Vitamin B9
14 benefits mapped to clinical evidence across supplements.
Dose per serving from products
502 products in our catalogue print how much Vitamin B9 a serving holds.
Most common: 250 mcg to 500 mcg, 27% of 502 products.
| Dose per serving | Products |
|---|---|
| 50 mcg or less | 24 |
| 50 mcg to 100 mcg | 38 |
| 100 mcg to 250 mcg | 78 |
| 250 mcg to 500 mcg | 137 |
| 500 mcg to 1 mg | 105 |
| 1 mg to 2.5 mg | 105 |
| over 2.5 mg | 15 |
Dose per serving from research
98 study groups in 69 studies say how much Vitamin B9 participants took a day.
These are the doses the studies gave. They are not a recommendation.
Most common: 250 mcg to 500 mcg, 37% of 98 study groups.
| Daily dose | Study groups |
|---|---|
| 100 mcg or less | 4 |
| 100 mcg to 250 mcg | 12 |
| 250 mcg to 500 mcg | 36 |
| 500 mcg to 1 mg | 10 |
| 1 mg to 2.5 mg | 2 |
| 2.5 mg to 5 mg | 5 |
| 5 mg to 10 mg | 3 |
| 10 mg to 25 mg | 17 |
| 25 mg to 50 mg | 4 |
| 50 mg to 100 mg | 2 |
| over 100 mg | 3 |
Commonly used together
35 of 99 study groups took Vitamin B9 with something else. Shown: what 3 or more different studies gave.
What was given together, not what works together.
| Taken with | Study groups |
|---|---|
| Vitamin B12 | 18 |
| Vitamin B6 | 15 |
| Folic Acid | 8 |
| Iron | 7 |
| Vitamin C | 5 |
| Vitamin E | 5 |
| Vitamin D | 4 |
Benefit Evidence
Pregnancy support: NTD/birthweight↓
Counseling: folate use↑ +26.5pp
Lower liver/blood toxicity
Higher folate biomarker levels
Better cancer control
Nerve symptoms, homocysteine
+30% homocysteine drop
Nerve conduction improves
Arsenic detox: +DMAs -InAs
Homocysteine detox: -30%
Liver enzymes: -0.6 IU/L
Fewer infections, shorter illness
Lower inflammation, better immunity
Lower liver/blood toxicity
Higher folate biomarker levels
Better cancer control
Arsenic detox: +DMAs -InAs
Homocysteine detox: -30%
Liver enzymes: -0.6 IU/L
Research sources
Heart health (395)
- Posttreatment Blood Pressure as a Key Predictor in a 5-Year Stroke Prediction Model
PubMed ID: 39821957
Large CSPPT analysis: folic acid allocation associated with lower 5‑year stroke risk (HR=0.79); strong cardiovascular relevance.
- 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
Randomized study in coronary patients: folic acid+B12 produced a large, significant (−32%) reduction in fasting plasma homocysteine.
- 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
Two weeks of 800 µg folic acid substantially raised serum folate and significantly lowered plasma tHcy in healthy men.
- Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamin supplementation
PubMed ID: 14699020
Study identified plasma betaine as a major determinant of post-methionine-load homocysteine and showed B‑vitamin supplementation attenuated relations—mechanistically informative for homocysteine control.
- Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations
PubMed ID: 15941890
Randomized trial in older adults showed dose-dependent folic acid increased betaine and significantly lowered plasma total homocysteine—strong biochemical evidence.
- Sex and menopausal status influence human dietary requirements for the nutrient choline
PubMed ID: 17490963
Choline-depletion protocol showed homocysteine rose and folic acid status affected the magnitude; folic acid influenced homocysteine changes though did not prevent organ dysfunction.
- The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people
PubMed ID: 17537289
Daily folic acid plus B12 reduced homocysteine by ~36% and raised betaine; robust biochemical effect though cognitive impact was small.
- Alcohol increases homocysteine and reduces B vitamin concentration in healthy male volunteers--a randomized, crossover intervention study
PubMed ID: 18790817
Two-week alcohol exposures lowered folate and modestly raised homocysteine, demonstrating the link between folate status and homocysteine.
- Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45-75 years
PubMed ID: 22850357
Large cross‑sectional study documented very high prevalence of elevated homocysteine and highlighted populations likely to benefit from folic acid programs (direct public‑health implication).
- Plasma trimethylamine-N-oxide following supplementation with vitamin D or D plus B vitamins
PubMed ID: 27569255
Small RCT: B‑vitamin supplementation including folic acid significantly lowered homocysteine versus control—supports biochemical homocysteine lowering.
- 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
Randomized folic acid supplementation in arsenic-exposed adults produced clear, dose-consistent improvements in one‑carbon metabolites (betaine, DMG, choline)—strong direct biochemical evidence.
- 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 trial in men found high‑dose folic acid (5 mg/day) substantially lowered plasma homocysteine over one month—direct evidence.
- Homocysteine and all-cause mortality in hypertensive adults without pre-existing cardiovascular conditions: Effect modification by MTHFR C677T polymorphism
PubMed ID: 28225483
Large CSPPT-context analysis highlights the clinical importance of tHcy and was conducted in a trial setting where folic acid therapy is central—supports homocysteine relevance.
- 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
Randomized trial: 400–800 µg folic acid significantly lowered homocysteine and improved arsenic methylation — high‑quality direct evidence.
- 5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial
PubMed ID: 37482222
5‑MTHF added to propranolol markedly lowered total homocysteine and improved BH4/ADMA markers in RCT.
- Additional benefit in CVD risk indices derived from the consumption of fortified milk when combined with a lifestyle intervention
PubMed ID: 23249766
Fortified milk + lifestyle counseling raised folate and lowered homocysteine significantly.
- Twelve-Week Daily Consumption of ad hoc Fortified Milk with ω-3, D, and Group B Vitamins Has a Positive Impact on Inflammaging Parameters: A Randomized Cross-Over Trial
PubMed ID: 33266447
Fortified milk with B vitamins (including folate) raised folate and decreased homocysteine by ~24% in older adults—direct strong evidence.
- Long-Chain Polyunsaturated Fatty Acids, Homocysteine at Birth and Fatty Acid Desaturase Gene Cluster Polymorphisms are Associated with Children's Processing Speed up to Age 9 Years
PubMed ID: 33396458
Maternal total homocysteine associated inversely with child processing speed; implicates maternal folate/homocysteine balance.
- Hyperhomocysteinaemia is not associated with increased levels of asymmetric dimethylarginine in patients with ischaemic heart disease
PubMed ID: 12814389
Repeated—vitamin B lowered homocysteine; included here as direct evidence.
- Homocyst(e)ine-lowering therapy does not affect plasma asymmetrical dimethylarginine concentrations in patients with peripheral artery disease
PubMed ID: 15634723
Folic acid plus B vitamins lowered homocysteine in PAD patients.
- No effect of B vitamins on ADMA levels in patients at increased cardiovascular risk
PubMed ID: 16649966
B‑vitamin therapy (including folic acid) markedly reduced homocysteine in subjects at increased CV risk.
- Asymmetric dimethylarginine and the effect of folate substitution in children with familial hypercholesterolemia and diabetes mellitus type 1
PubMed ID: 18380539
Folic acid supplementation reduced homocysteine (and hsCRP) in children with familial hypercholesterolemia or type 1 diabetes.
- Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial
PubMed ID: 19573556
Aged garlic extract plus B vitamins (including folic acid) improved vascular reactivity and slowed CAC progression; folate was a component.
- Acute effects of 5-methyltetrahydrofolate on endothelial function and asymmetric dimethylarginine in patients with chronic heart failure
PubMed ID: 19748251
IV 5‑MTHF reduced ADMA acutely in heart failure and controls (cardiovascular biomarker change).
- 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
Combined B12 + folate normalized homocysteine in dialysis patients (90% vs 30%)—clear, large biochemical effect.
- [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 produced a large (~9 µmol/L) homocysteine reduction over 12 weeks—strong direct evidence.
- The association between progression of atherosclerosis and the methylated amino acids asymmetric dimethylarginine and trimethyllysine
PubMed ID: 23734218
Folate/B12 supplementation decreased homocysteine ≈24.8% in CAD patients though ADMA/TML did not change—clear homocysteine lowering.
- Aged garlic extract with supplement is associated with increase in brown adipose, decrease in white adipose tissue and predict lack of progression in coronary atherosclerosis
PubMed ID: 23453866
Aged‑garlic supplement containing folic acid (300 µg) decreased homocysteine vs placebo, but effect attribution to folic acid alone is uncertain.
- 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
Folic acid 800 µg/day raised serum folate and decreased plasma tHcy in genotype‑specific subgroups—direct supplementation effect on homocysteine in some participants.
- L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation
PubMed ID: 27817128
Multi‑ingredient supplement containing folic acid lowered homocysteine significantly in mildly hypertensive adults.
- Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years
PubMed ID: 15309436
Multivitamin with folic acid increased folate markers and lowered homocysteine in older women—large RCT evidence of homocysteine lowering.
- Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial
PubMed ID: 9583842
Randomized trial: B‑vitamin supplementation including 1 mg folic acid reduced homocysteine by 27.9% — strong direct evidence.
- 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
Factorial trial confirmed B‑vitamin (including folic acid) lowering of total homocysteine, though antioxidant arms had different effects.
- 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
Fruit/vegetable concentrate intervention raised folate and lowered plasma homocysteine by ~20% in healthy subjects.
- Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers
PubMed ID: 18270369
Large prospective cohort: higher dietary folate linked to ≈20% lower ischemic stroke risk (cardiovascular benefit).
- 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
Large randomized trial: folic acid+B6+B12 lowered homocysteine by ~18.5% though no diabetes prevention benefit.
- 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
High‑quality randomized trial: folic acid 400 µg/day raised folate and substantially lowered homocysteine in the periconception/pregnancy period.
- No change in impaired endothelial function after long-term folic acid therapy of hyperhomocysteinaemia in haemodialysis patients
PubMed ID: 9481724
Folic acid therapy rapidly reduced very high homocysteine in hemodialysis patients (but no vascular improvement).
- Folic acid treatment of hyperhomocysteinemia in peritoneal dialysis patients: no change in endothelial function after long-term therapy
PubMed ID: 9663892
In peritoneal dialysis patients folic acid normalized homocysteine in ~39% at 12 weeks.
- Carotid artery stiffness in patients with end-stage renal disease: no effect of long-term homocysteine-lowering therapy
PubMed ID: 10661480
Folic acid lowered tHcy from ~44 to ~21 µmol/L in dialysis patients (large biochemical effect).
- Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure
PubMed ID: 11849459
Folate+pyridoxine baseline reduced fasting tHcy; addition of betaine further reduced post‑load tHcy (shows folate part of homocysteine control).
- High- but not low-dose folic acid improves endothelial function in coronary artery disease
PubMed ID: 17087779
5 mg/day folic acid improved endothelial function in CAD patients (functional vascular benefit at pharmacologic dose).
- Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial
PubMed ID: 27655522
Combined nutraceutical (including methylfolate) lowered homocysteine more than high‑dose folic acid in hypertensive subjects — clear homocysteine‑lowering evidence.
- 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 and folic acid both lowered plasma homocysteine vs placebo; l‑5‑MTHF raised folate more — direct RCT evidence.
- A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia
PubMed ID: 31408467
Tailored drink (B‑vitamins including folic acid) reduced plasma homocysteine substantially vs control in an RCT.
- 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 + B‑vitamins + betaine produced ~10% homocysteine reduction in adults with high baseline tHcy.
- Functionality of endogenous folates from rye and orange juice using human in vivo model
PubMed ID: 12474071
Endogenous food folates and fortified bread both improved serum/RBC folate; homocysteine decreased in highest tertile — relevant to homocysteine control.
- Plasma homocysteine concentration is decreased by dietary intervention
PubMed ID: 12696562
Dietary folate intervention raised folate status and decreased plasma tHcy ≈13% — supports homocysteine lowering by folate from foods.
- Effect of folic acid on fenofibrate-induced elevation of homocysteine and cysteine
PubMed ID: 12851616
Randomized comparison: folic acid co‑admin attenuated fenofibrate‑induced tHcy rise (51.3%→14.6%), robust biochemical result.
- Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12
PubMed ID: 11981075
Randomized comparison: high‑dose folinic acid or folic acid (with B6/B12) produced large (~42–46%) reductions in total homocysteine in haemodialysis patients—direct and strong evidence.
- 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 water significantly lowered plasma homocysteine in healthy adults.
- Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women
PubMed ID: 17302515
Folic‑acid fortified mineral water in pregnant women lowered plasma homocysteine significantly alongside large increases in folate biomarkers.
- High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial
PubMed ID: 19118243
High‑dose B‑vitamin supplementation (including folate) robustly lowered fasting homocysteine and produced vascular benefit in higher‑tHcy subgroup.
- Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium-dependent vasodilation in patients with cardiovascular disease
PubMed ID: 21884007
B‑vitamin treatment (including 1 mg folic acid) lowered homocysteine and improved endothelial function.
- Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial
PubMed ID: 23218892
L‑methylfolate+B12/B6 reduced homocysteine significantly over 24 weeks in neuropathy patients.
- One year B and D vitamins supplementation improves metabolic bone markers
PubMed ID: 23183751
B‑vitamin supplementation including folic acid produced a large (-29%) tHcy reduction in older adults.
- 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
Food fortification with folic acid or L‑5‑MTHF raised plasma/RBC folate, supporting improved homocysteine metabolism (biomarker evidence).
- Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine, but not cognitive performance
PubMed ID: 24481688
Three months of folic‑acid containing B‑vitamin supplementation raised folate and lowered homocysteine in preschool children.
- One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans
PubMed ID: 25283139
One‑year B‑vitamin supplementation (including 500 μg folic acid) markedly lowered plasma total homocysteine — strongest direct evidence.
- Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers
PubMed ID: 30401001
Large population RCT in hypertensive patients demonstrated modest but consistent tHcy reductions with long‑term low‑dose folic acid.
- Interaction of serum calcium and folic acid treatment on first stroke in hypertensive males
PubMed ID: 33148481
Large RCT: folic acid + enalapril halved first-stroke risk in hypertensive men with high serum calcium — direct clinically meaningful cardiovascular benefit.
- Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder-A Randomized, Controlled 12-Month Trial
PubMed ID: 29562612
Multi‑nutrition program (including folate/folinic acid) reduced homocysteine substantially alongside cognitive gains — direct biomarker improvement tied to folate.
- Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial
PubMed ID: 20571015
Large RCT: folic acid + B12 lowered plasma homocysteine by ~3.8 μmol/L (28%) — strong evidence that B9 helps reduce homocysteine.
- Folic acid and vitamin B(12) supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized, double-blind, placebo-controlled trial
PubMed ID: 23507227
Folic acid + B12 markedly lowered homocysteine in older women (small trial) — direct evidence of homocysteine lowering.
- Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial
PubMed ID: 26311810
Well‑powered RCT showing folic acid produced large (≈21–23%) reductions in plasma total homocysteine — direct, high-quality evidence.
- 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
Folate‑rich food intervention reduced homocysteine markedly (especially in MTHFR 677TT genotype carriers).
- 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
Fortified product including folic acid lowered total homocysteine in participants with high baseline tHcy.
- 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 product including folic acid reduced hs‑CRP and LDL/total cholesterol in cardiac rehab patients (multi‑nutrient study).
- 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 years of folate+B12+B6 produced a clear and clinically meaningful reduction in plasma homocysteine (−4.4 µmol/L).
- Milk enriched with "healthy fatty acids" improves cardiovascular risk markers and nutritional status in human volunteers
PubMed ID: 19084376
Milk fortified with folic acid (among other nutrients) raised serum folate and improved cholesterol/TG measures over 1 year.
- 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
Folic acid supplementation lowered homocysteine by ~6.5 μmol/L and increased SAM—supportive of folate's role in one‑carbon metabolism.
- Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?
PubMed ID: 10952955
In chronic renal failure folic acid greatly raised folate and lowered total homocysteine vs placebo—clear homocysteine-lowering effect.
- 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
Folic acid (5 mg/d) markedly reduced plasma homocysteine in CAD patients—robust homocysteine-lowering result.
- Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide?
PubMed ID: 11451751
Folic acid significantly lowered homocysteine by ~19% and improved endothelial function—strong, direct biochemical evidence.
- Folic acid therapy reduces plasma homocysteine levels and improves plasma antioxidant capacity in hemodialysis patients
PubMed ID: 17321110
High-dose folic acid in hemodialysis patients lowered homocysteine (normalized in many) vs placebo—strong biochemical evidence.
- 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
Randomized trial: low physiologic folic acid (400 µg/d) improved NO-mediated endothelium-dependent vasodilation and reduced vascular oxidative stress—direct vascular (cardiac) benefit.
- Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia
PubMed ID: 8416664
Combined B‑vitamin regimen including 1 mg folic acid normalized elevated homocysteine in men within weeks — strong biochemical evidence that folic acid lowers homocysteine.
- Vitamin requirements for the treatment of hyperhomocysteinemia in humans
PubMed ID: 7931701
Randomized, placebo‑controlled: folic acid (0.65 mg/day) reduced plasma homocysteine by ~41.7% — direct, strong evidence.
- Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid
PubMed ID: 7714461
Post‑MI intervention: both tested folic acid doses lowered homocysteine ~27%—robust effect in clinical population.
- Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations
PubMed ID: 7603218
Large elderly injection trial normalized homocysteine in 92% vs 20% with placebo — very strong biochemical evidence.
- Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects
PubMed ID: 8596381
400 µg/day folic acid raised RBC folate (status change that typically lowers homocysteine), supportive indirect evidence.
- Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers
PubMed ID: 9514403
Folic acid (0.5–5 mg) and multivitamin supplementation produced large, consistent reductions in plasma homocysteine.
- 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 and benefit was greater when combined with B12.
- Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment
PubMed ID: 10095804
Low‑dose folate in metformin users substantially increased folate and lowered homocysteine by ~22% at 12 weeks.
- Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults
PubMed ID: 9683174
Supplementing folate/B12 reduced high homocysteine (up to −37% in high‑baseline subgroup).
- Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease
PubMed ID: 9535664
Randomized trial of folic‑acid‑fortified cereal showed dose-dependent increases in plasma folate and significant homocysteine lowering.
- 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
Weekly folic acid prevented homocysteine rises in long‑term low‑dose MTX patients.
- The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study
PubMed ID: 9683392
Small dietary folic acid increases raised folate and reduced homocysteine by about 10% in healthy adults.
- Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease
PubMed ID: 10539749
Fortified diet raising folate intake produced a clinically relevant reduction in serum total homocysteine in high‑CV‑risk individuals.
- Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial
PubMed ID: 9925130
Low daily folic acid (250–500 µg) produced dose‑dependent decreases in total homocysteine (−11.4% and −21.8%).
- Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients
PubMed ID: 10591669
Higher‑dose folic acid (2.4 mg/day) produced greater homocysteine lowering than standard dosing in renal transplant patients.
- Effect of dietary patterns on serum homocysteine: results of a randomized, controlled feeding study
PubMed ID: 10952952
Dietary changes increasing fruit/vegetable intake raised serum folate and modestly lowered homocysteine; change inversely associated with serum folate.
- 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
Folic acid+B12 lowered homocysteine by about 23% in this pilot study.
- Polymorphisms in the CBS gene associated with decreased risk of coronary artery disease and increased responsiveness to total homocysteine lowering by folic acid
PubMed ID: 10833331
Genetic study showing CBS variants influence homocysteine response to folate and associated genotype underrepresentation in CAD cases (links folate responsiveness to CAD).
- Dietary strategies for lowering homocysteine concentrations
PubMed ID: 10837284
Supplements (437 µg/d) and fortified cereal significantly increased serum folate and decreased tHcy by ~21–24%.
- Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine
PubMed ID: 11076820
Folic acid + B12 markedly lowered homocysteine and produced a clinically meaningful improvement in flow‑mediated dilatation in coronary disease patients.
- Plasmatic homocysteine response to vitamin supplementation in elderly people
PubMed ID: 11152929
Folate‑rich diet (with/without pills) produced large decreases in homocysteine in older people.
- Hyperhomocysteinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins
PubMed ID: 10916110
Long‑term B‑vitamin supplementation including folate lowered high homocysteine in dialysis patients over 12 months.
- Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study
PubMed ID: 10820175
Very‑high‑dose folic acid (15–60 mg/day) produced substantial tHcy reductions in hemodialysis patients.
- Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet
PubMed ID: 11110875
Multivitamin containing folic acid raised folate/B12 and lowered homocysteine (~‑9.6%) in older adults.
- Folate status of elderly women following moderate folate depletion responds only to a higher folate intake
PubMed ID: 10827214
Repletion with 415 µg/day reversed elevated tHcy in elderly women; 200 µg/day was less effective (dose dependence).
- Controlled comparison of L-5-methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients
PubMed ID: 10859289
High‑dose methylfolate and folic acid both modestly lowered homocysteine in dialysis patients, though normalization was uncommon.
- Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease
PubMed ID: 10987596
Direct RCT: folic acid markedly raised plasma folate and improved endothelial function (FMD) in CAD patients.
- 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 caused large falls in fasting and postmethionine homocysteine vs placebo.
- Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women
PubMed ID: 11035344
500 µg/day folic acid for 4 weeks lowered homocysteine ~28% in postmenopausal women (RCT).
- Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial
PubMed ID: 11339442
Large RCT in healthy women: daily folic acid as low as 250 µg produced dose‑dependent, substantial reductions in plasma homocysteine.
- Randomized trial of folic acid supplementation and serum homocysteine levels
PubMed ID: 11231701
Dose response evidence (duplicate entry confirms strong support).
- 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 folate or 400 µg supplement increased folate and lowered homocysteine ~14–16% but no endothelial benefit observed.
- Folate supplementation in peritoneal dialysis patients with normal erythrocyte folate: effect on plasma homocysteine
PubMed ID: 11598393
Direct folic acid 5 mg/day in PD patients halved plasma homocysteine and massively increased serum/RBC folate (strong, direct effect).
- Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients
PubMed ID: 11169020
High‑dose folate/MTHF with B12/B6 reduced tHcy modestly in dialysis and transplant recipients (direct effect though variable).
- Decreased rate of coronary restenosis after lowering of plasma homocysteine levels
PubMed ID: 11757505
Folate+B12+B6 markedly lowered homocysteine and halved coronary restenosis and revascularization after angioplasty (direct clinical CV benefit).
- Oral vitamin B(12) and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia
PubMed ID: 11231366
1 mg folic acid (with multivitamin) substantially reduced tHcy in dialysis patients; B12 added further benefit (direct folate effect).
- Homocyst(e)ine metabolism in hemodialysis patients treated with vitamins B6, B12 and folate
PubMed ID: 11426667
IV combined folate/B12/B6 reduced homocysteine by ~30–40% in dialysis patients (direct lowering albeit combined therapy).
- 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
Folic acid + B6 produced small but significant reductions in systolic/diastolic blood pressure over 2 years (cardiovascular risk marker).
- Efficacy of folinic versus folic acid for the correction of hyperhomocysteinemia in hemodialysis patients
PubMed ID: 11273876
Folic acid and folinic acid produced ~30–34% reductions in tHcy in hemodialysis patients (direct homocysteine effect).
- Rapid communication: L-folinic acid versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients
PubMed ID: 11135086
Oral L-folinic acid and high‑dose folic acid produced similar modest (~20–22%) tHcy reductions in hemodialysis patients (direct but limited normalization).
- Homocysteine--a treatable risk factor for allograft vascular disease after heart transplantation?
PubMed ID: 11448801
Folic acid 5 mg/day lowered tHcy by ≈23% in heart transplant patients (clear biochemical lowering).
- 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/day supplement raised plasma folate and lowered tHcy; MTHFR TT genotype required higher folate intake (clear folate–tHcy effect).
- Randomized trial of methylcobalamin and folate effects on homocysteine in hemodialysis patients
PubMed ID: 12021520
High‑dose folic acid (10 mg/day) normalized or greatly reduced high homocysteine in hemodialysis patients (large effect).
- Hyperhomocysteinemia and endothelial function in young subjects: effects of vitamin supplementation
PubMed ID: 12430779
Vitamin combination including folic acid lowered homocysteine in young men (no vascular benefit).
- Fiber-multivitamin combination therapy: a beneficial influence on low-density lipoprotein and homocysteine
PubMed ID: 12200762
Fiber‑plus‑vitamin product modestly lowered homocysteine but contained multiple components.
- 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
Folic acid 5 mg/day rapidly raised folate and significantly reduced homocysteine in heavy smokers.
- 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
Randomized trial of homocysteine‑lowering vitamins (including folate) reduced major adverse cardiac events and repeat revascularization after PCI.
- 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 folic acid fortification produced dose‑related plasma folate increases and homocysteine reductions in older adults.
- Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis
PubMed ID: 12048292
Folate (folic/folinic) prevented methotrexate‑associated rises in homocysteine in RA patients in an RCT.
- Hyperhomocysteinemia in Japanese patients with convalescent stage ischemic stroke: effect of combined therapy with folic acid and mecobalamine
PubMed ID: 12220694
Folic acid + B12 combination lowered plasma homocysteine by ~38.5% in stroke patients (largest effect vs single vitamins).
- Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid
PubMed ID: 12421850
Both [6S]-5‑MTHF and folic acid increased folate markers significantly over 24 weeks (supporting tHcy control).
- Decreasing plasma endothelin-1 and unchanged plasma neopterin during folate supplementation in hyperhomocysteinemia
PubMed ID: 12110777
Large randomized trial showed ~48% homocysteine reduction in vascular patients with folate.
- Effect of homocysteine reduction by B-vitamin supplementation on markers of clotting activation
PubMed ID: 12195694
Listed again: strong homocysteine lowering with high‑dose B vitamins.
- The effect of folic acid supplementation on plasma homocysteine in an elderly population
PubMed ID: 11834770
Dose‑dependent homocysteine lowering in older adults; clear threshold for effect.
- 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 coronary disease (duplicate listing for emphasis).
- Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering
PubMed ID: 11772871
Rapid, clinically measurable improvement in endothelial function (FMD) after high-dose folic acid.
- 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
Folic acid 400 µg decreased tHcy substantially in young women, largest effect in MTHFR TT genotype.
- Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age
PubMed ID: 12391385
200–400 µg/day folic acid significantly decreased plasma homocysteine in women of childbearing age.
- Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial
PubMed ID: 14535967
Metformin use lowered folate and modestly increased homocysteine — shows folate's role in maintaining tHcy.
- 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
Folate+B12+B6 produced marked homocysteine lowering in older adults.
- Reduction in plasma total homocysteine through increasing folate intake in healthy individuals is not associated with changes in measures of antioxidant activity or oxidant damage
PubMed ID: 12627187
Dietary folate + 400 µg supplement lowered homocysteine in a randomized crossover trial.
- Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study
PubMed ID: 14576754
Low‑dose folic acid (200 µg/day) prevented coffee‑induced rise in homocysteine.
- Secondary prevention with folic acid: effects on clinical outcomes
PubMed ID: 12821232
Daily folic acid lowered homocysteine by ~18% in people with coronary disease.
- Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients
PubMed ID: 12792513
Folic acid + B6 + B12 reduced homocysteine from ~21.8 to 9.3 µmol/L (−57%).
- Measurement of carotid plaque and effect of vitamin therapy for total homocysteine
PubMed ID: 14656032
Vitamin therapy lowered homocysteine in observational cohort though randomized comparison was negative — mixed evidence.
- 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
Randomized trial: low‑dose L‑5‑MTHF and folic acid both lowered tHcy, with L‑MTHF slightly more effective.
- Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia
PubMed ID: 12823643
Folic acid + B12 lowered plasma homocysteine by ~30% (P<0.0001) in a randomized factorial trial.
- 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 (5 mg) + B6 produced ≈50% reduction in tHcy—very strong direct effect on homocysteine.
- 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 as effectively as daily dosing; clear homocysteine-lowering evidence.
- Folate catabolite excretion is responsive to changes in dietary folate intake in elderly women
PubMed ID: 12663292
Dietary depletion/repletion study showed plasma/RBC folate and urinary folate catabolites correlated with plasma homocysteine, supporting folate's role in homocysteine control.
- Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study
PubMed ID: 12716688
Large dose‑response trial: ~400 µg/day folic acid produced ≈22% lowering of plasma homocysteine—clear quantitative effect.
- Effects of folic acid treatment on homocysteine levels and vascular disease in hemodialysis patients
PubMed ID: 12709680
In hemodialysis patients folic acid lowered homocysteine modestly but many patients remained above normal—partial effect.
- 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, a direct vascular benefit.
- 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 with folic acid/B6/B12 significantly raised vitamins and lowered homocysteine in older adults.
- 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
Folic acid + B6 markedly lowered fasting tHcy (~39%) and post‑methionine tHcy (~29%) in a randomized study.
- Effect of cow milk on food folate bioavailability in young women
PubMed ID: 15585769
In low‑folate diets, cow milk kept erythrocyte folate stable and prevented rises in plasma homocysteine (dietary intervention effect).
- 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
Folic acid lowered total homocysteine by ~29% in type 2 diabetics with mild hyperhomocysteinaemia (direct, substantial effect).
- Oral folic acid enhances endothelial function in patients with hypercholesterolaemia receiving statins
PubMed ID: 15616416
Randomized trial: 5 mg folic acid improved endothelium-dependent flow‑mediated dilation (direct vascular benefit linked to heart health).
- Folic acid improves endothelial function in children and adolescents with type 1 diabetes
PubMed ID: 15069400
High‑dose folic acid improved endothelial function (FMD) in youth with type 1 diabetes — supports vascular/heart health.
- Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention
PubMed ID: 15321804
Folic acid+B12 produced strong tHcy reductions (-31%), directly demonstrating folate's effect on homocysteine.
- Determining bioavailability of food folates in a controlled intervention study
PubMed ID: 15447898
Controlled feeding showed synthetic folic acid increased serum folate and lowered homocysteine much more than equivalent natural food folates (demonstrates folic acid potency on tHcy).
- Effect of folic Acid supplementation on the folate status of buccal mucosa and lymphocytes
PubMed ID: 15247137
1.2 mg folic acid raised lymphocyte folate and plasma 5‑MeTHF — biochemical changes that commonly accompany homocysteine lowering (though tHcy not primary endpoint here).
- 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
Folate+B12 lowered homocysteine by ~28% in metabolic‑syndrome patients (clear reduction).
- Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women
PubMed ID: 14985224
Active methylfolate and folic acid both lowered homocysteine similarly in healthy women (direct RCT evidence).
- Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial
PubMed ID: 15569860
B‑vitamin therapy in post‑TIA/stroke patients reduced tHcy by ~3.7 μmol/L (consistent biochemical effect).
- Comparative study of response to treatment with supraphysiologic doses of B-vitamins in hyperhomocysteinemic hemodialysis patients
PubMed ID: 15115259
High‑dose folic acid plus B‑vitamins produced marked Hcy reductions in dialysis patients, including large genotype‑specific responses.
- 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
Folate‑containing multivitamin consistently lowered homocysteine by ~3–4 μmol/L in stroke patients across time — robust biochemical effect.
- The methylenetetrahydrofolate reductase C677T polymorphism is a major determinant of coffee-induced increase of plasma homocysteine: a randomized placebo controlled study
PubMed ID: 15138617
Low-dose folic acid (200 µg/day) partly prevented a coffee-induced homocysteine rise, demonstrating acute homocysteine modulation.
- Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults
PubMed ID: 14985217
Both dietary polyglutamyl folate and synthetic folic acid lowered homocysteine; monoglutamyl folic acid produced larger serum/RBC folate increases.
- Folic acid and vitamin E supplementation effects on homocysteinemia, endothelial function and plasma antioxidant capacity in young myocardial-infarction patients
PubMed ID: 14597156
High-dose folic acid reduced homocysteine by ~41% in post-MI patients—strong homocysteine-lowering evidence.
- The effect of homocysteine reduction by B-vitamin supplementation on markers of endothelial dysfunction
PubMed ID: 15543337
B-vitamin supplement including folic acid lowered tHcy by ~31% vs placebo in a randomized trial.
- The influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia
PubMed ID: 15717846
Randomized trial: folate lowered homocysteine in people with high tHcy (biochemical effect shown).
- Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease
PubMed ID: 16332666
Folic acid + B12 lowered homocysteine by ~5 μmol/L in older patients with vascular disease (clear biochemical change).
- Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial
PubMed ID: 15790610
Folic acid (and B vitamins) prevented or reduced metformin-related homocysteine rises in PCOS patients (clinically meaningful effect).
- Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease--a prospective randomized study of vitamin supplementation
PubMed ID: 16006259
Folic acid (5 mg) + B6 + B12 reduced tHcy from 17.4 to 9.2 μmol/L in CAD patients (large biochemical reduction).
- [Efficacy and safety of two vitamin supplement regimens on homocysteine levels in hemodialysis patients. Prospective, randomized clinical trial]
PubMed ID: 16053010
Folate-containing multivitamins lowered homocysteine in dialysis patients by ~23–28% though most patients remained above normal.
- Effect of lowering of homocysteine levels on inflammatory markers: a randomized controlled trial
PubMed ID: 15983288
0.8 mg folic acid daily raised folate ~400% and lowered total homocysteine by ~28% in a large RCT.
- Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation
PubMed ID: 16190942
1 mg/day folic acid in hyperhomocysteinemic children on antiepileptics significantly increased folate and normalized/decreased tHcy.
- 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 including folate produced substantial tHcy reductions, largest in B12‑deficient/high tHcy subgroups.
- The effect of postmenopausal hormone therapy with or without folic acid supplementation on serum homocysteine level
PubMed ID: 16390760
Adding folic acid to hormone therapy lowered fasting homocysteine versus HT alone (small RCT).
- Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma
PubMed ID: 15831910
Folic acid markedly increased serum/erythrocyte folate and DNA methylation; homocysteine effect not the primary report here.
- [Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid]
PubMed ID: 15847747
Low‑dose folic acid significantly decreased antiepileptic‑associated hyperhomocysteinemia back toward control levels.
- Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans
PubMed ID: 15928685
Daily 200 µg folic acid in fortified milk modestly lowered plasma homocysteine (−0.88 µmol/L) and raised folate.
