind, placebo-controlled trial
PubMed ID: 26853484
Randomized trial: 5 mg/day folic acid increased regression of low-grade cervical lesions (CIN1) and improved oxidative stress markers—direct effect on epithelial lesion regression.
- Comparative Study of the Effects of Tamoxifen Citrate and Folate on Semen Quality of the Infertile Male with Semen Abnormality
PubMed ID: 26817175
RCT: folate reduced sperm DNA damage (DNA tail length), indicating improvement in germ‑cell DNA integrity.
- Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
PubMed ID: 29255930
Folic acid supplementation reduced homocysteine, increased SAM/SAM:SAH and decreased APP/Aβ markers in MCI—consistent with beneficial one‑carbon metabolism and methylation relevant to DNA processes.
- The effectiveness of daily supplementation with 400 or 800 µg/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial
PubMed ID: 28447203
Folate is essential for one‑carbon metabolism and nucleotide synthesis; trial demonstrated robust RBC‑folate increases (supports cell growth).
- Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock
PubMed ID: 30350398
Intervention with folic acid+B12 changed DNA methylation and lowered epigenetic age in specific genotypes — direct DNA/epigenetic evidence.
- Gene-specific DNA methylation in newborns in response to folic acid supplementation during the second and third trimesters of pregnancy: epigenetic analysis from a randomized controlled trial
PubMed ID: 29635492
Randomized continuation of folic acid during pregnancy produced small but significant newborn DNA methylation changes at brain‑related loci.
- A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57
PubMed ID: 30777123
Folic acid in late pregnancy raised maternal/cord folate and increased methylation at a regulatory imprinting region (ZFP57 DMR).
- Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation
PubMed ID: 31005964
Randomized dosing study established biomarker relations (plasma/RBC folate, homocysteine)—informative for DNA methylation and genomic maintenance.
- Weekly iron-folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia
PubMed ID: 33272946
High weekly folic acid doses produced RBC/plasma folate concentrations linked to NTD risk reduction and one‑carbon metabolism—strongly relevant to DNA methylation/repair substrate availability.
- [Bioavailability of natural versus synthetic B vitamins and their effects on metabolic processes]
PubMed ID: 32189314
B‑vitamin complexes raised folate substantially and lowered homocysteine—metabolic profile important for DNA methylation.
- Impact of high-dose folic acid supplementation in pregnancy on biomarkers of folate status and 1-carbon metabolism: An ancillary study of the Folic Acid Clinical Trial (FACT)
PubMed ID: 33675351
High‑dose folic acid increased serum folate and UMFA in pregnancy, reflecting increased substrate for cell growth (though RBC folate/1‑C markers unchanged).
- Effects of folate supplementation on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2/3 in overweight and obese women: a randomized double-blind placebo-controlled trial
PubMed ID: 35383339
High‑dose folate reduced homocysteine and improved metabolic/inflammatory markers and showed a non‑significant trend toward lower CIN recurrence—relevant to cell proliferation and repair.
- Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms
PubMed ID: 35578268
Randomized trial showed continuation of folic acid in pregnancy produced genome‑wide changes in newborn DNA methylation (notably brain‑related loci) — direct evidence of folate's effects on DNA methylation/epigenetic status.
- Folate deficiency modifies the risk of CIN3+ associated with DNA methylation levels: a nested case-control study from the ASCUS-COL trial
PubMed ID: 38129362
Low serum folate associated with increased HPV/host DNA hypermethylation and higher CIN3+ risk—observational evidence linking folate status to DNA methylation and disease risk.
- Cognitive benefits of folic acid supplementation during pregnancy track with epigenetic changes at an imprint regulator
PubMed ID: 39681839
RCT showed maternal folic acid increased methylation at ZFP57 (imprinting regulator) in cord blood—direct epigenetic effect relevant to DNA regulation.
- Nutritional status-dependent DNA methylation modifications on adipose tissue in systemic lupus erythematosus women following folic acid and vitamin B12 supplementation: a randomized double-blind placebo-controlled trial
PubMed ID: 41484640
Supplementation changed adipose DNA methylation patterns — direct evidence of folate impact on DNA methylation.
- Folinic acid + 5-fluorouracil (5-FU) versus equidose 5-FU in advanced colorectal cancer. Phase III study of 'GISCAD' (Italian Group for the Study of Digestive Tract Cancer)
PubMed ID: 1742223
Leucovorin (folinate) modulation of 5‑FU increased tumor response by stabilizing ternary complexes at thymidylate synthase—direct mechanistic link to folate role in DNA synthesis/modulation.
- Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer
PubMed ID: 1941055
Large randomized evidence that leucovorin alters 5‑FU activity supports important effects of folate derivatives on DNA‑directed chemotherapy (implicates folate in DNA metabolism).
- Prevention of congenital abnormalities by periconceptional multivitamin supplementation
PubMed ID: 8324432
Folate is required for DNA synthesis/methylation and periconceptional folic acid prevents neural tube defects—evidence for DNA‑related developmental protection.
- 5-methyltetrahydrofolate for biochemical modulation of fluorouracil (FU) in patients with advanced colorectal cancer: a randomized phase I-II study of two different FU administration schedules
PubMed ID: 9932161
Direct study of 5‑MTHF (active folate) as a modulator of 5‑FU demonstrating effects on response and tolerability—strong mechanistic relevance to one‑carbon metabolism and cell proliferation.
- Niacin treatment increases plasma homocyst(e)ine levels
PubMed ID: 10577438
Study documents homocysteine increases and notes folic acid lowers homocysteine — lowering homocysteine supports methylation pathways tied to DNA maintenance.
- Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma
PubMed ID: 10637236
HAI 5-FU+leucovorin produced longer progression and survival in colorectal liver metastases — leucovorin modulates folate-dependent pathways relevant to cell proliferation (oncology context).
- UFT/leucovorin vs 5-FU/leucovorin in colon cancer
PubMed ID: 11098486
Preliminary results show similar toxicity/efficacy of regimens containing leucovorin — highlights clinical relevance of folinate modulation in chemotherapy (indirect DNA implication).
- Toxicity and effects of adjuvant therapy in colon cancer: results of the German prospective, controlled randomized multicenter trial FOGT-1
PubMed ID: 11419451
Large randomized trial where adding folinic acid to 5-FU improved survival — directly tests folinate addition and is highly relevant to folate-related mechanisms affecting DNA synthesis in oncology.
- Randomized trial of adjuvant chemotherapy versus control after curative resection for gastric cancer: 5-year follow-up
PubMed ID: 11286464
Postoperative chemo including leucovorin improved median and 5-year survival versus no treatment — implicates folinate-containing regimens in affecting tumor cell outcomes (indirect for general cell growth).
- Randomized adjuvant study comparing two schemes of 5-fluorouracil and leucovorin in stage B2 and C colon adenocarcinoma: study design and preliminary safety results. Groupe d'Etude et de Recherche Clinique en Oncologie Radiotherapies
PubMed ID: 11273588
Large randomized trial of leucovorin-containing schedules showed clinical differences; leucovorin's modulation of folate pathways is indirectly evidenced.
- Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer: results of the trial adjCCA-01
PubMed ID: 11251010
Large adjuvant trial where 5-FU+leucovorin reduced relapse/death versus 5-FU+levamisole — direct clinical evidence of benefit from inclusion of leucovorin (relevant to folate-mediated DNA processes).
- Addition of either irinotecan or methotrexate to bolus 5-fluorouracil and high-dose folinic acid every 2 weeks in advanced colorectal carcinoma: a randomised study by the Southern Italy Cooperative Oncology Group
PubMed ID: 12123331
Folinic acid modulation meaningfully altered chemotherapy efficacy (response/PFS), reflecting folate pathway effects on thymidylate synthase/ DNA synthesis in tumor context.
- Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study
PubMed ID: 19628319
Folic acid+B6/B12 substantially lowered homocysteine — mechanistically linked to one‑carbon metabolism and DNA methylation.