- Homocysteine-lowering therapy and early progression of transplant vasculopathy: a prospective, randomized, IVUS-based study
PubMed ID: 16095507
5‑MTHF lowered homocysteine after heart transplant; effect on clinical vasculopathy was subgroup‑dependent.
- Prospective evaluation of folic acid supplementation on plasma homocysteine concentrations during weight reduction: a randomized, double-blinded, placebo-controlled study in obese women
PubMed ID: 15826880
5 mg folic acid tripled serum folate; overall Hcy change limited to high‑baseline subgroup (moderate evidence).
- Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype
PubMed ID: 16002796
5 mg folic acid reduced pulse pressure and large‑artery stiffness—direct vascular improvement.
- 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 folic acid for 3 months produced large, genotype‑stratified reductions in plasma total homocysteine.
- [Treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients with vitamin B]
PubMed ID: 16083628
B‑vitamin therapy including folic acid reduced homocysteine by ~35% in hyperhomocysteinemic transplant recipients.
- No effect of folic acid supplementation in the course of 1 year on haemostasis markers and C-reactive protein in older adults
PubMed ID: 16113791
0.8 mg/day folic acid for 1 year lowered homocysteine by ~24% in older adults.
- 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
Folic acid with B6/B12 markedly lowered homocysteine and reduced carotid IMT.
- A controlled trial of homocysteine lowering and cognitive performance
PubMed ID: 16807413
Two‑year B‑vitamin supplementation including folate produced clear homocysteine lowering.
- Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: A randomized, placebo-controlled, double-blind trial
PubMed ID: 16960155
Daily B‑vitamin regimen (including folic acid) lowered homocysteine though did not lower recurrent VTE.
- Homocysteine lowering with folic acid and B vitamins in vascular disease
PubMed ID: 16531613
Combined folic acid/B6/B12 modestly lowered homocysteine in a large trial.
- Vitamins and entacapone in levodopa-induced hyperhomocysteinemia: a randomized controlled study
PubMed ID: 16801668
Folate+B12 lowered levodopa‑associated homocysteine in Parkinson’s patients (small study).
- 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 raised serum folate and lowered homocysteine in smokers and never‑smokers.
- Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus
PubMed ID: 16818571
High‑dose folate rapidly normalized endothelial (flow‑mediated dilation) function in children with type 1 diabetes.
- Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
PubMed ID: 16755160
Folate‑based homocysteine‑lowering therapy associated with fewer cardiovascular events in dialysis patients.
- Effect of fortified spread on homocysteine concentration in apparently healthy volunteers
PubMed ID: 17151589
Fortified spread raised serum folate and produced dose‑dependent tHcy reductions over 6 weeks.
- Homocysteine lowering and cardiovascular events after acute myocardial infarction
PubMed ID: 16531614
Post‑MI B‑vitamin (incl. folic acid) therapy lowered homocysteine by ~27%.
- Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in chronic renal failure: a multicenter, randomized, controlled trial
PubMed ID: 16545638
High‑dose folic acid in CRF lowered homocysteine by ~19%.
- Methylenetetrahydrofolate reductase polymorphisms and homocysteine-lowering effect of vitamin therapy in Singaporean stroke patients
PubMed ID: 16397167
Large randomized trial in stroke patients: folic acid + B12 + B6 reduced mean tHcy by ~3.8 µmol/L (robust effect).
- Effects of milk enriched with omega-3 fatty acid, oleic acid and folic acid in patients with metabolic syndrome
PubMed ID: 16701922
Enriched milk including folic acid lowered homocysteine modestly in metabolic syndrome.
- Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects
PubMed ID: 16491109
12‑week folic acid reduced homocysteine in overweight adults.
- Effect of folic acid on endothelial function following acute myocardial infarction
PubMed ID: 17293188
Post‑MI crossover trial showed clear FMD improvement with high‑dose folic acid.
- Effect of folic acid treatment on carotid intima-media thickness of patients with coronary disease
PubMed ID: 17052775
Folic acid 2.5 mg/day lowered homocysteine in coronary patients (clear biochemical effect).
- Effect of folate supplementation on N-terminal pro-brain natriuretic peptide
PubMed ID: 17052779
Dose‑response study: serum folate up and homocysteine down across folic acid doses.
- 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
High‑dose folic acid + B6/B12 lowered homocysteine in dialysis patients (~‑18.7%).
- Effects of folic acid before and after vitamin B12 on plasma homocysteine concentrations in hemodialysis patients with known MTHFR genotypes
PubMed ID: 16391331
Dialysis patients: folic acid strongly lowered homocysteine, with genotype dependence.
- No effect of homocysteine-lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease
PubMed ID: 16634837
B‑vitamin (incl. folic acid) markedly lowered homocysteine (~33%) in PAD patients.
- Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial
PubMed ID: 17848650
High‑dose folic acid + B vitamins substantially lowered homocysteine in advanced CKD (clear biochemical effect).
- Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients
PubMed ID: 18042476
Multivitamin including folic acid lowered homocysteine in mild–moderate AD patients (biochemical effect).
- Homocysteine-lowering therapy and risk for venous thromboembolism: a randomized trial
PubMed ID: 17470822
Daily folic acid with B6/B12 lowered homocysteine modestly over 5 years.
- Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease--results of the renal Hope-2 study
PubMed ID: 18003666
B‑vitamin therapy including folic acid produced marked homocysteine lowering in CKD, despite no benefit on CV events.
- [Effects of intervention therapy of methylcobalamin and folic acid on plasma homocysteine concentration and homocysteine thiolactonases/paraoxonase activity in patients with type 2 diabetes mellitus]
PubMed ID: 17425871
Folic acid (and B12) reduced homocysteine in type 2 diabetes patients over 12 weeks.
- Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): characteristics of a randomized trial among 12064 myocardial infarction survivors
PubMed ID: 17967584
Large MI‑survivor trial: folic acid+B12 lowered homocysteine by ~3–4 µmol/L (robust biochemical change).
- Uremic hyperhomocysteinemia: a randomized trial of folate treatment for the prevention of cardiovascular events
PubMed ID: 17403173
Dialysis trial: folic acid normalized homocysteine in most patients (major biochemical effect).
- 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
Three‑year folic acid markedly increased serum folate (+576%) and reduced homocysteine (~−26%).
- Folic acid does not improve endothelial function in obese children and adolescents
PubMed ID: 17519435
Obese children: folic acid reduced tHcy modestly (−0.95 μmol/L).
- Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study
PubMed ID: 17592099
Multi-component strategy that included homocysteine‑lowering (likely B vitamins) and produced improved carotid IMT and endothelial function.
- Effects of folic acid and vitamin B complex on serum C-reactive protein and albumin levels in stable hemodialysis patients
PubMed ID: 17605895
Hemodialysis folic acid+B complex decreased plasma tHcy significantly after 3 months.
- [Hyperhomocysteinemia and alternate vitamin supplementation]
PubMed ID: 17342693
Alternate folic acid/B12 dosing reduced homocysteine, with genotype‑dependent effects.
- Homocysteine-lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease
PubMed ID: 17645592
Folic acid+B12 lowered tHcy by ~33% in suspected CAD cohort.
- Lowering homocysteine with B vitamins has no effect on blood pressure in older adults
PubMed ID: 17449579
B‑vitamin supplements lowered homocysteine by ~4.3 μmol/L at 1 year in older adults.
- Effects of folic acid and N-acetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease
PubMed ID: 18214123
Folic acid reduced Hcy ~42% in CAD patients (large, clinically important biochemical effect).
- 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 reduced Hcy ~37% in transplant recipients; clear and large effect.
- 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 folic acid dosing produced predictable homocysteine reductions corresponding to folate increases.
- The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis
PubMed ID: 18803866
B‑vitamin treatment lowered tHcy by ~23% in stroke/TIA patients.
- 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
Fortified bread lowered homocysteine by ~13% in older adults.
- High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial
PubMed ID: 18854539
High‑dose folic acid/B6/B12 lowered plasma homocysteine ~27% in Alzheimer patients.
- Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial
PubMed ID: 18714059
Coronary angiography trial: folic acid+B12 lowered Hcy ~30% after 1 year.
- Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial
PubMed ID: 18460663
Large women’s trial: B vitamins lowered homocysteine ~18.5% though no CV benefit.
- A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease
PubMed ID: 19064521
Large long‑duration RCT: folic acid+B6+B12 lowered homocysteine ≈17%—robust biochemical effect.
- Long-term effect of folic acid therapy in heart transplant recipients: follow-up analysis of a randomized study
PubMed ID: 18431235
Post‑heart‑transplant randomized folate therapy linked to substantially better 7‑yr survival, suggesting cardiovascular benefit.
- Dietary intervention with Okinawan vegetables increased circulating endothelial progenitor cells in healthy young women
PubMed ID: 19013573
Dietary increase in folate lowered plasma homocysteine in a 2‑week intervention.
- Effects of plasma homocysteine levels on serum HTase/PON activity in patients with type 2 diabetes
PubMed ID: 18781288
Short RCT: folic acid (±B12) produced marked homocysteine reductions in type 2 diabetics (dose‑dependent effect).
- 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
Randomized trial showed weekly folic acid (various doses) raises serum folate and lowers homocysteine similarly to daily dosing.
- Effects of weight loss from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk in subjects with abdominal obesity
PubMed ID: 18326593
Diet-related folate decreases were accompanied by homocysteine increases (observational/experimental diet trial).
- Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery
PubMed ID: 18400808
Nitrous oxide exposure produced postoperative hyperhomocysteinaemia via folate-pathway inhibition (strong link to folate metabolism).
- Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet
PubMed ID: 19154566
B‑vitamin supplementation including folic acid lowered plasma homocysteine by ~34% in coeliac patients (direct trial evidence).
- Treatment of hyperhomocysteinemia and endothelial dysfunction in renal transplant recipients with B vitamins in the Chinese population
PubMed ID: 18206175
B‑vitamin therapy including folic acid reduced homocysteine by 37% in kidney transplant recipients.
- 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 markedly raised serum folate and produced significant homocysteine reductions; genotype-specific response documented.
- [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 blood-pressure control and lowered homocysteine in hypertensive patients.
- The effect of folic acid supplementation on carotid intima-media thickness in patients with cardiovascular risk: a randomized, placebo-controlled trial
PubMed ID: 19201496
5 mg/day folic acid lowered homocysteine and produced a small but significant regression in carotid IMT (direct vascular benefit).
- Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine - a six-year follow-up study
PubMed ID: 19917166
Folic acid use in RA patients associated with lower homocysteine; high homocysteine predicted vascular 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
A multinutrient preparation that included folic acid lowered homocysteine in a randomized trial.
- Plasma Abeta, homocysteine, and cognition: the Vitamin Intervention for Stroke Prevention (VISP) trial
PubMed ID: 19153374
High‑dose B vitamins (including folate) significantly lowered homocysteine in stroke patients.
- 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
Folate 5 mg/day substantially lowered homocysteine (~‑37%) in hypercholesterolemic adults.
- Randomized clinical trial of folate supplementation in patients with peripheral arterial disease
PubMed ID: 19672935
Folate or 5‑MTHF reduced plasma tHcy significantly in peripheral arterial disease patients.
- Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial
PubMed ID: 19228852
Large RCT showing B-vitamin (including folic acid) regimen reduced stroke incidence (~25%), supporting cardiovascular benefit.
- Role of folic acid in atherosclerosis after kidney transplant: a double-blind, randomized, placebo-controlled clinical trial
PubMed ID: 19364310
5 mg/day folic acid dramatically reduced homocysteine (~‑7.6 µmol/L) in kidney transplant recipients.
- Efficacy of folate and vitamin B12 in lowering homocysteine concentrations in hemodialysis patients
PubMed ID: 19736473
High‑dose folic acid plus B12 produced large, dose‑dependent homocysteine reductions in hemodialysis patients.
- Different doses of oral folic acid for homocysteine-lowering therapy in patients on hemodialysis: a randomized controlled trial
PubMed ID: 19841527
15 mg/day folic acid produced a modest but statistically significant homocysteine reduction vs 5 mg/day in hemodialysis.
- Effect of 2 pieces of nutritional advice on folate status in Swedish women: a randomized controlled trial
PubMed ID: 19190070
Dietary folate intake (folate‑rich breakfast) raised RBC folate and lowered plasma homocysteine by ~2.3 µmol/L.
- Ethnicity does not affect the homocysteine-lowering effect of B-vitamin therapy in Singaporean stroke patients
PubMed ID: 19372453
B‑vitamin therapy consistently lowered homocysteine ~3–5 µmol/L across ethnic groups in stroke patients.
- Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina
PubMed ID: 19491420
5 mg folic acid produced rapid, large homocysteine reductions (‑20% at 4 wk, ‑55% at 8 wk) in unstable angina patients.
- Effect of long-term homocysteine reduction with B vitamins on arterial wall inflammation assessed by fluorodeoxyglucose positron emission tomography: a randomised double-blind, placebo-controlled trial
PubMed ID: 19202330
B‑vitamin therapy (including folic acid) reduced plasma total homocysteine by ~3.2 μmol/L in stroke patients—clear biochemical effect.
- [Efficacy of enalapril combined with folic acid in lowering blood pressure and plasma homocysteine level]
PubMed ID: 20058594
Enalapril+folic acid groups had greater reductions in plasma homocysteine than enalapril alone.
- Comparison study on the effect of prenatal administration of high dose and low dose folic acid
PubMed ID: 19139780
High‑dose folic acid markedly reduced maternal homocysteine (−5.37 vs −1.64 μmol/L), robust evidence of Hcy lowering.
- Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial
PubMed ID: 20424250
High‑dose B‑vitamin regimen produced a mean tHcy reduction (~−4.8 μmol/L) though clinical outcomes were adverse in this kidney disease population.
- Effect of physiological doses of oral vitamin B12 on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India
PubMed ID: 20216560
Community trial showed small daily folic acid raised folate and reduced tHcy substantially (F200 vs F0 −4.8 μmol/L).
- Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke: a possible linkage to homocysteine
PubMed ID: 20092401
Folic acid+B12 for 2 months lowered homocysteine in stroke patients; decreases correlated with CF6 reductions.
- 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, a direct physiological cardiac improvement.
- 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 elderly halved total homocysteine and massively increased 5‑MTHF—very strong biochemical effect.
- Baseline plasma total homocysteine and adenoma recurrence: results from a double blind randomized clinical trial of aspirin and folate supplementation
PubMed ID: 20841390
Large randomized trial: folic acid (1 mg/day) lowered homocysteine though it did not affect adenoma recurrence.
- Homocysteine-lowering vitamins do not lower plasma S-adenosylhomocysteine in older people with elevated homocysteine concentrations
PubMed ID: 20089204
B-vitamin supplementation (including folate) significantly lowered homocysteine in older people (mean difference −4.4 μmol/L).
- Do novel risk biomarkers reflect the severity of peripheral arterial disease?
PubMed ID: 20834026
Cross-sectional: lower red-cell folate and higher homocysteine associated with greater arterial stiffness (PAD patients), linking folate status to vascular health.
- A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy
PubMed ID: 20980493
Randomized 6‑month folic acid dosing produced substantial, dose-related reductions in homocysteine, especially in those with higher baseline tHcy.
- Folic acid treatment normalizes NOS-dependence of vascular tone in the metabolic syndrome
PubMed ID: 20864946
Randomized folic acid (5 mg) in metabolic syndrome improved NO-dependence and oxidative-stress marker—physiologic vascular benefit.
- Effect of homocysteine-lowering B vitamin treatment on angiographic progression of coronary artery disease: a Western Norway B Vitamin Intervention Trial (WENBIT) substudy
PubMed ID: 20494665
Folic acid+B12 lowered homocysteine substantially in patients with coronary disease—clear biochemical effect despite no clinical angiographic benefit.
- Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
PubMed ID: 21780182
B‑vitamin supplementation (including folic acid) reduced plasma homocysteine ~30% — strong RCT evidence of homocysteine lowering.
- Coronary blood flow in patients with stable coronary artery disease treated long term with folic acid and vitamin B12
PubMed ID: 21389855
RCT (folic acid + B12) increased basal and maximal coronary microvascular blood flow — direct vascular 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
Dose/genotype trial showed that homocysteine response to folic acid depends on MTHFR genotype and dose.
- Effect of folic acid supplementation on biochemical indices in overweight and obese men with type 2 diabetes
PubMed ID: 21802161
Five mg/day folic acid in T2D patients lowered homocysteine by ~21% (randomized trial).
- Effect of folic acid supplementation on homocysteine, serum total antioxidant capacity, and malondialdehyde in patients with type 2 diabetes mellitus
PubMed ID: 21896879
High‑dose folic acid (5 mg/day) lowered homocysteine significantly (~20%) in T2D men over 8 weeks.
- Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial
PubMed ID: 21482964
High‑dose folate‑based multivitamin significantly reduced total homocysteine in kidney transplant recipients.
- Effect of 3 y of folic acid supplementation on the progression of carotid intima-media thickness and carotid arterial stiffness in older adults
PubMed ID: 21430116
800 μg folic acid produced a ~26% reduction in plasma homocysteine over 3 years.
- No effect of folic acid supplementation on global DNA methylation in men and women with moderately elevated homocysteine
PubMed ID: 21966393
Three‑year 800 µg folic acid trial raised folate and lowered plasma total homocysteine by ~21.6% (clear biomarker effect).