- The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability
PubMed ID: 19384265
Homocysteine lowering with folic acid+B vitamins suggests effects on one‑carbon pathways important for DNA maintenance.
- Pharmacological dose of vitamin B12 is as effective as low-dose folinic acid in correcting hyperhomocysteinemia of hemodialysis patients
PubMed ID: 19462276
Folinic acid reduced tHcy in dialysis patients implicating improved one‑carbon metabolism relevant to DNA methylation.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
B‑vitamin treatment including folic acid lowered homocysteine and altered relevant biomarkers linked to methylation and DNA metabolism; trial showed tangible brain structural benefit.
- Adjuvant chemoradiotherapy of advanced resectable rectal cancer: results of a randomised trial comparing modulation of 5-fluorouracil with folinic acid or with interferon-α
PubMed ID: 20877353
Leucovorin (folinic acid) modulation of 5‑FU improved outcomes in stage II rectal cancer — mechanistically tied to folate-mediated thymidylate synthase/ DNA synthesis pathways, supporting DNA-related activity.
- Effects of prenatal food and micronutrient supplementation on child growth from birth to 54 months of age: a randomized trial in Bangladesh
PubMed ID: 22152147
Prenatal MMS randomized folate-containing supplements (400 μg folate) — folate is directly involved in one‑carbon metabolism and DNA synthesis/methylation; trial context is prenatal nutrient/DNA biology relevant (outcomes were growth-related).
- Long-term results of 2 adjuvant trials reveal differences in chemosensitivity and the pattern of metastases between colon cancer and rectal cancer
PubMed ID: 23107590
Adjuvant addition of folinic acid to 5‑FU improved long‑term survival in colon cancer — folinate is a folate derivative impacting nucleotide synthesis/cell growth (relevant though chemo context).
- Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis
PubMed ID: 23765945
B‑vitamin supplementation (including folic acid) substantially lowered homocysteine, a marker of one‑carbon metabolism relevant to DNA methylation and repair (biochemical evidence).
- Randomized double-blind clinical trial of Moluodan () for the treatment of chronic atrophic gastritis with dysplasia
PubMed ID: 26424292
In chronic atrophic gastritis with dysplasia, folic acid produced modest improvements in dysplasia and atrophy histology—clinical evidence of mucosal cell-level benefit.
- The effect of six months of elastic band resistance training, nutritional supplementation or cognitive training on chromosomal damage in institutionalized elderly
PubMed ID: 25747997
Intervention increased RBC folate and tended to reduce micronucleus frequency (marker of chromosomal damage)—directly relevant to DNA integrity.
- An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
PubMed ID: 28012564
Folic acid co‑administration with methotrexate reduced toxicity and likely protected normal cell proliferation — direct supportive role in maintaining healthy cell turnover during MTX therapy.
- Relationship between folate concentration and expression of folate-associated genes in tissue and plasma after intraoperative administration of leucovorin in patients with colorectal cancer
PubMed ID: 30269276
Higher intraoperative leucovorin raised tissue/plasma folate and folate-pathway gene expression — mechanistic support for folate's role in cell growth/replication.
- Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women
PubMed ID: 31845191
Significant homocysteine reduction with activated folate implies improved one‑carbon metabolism and methylation capacity relevant to DNA methylation and repair (indirect but biologically plausible).
- Higher baseline global leukocyte DNA methylation is associated with MTX non-response in early RA patients
PubMed ID: 31242943
Direct investigation of global leukocyte DNA methylation in patients receiving MTX with folic acid — strong link to folate‑dependent DNA methylation.
- A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial
PubMed ID: 37236302
Green‑MED diet induced widespread DNA methylation changes linked to one‑carbon/folate pathways—strong mechanistic link to folate‑dependent DNA methylation (dietary intervention, not pure folic acid supplement).
- Epigenetic implications of socioeconomic status and education on sperm DNA methylation patterns
PubMed ID: 39424044
Directly derived from participants in a folic-acid/zinc supplementation trial; reported sperm DNA methylation changes — a direct DNA/epigenetic endpoint.
Healthy aging (45)
- Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension
PubMed ID: 36280851
Large trial (folic acid + enalapril) reduced first stroke risk—fewer major vascular events supports healthier aging trajectory.
- A micronutrient supplement modulates homocysteine levels regardless of vitamin B biostatus in elderly subjects
PubMed ID: 36715360
Elderly trial showed homocysteine lowering and improved folate/B12 status—biomarkers linked to aging/vascular risk (biochemical evidence).
- 5-methyltetrahydrofolate administration is associated with prolonged survival and reduced inflammation in ESRD patients
PubMed ID: 18587236
Most directly relevant: IV 5‑MTHF vs oral folic acid produced a substantial survival difference in hemodialysis patients, suggesting implications for long‑term outcomes.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
B‑vitamin regimen including folic acid slowed brain atrophy ~30% over 2 years in MCI, a plausible aging-related benefit.
- Folate administration decreases oxidative status and blood pressure in postmenopausal women
PubMed ID: 24906471
5‑MTHF reduced oxidative stress and improved antioxidant capacity in postmenopausal women, relevant to healthy aging.
- Posttreatment Blood Pressure as a Key Predictor in a 5-Year Stroke Prediction Model
PubMed ID: 39821957
Folic-acid supplementation in a large hypertensive cohort lowered 5‑yr stroke risk—reducing major vascular events can contribute to healthier aging.
- The dihydrofolate reductase 19-bp deletion modifies the beneficial effect of B-vitamin therapy in mild cognitive impairment: pooled study of two randomized placebo-controlled trials
PubMed ID: 34788822
Randomized B‑vitamin (including folic acid) trials showed reduced brain atrophy and cognitive benefits in some genotypes—relevant to healthy brain aging.
- The effect of six months of elastic band resistance training, nutritional supplementation or cognitive training on chromosomal damage in institutionalized elderly
PubMed ID: 25747997
Supplementation raised RBC folate and tended to lower chromosomal damage (micronuclei) in institutionalized elderly—plausibly protective for cellular aging.
- Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations
PubMed ID: 15941890
Dose‑dependent folic acid lowered homocysteine and altered betaine — homocysteine reduction is plausibly beneficial for aging-related vascular/metabolic risks.
- Traditional Korean diet high in one-carbon nutrients increases global DNA methylation: implication for epigenetic diet
PubMed ID: 38867083
Dietary increase in folate raised plasma 5‑MTHF, lowered homocysteine and increased global DNA methylation—mechanistically relevant to aging biology.
- Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years
PubMed ID: 15309436
B‑vitamin supplement including folic acid improved folate status and lowered homocysteine/MMA in older women, beneficial biochemical changes in aging.
- The effect of folic acid on the development of stomach and other gastrointestinal cancers
PubMed ID: 12667380
Folic acid reduced GI cancer occurrence and improved precancerous gastric lesions—relevant to aging-related cancer risk.
- Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, beta-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability--results from a dietary intake and micronucleus index survey in South Australia
PubMed ID: 15705599
Higher folate intake associated with substantially less genome damage (micronuclei), linked to healthier cellular aging.
- Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium-dependent vasodilation in patients with cardiovascular disease
PubMed ID: 21884007
B‑vitamin (including folic acid) supplementation improved endothelial function and lowered homocysteine in adults — relevant to vascular aging.
- Effect of adding B-vitamins to vitamin D and calcium supplementation on CpG methylation of epigenetic aging markers
PubMed ID: 29395637
B‑vitamin (including folic acid) supplementation altered epigenetic methylation markers linked to epigenetic/biological age in older adults.
- Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 does not affect the proportion of (n-3) long chain polyunsaturated fatty acids in plasma phosphatidylcholine
PubMed ID: 18287365
Two-year trial in older adults: folate+B12+B6 substantially lowered homocysteine—biomarker linked to aging-related vascular risk.
- Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial
PubMed ID: 25877495
B‑vitamin treatment (including folate) markedly slowed brain atrophy in MCI participants with high omega‑3 levels.
- Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment
PubMed ID: 26757190
B‑vitamin (includes folate) improved memory/global cognition in MCI when omega‑3 levels were high — supports cognitive ageing outcomes.
- Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial
PubMed ID: 33749643
FA+DHA improved memory and lowered amyloid peptides in MCI, supporting neuroprotective ageing effects.
- DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial
PubMed ID: 35704085
Post‑hoc RCT analysis: cognitive benefit of B‑vitamins occurred only in those with higher DHA — conditional support for ageing-related cognition.
- Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage
PubMed ID: 38952108
Large RCT showed folic acid ± DHA improved cognition and reduced oxidative DNA damage (8‑OHdG) and increased mtDNA — mechanistic ageing markers.
- Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations
PubMed ID: 7603218
Rapid correction of homocysteine/MMA with B12+folate injections in older people indicates restoration of age‑related one‑carbon metabolic defects relevant to healthy aging.
- Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults
PubMed ID: 9683174
Folate+B12 reduced chromosome damage (micronuclei) in high-baseline subgroup — relevant to cellular aging.
- Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet
PubMed ID: 11110875
Multivitamin including folate raised B‑vitamins and modestly lowered homocysteine in older adults.
- Folate status of elderly women following moderate folate depletion responds only to a higher folate intake
PubMed ID: 10827214
Study in older women: 415 µg/day restored folate and reversed homocysteine rise—directly relevant to aging population biomarker improvement.
- Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women
PubMed ID: 11035344
Postmenopausal women: 500 µg/day significantly lowered homocysteine, a risk marker relevant to aging.
- Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial
PubMed ID: 14576756
B‑vitamin (including folic acid) trial in older adults corrected homocysteine/MMA—relevant to healthy aging physiology.
- Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients
PubMed ID: 12792513
High‑dose B‑vitamin including folic acid produced large homocysteine decline and regression of carotid atherosclerosis—aging-relevant vascular benefit.
- Oral folic acid enhances endothelial function in patients with hypercholesterolaemia receiving statins
PubMed ID: 15616416
High‑dose folic acid improved endothelial function in statin‑treated adults, a marker relevant to vascular aging.
- Folic acid improves endothelial function in children and adolescents with type 1 diabetes
PubMed ID: 15069400
5 mg folic acid improved endothelial function in adolescents with type 1 diabetes, suggesting vascular benefit that may relate to healthy aging.
- Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial
PubMed ID: 15741530
Large RCT in elderly: folate+B12 markedly lowered homocysteine and produced a large, significant reduction in hip fractures—clinically meaningful aging outcome.
- Methylenetetrahydrofolate reductase polymorphisms and homocysteine-lowering effect of vitamin therapy in Singaporean stroke patients
PubMed ID: 16397167
One-year folic-acid–containing therapy produced a robust homocysteine reduction in stroke patients, a biochemical change linked to age-related vascular risk.
- Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial
PubMed ID: 17240287
Large 3‑yr RCT: folic acid raised folate, lowered homocysteine and produced small but significant cognitive improvements in older adults.
- Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study
PubMed ID: 19237716
Large RCT (folic acid+B6+B12) significantly reduced incident AMD — a clinically relevant aging outcome.
- Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial
PubMed ID: 19228852
Large RCT in CVD patients showed folic acid (with B vitamins) reduced stroke incidence—relevant to healthy aging/vascular risk.
- Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
PubMed ID: 21780182
B‑vitamin treatment including folic acid slowed cognitive decline in MCI patients with high baseline homocysteine — relevant to aging cognition.
- Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly
PubMed ID: 24916013
12‑month low‑dose B‑vitamin regimen including folic acid improved HDL and modestly lowered calculated CVD risk in elderly.
- Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial
PubMed ID: 25771069
Large RCT in hypertensive adults: folic acid added to enalapril reduced stroke/CVD—relevant to aging cardiovascular risk.
- Effects of 6-Month Folic Acid Supplementation on Cognitive Function and Blood Biomarkers in Mild Cognitive Impairment: A Randomized Controlled Trial in China
PubMed ID: 26508298
Folic acid raised folate, lowered homocysteine and produced small cognitive benefits in older adults with MCI (relevant to healthy brain aging).
- Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial
PubMed ID: 26559255
Dose-dependent reduction in urinary 8-OHdG (oxidative DNA damage), a marker linked to aging processes.
- Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients
PubMed ID: 27729579
Large RCT (enalapril+0.8 mg folic acid) reduced first‑stroke risk in a high‑cholesterol subgroup — a clinically meaningful benefit with implications for healthy aging.
- Interaction of serum vitamin B(12) and folate with MTHFR genotypes on risk of ischemic stroke
PubMed ID: 31932513
Large trial showed folic acid reduced first ischemic stroke in subgroups—reduction in major vascular events supports healthy aging.
- Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer's Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial
PubMed ID: 34101780
Folic acid+B12 in Alzheimer's produced modest cognitive benefit and reduced Hcy/TNFα over 6 months—supports aging brain outcomes.
- Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment
PubMed ID: 33935094
Long RCT of B‑vitamins including folic acid markedly lowered homocysteine and mitigated cognitive decline in MCI—relevant to healthy aging.
- Positive effects of folic acid supplementation on cognitive aging are dependent on ω-3 fatty acid status: a post hoc analysis of the FACIT trial
PubMed ID: 33564824
RCT showed folic acid slowed cognitive decline (global cognition/processing speed) in older adults with low omega‑3—relevant to healthy aging.
Brain health (61)
- Posttreatment Blood Pressure as a Key Predictor in a 5-Year Stroke Prediction Model
PubMed ID: 39821957
Demonstrated reduction in stroke (a major brain outcome) with folic-acid supplementation—directly relevant to brain health.
- The dihydrofolate reductase 19-bp deletion modifies the beneficial effect of B-vitamin therapy in mild cognitive impairment: pooled study of two randomized placebo-controlled trials
PubMed ID: 34788822
Randomized B‑vitamin (including folic acid) supplementation lowered homocysteine and improved cognitive outcomes and slowed brain atrophy in genotype‑defined subgroups—direct evidence for brain health support.
- Enhanced physical and cognitive performance in active duty Airmen: evidence from a randomized multimodal physical fitness and nutritional intervention
PubMed ID: 33077817
Exercise + multinutrient (including folic acid) improved some cognitive measures alongside raised blood folate.
- Folinic Acid as Adjunctive Therapy in Treatment of Inappropriate Speech in Children with Autism: A Double-Blind and Placebo-Controlled Randomized Trial
PubMed ID: 33029705
Double‑blind RCT: adjunct folinic acid improved speech and behavioral subscales in ASD — supports central nervous system/behavioral effects.
- Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial
PubMed ID: 27752075
Randomized double‑blind trial: high‑dose folinic acid improved verbal communication and behavioral measures in children with autism, particularly FRAA‑positive—direct evidence of folate‑form benefit for brain/behavior.
- Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial
PubMed ID: 24813065
Adjunctive L‑methylfolate improved depressive symptoms in SSRI‑resistant patients—direct CNS/mental‑health benefit.
- L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials
PubMed ID: 23212058
Randomized trials of L‑methylfolate showed clinically meaningful adjunctive benefit in SSRI‑resistant depression — direct support for a CNS/brain‑health role of folate derivatives.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
Randomized B‑vitamin (including folic acid 0.8 mg) trial in MCI showed ~30% reduction in brain atrophy rate—robust direct evidence for brain‑related benefit.
- The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability
PubMed ID: 19384265
Small RCT: folic acid+B6/B12 lowered homocysteine and halved migraine disability — direct neurological benefit signal.
- Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials
PubMed ID: 15260915
Randomized trials pooled showed adjunctive folate gave a modest but significant improvement in depression scores/response — direct evidence linking folate to mood/brain function.
- Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report
PubMed ID: 7979565
Periconceptional folic acid–containing multivitamin significantly reduced neural‑tube defects (directly relevant to brain/spinal cord development).
- Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study
PubMed ID: 8257478
Methylfolate reduced depression scores in elderly with dementia—direct positive effect on mood/cognitive domain (small trial).
- Folic acid supplementation improves cognitive function in participants with cerebral small vascular disease-related cognitive impairment: a randomized controlled trial
PubMed ID: 40945966
Randomized trial: low‑dose folic acid modestly improved cognition and lowered homocysteine in CSVD‑CI patients.
- Safety and Efficacy of High-Dose Folinic Acid in Children with Autism: The Impact of Folate Metabolism Gene Polymorphisms
PubMed ID: 40362912
High‑dose folinic acid improved social reciprocity in ASD RCT with genotype interactions—clinical support for folate‑family effects on brain function.
- Cognitive benefits of folic acid supplementation during pregnancy track with epigenetic changes at an imprint regulator
PubMed ID: 39681839
Maternal folic acid in later pregnancy increased cord folate and ZFP57 methylation and was associated with preserved processing‑speed cognitive measures in a genotype subgroup (RCT, molecular & cognitive signals).
- Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial
PubMed ID: 39243316
Double‑blind RCT: folinic acid (reduced folate) improved autism symptoms and behaviors—direct clinical neurodevelopmental benefit, especially with folate‑receptor autoantibodies.
- Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms
PubMed ID: 35578268
Randomized trial continuing folic acid in pregnancy produced higher maternal/foetal folate, altered newborn DNA methylation (notably at brain genes), and was associated with better child cognitive outcomes—direct support for neurodevelopmental effects.
- A pilot study of thiamin and folic acid in hemodialysis patients with cognitive impairment
PubMed ID: 33913373
Thiamin+folic acid improved cognition (MoCA) and lowered homocysteine in hemodialysis patients—positive but combined‑vitamin design limits attribution to folate alone.
- Positive effects of folic acid supplementation on cognitive aging are dependent on ω-3 fatty acid status: a post hoc analysis of the FACIT trial
PubMed ID: 33564824
RCT: folic acid (800 μg/day) slowed cognitive decline and improved processing speed in older adults with low omega‑3—strong brain benefit in a subgroup.
- Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment
PubMed ID: 33935094
Two‑year B‑vitamin treatment (including folic acid) lowered homocysteine markedly and mitigated cognitive decline in MCI—strong brain‑health signal.
- Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial
PubMed ID: 33750355
Continuing low‑dose folic acid through pregnancy improved language/processing and MEG brain activity in 11‑year‑olds—supports developmental brain outcomes.
- Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer's Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial
PubMed ID: 34101780
Folic acid + B12 in Alzheimer's modestly improved cognitive scores and lowered homocysteine and TNFα over 6 months—direct brain benefit.
- Effects of Folic Acid and Vitamin B12, Alone and in Combination on Cognitive Function and Inflammatory Factors in the Elderly with Mild Cognitive Impairment: A Single-blind Experimental Design
PubMed ID: 31345146
Folic acid+B12 in elderly MCI produced modest cognitive improvements and lowered inflammatory markers.
- Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial
PubMed ID: 28289280
High‑dose L‑methylfolate markedly raised methylfolate and produced modest symptom and brain‑imaging improvements in schizophrenia—supports neural effects of folate derivatives.
- Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
PubMed ID: 29255930
Randomized 400 µg/day folic acid for 24 months in MCI improved cognitive test scores and reduced AD‑related blood biomarkers—strong direct evidence for brain benefits in MCI.
- Folic Acid Supplementation Mitigates Alzheimer's Disease by Reducing Inflammation: A Randomized Controlled Trial
PubMed ID: 27340344
Small RCT: adding folic acid (1.25 mg) to donepezil modestly improved MMSE and reduced inflammatory/amyloid markers in mild–moderate AD—suggests cognitive benefit in this context.
- Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial
PubMed ID: 26098427
Six months B12+folic acid improved gross motor and problem-solving scores and lowered homocysteine in young children (developmental/brain outcomes).
- Effects of 6-Month Folic Acid Supplementation on Cognitive Function and Blood Biomarkers in Mild Cognitive Impairment: A Randomized Controlled Trial in China
PubMed ID: 26508298
Six months folic acid in older adults with MCI raised folate, lowered homocysteine and produced small cognitive test improvements.
- Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial
PubMed ID: 26561619
Prenatal 5‑MTHF improved children's conflict-resolution attention and altered brain activation at 8.5 years (direct cognitive/neurodevelopment benefit).
- B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial
PubMed ID: 25257064
B‑vitamin adjunct (including folic acid) improved sustained antidepressant response and lowered relapse over 1 year (clinical brain/mental health outcome).
- Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia
PubMed ID: 23467813
Adjunctive folate+B12 modestly improved negative symptoms in schizophrenia (genotype‑dependent) and raised RBC folate.
- B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy
PubMed ID: 23093615
Two‑year B‑vitamin supplementation (including folic acid) showed diminished WMH progression in patients with severe baseline small‑vessel disease — subgroup evidence of brain benefit.
- Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
PubMed ID: 21780182
B‑vitamin treatment including folic acid lowered homocysteine and slowed cognitive decline in MCI, especially in those with higher baseline tHcy — clinically relevant brain benefit.
- Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms--the Beyond Ageing Project: a randomized controlled trial
PubMed ID: 22170358
Large RCT of folic acid + B12 showed small but statistically significant improvements in immediate and delayed memory in older adults over 2 years.
- Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal
PubMed ID: 21177506
Children whose mothers received prenatal iron+folate showed modestly better IQ and motor scores at 7–9 years (longitudinal developmental cognitive benefit).
- Impact of a multiple-micronutrient fortified salt on the nutritional status and memory of schoolchildren
PubMed ID: 20533221
Schoolchildren receiving fortified salt (including folic acid) showed improved memory performance—cognitive benefit in a multinutrient intervention.
- Effects of maternal multimicronutrient supplementation on the mental development of infants in rural western China: follow-up evaluation of a double-blind, randomized, controlled trial
PubMed ID: 19336358
Maternal multimicronutrient supplementation including folic acid modestly improved infant mental development at 1 year (multinutrient trial).
- A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease
PubMed ID: 17600848
Add‑on folic acid (1 mg) to cholinesterase inhibitors modestly improved daily function/social behaviour in Alzheimer patients though cognition unchanged.
- Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial
PubMed ID: 17240287
Large 3‑yr RCT: 800 µg folic acid raised folate, lowered homocysteine and produced modest but significant improvements in memory and processing speed.
- Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia
PubMed ID: 16412989
B‑vitamin therapy including folic acid lowered homocysteine and improved schizophrenia symptoms and some cognitive tests in hyperhomocysteinemic subjects.
- Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 2: predictors of relapse during the continuation phase of pharmacotherapy
PubMed ID: 15323595
Remitted depressed patients with low folate had much higher relapse during continuation therapy—strong predictive association with mood/brain health.
- Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression
PubMed ID: 15323594
Observational: low blood folate strongly predicted poor antidepressant response—links folate status to brain function and treatment outcome.
- Effect of homocysteine-lowering treatment with folic acid plus vitamin B on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo-controlled, randomized trial
PubMed ID: 15086356
B‑vitamin therapy markedly lowered homocysteine; cerebrovascular/MRI outcomes trended toward benefit but were non-significant.
- Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia
PubMed ID: 12823643
B‑vitamin supplementation (folic acid 2 mg + B12) lowered homocysteine ~30% in high‑dementia‑risk subjects—biochemical support though short‑term cognition unchanged.
- Genomic DNA methylation decreases in response to moderate folate depletion in elderly women
PubMed ID: 11010943
Folate depletion reduced leukocyte DNA methylation in older women—mechanistic evidence relevant to neural/brain aging via methylation pathways.
- Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial
PubMed ID: 10967371
Adjunctive 500 µg folic acid with fluoxetine improved depression outcomes (esp. women), relevant to brain/mental health.
- Enhancement of recovery from psychiatric illness by methylfolate
PubMed ID: 1974941
Methylfolate improved psychiatric clinical and social recovery in folate‑deficient patients — direct brain/mental‑health benefit.
- Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage
PubMed ID: 38952108
Large double‑blind RCT: folic acid and DHA improved full‑scale IQ/WAIS subtests and reduced DNA oxidative damage in MCI — strong brain health evidence.
- DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial
PubMed ID: 35704085
Post‑hoc analysis: cognitive improvements with B‑vitamins only in those with higher DHA, highlighting interaction but supporting brain benefit in subgroups.
- Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial
PubMed ID: 33749643
FA+DHA improved specific memory/attention scores and reduced plasma Aβ peptides and homocysteine; increased SAM — supportive mechanisms.
- Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial
PubMed ID: 32856190
6‑month folic acid and/or DHA improved intelligence test scores and lowered inflammatory markers in MCI, combination best.
- Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial
PubMed ID: 32690472
B‑vitamin co‑supplementation with high‑dose DHA increased CSF DHA/EPA, demonstrating brain uptake relevant to cognitive support.
- Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment
PubMed ID: 26757190
Large RCT: B‑vitamin treatment helped memory and global cognition in MCI participants with high omega‑3 levels.
- Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial
PubMed ID: 25877495
B‑vitamin treatment slowed brain atrophy in MCI when omega‑3 status was high (MRI outcome).
- Effects of dietary folate intake on migraine disability and frequency
PubMed ID: 25598270
Observational data: higher dietary folate/FA intake associated with fewer migraine attacks — relevant to brain function and neurological symptoms.
- Trial using multiple micronutrient food supplement and its effect on cognition
PubMed ID: 18716734
Year‑long multi‑vitamin fortification (including folic acid) improved memory and attention scores in children.
- Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children
PubMed ID: 17704033
Fortified salt (including folic acid) improved several memory and attention tests in children.
- The effect of multivitamins on anxiety and depression in patients undergoing methadone maintenance treatment: A double-blind randomized controlled trial
PubMed ID: 37256965
Multivitamin including folic acid improved depressive symptoms in men on methadone — direct neuropsychiatric benefit in a clinical population.
- The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people
PubMed ID: 17537289
B12+folic acid led to large biomarker shifts and borderline memory improvements in older adults — plausible brain benefit.
- A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer's Disease
PubMed ID: 25589719
Multi‑nutrient supplement including folate yielded modest cognitive gains in Alzheimer’s patients; provides some support for brain-related outcomes though folate-specific effect unclear.
- A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia
PubMed ID: 20191258
Multi‑vitamin including folic acid produced modest improvements in memory and executive function vs placebo in non-demented adults; folic acid contribution uncertain.
Mood balance (18)
- Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial
PubMed ID: 24813065
L‑methylfolate significantly augmented antidepressant response in biomarker/genotype‑selected SSRI‑resistant patients (direct mood benefit).
- L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials
PubMed ID: 23212058
Randomized trials of adjunctive L‑methylfolate in SSRI‑resistant depression showed significantly higher response and symptom improvement (direct clinical evidence for mood benefit).
- B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial
PubMed ID: 20976769
Randomized long-term trial: folic acid + B6/B12 reduced major post-stroke depression hazard substantially — strong RCT evidence for mood benefit though multi‑vitamin combination limits attribution to folic acid alone.
- Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials
PubMed ID: 15260915
Pooled randomized trials show that adding folate to antidepressant therapy provided a modest but statistically significant additional reduction in depression scores and improved responder rates — direct evidence for mood benefit.
- Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study
PubMed ID: 8257478
Oral methylfolate reduced depression (HDRS) in elderly dementia patients over 8 weeks—clinically relevant mood improvement.
- Short-Term Effects of Folate Supplementation in Combination With Vitamin B6 for Treating Acute Manic Episodes in Bipolar I Disorder: A Randomized Controlled Trial
PubMed ID: 40200764
Randomized double‑blind trial: adding folate to valproate produced marked improvements in mania severity (large symptomatic effect in small sample).
- Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults
PubMed ID: 36169979
Huge observational claims study found months covered by folic‑acid prescriptions were associated with roughly half the rate of suicide attempts compared with uncovered months—strong population association with mood/behavior outcomes (observational).
- Effects of antenatal micronutrient supplementation regimens on adolescent emotional and behavioral problems: A 14-year follow-up of a double-blind, cluster-randomized controlled trial
PubMed ID: 36527827
Adolescents whose mothers received IFA in pregnancy had slightly lower emotional/behavior problem scores at 12–14 years—suggests perinatal folate may influence later mood/behavior.
- Evaluation of Nutritional Status of Patients with Depression
PubMed ID: 26413529
Cross-sectional study found lower serum folate in patients with major depression vs controls (associative evidence linking folate to mood).
- B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial
PubMed ID: 25257064
Adjunctive B‑vitamin formula (includes 2 mg folic acid) improved sustained antidepressant response and reduced relapse over 1 year.
- A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes
PubMed ID: 23507369
High‑dose folic acid (5 mg) added to fluoxetine produced greater symptom improvement and higher remission/response rates than lower folic acid dose (small RCT).
- Folic acid efficacy as an alternative drug added to sodium valproate in the treatment of acute phase of mania in bipolar disorder: a double-blind randomized controlled trial
PubMed ID: 19392814
Adjunctive folic acid with valproate produced a modest but significant reduction in mania severity over 3 weeks.
- Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet
PubMed ID: 19154566
Double‑blind RCT including folic acid reported significant improvements in PGWB scores, particularly Anxiety and Depressed Mood domains.
- Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 2: predictors of relapse during the continuation phase of pharmacotherapy
PubMed ID: 15323595
Remitted depressed patients with low folate had much higher relapse during continuation therapy—strong predictive association with mood stability.
- Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression
PubMed ID: 15323594
Low baseline folate strongly predicted very poor antidepressant response—associative evidence linking folate to mood regulation.
- Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial
PubMed ID: 10967371
Randomized trial: adjunct 500 µg folic acid with fluoxetine improved depression scores (notably in women) and lowered homocysteine.
- Enhancement of recovery from psychiatric illness by methylfolate
PubMed ID: 1974941
Methylfolate supplementation in folate‑deficient psychiatric patients improved clinical and social recovery — strong mood‑related effect.
- The effect of multivitamins on anxiety and depression in patients undergoing methadone maintenance treatment: A double-blind randomized controlled trial
PubMed ID: 37256965
Multivitamin including folic acid improved depressive symptoms in men on methadone (clinical mood benefit).
Wellbeing (26)
- 5-methyltetrahydrofolate for biochemical modulation of fluorouracil (FU) in patients with advanced colorectal cancer: a randomized phase I-II study of two different FU administration schedules
PubMed ID: 9932161
5‑MTHF modulation produced higher response and longer survival with certain 5‑FU schedules—applies to clinical outcomes.
- The impact of adding low-dose leucovorin to monthly 5-fluorouracil in advanced colorectal carcinoma: results of a phase III trial. Swiss Group for Clinical Cancer Research (SAKK)
PubMed ID: 9653495
Low‑dose leucovorin +5‑FU improved response, PFS and OS vs FU alone—clear clinical improvement.
- Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study
PubMed ID: 9552032
Concurrent chemo including leucovorin‑modulated 5‑FU doubled 3‑year survival vs RT—major effect on patient outcomes.
- Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer
PubMed ID: 9440756
Adding leucovorin to 5‑FU improved 5‑year survival in high‑risk colon cancer—meaningful benefit for overall outcomes.
- GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon
PubMed ID: 9610692
Large RCT: adding high‑dose folinic acid +5‑FU reduced mortality and events without QoL harm—strong clinical outcome evidence.
- Efficacy of 4.0 mg versus 0.4 mg Folic Acid Supplementation on the Reproductive Outcomes: A Randomized Controlled Trial
PubMed ID: 34959975
Higher periconceptional folic acid dose was associated with fewer spontaneous abortions and preterm births—meaningful improvements in pregnancy outcomes and wellbeing.