- Influence of diabetes on homocysteine-lowering therapy in chronic hemodialysis patients
PubMed ID: 21439275
Folate‑based therapy produced large, significant reductions in total homocysteine in non‑diabetic hemodialysis patients.
- Long-term effect of low-dose folic acid intake: potential effect of mandatory fortification on the prevention of neural tube defects
PubMed ID: 21593499
Low‑dose folic acid steadily raises RBC folate (clinical precursor to homocysteine lowering); modelling suggests eventual equivalence to 400 µg/day with time.
- Effect of different doses of folic acid on serum homocysteine level in patients on hemodialysis
PubMed ID: 21368386
Oral folic acid at multiple doses significantly lowered homocysteine in hemodialysis patients (consistent and robust effect).
- 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 randomized B‑vitamin trial produced consistent homocysteine lowering alongside folate increases.
- 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
B‑vitamin supplementation reduced homocysteine (implied) and showed subgroup MRI benefits; homocysteine lowering reported though not quantified in abstract.
- 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 intervention raised folate and lowered homocysteine in older men (short RCT).
- MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults
PubMed ID: 22230384
Randomized double‑blind trial showing higher folic acid (0.8 mg) lowers homocysteine more than 0.4 mg, with pronounced genotype (MTHFR TT) effects.
- The effects of folic acid on markers of endothelial function in patients with type 1 diabetes mellitus
PubMed ID: 22482335
5 mg folic acid improved endothelial dysfunction markers and reduced microalbuminuria—direct vascular benefit.
- Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation
PubMed ID: 22926161
Randomized B‑vitamin supplementation including folic acid significantly lowered homocysteine and improved migraine outcomes.
- Effects of mixed dietary supplements on total plasma homocysteine concentrations (tHcy): a randomized, double-blind, placebo-controlled trial
PubMed ID: 23591663
Mixed B‑vitamin supplement containing folic acid reduced mean plasma total homocysteine in older hospitalized patients.
- 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
Continuing 400 μg/day folic acid during pregnancy prevented the expected late‑pregnancy rise in plasma homocysteine.
- 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
Randomized crossover trial: 400 µg/day folic acid raised serum/RBC folate and lowered homocysteine in adults — direct, high‑quality evidence.
- An encapsulated juice powder concentrate improves markers of pulmonary function and cardiovascular risk factors in heavy smokers
PubMed ID: 24015696
Multinutrient concentrate containing folate reduced total homocysteine significantly in heavy smokers.
- Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism
PubMed ID: 23740686
500 µg/day folic acid lowered plasma homocysteine but did not correct intracellular PBMC homocysteine—plasma effect clear, intracellular nuance noted.
- Effect of folic acid supplementation on levels of circulating Monocyte Chemoattractant Protein-1 and the presence of intravascular ultrasound derived virtual histology thin-cap fibroatheromas in patients with stable angina pectoris
PubMed ID: 23936148
Folate+B12 supplementation raised serum folate and reduced total homocysteine substantially in CAD patients (biochemical effect confirmed).
- Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia
PubMed ID: 23698160
Folate‑rich diet or low‑dose folic acid/5‑MTHF lowered homocysteine ~20% in adults with hyperhomocysteinemia (randomized comparison).
- 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
5 mg/day folic acid for 8 weeks in PCOS significantly lowered homocysteine vs 1 mg and placebo.
- 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 regimen including folate raised HDL and modestly lowered predicted 10‑yr CV risk in older adults.
- 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
Diet+probiotic raised folate and reduced homocysteine, especially in participants with low‑grade inflammation.
- Metabolic response to folate supplementation in overweight women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial
PubMed ID: 24828019
In obese women with PCOS, 5 mg/day folate significantly reduced homocysteine (and improved metabolic markers).
- Results of 2-year vitamin B treatment on cognitive performance: secondary data from an RCT
PubMed ID: 25391305
Two years of folic acid+B12 substantially reduced homocysteine in older adults (clear biochemical effect).
- Effect of folic acid supplementation on plasma homocysteine in obese children: a randomized, double-blind, placebo-controlled trial
PubMed ID: 25391194
Randomized trial in obese children: 5 mg daily folic acid significantly lowered plasma homocysteine versus placebo.
- Influence of dialysis techniques and alternate vitamin supplementation on homocysteine levels in patients with known MTHFR genotypes
PubMed ID: 24652221
Dialysis patients: alternating folic acid/B12 therapy reduced plasma homocysteine while on therapy (clear biochemical effect).
- 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: folic acid (0.8 mg) added to enalapril reduced first stroke and ischemic stroke risk significantly (direct CVD outcome).
- 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 significantly lowered plasma homocysteine in healthy volunteers (direct biomarker evidence).
- Methyltetrahydrofolate vs Folic Acid Supplementation in Idiopathic Recurrent Miscarriage with Respect to Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms: A Randomized Controlled Trial
PubMed ID: 26630680
5‑MTHF and folic acid both lowered plasma total homocysteine in women with recurrent miscarriage (direct effect).
- The C677T MTHFR genotypes influence the efficacy of B9 and B12 vitamins supplementation to lowering plasma total homocysteine in hemodialysis
PubMed ID: 26559681
Hemodialysis patients: folic acid (10 mg/d) and/or B12 supplementation lowered tHcy with genotype-dependent effects (clear intervention effect).
- Effects of metformin plus gliclazide versus metformin plus glimepiride on cardiovascular risk factors in patients with type 2 diabetes mellitus
PubMed ID: 26408873
T2D patients: treatment combination raised folate and lowered homocysteine (indirect evidence of folate-related homocysteine improvements).
- 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
Large RCT: two years of folic acid+B12 clearly lowered plasma homocysteine (−3.6 μmol/L).
- Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women
PubMed ID: 25573400
High‑dose folic acid and B vitamins lowered homocysteine though depression outcomes were unchanged.
- Effects of Two-Year Vitamin B(12) and Folic Acid Supplementation on Depressive Symptoms and Quality of Life in Older Adults with Elevated Homocysteine Concentrations: Additional Results from the B-PROOF Study, an RCT
PubMed ID: 27886078
Two-year B12+folic acid markedly lowered plasma homocysteine (~−4.4 μmol/L) vs placebo — strong evidence folate lowers Hcy when combined with B12.
- The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial
PubMed ID: 27166794
Pregnancy RCT: 5 mg folic acid lowered maternal homocysteine more than 0.5 mg — dose-response evidence for Hcy lowering.
- Folic acid supplementation reduces plasma homocysteine in postmenopausal women
PubMed ID: 26758937
Randomized trial in postmenopausal women: folic acid supplementation significantly reduced plasma homocysteine (~−21.8%) — direct strong evidence.
- The Effects of Folate Supplementation on Carotid Intima-Media Thickness and Metabolic Status in Patients with Metabolic Syndrome
PubMed ID: 27450552
Randomized trial in metabolic-syndrome patients: 5 mg/day folate improved carotid intima-media thickness and metabolic markers — direct vascular benefit.
- Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients
PubMed ID: 27729579
Large RCT: 0.8 mg folic acid added to enalapril reduced first-stroke incidence (major cardiovascular endpoint) — strong clinical CVD benefit.
- Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients
PubMed ID: 27834686
Large trial analysis: higher homocysteine attenuated BP response to ACE inhibitor — shows clinical relevance of Hcy (folate-related) and supports targeting Hcy.
- Efficacy of Folic Acid Therapy on the Progression of Chronic Kidney Disease: The Renal Substudy of the China Stroke Primary Prevention Trial
PubMed ID: 27548766
Large RCT adding 0.8 mg folic acid showed renal benefits; folate likely lowered homocysteine which may mediate some renal/vascular effects.
- 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
Pregnancy RCT showed both low and high folic acid doses reduced plasma homocysteine and markers of protein oxidation.
- Homocysteine and Stroke Risk: Modifying Effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention
PubMed ID: 28360116
CSPPT RCT directly demonstrated folic acid lowered homocysteine and mediated stroke risk reduction in subgroups—strong evidence.
- Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
PubMed ID: 29255930
24‑month folic acid supplementation in MCI significantly decreased homocysteine and SAH while increasing SAM and SAM/SAH ratio.
- 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 (with folate/B12) increased serum folate and prevented homocysteine rises in elderly with low B12.
- Effects of folic acid combined with vitamin B12 on DVT in patients with homocysteine cerebral infarction
PubMed ID: 28617530
Randomized folic acid+B12 in hyperhomocysteinemic stroke patients produced marked Hcy reductions and large clinical benefit (reduced DVT recurrence).
- Association between percent decline in serum total homocysteine and risk of first stroke
PubMed ID: 29030456
Observational/trial data show greater tHcy reductions over ~4.5 years were associated with modestly lower first-stroke risk.
- B-Vitamin Therapy for Kidney Transplant Recipients Lowers Homocysteine and Improves Selective Cognitive Outcomes in the Randomized FAVORIT Ancillary Cognitive Trial
PubMed ID: 29182708
High‑dose B‑vitamin therapy including folic acid produced substantial tHcy lowering (mean −6.0 µmol/L vs −1.5 µmol/L).
- 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 folate produced larger increases in RBC/serum folate and modest tHcy decreases vs 400 µg/day, supporting homocysteine control.
- Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces serum homocysteine concentrations in older adults
PubMed ID: 28460586
Randomized comparison: folic acid and 5‑MTHF both lowered homocysteine similarly over 4 weeks in older adults.
- Lactating Canadian Women Consuming 1000 µg Folic Acid Daily Have High Circulating Serum Folic Acid Above a Threshold Concentration of Serum Total Folate
PubMed ID: 29901753
High‑dose folic acid in lactating women produced very high total folate and rising unmetabolized folic acid; shows strong biochemical effect on folate pools relevant to tHcy metabolism.
- Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke
PubMed ID: 29747834
Large RCT: folic acid (0.8 mg) greatly reduced first-stroke risk in a defined high‑risk subgroup (low platelets + high tHcy).
- Efficacy of Folic Acid and Vitamin B(12) Replacement Therapies in the Reduction of Adverse Effects of Isotretinoin: A Randomized Controlled Trial
PubMed ID: 30207526
Folic acid + B12 during isotretinoin prevented folate decline and significantly decreased plasma homocysteine over 2 months.
- Effect of Combined Treatment With Folic Acid, Vitamin B(6), and Vitamin B(12) on Plasma Biomarkers of Inflammation and Endothelial Dysfunction in Women
PubMed ID: 29776960
Long‑term B‑vitamin treatment (folic acid+B6+B12) substantially lowered homocysteine (~−18.3%) in high‑risk women.
- Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer
PubMed ID: 29696360
Folic acid + B12 markedly lowered homocysteine in patients (clear biochemical effect).
- Urinary excretion of homocysteine thiolactone and the risk of acute myocardial infarction in coronary artery disease patients: the WENBIT trial
PubMed ID: 30193001
Folic acid/B-vitamin supplementation lowered total homocysteine in coronary disease patients (though not the specific Hcy-thiolactone metabolite).
- The Effects of Folic Acid Supplementation on Recurrence and Metabolic Status in Endometrial Hyperplasia: A Randomized, Double-Blind, Placebo-Controlled Trial
PubMed ID: 30415553
Folic acid improved triglycerides and insulin resistance in women with endometrial hyperplasia, metabolic changes relevant to cardiovascular risk.
- 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
Randomized folic acid supplementation reduced arterial stiffness (ba-PWV), a direct vascular/heart-health measure, with genotype-modified effect.
- MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment
PubMed ID: 29371246
Large trial analysis showed folic acid lowers total homocysteine with clear MTHFR genotype interactions; robust evidence.
- Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men
PubMed ID: 29273594
Large RCT showed folic acid added to enalapril reduced first-stroke risk in prespecified subgroups, a major cardiovascular outcome.
- 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
Folate+B12 raised folate and lowered homocysteine in older adults with MCI, correlating with cognitive and inflammatory changes.
- A randomized placebo-controlled trial of using B vitamins to prevent cognitive decline in older mild cognitive impairment patients
PubMed ID: 31787369
B12+folic acid produced a substantial reduction in homocysteine in older individuals, though cognitive decline was not prevented long-term.
- A Pilot Randomized Controlled Double-Blind Trial of High- Versus Low-Dose Weekly Folic Acid in People With Rheumatoid Arthritis Receiving Methotrexate
PubMed ID: 30001258
Higher weekly folic acid substantially increased RBC folate (biomarker closely linked to homocysteine metabolism), though clinical outcomes unchanged.
- The Vitamins in Psychosis Study: A Randomized, Double-Blind, Placebo-Controlled Trial of the Effects of Vitamins B(12), B(6), and Folic Acid on Symptoms and Neurocognition in First-Episode Psychosis
PubMed ID: 30771856
High-dose B-vitamin regimen (including folic acid) significantly reduced total homocysteine in first-episode psychosis patients.
- Effect of folic acid supplementation on nerve conduction velocity in diabetic polyneuropathy patients
PubMed ID: 30730785
RCT in diabetic polyneuropathy: 1 mg/day folic acid raised folate and lowered homocysteine with concomitant nerve conduction improvements.
- Estimated Stroke-Free Survival of Folic Acid Therapy for Hypertensive Adults: Projection Based on the CSPPT
PubMed ID: 31865785
Modeling based on large RCT (CSPPT) projects a clear modest gain in stroke‑free survival with enalapril+folic acid vs enalapril alone.
- Influence of Dietary Supplementation for Hyperhomocysteinemia Treatments
PubMed ID: 32630031
Randomized controlled trial: folate‑containing regimens produced substantial (≈49–57%) reductions in plasma homocysteine — direct strong evidence.
- [Bioavailability of natural versus synthetic B vitamins and their effects on metabolic processes]
PubMed ID: 32189314
Crossover B‑vitamin complex substantially increased folate and reduced homocysteine in a pilot study — good biochemical evidence.
- Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial
PubMed ID: 33066869
Small trial in T2D: folic acid ± B12 lowered homocysteine while improving glycemic markers — direct Hcy reduction.
- Interaction of serum vitamin B(12) and folate with MTHFR genotypes on risk of ischemic stroke
PubMed ID: 31932513
Large RCT: folic acid (0.8 mg) lowered first ischemic stroke risk — direct cardiovascular benefit.
- Interaction of neutrophil counts and folic acid treatment on new-onset proteinuria in hypertensive patients
PubMed ID: 33308359
Folic acid added to enalapril halved new-onset proteinuria in a high‑neutrophil subgroup — kidney marker related to cardio‑renal risk.
- 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
Folate+B12 in AD lowered plasma homocysteine significantly alongside cognitive improvements.
- Effects of vitamin B12, folate, and entacapone on homocysteine levels in levodopa-treated Parkinson's disease patients: A randomized controlled study
PubMed ID: 33992189
In levodopa‑treated Parkinson's, B12+folate significantly lowered elevated homocysteine — direct clinical evidence.
- Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment
PubMed ID: 33935094
B‑vitamin RCT including folic acid robustly lowered plasma tHcy and linked this to preserved cognition.
- A Randomized Trial of Short-term Treatment with Folic Acid to Reduce the Oxidative Stress of Patients with Chronic Kidney Disease
PubMed ID: 34895119
High‑dose folic acid normalized homocysteine in CKD patients over 3 months.
- A pilot study of thiamin and folic acid in hemodialysis patients with cognitive impairment
PubMed ID: 33913373
Folate + thiamin markedly lowered homocysteine in hemodialysis patients (combination therapy).
- Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension
PubMed ID: 36280851
Large RCT: adding folic acid (0.8 mg) to enalapril reduced first-stroke risk by ~21% — strong clinical cardiovascular benefit.
- A 2-Year Randomized Controlled Trial With Low-Dose B-Vitamin Supplementation Shows Benefits on Bone Mineral Density in Adults With Lower B12 Status
PubMed ID: 36128889
Two‑year low‑dose B‑vitamin supplementation raised folate and lowered homocysteine (but bone outcomes were null).
- 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
5 mg folate significantly decreased homocysteine in overweight/obese women with CIN2/3.
- 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
Randomized, genotype‑tailored folic acid dosing produced large, clinically meaningful reductions in plasma homocysteine.
- Homocysteine thiolactone contributes to the prognostic value of fibrin clot structure/function in coronary artery disease
PubMed ID: 36301961
Large CAD patient study: folic‑acid/B‑vitamin supplementation clearly lowered tHcy though clot properties were unchanged.
- B Vitamin Supplementation Slows Cognitive Decline in Mild Cognitive Impairment Patients with Frontal Lobe Atrophy
PubMed ID: 36057827
B12+folic acid in MCI reliably lowered homocysteine; subgroup cognitive effects noted.
- Folic acid effect on homocysteine, sortilin levels and glycemic control in type 2 diabetes mellitus patients
PubMed ID: 35732620
Double‑blind trial of 5 mg/day folic acid in T2DM significantly lowered homocysteine by ~28%.
- 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
Double‑blind randomized folic acid added to amlodipine produced marked tHcy reductions (0.4/0.8 mg arms) — very strong direct evidence.
- 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
Randomized early‑childhood folic acid/B12 supplementation produced lower homocysteine measured 6–7 years later — durable homocysteine effect.
- A micronutrient supplement modulates homocysteine levels regardless of vitamin B biostatus in elderly subjects
PubMed ID: 36715360
12‑week randomized supplement with 400 µg folic acid significantly reduced homocysteine in elderly participants—clear clinical biomarker effect.
- Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)
PubMed ID: 38478042
Large randomized dose–response trial showing folic acid dose‑dependently and robustly lowers total homocysteine, with stronger effects in MTHFR TT genotype.
- Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children
PubMed ID: 38728816
Folic acid+B12 supplementation altered arsenic methylation (one‑carbon metabolism), consistent with effects on homocysteine‑related pathways (measured changes to methylation indices).
- Folate and vitamin B12 supplementation in patients with schizophrenia and low serum folate level: A 24-week randomized, double-blind, placebo-controlled study
PubMed ID: 39645464
Folate+B12 supplementation corrected biochemical folate deficiency and lowered homocysteine in schizophrenia patients—direct homocysteine lowering evidence though no clinical symptom change.
- Folic acid supplementation improves cognitive function in participants with cerebral small vascular disease-related cognitive impairment: a randomized controlled trial
PubMed ID: 40945966
Folic acid substantially raised serum folate and lowered homocysteine (~−7.49 µmol/L) in CSVD patients — strong direct evidence.
- 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
Daily folate lowered total homocysteine by ~19% in ESRD patients; B12 added further benefit — clear homocysteine-lowering effect.
- Untitled
PubMed ID: 22811376
Multivitamin containing folic acid produced a modest but significant homocysteine reduction in adults.
- Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation
PubMed ID: 8882400
Large RCT of periconceptional multivitamin with 0.8 mg folic acid reported significant reduction in sporadic cardiovascular malformations—direct relevance to congenital cardiac outcomes.
- Niacin treatment increases plasma homocyst(e)ine levels
PubMed ID: 10577438
Study documents niacin-induced increases in plasma homocysteine; this is mechanistically relevant because folic acid can lower homocysteine—indirect evidence linking folate to homocysteine control.
- The VITATOPS (Vitamins to Prevent Stroke) Trial: rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke
PubMed ID: 11867886
Trial was explicitly designed to test folic acid-containing vitamins (including folic acid) to lower total homocysteine in secondary stroke prevention.
- Study of the effect of a liquid nutrition supplement on the nutritional status of psycho-geriatric nursing home patients
PubMed ID: 11960300
Multi‑nutrient supplement (included folate) produced a significant decrease in plasma homocysteine in elderly psychiatric patients — consistent with folate lowering homocysteine, though the formulation was combined.
- Homocysteine in patients with rheumatoid arthritis in relation to inflammation and B-vitamin treatment
PubMed ID: 14626626
Randomized double‑blind B‑vitamin regimen including folic acid produced a clear decrease in homocysteine versus placebo — direct evidence for folic acid's role in homocysteine lowering.
- Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins
PubMed ID: 15780109
Multivitamin containing 1 mg folic acid substantially reduced the prevalence of hyperhomocysteinemia in CKD patients—strong biochemical evidence of folate 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
Six weeks of B‑complex (including 400 µg folic acid) significantly lowered total serum homocysteine in older adults — direct evidence for homocysteine lowering.
- VITATOPS, the VITAmins TO prevent stroke trial: rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke (NCT00097669) (ISRCTN74743444)
PubMed ID: 18705976
VITATOPS was explicitly designed to test folic acid+B‑vitamins for lowering total homocysteine and reducing recurrent vascular events — directly relevant to homocysteine management (design paper).
- Association of carotid intima-medial thickness and indices of arterial stiffness with cardiovascular disease outcomes in CKD
PubMed ID: 17900462
Analysis drawn from cohort enrolled in an atherosclerosis/folic-acid supplementation trial and links arterial indices to CVD events — contextually relevant to folate/vascular outcomes.
- Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients
PubMed ID: 18206891
Multi‑B vitamin therapy including folic acid produced a clear reduction in homocysteine levels in metformin‑treated diabetics.
- 5-methyltetrahydrofolate administration is associated with prolonged survival and reduced inflammation in ESRD patients
PubMed ID: 18587236
IV 5‑MTHF vs oral folic acid in hemodialysis patients produced longer survival and reduced inflammation, outcomes relevant to cardiovascular risk/mortality.
- Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study
PubMed ID: 19628319
High‑dose folic acid with B6/B12 reduced plasma total homocysteine by ~25.8% in a large randomized trial — direct, strong evidence in this dataset.
- The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability
PubMed ID: 19384265
Daily folic acid–containing B‑vitamin therapy produced a ~39% homocysteine reduction in migraine patients — a clear effect on homocysteine.
- Pharmacological dose of vitamin B12 is as effective as low-dose folinic acid in correcting hyperhomocysteinemia of hemodialysis patients
PubMed ID: 19462276
Folinic acid modestly reduced plasma tHcy in hemodialysis patients; vitamin B12 or combined therapy gave larger reductions.
- 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
Frequent post‑dialysis B‑vitamin injections (including folic acid) lowered homocysteine though without clinical CV benefit.
- 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 randomized trial: folic acid+B6+B12 regimen significantly lowered total homocysteine (tHcy).
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
Direct evidence: high-dose folic acid+B12+B6 lowered plasma total homocysteine by ~22.5% and raised folate markedly in older adults.
- B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial
PubMed ID: 20976769
Long-term folic acid with B6/B12 lowered homocysteine levels and reduced risk of major depression in stroke survivors — homocysteine decline was part of the intervention effect.
- Effects of exercise and B vitamins on homocysteine and glutathione in Parkinson's disease: a randomized trial
PubMed ID: 22261439
Small randomized trial showed B‑vitamin supplementation (B6, B12, folic acid) lowered homocysteine — direct biochemical evidence.
- Kidney function and risk of cardiovascular disease and mortality in kidney transplant recipients: the FAVORIT trial
PubMed ID: 22594581
Trial explicitly tested high‑dose folic acid (part of homocysteine‑lowering regimen) in transplant recipients; it targeted homocysteine though clinical CVD outcomes were unchanged.
- Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study
PubMed ID: 22775763
Baseline report from a homocysteine‑lowering vitamin trial (FAVORIT) documents cohort entry with elevated homocysteine and trial intent to lower it using B‑vitamins including folic acid (indirect evidence).
- 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 randomized trial: B‑vitamin regimen including folic acid produced a clear and statistically significant lowering of plasma total homocysteine compared with placebo.
- Short-term folinic acid supplementation improves vascular reactivity in HIV-infected individuals: a randomized trial
PubMed ID: 23660169
Randomized trial: folinic acid (5 mg/day) improved endothelium‑dependent reactive hyperemia versus placebo over 4 weeks, indicating a measurable vascular (cardiovascular) benefit.
- The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial
PubMed ID: 24004645
Large randomized trial of folic acid/B6/B12 in patients with recent stroke/TIA showed a modest but clear lowering of plasma total homocysteine (~3.8 μmol/L).
- Folate administration decreases oxidative status and blood pressure in postmenopausal women
PubMed ID: 24906471
High‑dose 5‑MTHF RCT significantly lowered homocysteine vs placebo over 3 weeks — direct, strong evidence.
- 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
Clear pilot finding: supplementation (natural B‑complex) produced a meaningful decrease in total homocysteine in this small crossover study.
- Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women
PubMed ID: 31845191
Activated 1‑carbon micronutrient supplement containing 5‑methylfolate produced a large (~32%) drop in fasting homocysteine — direct and strong evidence.
- Sex-Related Differences in Impact on Safety of Pharmacogenetic Profile for Colon Cancer Patients Treated with FOLFOX-4 or XELOX Adjuvant Chemotherapy
PubMed ID: 31395900
MTHFR and other one‑carbon genetic findings affect homocysteine metabolism and folate handling — mechanistic relevance.
- Association between serum 5-methyltetrahydrofolate and homocysteine in Chinese hypertensive participants with different MTHFR C677T polymorphisms: a cross-sectional study
PubMed ID: 35562805
Large cross‑sectional study shows a strong, dose‑dependent inverse association between active folate (5‑MeTHF) and homocysteine, with genotype interactions — direct, high‑quality evidence.
- 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
Pooled B‑vitamin RCTs (including folic acid) reduced total homocysteine and produced cognitive/atrophy benefits in certain genotypes — supports folate's role in homocysteine lowering.
- 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 trial of methylfolate+B6+B12 produced large, significant homocysteine reductions (robust direct evidence).
- Relationships of B12 and Homocysteine with Outcomes in the SURE-PD, SURE-PD3, and STEADY-PDIII Trials
PubMed ID: 39240650
Analyses across PD trials showed multivitamin users (often containing folate) had substantially lower tHcy and mitigated levodopa‑related tHcy rises.
- Efficacy of L-methylfolate and methylcobalamin in treating resistant hypertension associated with elevated serum homocysteine in hemodialysis patients
PubMed ID: 41580678
L‑methylfolate (with methylcobalamin) significantly lowered serum homocysteine in a randomized trial.
- The effects of multivitamin supplementation on diurnal cortisol secretion and perceived stress
PubMed ID: 24284609
16‑week multivitamin (including folic acid) reduced homocysteine by ~1.6 μmol/L vs placebo.
Pregnancy support (178)
- Inositol for the prevention of neural tube defects: a pilot randomised controlled trial
PubMed ID: 26847388
Pilot study in high‑risk women where all received high‑dose folic acid (5 mg); no NTDs occurred in the inositol+FA group—direct folate-related pregnancy/NTD context.
- Long-Chain Polyunsaturated Fatty Acids, Homocysteine at Birth and Fatty Acid Desaturase Gene Cluster Polymorphisms are Associated with Children's Processing Speed up to Age 9 Years
PubMed ID: 33396458
Maternal folate status, lower tHcy and AA/DHA balance during pregnancy were associated with better child processing speed—strong prenatal folate relevance.
- 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
Multimicronutrient supplementation including folic acid increased birth weight and reduced low birth weight incidence — relevant pregnancy benefit.
- Multivitamin supplementation of HIV-positive women during pregnancy reduces hypertension
PubMed ID: 15987864
Maternal multivitamin including folic acid reduced risk of hypertension during pregnancy by ~38% (multi‑nutrient trial).
- 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
Food‑based folate intervention in Indian women increased birth weight in those starting ≥3 months preconception (per‑protocol effect).
- 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
Randomized preconception-to-pregnancy trial: folic acid 400 µg/day markedly reduced marginal folate prevalence and lowered homocysteine—strong pregnancy evidence.
- l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women
PubMed ID: 29878267
Because l‑5‑MTHF produced superior increases in blood folate, it is relevant to pregnancy folate requirements though no pregnancy outcomes were reported.
- Multicentric study of efficacy of periconceptional folic acid containing vitamin supplementation in prevention of open neural tube defects from India
PubMed ID: 11247198
Periconceptional folic acid (4 mg) substantially reduced recurrence of open neural tube defects (~60% relative reduction) — direct, high‑relevance evidence for fetal development.
- Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women
PubMed ID: 17302515
Folic‑acid fortified water in pregnant women produced marked increases in serum/erythrocyte folate and lowered homocysteine—direct, pregnancy‑specific folate benefit.
- Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study
PubMed ID: 22067790
Levomefolate co‑administration with an oral contraceptive strongly increased RBC/plasma folate — relevant for women planning pregnancy (improves folate stores).
- 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
Food fortification with folic acid or L‑5‑MTHF raised plasma and RBC folate — improved maternal folate status supports fetal neural development (biomarker evidence).
- 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
Nutrition‑integrated MNCH markedly increased IFA consumption (iron+folic acid), improving a proven pregnancy supplement uptake metric linked to healthy pregnancy.
- Maternal nutrition intervention and maternal complications in 4 districts of Bangladesh: A nested cross-sectional study
PubMed ID: 31584939
Integrated maternal program including iron/folic acid linked to fewer maternal complications (retained placenta, PPH) — supports pregnancy health (multicomponent but folate is central).
- 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
Program-level increases in receipt/consumption of IFA supplements — direct support for healthier pregnancy through better folate delivery.
- 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
Randomized folate dosing (400/800 µg) produced large increases in active folate — biomarker evidence highly relevant to fetal folate sufficiency.
- 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 increased pregnant women's supplement use including folic acid — practical support for healthier pregnancy.
- Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation
PubMed ID: 1307234
Large randomized trial: periconceptional multivitamin containing 0.8 mg folic acid strongly prevented first‑occurrence neural‑tube defects — direct, high‑quality evidence that folate supports fetal neural development.
- [Prevention of the first occurrence of anencephaly and spina bifida with periconceptional multivitamin supplementation (conclusion)]
PubMed ID: 7970646
Large randomized trial: periconceptional multivitamin (0.8 mg folic acid) prevented neural‑tube defects — strong direct evidence for folic acid in fetal development.
- Prophylactic iron supplementation in pregnant women in Norway
PubMed ID: 11787984
Supplement (low‑iron + folate) preserved maternal folate during pregnancy vs high‑dose iron alone — supports maternal folate status important for fetal development.
- Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal
PubMed ID: 16600929
Antenatal multiple micronutrients including folic acid raised serum folate and lowered deficiency in pregnant women — biochemical support for fetal folate supply (no direct clinical endpoints).
- 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
Improved embryo quality when folic acid was included as background and additional micronutrients were tested; supports importance of folate in early reproduction/pregnancy context.
- Inter-pregnancy folate and iron status of women in an inner-city population
PubMed ID: 11432768
Postpartum women remained folate‑deficient without supplements; supplementation raised serum and erythrocyte folate — relevant to perinatal/fetal folate status.
- The effect of docosahexaenoic acid and folic acid supplementation on placental apoptosis and proliferation
PubMed ID: 16870008
Increased placental PCNA with 5‑MTHF + DHA suggests a positive effect on placental biology during pregnancy.
- 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
Methylfolate (5‑MTHF) with fish oil modestly increased maternal DHA and cord DHA was driven by fish oil; folate may augment DHA status relevant to fetal development.
- Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group
PubMed ID: 1677062
Strong RCT evidence that periconceptional folic acid prevents recurrence of NTDs — core pregnancy‑health benefit.
- A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group
PubMed ID: 1489222
Underpowered trial but observed zero recurrences in folic acid arms — supportive for pregnancy benefit though not definitive alone.
- Postpartum folic acid supplementation of adolescents: impact on maternal folate and zinc status and milk composition
PubMed ID: 7625346
Postpartum adolescent mothers: 300 µg/day folic acid prevented RBC folate decline—supports maternal folate status maintenance.
- Blood folic acid and vitamin B12 in relation to neural tube defects
PubMed ID: 8605127
Case‑control: pregnancies affected by neural tube defects had markedly lower serum and RBC folate — strong direct link between folate status and fetal neural development.
- Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects
PubMed ID: 8596381
400 µg/day folic acid (supplement or fortified food) increased RBC folate over 3 months—supports achieving folate status protective for fetal development.
- Minimum effective dose of folic acid for food fortification to prevent neural-tube defects
PubMed ID: 9400511
Demonstrated folic acid doses that achieve red‑cell folate protective of neural-tube defects—core pregnancy benefit.
- The influence of folic acid supplement on the outcome of pregnancies in the county of Funen in Denmark. Part I
PubMed ID: 10597955
Large program: preconception/early folic acid modestly raised birth weight and reduced preterm birth and SGA—direct fetal outcome benefits.
- 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 reduced anemia and improved hematology at term (supports maternal health during pregnancy).
- Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone)
PubMed ID: 11355560
Iron‑folate preserved maternal hemoglobin during pregnancy (clinically meaningful protective effect).
- The increasing knowledge of the role of periconceptional folate in Victorian women of child-bearing age: follow-up of a randomised community intervention trial
PubMed ID: 11688615
Educational intervention raised women's awareness that folate prevents neural tube defects, supporting pregnancy health decisions and uptake.
- 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 [6S]-5‑MTHF and folic acid both raised plasma and RBC folate in women of childbearing age—key biomarkers for fetal neural tube prevention.
- 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
In pregnant women with iron‑deficiency anemia, adding folate improved hemoglobin recovery, a clinically meaningful pregnancy benefit.
- Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women
PubMed ID: 12495257
Iron+folate raised haemoglobin in pregnant women; supports maternal health during pregnancy.
- Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age
PubMed ID: 12391385
Improves maternal folate stores and lowers homocysteine in women of childbearing age — relevant to pregnancy.
- Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal
PubMed ID: 14668283
Maternal folic acid supplementation in Nepal reduced early mortality among preterm infants (direct maternal/infant benefit).
- [Changes in plasma zinc and folic acid concentrations in pregnant adolescents submitted to different supplementation regimens]
PubMed ID: 12700794
Pregnant adolescents given folic acid had improved folate status; folate status is directly relevant to fetal development.
- Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial
PubMed ID: 12637400
Large community trial: folic acid combined with iron or multiple micronutrients modestly increased newborn weight and reduced low birthweight risk (effect seen only with combined regimens).
- Exclusive breast-feeding for 6 months, with iron supplementation, maintains adequate micronutrient status among term, low-birthweight, breast-fed infants in Honduras
PubMed ID: 15113951
Exclusive breastfeeding with iron supplementation maintained adequate infant folate — supports adequate folate during critical early development.
- Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe
PubMed ID: 15213046
Prenatal multimicronutrient supplementation (with iron/folic acid standard) associated with modestly larger infants—supports pregnancy outcomes though attribution not folate‑specific.