- Equity in adherence to and effect of prenatal food and micronutrient supplementation on child mortality: results from the MINIMat randomized trial, Bangladesh
PubMed ID: 24393610
Prenatal early food + MMS (incl. folic acid) substantially reduced under‑five mortality and inequalities—major public‑health wellbeing effect of combined intervention.
- Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet
PubMed ID: 19154566
B‑vitamin supplementation (including 0.8 mg folic acid) produced significant improvements in psychological general well‑being metrics in coeliac patients.
- Responses of biomarkers of folate and riboflavin status to folate and riboflavin supplementation in healthy and colorectal polyp patients (the FAB2 Study)
PubMed ID: 17932361
Folic acid supplementation raised systemic and mucosal folate — improved biochemical status likely contributes to general nutrient sufficiency.
- Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study
PubMed ID: 11465701
In RA patients on methotrexate, folic/folinic acid substantially reduced adverse events and treatment withdrawal—clear patient wellbeing benefit.
- Subjectively healthy elderly consuming a liquid nutrition supplement maintained body mass index and improved some nutritional parameters and perceived well-being
PubMed ID: 10608948
Liquid nutrition supplement increased folate intake and was associated with modest improvements in vitality and general well‑being in older adults.
- Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age
PubMed ID: 15927936
Marked improvements in RBC/plasma folate in women of childbearing age indicate better micronutrient status, a component of wellbeing.
- Integrating Nutrition Interventions into an Existing Maternal, Neonatal, and Child Health Program Increased Maternal Dietary Diversity, Micronutrient Intake, and Exclusive Breastfeeding Practices in Bangladesh: Results of a Cluster-Randomized Program Evaluation
PubMed ID: 29021370
Intensified counseling + free IFA increased supplement uptake, dietary diversity, and exclusive breastfeeding—broad improvements in maternal/child wellbeing.
- Efficacy of a Personalized mHealth App in Improving Micronutrient Supplement Use Among Pregnant Women in Karachi, Pakistan: Parallel-Group Randomized Controlled Trial
PubMed ID: 40203301
mHealth app markedly increased folic acid and other supplement uptake and improved self‑reported adherence and some biochemical markers—supports improved general micronutrient‑related wellbeing.
- Inter-pregnancy folate and iron status of women in an inner-city population
PubMed ID: 11432768
Postpartum supplementation corrected folate deficiency—improving nutrient status that contributes to general wellbeing.
- Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects
PubMed ID: 2296932
High‑dose folic acid produced strong biochemical improvements (plasma/RBC folate and dUST) that often correlate with general health benefits.
- Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial
PubMed ID: 7978695
By reducing methotrexate toxicity without reducing efficacy, folic acid improves treatment tolerability and likely patient wellbeing.
- Postpartum folic acid supplementation of adolescents: impact on maternal folate and zinc status and milk composition
PubMed ID: 7625346
Postpartum folic acid prevented declines in RBC folate in adolescent mothers — maintaining maternal nutritional status can contribute to general wellbeing.
- Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg daily need to continue folic acid supplements long term?
PubMed ID: 11035130
Stopping folic acid increased nausea/mouth ulcers and dropouts in MTX patients—continuation supports tolerability and wellbeing.
- Posttreatment Blood Pressure as a Key Predictor in a 5-Year Stroke Prediction Model
PubMed ID: 39821957
Large trial-level cardiovascular benefit from folic acid suggests a meaningful contribution to overall health.
- The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT
PubMed ID: 31776782
Optimized multivitamin improved folate status and decreased anemia—likely to enhance overall wellbeing post‑surgery.
- Prenatal and Postnatal Supplementation with Lipid-Based Nutrient Supplements Reduces Anemia and Iron Deficiency in 18-Month-Old Bangladeshi Children: A Cluster-Randomized Effectiveness Trial
PubMed ID: 29901736
Interventions including folic acid led to substantial reductions in child anemia — a broad contributor to child wellbeing (activity, development), so reasonably supportive.
- Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial
PubMed ID: 24813065
L‑methylfolate augmentation improved depression severity/clinical global impressions—translates to better wellbeing.
- The effects of iron and/or zinc supplementation on maternal reports of sleep in infants from Nepal and Zanzibar
PubMed ID: 19322104
Iron–folic acid increased infant sleep duration in two RCTs — likely to improve general wellbeing/behavior.
- The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability
PubMed ID: 19384265
Reduced migraine disability with folic acid‑based vitamin therapy improved daily functioning in sufferers.
- Combined intravenous and intraperitoneal chemotherapy with fluorouracil + leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon carcinoma
PubMed ID: 9579845
i.p.+i.v. FU + leucovorin markedly improved disease‑free and overall survival vs FU+levamisole—substantial outcome advantage.
Fertility (20)
- Association between markers of female adiposity and live birth among patients undergoing fertility treatment or attempting unassisted conception
PubMed ID: 40605077
Analysis used data from the FAZST folic‑acid trial (infertility dataset); directly relevant to fertility outcomes though the paper analyzed adiposity effects rather than folic acid efficacy.
- Epigenetic implications of socioeconomic status and education on sperm DNA methylation patterns
PubMed ID: 39424044
Analysis came from a Folic Acid + Zinc Supplement Trial cohort and reported sperm DNA methylation differences by socioeconomic factors — direct link to sperm epigenetics from a folic-acid trial cohort.
- Promoting fertility awareness and preconception health using a chatbot: a randomized controlled trial
PubMed ID: 33039321
Intervention increased intentions to take folic acid preconception — directly relevant to fertility/preconception behaviours.
- Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women
PubMed ID: 31845191
Activated‑folate‑containing micronutrient in women with PCOS significantly reduced homocysteine and increased AMH — direct, clinically relevant fertility signal in a small RCT.
- Using reproductive life plan-based information in a primary health care center increased Iranian women's knowledge of fertility, but not their future fertility plan: A randomized, controlled trial
PubMed ID: 30267937
Reproductive-life-plan counseling strongly increased preconception folic-acid uptake (85% vs 25%) and fertility knowledge — strong evidence for uptake/behavior relevant to fertility preparation (not a direct biological fertility outcome).
- The higher rate of multiple births after periconceptional multivitamin supplementation: an analysis of causes
PubMed ID: 8588492
Same large periconceptional trial reported a modestly higher multiple-birth rate in multivitamin (folic acid) group (supports fertility/multiple conception signal).
- Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report
PubMed ID: 7979565
Periconceptional multivitamin containing 0.8 mg folic acid increased cumulative conceptions and multiple births (direct fertility-related outcome).
- Prevention of congenital abnormalities by periconceptional multivitamin supplementation
PubMed ID: 8324432
Periconceptional multivitamin with 0.8 mg folic acid given around conception reduced major congenital anomalies—direct relevance to preconception/fertility planning.
- Effect of Picture-based health education and counselling on knowledge and adherence to preconception Iron-folic acid supplementation among women planning to be pregnant in Eastern Ethiopia: a randomized controlled trial
PubMed ID: 35912303
Preconception picture‑based education markedly increased IFA (folic acid) use among women planning pregnancy—supports fertility planning and peri‑conception health.
- Comparative Study of the Effects of Tamoxifen Citrate and Folate on Semen Quality of the Infertile Male with Semen Abnormality
PubMed ID: 26817175
RCT: folate (5 mg/day), especially with tamoxifen, improved semen concentration/motility and reduced sperm DNA damage in infertile men.
- Effect of different dosage and administration schedules of folic acid on blood folate levels in a population of Honduran women of reproductive age
PubMed ID: 18426639
Dose/timing RCT in women showed daily 1 mg folic acid achieves protective blood folate levels faster—relevant to preconception fertility support.
- Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men?
PubMed ID: 16533356
Randomized trial: folic acid+zinc raised sperm concentration in subfertile men, indicating potential fertility benefit (combination product).
- C677T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration
PubMed ID: 14607573
RCT: folic acid (with zinc) increased sperm concentration in men without MTHFR C677T variant—direct fertility evidence in subgroup.
- Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial
PubMed ID: 11872201
Combined folic acid (5 mg) + zinc markedly increased normal sperm counts, especially in subfertile men — strong fertility signal though combined therapy.
- The Impact of a Standardized Oral Multinutrient Supplementation on Embryo Quality in in vitro Fertilization/Intracytoplasmic Sperm Injection: A Prospective Randomized Trial
PubMed ID: 27832646
Multinutrient supplement containing FA improved chance of obtaining ≥1 good‑quality embryo vs 400 µg FA alone—suggests a reproductive benefit in periconception context (but FA was present in both arms).
- Smartphone-based lifestyle coaching modifies behaviours in women with subfertility or recurrent miscarriage: a randomized controlled trial
PubMed ID: 34053852
App‑based coaching raised folic acid use and was associated with higher odds of pregnancy at 24 weeks—behavioral evidence linking folic acid uptake to conception odds.
- First effective mHealth nutrition and lifestyle coaching program for subfertile couples undergoing in vitro fertilization treatment: a single-blinded multicenter randomized controlled trial
PubMed ID: 32741619
mHealth coaching improved folic acid supplement use in couples undergoing IVF/ICSI—supports periconception folic acid uptake relevant to fertility outcomes.
- An intervention in contraceptive counseling increased the knowledge about fertility and awareness of preconception health-a randomized controlled trial
PubMed ID: 31495254
Reproductive‑life‑plan counseling substantially increased women's knowledge that folic acid should be taken preconception—strong behavioral link to fertility/preconception care.
- The effect of preconception counselling on lifestyle and other behaviour before and during pregnancy
PubMed ID: 19059545
Preconception counseling substantially increased preconception folic acid use — supports fertility/pregnancy planning.
- Dietary supplementation with a novel l-carnitine multi-micronutrient in idiopathic male subfertility involving oligo-, astheno-, teratozoospermia: A randomized clinical study
PubMed ID: 32330373
Multi‑nutrient supplement including folic acid significantly improved semen parameters and pregnancy rates in men with idiopathic infertility — clinically meaningful but folic acid-specific effect not isolated.
Mental clarity (20)
- Trial using multiple micronutrient food supplement and its effect on cognition
PubMed ID: 18716734
Multi‑fortified food intake produced improvements in memory and attention tests in children (folic acid was one component).
- Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial
PubMed ID: 25877495
B‑vitamin slowed brain atrophy in MCI with high ω‑3, a structural correlate of preserved focus/clarity.
- Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment
PubMed ID: 26757190
B‑vitamin treatment improved verbal episodic memory and global cognition in MCI among those with high ω‑3 — supports focused cognition in subgroups.
- Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial
PubMed ID: 32856190
6‑month folic acid and/or DHA improved intelligence test scores; combined treatment best.
- Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial
PubMed ID: 33749643
FA+DHA improved arithmetic and digit span (attention/working memory) and biochemical markers supporting cognitive performance.
- Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage
PubMed ID: 38952108
FA+DHA produced robust improvements in FSIQ and WAIS subtests over 12 months in people with MCI.
- Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial
PubMed ID: 17240287
3‑yr RCT found small but significant improvements in memory and information processing speed with 800 µg folic acid in older adults — supports focus/clarity.
- Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial
PubMed ID: 26561619
Prenatal 5‑MTHF significantly improved childhood conflict-resolution attention and altered relevant brain activation (strong direct evidence for improved focus).
- Effects of 6-Month Folic Acid Supplementation on Cognitive Function and Blood Biomarkers in Mild Cognitive Impairment: A Randomized Controlled Trial in China
PubMed ID: 26508298
Folic acid in older adults with MCI produced small improvements in attention/working memory test scores (Digit Span).
- Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial
PubMed ID: 26098427
B12+folic acid improved problem-solving scores in young children (cognitive domains relevant to clarity/attention).
- Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
PubMed ID: 29255930
Folic acid improved full‑scale and verbal IQ and subdomain cognitive scores in MCI over 24 months—relevant to attention and cognitive clarity.
- Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial
PubMed ID: 27752075
High‑dose folinic acid improved verbal communication and several behavioral/adaptive outcomes in autistic children—supports cognitive/attention-related benefits in that population.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
Slowing of brain atrophy in MCI with B‑vitamin regimen including folic acid suggests potential benefits for cognition, focus and clarity.
- Positive effects of folic acid supplementation on cognitive aging are dependent on ω-3 fatty acid status: a post hoc analysis of the FACIT trial
PubMed ID: 33564824
RCT demonstrated improved information processing speed and global cognition with folic acid in older adults with low omega‑3—direct evidence for improved cognitive clarity.
- Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment
PubMed ID: 33935094
B‑vitamin regimen (including folic acid) mitigated cognitive decline in MCI—supports sustained focus and cognition.
- Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial
PubMed ID: 33750355
Maternal folic acid in 2nd/3rd trimester associated with better processing speed and verbal scores and increased MEG activity in 11‑year‑olds—strong evidence for improved cognitive processing in offspring.
- Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer's Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial
PubMed ID: 34101780
Folic acid+B12 produced modest improvements in cognitive test scores in Alzheimer's patients—relevant to focus/clarity in adults.
- The dihydrofolate reductase 19-bp deletion modifies the beneficial effect of B-vitamin therapy in mild cognitive impairment: pooled study of two randomized placebo-controlled trials
PubMed ID: 34788822
B‑vitamin supplementation improved executive function and other cognitive measures in genotype‑defined subgroups—relevant to focus and mental clarity.
- Folinic Acid as Adjunctive Therapy in Treatment of Inappropriate Speech in Children with Autism: A Double-Blind and Placebo-Controlled Randomized Trial
PubMed ID: 33029705
Adjunct folinic acid produced improvements in speech and behavioral measures in ASD — relevant to focus/clarity.
- Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children
PubMed ID: 17704033
Fortified salt (including folic acid) improved several memory tests and an attention test in children.
Energy & Fatigue (14)
- Impact of a multiple-micronutrient food supplement on the nutritional status of schoolchildren
PubMed ID: 17542110
Large school feeding study (with folic acid) produced hemoglobin gains that commonly translate to improved energy and reduced anemia symptoms.
- Trial using multiple micronutrient food supplement and its effect on cognition
PubMed ID: 18716734
Food fortification including folic acid raised hemoglobin/red cell counts in children — supports improved energy.
- School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls
PubMed ID: 10357747
Weekly iron + 3.5 mg folic acid improved hemoglobin/ferritin in adolescent girls — improved hematologic status can translate to better energy.
- Randomized intervention study comparing several regimens for the treatment of moderate anemia among refugee children in Kigoma Region, Tanzania
PubMed ID: 11442213
Restoration of hemoglobin in children after combined infection treatment and iron+folic acid — supports improved energy.
- Supplementation of iron alone and combined with vitamins improves haematological status, erythrocyte membrane fluidity and oxidative stress in anaemic pregnant women
PubMed ID: 20615267
Iron+folic acid in anemic pregnant women produced substantive Hb increases (directly linked to energy/fatigue improvements).
- Addition of cobalamin to iron and folic acid improves hemoglobin rise in nutritional anemia
PubMed ID: 22415494
Faster hemoglobin recovery when adding B12 to iron+folate implies likely improvements in energy/fatigue from anemia correction.
- Weekly iron folate supplementation in adolescent girls--an effective nutritional measure for the management of iron deficiency anaemia
PubMed ID: 23618489
Iron+folate corrected anemia with meaningful Hb increases—directly linked to improved energy and reduced fatigue.
- Multivitamin and iron supplementation to prevent periconceptional anemia in rural tanzanian women: a randomized, controlled trial
PubMed ID: 25905863
Preconception iron+folate reduced iron-deficiency anemia (microcytic), which is strongly linked to fatigue and energy; folate contributed as part of IFA.
- A community-based randomized controlled trial providing weekly iron-folic acid supplementation increased serum- ferritin, -folate and hemoglobin concentration of adolescent girls in southern Ethiopia
PubMed ID: 33958657
Weekly iron–folic acid over 3 months significantly raised hemoglobin and iron stores in adolescent girls—likely to improve energy via anemia correction.
- Effectiveness of Health Information Package Program on Knowledge and Compliance among Pregnant Women with Anemia: A Randomized Controlled Trial
PubMed ID: 35270420
Education+reminders increased IFA use and raised hemoglobin in anemic pregnant women—improved hemoglobin can translate to better energy.
- The potential adding therapeutic effect of pentoxifylline and/or folic acid for chronic kidney disease patients: randomized controlled trial
PubMed ID: 40826392
CKD trial with PTX±folic acid reported reduced fatigue (FAS) and increased hemoglobin — direct patient‑reported energy improvement (small study, combo therapy).
- The effect of weekly iron supplementation on anaemia and on iron deficiency among female tea pluckers in Bangladesh
PubMed ID: 11424510
Weekly iron+folic acid produced a modest rise in hemoglobin and more self-reported 'feeling better' vs placebo — plausible mechanism for improved energy but iron is a major contributor.
- The effects of iron and/or zinc supplementation on maternal reports of sleep in infants from Nepal and Zanzibar
PubMed ID: 19322104
Daily iron–folic acid (infants) increased nighttime and total sleep duration in two RCTs—plausible downstream benefit for energy/wellbeing.
- The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT
PubMed ID: 31776782
Optimized multivitamin raised folate and sharply reduced anemia rates after bariatric surgery—likely to improve energy.
Illness recovery (15)
- Comparison of efficacy of folic acid and silymarin in the management of antiepileptic drug induced liver injury: a randomized clinical trial
PubMed ID: 28603098
In children with antiepileptic drug–induced liver injury, folic acid more rapidly normalized liver enzymes vs comparator, indicating faster recovery of hepatic injury.
- An open-label, randomized, parallel-group comparative study of the efficacy of sorghum bicolor extract in preoperative anemia
PubMed ID: 27461168
Preoperative iron + FA produced larger increases in hemoglobin/hematocrit/RBC vs baseline — supports recovery from anemia before surgery.
- Enhancement of recovery from psychiatric illness by methylfolate
PubMed ID: 1974941
Methylfolate in folate‑deficient psychiatric patients produced clear improvements in clinical and social recovery.
- Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial
PubMed ID: 7978695
Weekly folic acid substantially reduced methotrexate toxicity in rheumatoid arthritis while preserving efficacy — clinically meaningful improvement in treatment tolerability and recovery from side effects.
- Recombinant human erythropoietin treatment of postpartum anemia. Preliminary results
PubMed ID: 9846709
Postpartum erythropoietin + iron+folic acid group recovered blood counts faster than iron+folic acid alone — folate present but primary effect driven by rHuEPO.
- Economic evaluation of folate supplementation during methotrexate treatment in rheumatoid arthritis
PubMed ID: 15124248
Folic acid supplementation increased methotrexate drug survival in RA, helping patients remain on effective therapy (better clinical course/drug tolerability).
- Treatment and prevention of anemia with ferrous sulfate plus folic acid in children attending daycare centers in Goiânia, Goiás State, Brazil: a randomized controlled trial
PubMed ID: 18670706
Iron + folic acid therapy significantly reduced anemia prevalence and raised hemoglobin in children—clear recovery effect for hematologic deficit.
- Physical work capacity of young underprivileged school girls impact of daily vs intermittent iron folic acid supplementation: a randomized controlled trial
PubMed ID: 19430082
Iron+folic acid improved recovery time and physical work capacity in schoolgirls (direct trial endpoint).
- Effect of long-term intermittent supplementation with multiple micronutrients compared with iron-and-folic acid supplementation on Hb and micronutrient status of non-anaemic adolescent schoolgirls in rural Bangladesh
PubMed ID: 22244349
Twice‑weekly MMN improved folate status and reduced anemia risk vs intermittent iron+folate — supports faster/better hematologic recovery at population level.
- Addition of cobalamin to iron and folic acid improves hemoglobin rise in nutritional anemia
PubMed ID: 22415494
Adding cobalamin to iron+folate in anemic children produced faster and larger hemoglobin increases — clear hematologic recovery benefit in combination including folate.
- Weekly iron folate supplementation in adolescent girls--an effective nutritional measure for the management of iron deficiency anaemia
PubMed ID: 23618489
Weekly iron+folate raised hemoglobin and reduced anaemia comparably to daily dosing—helps recovery from anemia-related fatigue/weakness.
- Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multicenter randomized, double-blind, placebo-controlled trial
PubMed ID: 8507221
Oral leucovorin after weekly methotrexate halved side‑effects and withdrawals in RA—meaningful symptomatic recovery/supportive effect.
- Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases: a randomized multi-institutional trial
PubMed ID: 7932825
Chronomodulated regimen including folinate markedly reduced severe stomatitis (less toxicity → faster recovery from chemo toxicity).
- GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon
PubMed ID: 9610692
High‑dose folinic acid +5‑FU after colectomy reduced deaths/recurrences—consistent with faster clinical benefit/less recurrence.
- Combined intravenous and intraperitoneal chemotherapy with fluorouracil + leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon carcinoma
PubMed ID: 9579845
Combined i.p. + i.v. FU + leucovorin substantially increased disease‑free and overall survival vs FU+levamisole.
Immune support (11)
- [Dietary efficacy of a micronutrient combination in patients with recurrent upper respiratory tract infections. Results of a placebo-controlled double-blind study]
PubMed ID: 22184801
Multi‑micronutrient trial including folic acid showed modest improvement in common cold symptom scores; folic acid was a component (effect not isolated).
- Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial
PubMed ID: 32019154
Direct folate-rich food intervention lowered TNF-α, IL-6 and IL-1β—clear anti-inflammatory/immune-modulating signal.
- Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program
PubMed ID: 17237316
Fortified dairy including folic acid reduced hs-CRP (inflammation) after MI—supports immune/inflammatory modulation (multi-nutrient intervention).
- A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti-Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women-A Randomized Controlled Trial
PubMed ID: 27187447
Transcriptomic upregulation of interferon pathways after a product containing folic acid; conventional inflammatory markers unchanged.
- Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial
PubMed ID: 32856190
Folic acid + DHA reduced inflammatory cytokines in MCI patients, implying anti-inflammatory/immune modulation.
- Folic acid supplementation reduces the development of some blood cell abnormalities in children receiving carbamazepine
PubMed ID: 16380297
Reduced leukopenia and higher WBC/PMN counts in children on carbamazepine indicate an immune/hematologic protective effect.
- Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural Nepal
PubMed ID: 19368922
Maternal iron+folic acid reduced puerperal sepsis and postpartum infections—direct infection-related outcome.
- A combination of iron and retinol supplementation benefits iron status, IL-2 level and lymphocyte proliferation in anemic pregnant women
PubMed ID: 21147712
Trial in anemic pregnant women where iron+retinol+folic acid improved IL-2 and lymphocyte proliferation vs iron alone (folic acid part of active arm).
- Folic Acid Supplementation Mitigates Alzheimer's Disease by Reducing Inflammation: A Randomized Controlled Trial
PubMed ID: 27340344
RCT: folic acid (1.25 mg) + donepezil lowered TNFα and inflammatory markers, suggesting anti‑inflammatory/immune modulation.
- Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death
PubMed ID: 7930736
Adjunctive folinic acid reduced neutropenia during PCP therapy (direct immune/hematologic effect), though clinical outcomes were worse.
- Effect of vitamin A, vitamin A plus iron and multiple micronutrient-fortified seasoning powder on infectious morbidity of preschool children
PubMed ID: 20605698
Multi‑micronutrient seasoning (including folic acid) significantly reduced respiratory and diarrheal morbidity in preschoolers.
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Being studied right now
Recruiting clinical trials registered on ClinicalTrials.gov. A trial in progress has no result yet — this is what the field is asking, not what it found.