- Intermittent iron supplementation regimens are able to maintain safe maternal hemoglobin concentrations during pregnancy in Venezuela
PubMed ID: 15113952
Intermittent iron regimens including folic acid sustained maternal hemoglobin in most women — supports maternal health in pregnancy.
- Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities
PubMed ID: 15523663
Periconceptional folic-acid containing multivitamin markedly decreased neural tube defects—core pregnancy benefit.
- Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women
PubMed ID: 14985695
Daily 400 µg folic acid raised RBC folate to levels associated with reduced NTD risk (directly relevant to fetal neural development).
- 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
Earlier initiation of prenatal iron+folic acid preserved maternal folate status—benefit for pregnancy health.
- Randomized trial of a physician-based intervention to increase the use of folic acid supplements among women
PubMed ID: 15846191
Physician intervention increased folic-acid supplement uptake among women—helps achieve periconceptional folate coverage.
- Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age
PubMed ID: 15927936
In women of childbearing age, folic acid‑fortified milk produced large RBC folate increases and lowered homocysteine—key for neural tube defect prevention.
- Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women
PubMed ID: 16740440
Daily iron+folic acid+B12 reduced maternal anemia compared with weekly dosing—clinically relevant pregnancy outcome (mixed risks due to hemoconcentration).
- Milk folate secretion is not impaired during iron deficiency in humans
PubMed ID: 16988136
Maternal folic acid supplementation improved maternal folate status and preserved breast‑milk folate—supports infant nutrient supply postpartum.
- 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
Direct pregnancy trial showing folic acid (with iron) is safe with antimalarial therapy and increases Hb slightly.
- A randomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy
PubMed ID: 17915799
Study in pregnant anemic women used folic acid (1.5 mg) with iron/B12 and achieved comparable Hb increases—supports pregnancy care.
- Community-level micronutrient fortification of a food supplement in India: a controlled trial in preschool children aged 36-66 mo
PubMed ID: 17413115
Community fortification including folic acid improved anemia in young children and supports maternal/child nutrition programs.
- Determinants of compliance with iron supplementation among pregnant women in Senegal
PubMed ID: 17764606
Improved adherence to iron+folic acid tablets among pregnant women increases effective supplementation during pregnancy.
- Computerized counseling for folate knowledge and use: a randomized controlled trial
PubMed ID: 19000845
Behavioral RCT that increased folic acid supplement uptake among women—practical support for pregnancy folate coverage.
- 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 folic acid dosing in pregnancy directly showed faster attainment of neural‑tube‑protective RBC/serum folate levels with 1 mg/day.
- Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial
PubMed ID: 18207017
MMN vs iron+folic acid trial reduced early infant mortality (maternal supplementation in pregnancy improved infant outcomes; folate included).
- Antenatal and postnatal iron supplementation and childhood mortality in rural Nepal: a prospective follow-up in a randomized, controlled community trial
PubMed ID: 19778983
Maternal iron–folic acid linked to a large reduction in child mortality through age 7 (supports benefit of prenatal folate-containing programs).
- Treatment response to standard of care for severe anemia in pregnant women and effect of multivitamins and enhanced anthelminthics
PubMed ID: 19176737
High-dose iron–folic acid raised hemoglobin in severely anemic pregnant women (improves maternal health during pregnancy).
- Antenatal micronutrient supplementation reduces metabolic syndrome in 6- to 8-year-old children in rural Nepal
PubMed ID: 19549749
Maternal folic acid supplementation associated with lower risk of child microalbuminuria and reduced metabolic syndrome risk at 6–8 years—strong antenatal effect.
- 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
Prenatal multimicronutrient supplementation including folate yielded small but significant improvements in infant mental development.
- Programmatic effects of a large-scale multiple-micronutrient supplementation trial in Indonesia: using community facilitators as intermediaries for behavior change
PubMed ID: 20496613
Large program including pregnancy multiple micronutrients (with folic acid) reduced early infant mortality at population level.
- A comparative evaluation of multiple micronutrient and iron-folic acid supplementation during pregnancy in Pakistan: impact on pregnancy outcomes
PubMed ID: 20120791
Multiple micronutrients (including folic acid) slightly increased birthweight vs iron‑folic acid alone in a large trial.
- Providing iron/folic acid tablets free of charge improves compliance in pregnant women in Senegal
PubMed ID: 19203773
Practical trial showed free iron+folic acid doubles adherence and halves anemia in pregnancy—important pregnancy health effect.
- Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural Nepal
PubMed ID: 19368922
Prenatal folic acid+iron reduced postpartum hemorrhage and puerperal sepsis in a large field trial—maternal benefit during/after pregnancy.
- Comparison study on the effect of prenatal administration of high dose and low dose folic acid
PubMed ID: 19139780
Higher folic acid dose reduced maternal homocysteine much more than low dose—relevant to pregnancy metabolic health.
- 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 rapidly raised RBC folate above the neural‑tube‑preventive threshold in healthy women—a direct and strong link to fetal neural development.
- 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 MMS including folate marginally reduced fetal loss vs iron–folate, suggesting a role in fetal outcomes (though mixed overall).
- Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal
PubMed ID: 21177506
Prenatal iron+folic acid improved later child cognitive outcomes, indicating benefit to fetal/early brain development.
- Impact of a stage-tailored, web-based intervention on folic acid-containing multivitamin use by college women
PubMed ID: 20594096
Intervention increased folic-acid multivitamin use in college women (preconception), supporting recommended folate intake to prevent pregnancy complications.
- 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
Multiple-micronutrient supplementation including folic acid improved maternal Hb/folate and reduced SGA in compliant pregnant women—direct pregnancy benefit.
- 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
Dose‑finding RCT demonstrated RBC folate increases and reduction in sub‑protective RBC folate prevalence, directly relevant to NTD prevention in pregnancy.
- Randomized controlled trial of 2 prenatal iron supplements: is there a dose-response relation with maternal hemoglobin?
PubMed ID: 21367950
In pregnant women, UNIMMAP (includes folate) and higher‑dose iron+folate raised hemoglobin in anemic women, a pregnancy health metric.
- 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 MMS (including folic acid) with earlier food support reduced infant mortality, a key pregnancy outcome, though multiple interventions were used.
- Maternal multiple micronutrient supplements and child cognition: a randomized trial in Indonesia
PubMed ID: 22908103
Maternal MMN improved some neurodevelopmental outcomes in offspring of undernourished/anemic mothers; folic acid was included in MMN.
- 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
Daily 1 mg folate raised erythrocyte folate (biomarker relevant to neural tube prevention and fetal folate stores).
- Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women
PubMed ID: 22932279
Supplementation raised maternal serum folate and breast‑milk folic acid—improves maternal–neonatal folate exposure in pregnancy/lactation.
- Prenatal micronutrient supplements cumulatively increase fetal growth
PubMed ID: 22298571
Randomized prenatal micronutrient supplementation (including folic acid) raised birth weight and reduced odds of SGA—strong trial evidence linking prenatal micronutrients to 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
Continuing 400 μg/day folic acid after 12 weeks increased maternal and cord folate and prevented homocysteine rise—directly improves fetal folate status.
- High dosage folic acid supplementation, oral cleft recurrence and fetal growth
PubMed ID: 23380913
Periconceptional folic acid (both 0.4 and 4 mg) associated with lower oral cleft recurrence vs historic rates — direct fetal developmental benefit.
- Introducing reproductive life plan-based information in contraceptive counselling: an RCT
PubMed ID: 23842564
Reproductive life‑plan counselling increased knowledge about folic acid and strengthened pregnancy‑planning intentions — supports uptake of preconception folate.
- Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil
PubMed ID: 23669628
High‑dose folic acid (4 mg) did not increase miscarriage vs 0.4 mg — reassuring safety data during pregnancy.
- The folate status of reproductive-aged women in a randomised trial of a folate-fortified oral contraceptive: dietary and blood assessments
PubMed ID: 23534865
Folate‑fortified oral contraceptive markedly increased blood folate in reproductive‑aged women — relevant to ensuring preconception folate sufficiency.
- Effect of iron deficiency anemia in pregnancy on child mental development in rural China
PubMed ID: 23400604
Prenatal iron/folate supplementation protected against the adverse effect of prenatal iron‑deficiency anemia on child mental development (folate included in antenatal regimen).
- 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 increased maternal and cord folate and was associated with modestly higher birth weight and length — direct folate‑related fetal benefit.
- 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+MMN (including folate) reduced child mortality and improved adherence patterns, indicating benefits of prenatal nutrition including folate.
- Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial
PubMed ID: 25442690
Antenatal MMN including folic acid raised birthweight modestly, indicating benefit to fetal growth though multiple nutrients contributed.
- 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‑comparison in pregnancy showed 5 mg folic acid raises RBC folate earlier and more consistently — relevant to dosing recommendations for pregnancy.
- 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 supplementation produced measurable long-term improvements in children's attention and brain activation (strong evidence for fetal brain development).
- Lipid-based nutrient supplement increases the birth size of infants of primiparous women in Ghana
PubMed ID: 25833980
Prenatal lipid‑based supplement including folic acid increased newborn size (birth weight/length/head circumference), though multi‑nutrient.
- 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 pregnancy food + MMS including folic acid substantially reduced infant mortality in a large RCT (combined intervention).
- A Prenatal Multiple Micronutrient Supplement Produces Higher Maternal Vitamin B-12 Concentrations and Similar Folate, Ferritin, and Zinc Concentrations as the Standard 60-mg Iron Plus 400-μg Folic Acid Supplement in Rural Bangladeshi Women
PubMed ID: 27798335
Large prenatal trial demonstrated that maternal folate concentrations rose with capsule intake — supports effectiveness of folate supplementation 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
Higher-dose folic acid (5 mg) during pregnancy lowered homocysteine, raised birthweight and decreased early abortions — direct pregnancy outcome benefits.
- 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
400 μg folic acid in pregnancy raised cord-blood total folate and 5‑MTHF substantially — direct biochemical evidence supporting fetal folate supply.
- 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
Double-blind RCT: fortified milk with 400 μg folic acid raised red-cell/plasma folate so most women reached levels linked to very low neural-tube-defect risk — very strong direct fetal-development relevance.
- 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
Randomized trial in pregnancy: folic acid (low and high dose) reduced homocysteine and protein oxidation markers, supportive of healthier pregnancy physiology.
- 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 iron+folic acid vs folic acid alone improved child linear growth and fine motor development at 2 years.
- Effects of Prenatal Micronutrient Supplementation on Spontaneous Preterm Birth: A Double-Blind Randomized Controlled Trial in China
PubMed ID: 28472219
Large RCT demonstrated that earlier initiation of folic acid‑containing supplements substantially lowered spontaneous preterm birth 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 folate rapidly produced protective RBC‑folate levels in women of childbearing age — direct evidence supporting pregnancy/neural‑tube prevention preparedness.
- Response of Red Blood Cell Folate to Supplementation in Nonpregnant Women is Predictable: A Proposal for Personalized Supplementation
PubMed ID: 29143484
Dose/time modeling of RBC folate (400 vs 800 µg) gives actionable guidance to reach pregnancy‑protective folate concentrations.
- Acceptability and Utilization of Three Nutritional Supplements during Pregnancy: Findings from a Longitudinal, Mixed-Methods Study in Niger
PubMed ID: 30103529
Real-world adherence/acceptability data for prenatal IFA (folic acid) showing moderate correct use—relevant to achieving pregnancy benefits.
- Effectiveness of a Pediatric Primary Care Intervention to Increase Maternal Folate Use: Results from a Cluster Randomized Controlled Trial
PubMed ID: 29246348
Intervention increased maternal daily folate/multivitamin use in a pragmatic cluster-RCT, improving prenatal folate exposure.
- 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
RCT showed maternal folic acid in late pregnancy produced gene-specific changes in newborn cord-blood DNA methylation (IGF2, BDNF, LINE-1), a mechanistic fetal-development effect.
- Folic Acid Supplementation throughout pregnancy: psychological developmental benefits for children
PubMed ID: 29469926
Maternal folic acid throughout pregnancy associated with improved child emotional/cognitive outcomes at 6–7 y in a small RCT.
- Cohort Profile: The Maternal and Infant Nutrition Interventions in Matlab (MINIMat) cohort in Bangladesh
PubMed ID: 29868907
Early food supplementation plus MMS (including folic acid) significantly reduced infant mortality in a large randomized trial, a key pregnancy outcome.
- 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
Randomized continuation of folic acid in pregnancy markedly raised maternal/cord folate and produced a small cognitive benefit in offspring—strong direct relevance to fetal development.
- Multi-Micronutrient Fortified Rice Improved Serum Zinc and Folate Concentrations of Cambodian School Children. A Double-Blinded Cluster-Randomized Controlled Trial
PubMed ID: 31756911
Fortified school meals raised serum folate and eliminated deficiency—population nutrition relevance to reproductive‑age women.
- A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57
PubMed ID: 30777123
RCT in pregnancy showed maintained maternal/cord folate and changed offspring DNA methylation at an imprinted DMR—clear biologic effect on fetal epigenetics/development.
- 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
Defines plasma folate threshold corresponding to RBC target for NTD prevention—directly informs pregnancy folate adequacy.
- 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
Weekly 2.8 mg folic acid greatly increased RBC folate and the percentage reaching thresholds tied to low NTD risk—directly relevant to pregnancy health policy.
- 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
Antenatal MMN (including folic acid) modestly improved cord ferritin, 25(OH)D and zinc — positive newborn biomarker effects.
- 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 reduced recurrent pre‑eclampsia in high‑risk women — clinically meaningful pregnancy outcome.
- 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 pregnancy produced long‑term neurodevelopmental benefits in offspring — strong fetal development signal.
- 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 early pregnancy raised maternal serum folate and UMFA but did not change RBC folate — shows pharmacokinetic impact relevant to fetal exposure.
- Efficacy of 4.0 mg versus 0.4 mg Folic Acid Supplementation on the Reproductive Outcomes: A Randomized Controlled Trial
PubMed ID: 34959975
4 mg folic acid before/into early pregnancy reduced composite adverse pregnancy outcomes and spontaneous abortion vs 0.4 mg — strong pregnancy benefit.
- 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 IFA adherence intervention increased supplement uptake and hemoglobin — directly relevant to optimizing pregnancy nutrition and outcomes.
- Effectiveness of Health Information Package Program on Knowledge and Compliance among Pregnant Women with Anemia: A Randomized Controlled Trial
PubMed ID: 35270420
Health‑information program in pregnant women increased IFA adherence and Hb—clear pregnancy‑relevant benefit from folate‑containing supplements.
- Prenatal fortified balanced energy-protein supplementation and birth outcomes in rural Burkina Faso: A randomized controlled efficacy trial
PubMed ID: 35560315
Large prenatal BEP trial including folic acid modestly increased birth weight and reduced low birthweight — relevant to fetal growth/outcomes (multifactorial intervention).
- Effect of Lipid-Based Multiple Micronutrients Supplementation in Underweight Primigravida Pre-Eclamptic Women on Maternal and Pregnancy Outcomes: Randomized Clinical Trial
PubMed ID: 36556974
LNS‑PLW plus IFA improved maternal hemoglobin and gestation length in pre‑eclamptic underweight women—supports healthier pregnancy course.
- Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms
PubMed ID: 35578268
Randomized maternal folic acid continuation altered newborn cord‑blood DNA methylation at brain genes and links to improved child cognition — strong mechanistic support for fetal neurodevelopment.
- Fortified balanced energy-protein supplementation during pregnancy and lactation and infant growth in rural Burkina Faso: A 2 × 2 factorial individually randomized controlled trial
PubMed ID: 36745684
Prenatal BEP+IFA trial modestly improved infant length and reduced stunting at 6 months — folic acid present in IFA but effect is from combined intervention.
- Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomised controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA)
PubMed ID: 36632790
Preconception micronutrient RCT (including folate in MMN) altered newborn cord‑blood gene expression related to mitosis and increased newborn ponderal index—direct links to fetal growth/development.
- Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada
PubMed ID: 37649241
Randomized comparison in pregnant women showing 5‑MTHF maintained erythrocyte/serum folate similar to folic acid but with substantially lower unmetabolized folic acid—important pregnancy biomarker implications.
- The Interactions between Maternal Iron Supplementation and Iron Metabolism-Related Genetic Polymorphisms on Birth Outcomes: A Prospective Study in Chinese
PubMed ID: 37390907
Adding iron to folic acid in pregnancy raised newborn birthweight (genotype‑dependent), indicating improved fetal growth outcomes in presence of folate.
- Cognitive benefits of folic acid supplementation during pregnancy track with epigenetic changes at an imprint regulator
PubMed ID: 39681839
Maternal folic acid supplementation produced cord‑blood methylation changes and mitigated offspring processing‑speed deficits—evidence for beneficial neurodevelopmental programming.
- 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 manipulating continued folic acid late in pregnancy demonstrated clear differences in maternal folate biomarkers and UMFA—relevant to pregnancy folate policy/ exposures.
- 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
Fortifying salt with folic acid greatly reduced folate insufficiency in women of reproductive age — directly promotes healthy pregnancy risk reduction.
- Assessing the adherence and acceptability to iron and folic acid compared with multiple micronutrient supplements during pregnancy: a cluster-randomized noninferiority trial in Cambodia
PubMed ID: 40334750
MMS (including folic acid) had higher adherence and fewer side effects than standard IFA in pregnant women — supports effective pregnancy supplementation.
- Prenatal and preschool micronutrient supplementation and behavioral outcomes in school-aged children in Nepal-a cohort study
PubMed ID: 41092983
Antenatal iron‑folate exposure associated with modest reductions in later child behavioral problems — developmental benefit signal.
- 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
Provider training and brochures markedly increased iron‑folic acid use and dietary practices in pregnant women — programmatic support for healthy pregnancy.
- Impact of anaemia prophylaxis in pregnancy on maternal haemoglobin, serum ferritin & birth weight
PubMed ID: 1959958
Large community supplementation trial (iron + 500 µg folic acid) in pregnancy increased maternal hematologic indices and substantially lowered low-birth-weight incidence — strong direct evidence of fetal benefit for a folic-acid-containing supplement.
- Prevention of congenital abnormalities by periconceptional multivitamin supplementation
PubMed ID: 8324432
Large randomized trial: periconceptional multivitamin including 0.8 mg folic acid markedly reduced neural-tube and major congenital defects — direct, high-quality evidence for fetal development.
- Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report
PubMed ID: 7979565
Large randomized trial: periconceptional multivitamin with 0.8 mg folic acid increased conceptions and reduced neural-tube defects.
- The higher rate of multiple births after periconceptional multivitamin supplementation: an analysis of causes
PubMed ID: 8588492
Large trial showed periconceptional multivitamin (including folic acid) affected multiple-birth rates, directly relevant to pregnancy/fetal outcomes.
- Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation
PubMed ID: 8882400
Large randomized double‑blind trial showing periconceptional multivitamin with 0.8 mg folic acid roughly halved major congenital malformations—strong, direct evidence for fetal development benefits.
- Long-term somatic and mental development of children after periconceptional multivitamin supplementation
PubMed ID: 9776529
Periconceptional folic-acid–containing multivitamin RCT directly addresses periconceptional supplementation and shows safety with respect to growth/development—supports folic acid use in pregnancy.
- Effect of multivitamin and vitamin A supplements on weight gain during pregnancy among HIV-1-infected women
PubMed ID: 12399282
Multivitamin (including folic acid) in pregnant HIV+ women produced a small but significant increase in third‑trimester maternal weight — a pregnancy outcome; folate contribution cannot be isolated.
- Impact of daily versus weekly hematinic supplementation on anemia in pregnant women
PubMed ID: 11976463
Weekly vs daily iron+folic acid maintained maternal hemoglobin and was associated with better neonatal anthropometrics; folic acid was part of the regimen supporting pregnancy outcomes.
- Prevention of anaemia in pregnancy using insecticide-treated bednets and sulfadoxine-pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial
PubMed ID: 15228241
Routine antenatal iron + folic acid was part of the intervention and was associated with improved maternal haemoglobin at delivery — supports pregnancy health.
- Daily versus weekly iron supplementation and prevention of iron deficiency anaemia in lactating women
PubMed ID: 12755236
Study of lactating women where iron with folic acid decreased anaemia prevalence — supports maternal postpartum/peripartum haematologic health relevant to pregnancy 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
Folic acid was part of prenatal anemia management that improved hemoglobin and iron indices—consistent with folate’s known role in pregnancy health (though folate was not the variable tested).
- Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial
PubMed ID: 15766997
Large RCT: multi-micronutrient supplement (including folic acid) vs iron+folic acid increased mean birthweight and reduced low-birthweight prevalence — supports improved fetal growth, but effect cannot be ascribed to folic acid alone.
- Multimicronutrient supplementation for undernourished pregnant women and the birth size of their offspring: a double-blind, randomized, placebo-controlled trial
PubMed ID: 17199068
In undernourished pregnant women, multimicronutrients were given on a background of iron+folate; results showed notably larger babies and fewer low‑birth‑weight infants — strong real‑world evidence implicating antenatal folate as part of effective supplementation.
- Vitamins and perinatal outcomes among HIV-negative women in Tanzania
PubMed ID: 17409323
Large trial gave iron+folate to all and tested multivitamins on top; multivitamins reduced low birth weight and increased mean birth weight — supports role of antenatal folic acid as part of pregnancy nutrient strategies.
- 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 cluster RCT in pregnant women showed iron–folic acid (vs folic acid alone) and multiple micronutrient supplements modestly increased birth weight/gestation and iron–folic acid reduced early neonatal mortality — strong clinical evidence for pregnancy/fetal outcomes involving folate.
- The effects of iron and/or zinc supplementation on maternal reports of sleep in infants from Nepal and Zanzibar
PubMed ID: 19322104
Infant iron–folic acid supplementation was associated with increased night/total sleep; while postnatal, it supports early life nutritional status relevant to development.
- Effect of maternal multiple micronutrient supplements on cord blood hormones: a randomized controlled trial
PubMed ID: 20375185
Pregnant women received MMN including folic acid and newborn cord-hormone changes were observed (sex/parity-specific) — direct perinatal relevance though folate not isolated.
- Once a week (200 mg) elemental iron: an effective option for prophylaxis in non-anaemic pregnant women
PubMed ID: 22480099
Trial in pregnant women compared iron+folic acid dosing regimens and showed hematologic improvements and better tolerability/compliance; folic acid was included though iron drove much of the hematologic response.
- Impact of prenatal multiple micronutrients on survival and growth during infancy: a randomized controlled trial
PubMed ID: 22378724
Randomized prenatal multiple‑micronutrient supplement (includes folic acid) reduced stunting and improved infant growth — supports a role in fetal/early child development, though effect not solely attributable to folic acid.
- The effect of intermittent antenatal iron supplementation on maternal and infant outcomes in rural Viet Nam: a cluster randomised trial
PubMed ID: 23853552
Antenatal IFA/MMN trial included folic acid in all regimens and found comparable maternal outcomes; folic acid is a component of standard prenatal supplementation though the trial does not isolate its specific effect.
- Antenatal micronutrient supplementation and third trimester cortisol and erythropoietin concentrations
PubMed ID: 25059838
Antenatal supplement arms (including folic acid) showed changes linked with better birth outcomes; folic acid included but not isolated.
- Prenatal Hemoglobin Levels and Early Cognitive and Motor Functions of One-Year-Old Children
PubMed ID: 26055847
Iron + folic acid during pregnancy increased maternal hemoglobin and reduced anemia prevalence at delivery—direct supportive evidence for pregnancy health when folic acid is included.
- 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
Prenatal LNS (includes folic acid) improved child outcomes (length, stunting), implying benefits of maternal supplementation during pregnancy.
- 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
Prenatal fortified CSB Plus (contains folate) reduced preterm birth and late‑pregnancy anemia — directly supportive of pregnancy health.
- Home fortification during the first 1000 d improves child development in Bangladesh: a cluster-randomized effectiveness trial
PubMed ID: 28275128
Large trial of antenatal/postnatal supplementation strategies that included antenatal iron+folic acid was associated with better motor/language outcomes in offspring—consistent with a role in fetal/early development though folate not isolated.
- Prenatal early food and multiple micronutrient supplementation trial reduced infant mortality in Bangladesh, but did not influence morbidity
PubMed ID: 28779492
Prenatal multiple micronutrient supplements included folic acid; although this study reported no change in childhood infection rates, it is directly relevant to prenatal supplementation and prior reports showed infant mortality benefits—strong indirect support for fetal/infant outcomes.
- 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
Conditional cash transfer program increased antenatal iron–folic acid tablet receipt and counseling — directly improves antenatal service coverage relevant to pregnancy health.
- Micronutrient supplementation during pregnancy and the risk of pregnancy-induced hypertension: A randomized clinical trial
PubMed ID: 29428785
Large RCT directly testing prenatal micronutrient/iron‑folic acid regimens vs folic acid alone with maternal outcomes (pregnancy‑induced hypertension) — directly relevant to pregnancy health and folic acid policy.
- 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
Prenatal/postnatal small‑quantity LNS and MNP interventions included folic acid and produced measurable child health benefits (reduced anemia) at 18 months—relevant to fetal/postnatal development from maternal supplementation.
- Effect of Nutritional Interventions on Micronutrient Status in Pregnant Malawian Women with Moderate Malnutrition: A Randomized, Controlled Trial
PubMed ID: 29986492
Randomized trial in pregnant, moderately malnourished women: maternal folate increased and higher maternal folate associated with modestly greater infant birth length — direct evidence linking folate status to fetal growth.
- 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
Intervention substantially increased preconception folic‑acid intake — supports uptake of an established pregnancy‑protective nutrient.
- Cluster Randomized Trial of a Pre/Interconception Health Intervention for Mothers in Pediatric Visits
PubMed ID: 31629944
Pediatric‑visit intervention significantly increased odds of daily folic acid use among mothers — supports recommended folate intake during pregnancy.
- A Mobile App Lifestyle Intervention to Improve Healthy Nutrition in Women Before and During Early Pregnancy: Single-Center Randomized Controlled Trial
PubMed ID: 32412417
Preconception lifestyle app specifically measured folic acid behavior; improved dietary risk scores and targeted folic acid uptake—direct behavioral support for fetal health via folate.
- Supplementation with Small-Quantity Lipid-Based Nutrient Supplements Does Not Increase Child Morbidity in a Semiurban Setting in Ghana: A Secondary Outcome Noninferiority Analysis of the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD Randomized Controlled Trial
PubMed ID: 31603205
Maternal supplementation arms included iron+folate or MMN (including folic acid); supports pregnancy nutrition though trial showed minimal differences in child morbidity.
- Preconception micronutrient supplementation positively affects child intellectual functioning at 6 y of age: A randomized controlled trial in Vietnam
PubMed ID: 33668050
Preconception MMS including folic acid improved later child neurodevelopmental outcomes, indicating benefit for early development.
- Fortified Balanced Energy-Protein Supplements Increase Nutrient Adequacy without Displacing Food Intake in Pregnant Women in Rural Burkina Faso
PubMed ID: 34494113
BEP supplement during pregnancy increased maternal nutrient adequacy including folate to recommended levels — directly relevant to healthy pregnancy nutrition.
- Improving Micronutrient Status of Children and Women in Rural Communities in India Using Crystal Salt Enriched with Multiple Micronutrients
PubMed ID: 33952731
Population folic acid fortification improved anemia in women, an outcome relevant to healthy pregnancy though pregnancy‑specific endpoints were not primary.
- 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
Study in iron‑deficient pregnant women used folinic acid and reported improved maternal iron markers and slightly higher newborn weight — directly relevant to fetal health.
- Multivitamin Supplementation Is Associated with Greater Adequacy of Gestational Weight Gain among Pregnant Women in Tanzania
PubMed ID: 34964890
Prenatal multivitamin (including folic acid) modestly reduced risks of inadequate gestational weight gain — consistent with a beneficial role in pregnancy outcomes.
- Prenatal and postnatal small-quantity lipid-based nutrient supplements and children's social-emotional difficulties at ages 9-11 y in Ghana: follow-up of a randomized controlled trial
PubMed ID: 37257564
SQ‑LNS containing folic acid used in maternal/child trials—direct programmatic inclusion though the trial evaluates package effects rather than isolating folic acid.
- 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
Large randomized MMS (including folic acid) reduced risk of low birth weight most in women with poor diets — direct evidence for fetal outcomes.
- myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study
PubMed ID: 23340885
Myo‑inositol RCT given with folic acid reduced GDM and macrosomia; folic acid was present throughout pregnancy in both arms and is central to pregnancy care.
- Inositol: effects on oocyte quality in patients undergoing ICSI. An open study
PubMed ID: 24302192
ICSI trial baseline folic acid use and better pregnancy rates with added inositol; folic acid is established prenatal supplement although not isolated as active.
- The effect of preconception counselling on lifestyle and other behaviour before and during pregnancy
PubMed ID: 19059545
Randomized preconception counseling substantially increased preconception folic-acid use and reduced early pregnancy alcohol use, directly improving pregnancy folate exposure.
- 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
Implementation of a preventive-care checklist significantly increased rates of folic-acid counseling at health checks, increasing the likelihood of folate use in pregnancy.
- Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring
PubMed ID: 8585581
Population case-control data showed periconceptional multivitamin use including folic acid associated with ~30–47% lower odds of certain congenital heart and limb defects, supporting fetal development benefit (observational).
- 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‑micronutrient including folic acid in men increased pregnancy rates vs placebo; supports an effect on fertility/pregnancy outcomes although folate was one of several actives.
Nutrition source (166)
- Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia
PubMed ID: 23698160
Folate supplements/diet raised RBC folate and lowered homocysteine in adults with hyperhomocysteinemia (biomarker improvements relevant to erythrocyte status).
- A comparison of iron and folate with folate alone in hematologic recovery of children treated for acute malaria
PubMed ID: 20889877
In malarial anemia, iron+folate produced greater hematocrit recovery than folate alone—folate is part of hematologic recovery regimen.
- A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy
PubMed ID: 20980493
Randomized trial: daily folic acid raised RBC folate substantially—direct evidence of improved folate status in red blood cells.
- A combination of iron and retinol supplementation benefits iron status, IL-2 level and lymphocyte proliferation in anemic pregnant women
PubMed ID: 21147712
Pregnant women receiving iron+folic acid (and with retinol) had larger hemoglobin and ferritin gains vs iron alone—improvement in hematologic indices.
- 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 significantly increased hemoglobin (+17.3 g/L) and ferritin in anemic pregnant women—direct evidence of supporting erythropoiesis.
- 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 quickly to protective levels, supporting folate‑dependent erythropoiesis.
- Periconceptional iron supplementation does not reduce anemia or improve iron status among pregnant women in rural Bangladesh
PubMed ID: 19793860
Daily iron+folic acid reduced anemia and improved iron stores in nonpregnant women—strong clinical hematologic benefit.
- 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 hemoglobin and physical work capacity in adolescent girls—consistent with improved RBC production.
- 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 alone cured/semi‑cured severe anemia comparably to combined regimens in young children—direct RBC production benefit.
- Providing iron/folic acid tablets free of charge improves compliance in pregnant women in Senegal
PubMed ID: 19203773
Free iron+folic acid massively improved compliance and halved anemia prevalence in pregnancy—strong evidence for RBC/hemoglobin effects.
- Effect of 2 pieces of nutritional advice on folate status in Swedish women: a randomized controlled trial
PubMed ID: 19190070
Dietary folate intake increased RBC folate and lowered homocysteine in healthy women—biomarker support for folate status and erythropoiesis.
- Impact of a multiple-micronutrient fortified salt on the nutritional status and memory of schoolchildren
PubMed ID: 20533221
Salt fortified with folic acid (plus other nutrients) increased hemoglobin by ~0.67 g/dL and raised serum folate in children.
- Treatment response to standard of care for severe anemia in pregnant women and effect of multivitamins and enhanced anthelminthics
PubMed ID: 19176737
Programmatic high-dose iron–folic acid substantially improved hemoglobin in severely anemic pregnant women (direct RBC production benefit).
- 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 raised serum folate and lowered homocysteine—biochemical changes that support erythropoiesis.
- 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
Folic acid supplementation raised serum and RBC folate rapidly, supporting erythropoiesis and NTD prophylaxis.
- 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 raised serum folate and lowered homocysteine in reproductive‑age women—supports folate status relevant to erythropoiesis.
- 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 pediatric trial: adding folic acid to iron therapy greatly reduced anemia prevalence and raised hemoglobin—direct RBC production evidence.
- 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 trial increased serum folate and lowered homocysteine in older adults—improves folate availability for erythropoiesis.
- 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 dose–response trial produced dose‑dependent rises in plasma and RBC folate.
- Folic acid does not improve endothelial function in obese children and adolescents
PubMed ID: 17519435
Obese children given 5 mg folic acid had large increases in red‑cell folate (direct RBC biomarker change).
- Community-level micronutrient fortification of a food supplement in India: a controlled trial in preschool children aged 36-66 mo
PubMed ID: 17413115
Complementary food fortification including folic acid reduced anemia and iron deficiency in preschool children (large trial).
- A randomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy
PubMed ID: 17915799
Pregnant anemic women receiving iron with folic acid showed significant hemoglobin increases (all arms included folic acid).
- 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 nearly eradicated infant IDA and significantly raised hemoglobin and ferritin—strong evidence for RBC support.
- 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
Active folate ([6S]‑5‑MTHF) raised RBC and plasma folate more than folic acid in healthy women.
- [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 preserved RBC folate during lactation better than folic acid — direct RBC folate outcome.
- 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
Daily sprinkles with folic acid+iron improved anemia recovery and stabilized iron stores in infants — strong RBC outcome.
- 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
Iron+folic acid reduced anaemia prevalence in preschool children in a large community trial.
- Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women
PubMed ID: 16740440
Daily iron+folic acid+B12 prevented anemia better than weekly dosing in pregnancy—combined effect includes folate contribution.
- 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
In very‑low‑birth‑weight infants, added B12+folate to erythropoietin and iron increased RBC counts and helped maintain hemoglobin.
- Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age
PubMed ID: 15927936
Marked RBC folate increases after fortified milk in women of childbearing age (important for erythropoiesis and fetal protection).
- Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans
PubMed ID: 15928685
Daily 200 µg folic acid in milk raised serum and RBC folate (supports erythrocyte folate status).
- Folic acid supplementation reduces the development of some blood cell abnormalities in children receiving carbamazepine
PubMed ID: 16380297
Folic acid reduced hemoglobin decline and improved WBC/PMN counts in children treated with carbamazepine.
- Efficacy of twice-weekly multiple micronutrient supplementation for improving the hemoglobin and micronutrient status of anemic adolescent schoolgirls in Bangladesh
PubMed ID: 16210713
Twice‑weekly iron+folic acid increased hemoglobin in anemic girls (RCT).
- Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women
PubMed ID: 14985695
Daily folic acid raised RBC folate substantially (from 615 to 1053 nmol/L), supporting erythropoiesis and folate-dependent RBC maturation.
- 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 + folic acid product produced significantly greater increases in hemoglobin and ferritin vs comparator—direct hematologic improvement.
- Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults
PubMed ID: 14985217
Monoglutamyl folic acid produced larger increases in serum and erythrocyte folate vs dietary polyglutamyl folate—relevant to RBC folate status.
- Intermittent iron supplementation regimens are able to maintain safe maternal hemoglobin concentrations during pregnancy in Venezuela
PubMed ID: 15113952
Intermittent iron with folic acid maintained acceptable maternal hemoglobin in most pregnant women — supports RBC maintenance.
- Exclusive breast-feeding for 6 months, with iron supplementation, maintains adequate micronutrient status among term, low-birthweight, breast-fed infants in Honduras
PubMed ID: 15113951
Breastfeeding + iron in infants maintained plasma folate and hemoglobin measures — supports infant folate status with implications for RBCs.
- Effect of cow milk on food folate bioavailability in young women
PubMed ID: 15585769
Cow's milk preserved erythrocyte folate and prevented homocysteine rises in low‑folate diets — direct effect on red‑cell folate (relevant to RBC health/production).
- 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 raised plasma folate and lowered homocysteine in older adults; raised folate status supports RBC health.
- Anemia prophylaxis in adolescent school girls by weekly or daily iron-folate supplementation
PubMed ID: 12736400
Large trial: weekly or daily iron–folate supplements raised iron stores and helped prevent anemia in adolescent schoolgirls—clear hematologic benefit.
- A micronutrient-fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women
PubMed ID: 12730420
Multi‑micronutrient drink including folate modestly raised hemoglobin and reduced anemia risk in pregnancy.
- Weekly high-dose folic Acid supplementation is effective in lowering serum homocysteine concentrations in women
PubMed ID: 12652055
Daily and weekly folic acid both lowered homocysteine and daily dosing raised erythrocyte folate substantially—direct effect on RBC folate pool.
- 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‑5‑MTHF and folic acid raised plasma and red‑cell folate in a randomized trial—relevant to RBC folate status.
- 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
Folate+B12+B6 normalized homocysteine and methylmalonate in elderly — supports hematologic micronutrient status.
- Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age
PubMed ID: 12391385
Red‑cell folate rose with low‑dose folic acid in women of childbearing age (direct RBC biomarker).
- Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women
PubMed ID: 12495257
Iron with folate increased haemoglobin in pregnant women in a supplementation trial.
- 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
Double‑blind RCT: adding folate (folinic acid) to iron produced substantially greater haemoglobin increases in pregnant women.
- Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls
PubMed ID: 11814373
Supervised iron with folic acid greatly reduced anemia and raised hematocrit in adolescent girls.
- Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid
PubMed ID: 12421850
Folate and [6S]-5‑MTHF increased red cell folate substantially in women of childbearing age (marker of erythrocyte folate status).
- 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
Folic acid‑fortified cereal increased serum folate and lowered homocysteine in older adults—supporting folate status for erythropoiesis.
- 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
High‑dose folic acid raised serum and red cell folate in heavy smokers.
- 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 in treated refugee children raised hemoglobin substantially over 12 weeks (large RBC effect).
- Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone)
PubMed ID: 11355560
Iron‑folate supplementation meaningfully preserved maternal hemoglobin between trimesters.
- Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial
PubMed ID: 11339442
Dose‑response trial in young women showed RBC folate increases at low supplemental doses (direct effect on erythrocyte folate pools).
- Changes in iron status during pregnancy in peruvian women receiving prenatal iron and folic acid supplements with or without zinc
PubMed ID: 10731503
Large prenatal trial: iron + folic acid improved hemoglobin and reduced anemia prevalence at end of pregnancy.
- Folate status of elderly women following moderate folate depletion responds only to a higher folate intake
PubMed ID: 10827214
Elderly women repleted with 415 µg/day folate normalized folate biomarkers and improved homocysteine; RBC folate responded to intake.
- Maternal folate status during extended lactation and the effect of supplemental folic acid
PubMed ID: 9989694
1 mg folic acid increased erythrocyte folate and hemoglobin and prevented rises in homocysteine in lactating women.
- 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
In MTX-treated RA patients, folic acid prevented declines in folate stores and homocysteine rises, preserving folate status tied to erythropoiesis.
- Use of folic acid-fortified milk in the elderly population
PubMed ID: 9813433
Folic‑acid‑fortified milk substantially raised red‑cell folate in elderly residents.
- Minimum effective dose of folic acid for food fortification to prevent neural-tube defects
PubMed ID: 9400511
Folic acid raised red‑cell folate strongly in a randomized dose–response trial—supports erythrocyte folate pools.
- Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects
PubMed ID: 8596381
400 µg/day folic acid (supplement/fortified food) increased red‑cell folate over 3 months—direct evidence of improving RBC folate status.
- Postpartum folic acid supplementation of adolescents: impact on maternal folate and zinc status and milk composition
PubMed ID: 7625346
Postpartum trial: 300 µg/day folic acid prevented decline in RBC folate vs placebo — strong evidence folate preserves RBC folate pools.
- [Folic acid and vitamin B12 in children under long-term anticonvulsant therapy]
PubMed ID: 8439095
Children on long‑term anticonvulsants had lower serum folate and larger MCV; folate replacement was safe — direct link to RBC status and macrocytosis.
- Thiamine, riboflavin, folate, and vitamin B12 status of low birth weight infants receiving parenteral and enteral nutrition
PubMed ID: 1501354
Parenteral multivitamin feeding in low‑birth‑weight infants increased plasma folate compared with enteral feeding — supports folate status relevant to RBC production.
- Elderly patients' responses to preoperative autologous blood collection
PubMed ID: 1875807
Iron plus folic acid during preoperative collection maintained hematologic parameters in elderly donors — supports maintaining erythropoiesis during blood donation.
- Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects
PubMed ID: 2296932
High‑dose folic acid dramatically raised plasma/erythrocyte folate and improved a functional folate assay (dUST) — strong support for red‑cell folate status.
- Influence of folate status and polyphenol intake on thiamin status of Irish women
PubMed ID: 2239785
Folic acid 400 µg increased plasma folate ~5‑fold and erythrocyte folate ~3‑fold — direct biochemical evidence supporting RBC folate.
- Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?
PubMed ID: 10952955
Folic acid raised serum and red cell folate substantially in chronic renal failure patients and lowered homocysteine—direct evidence of improving folate stores relevant to erythropoiesis.
- Multimicronutrient and omega-3 fatty acid supplementation reduces low-grade inflammation in older participants: An exploratory study
PubMed ID: 40644954
Multinutrient + n‑3 intervention including folic acid increased red blood cell folate—supports folate status relevant to RBC production, but RBC count/hematopoiesis not directly reported.
- Inter-pregnancy folate and iron status of women in an inner-city population
PubMed ID: 11432768
Supplementation raised serum and erythrocyte folate in postpartum women — direct biomarker relevant to erythropoiesis and RBC folate stores.
- One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans
PubMed ID: 25283139
One‑year B‑vitamin supplementation (500 μg folic acid) strongly increased serum and whole‑blood 5‑methylTHF and lowered tHcy — supports erythropoiesis and folate status for RBC production.
- Impact of Sorghum Supplementation on Growth and Micronutrient Status of School Going Children in Southern India - A Randomized Trial
PubMed ID: 26001905
Dietary intervention (sorghum) increased serum folic acid and improved hemoglobin and iron markers in schoolchildren — supports erythropoiesis though folate was one of several nutritional changes.
- Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine, but not cognitive performance
PubMed ID: 24481688
Three months of folic‑acid containing B‑vitamin supplementation raised blood folate and lowered homocysteine in children — biomarker evidence supporting RBC health.
- 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
Fortification with folic acid or L‑5‑MTHF produced clear, equivalent increases in erythrocyte and plasma folate — directly relevant to preventing folate‑responsive megaloblastic anemia and supporting RBC production.
- Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study
PubMed ID: 22067790
Direct levomefolate administration produced large, statistically significant increases in RBC folate — strong biochemical support for erythropoiesis support.
- Improvement of bone formation biomarkers after 1-year consumption with milk fortified with eicosapentaenoic acid, docosahexaenoic acid, oleic acid, and selected vitamins
PubMed ID: 20579524
Multi‑nutrient fortified milk increased red blood cell folate by 21% over 1 year (supports RBC folate status).
- 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
Six‑month multi‑micronutrient fortification (including folic acid) improved hemoglobin and iron markers in preschool children.
- Trial using multiple micronutrient food supplement and its effect on cognition
PubMed ID: 18716734
School food supplement with folic acid improved hemoglobin/hematologic indices versus controls 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 produced large increases in erythrocyte folate (supportive of RBC production).
- Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children
PubMed ID: 17704033
Micronutrient‑fortified salt (incl. folic acid) improved hemoglobin and eliminated angular stomatitis in schoolchildren after 1 year.
- Impact of a multiple-micronutrient food supplement on the nutritional status of schoolchildren
PubMed ID: 17542110
Food‑based multi‑micronutrient supplement (including folic acid) increased hemoglobin and serum folate in schoolchildren over 9 months.
- 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
Fortified mineral water raised serum and erythrocyte folate — biomarkers linked to healthy erythropoiesis.
- Nutritional efficacy of a fortified weaning rusk in a rural area near Beijing
PubMed ID: 8460605
Randomized trial in infants: micronutrient‑fortified rusk including folic acid prevented the decline in hemoglobin seen with unfortified rusk—direct evidence supporting erythropoiesis.
- Plasma homocysteine concentration is decreased by dietary intervention
PubMed ID: 12696562
High‑folate food intake substantially raised serum folate and modestly increased RBC folate, supporting erythropoietic substrate supply.
- Functionality of endogenous folates from rye and orange juice using human in vivo model
PubMed ID: 12474071
Endogenous food folates raised serum and red cell folate comparably to fortified bread — clear demonstration of improving RBC folate indices.
- Postoperative Vitamin Profile after Receiving a Novel Peripheral Parenteral Nutrition Solution: Multicenter Randomized Controlled Phase III Trial
PubMed ID: 35439754
Multivitamin‑containing PPN maintained folate in the normal range post‑op whereas standard PPN did not — relevant to preventing perioperative folate‑deficiency anemia.
- 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 significantly increased RBC folate vs folic acid — direct evidence supporting RBC folate status and thus erythropoiesis.
- 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
Folic acid supplementation effectively corrected marginal folate status—biologically important for erythropoiesis though direct RBC measures not reported.
- Safety of a fat-reduced diet: the Dietary Intervention Study in Children (DISC)
PubMed ID: 9200359
Large study found children on lower‑fat diets had higher blood folate and hemoglobin, linking folate intake/status to hematologic measures.
- Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years
PubMed ID: 15309436
Multivitamin containing folic acid raised folate markers and lowered homocysteine and MMA in older women—biomarkers consistent with improved B‑vitamin status that supports erythropoiesis.
- Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis
PubMed ID: 12695153
Randomized trial: folates given with methotrexate substantially reduced hepatotoxicity and improved tolerability/dosing—consistent with mitigation of folate‑antagonist effects on rapidly dividing cells (including marrow).
- A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours
PubMed ID: 16940981
Adding folate+B12 to pemetrexed regimens was associated with markedly less severe hematologic toxicity and higher tolerated dose, consistent with folate protecting normal hematopoiesis.
- Leaf concentrate as an alternative to iron and folic acid supplements for anaemic adolescent girls: a randomised controlled trial in India
PubMed ID: 19706212
Randomized trial compared leaf concentrate to standard iron + folic acid for anaemic adolescent girls; hematologic outcomes improved with the folic acid‑containing comparator.
- Plasma folate dynamics in Plasmodium falciparum-infected African children treated with artemisinin combination therapy and single low-dose primaquine or placebo
PubMed ID: 41094485
In children with falciparum malaria plasma folate fell transiently after treatment and folate change correlated with hemoglobin recovery—links folate status to hemoglobin dynamics.
- 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
Study of moderately anemic pregnant women used oral iron+folic acid and showed hemoglobin improvement—consistent with folate’s established role in erythropoiesis (though iron was the main variable).
- Daily versus weekly iron supplementation and prevention of iron deficiency anaemia in lactating women
PubMed ID: 12755236
Both weekly and daily iron regimens included folic acid and significantly reduced anaemia in lactating women — supports folic acid's role in preventing/measuring anaemia.
- Prevention of anaemia in pregnancy using insecticide-treated bednets and sulfadoxine-pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial
PubMed ID: 15228241
Antenatal routine iron + folic acid was associated with improved maternal haemoglobin at delivery in primigravidae — direct evidence supporting erythropoiesis.
- Impact of daily versus weekly hematinic supplementation on anemia in pregnant women
PubMed ID: 11976463
Iron+folic acid maternal regimens produced comparable improvements in maternal hemoglobin (treating anemia); folic acid is a hematinic component though iron is the dominant agent.
- The effect of weekly iron supplementation on anaemia and on iron deficiency among female tea pluckers in Bangladesh
PubMed ID: 11424510
Iron+folic acid improved mean hemoglobin modestly over 24 weeks in female workers; folic acid is part of erythropoiesis support though iron likely drove most effect.
- [Primary prophylaxis against cerebral toxoplasmosis. Efficacy of folinic acid in the prevention of hematologic toxicity of pyrimethamine]
PubMed ID: 8029191
Small randomized trial: folate given with pyrimethamine modestly preserved hemoglobin compared with no folate — direct evidence for erythropoiesis/hemoglobin support.
- 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 folinic acid after weekly methotrexate cut toxicity and withdrawals by ~half without reducing efficacy — consistent with protection against marrow toxicity.
- Impact of anaemia prophylaxis in pregnancy on maternal haemoglobin, serum ferritin & birth weight
PubMed ID: 1959958
Trial showed significant increases in maternal haemoglobin and ferritin with iron + folic acid supplementation; while iron is the primary driver, folic acid is a required cofactor for erythropoiesis and part of the effective supplement.
- 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
School MMS (includes folic acid) lowered the risk of moderate/severe anemia versus control — strong anemia/RBC production signal.
- 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 formula with higher folic acid produced higher blood folate concentrations in CKD patients — biomarker evidence relevant to RBC production potential.
- The potential adding therapeutic effect of pentoxifylline and/or folic acid for chronic kidney disease patients: randomized controlled trial
PubMed ID: 40826392
Folic acid in CKD increased hemoglobin significantly over 6 months — direct RBC production improvement.
- Comparative effectiveness of daily therapeutic supplementation with multiple micronutrients and iron-folic acid versus iron-folic acid alone in children with mild-to-moderate anaemia in rural India: an open-label, randomised controlled trial
PubMed ID: 40021307
Iron‑folic acid interventions in anemic children produced ~80% anemia cure rates — direct evidence of folate's role in supporting RBC indices (as part of IFA).
- 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 nutrient supplement including folate increased plasma folate and modestly raised hemoglobin in stunted children—direct improvement in hematologic markers.
- A micronutrient supplement modulates homocysteine levels regardless of vitamin B biostatus in elderly subjects
PubMed ID: 36715360
Elderly RCT with 400 µg folic acid increased RBC folate and lowered homocysteine—direct hematologic biomarker changes.
- 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
Weekly iron‑folic acid produced a small but significant hemoglobin increase in adolescents—evidence folate-containing regimens can improve haemoglobin when combined with iron.
- Infant blood concentrations of folate markers and catabolites are modified by 5,10-methylenetetrahydrofolate reductase C677T genotype and dietary folate source
PubMed ID: 36872017
Infant RCT: formula with 5‑MTHF raised RBC folate substantially vs folic acid—direct evidence of folate form increasing RBC folate (erythropoietic substrate).
- Effect of Lipid-Based Multiple Micronutrients Supplementation in Underweight Primigravida Pre-Eclamptic Women on Maternal and Pregnancy Outcomes: Randomized Clinical Trial
PubMed ID: 36556974
LNS+IFA improved maternal hemoglobin at delivery relative to IFA alone — indicates better erythropoiesis with combined supplementation including folic acid.
- Effectiveness of Health Information Package Program on Knowledge and Compliance among Pregnant Women with Anemia: A Randomized Controlled Trial
PubMed ID: 35270420
Pregnancy education RCT increased iron–folic acid adherence and improved hemoglobin — strong clinical evidence of improved RBC production with IFA programs.
- 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 iron–folic acid RCT markedly increased adherence and significantly raised hemoglobin — direct evidence folate in IFA supports RBC/Hb.
- 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
Trial of iron–folate found a small but significant hemoglobin rise with blister packaging; folic acid present though iron likely drove Hb change.
- 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 in adolescents significantly increased hemoglobin, ferritin and serum folate — strong evidence for RBC support.
- 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
Supervised IFA for 90 days raised hemoglobin and ferritin in adolescent girls; folic acid was part of effective IFA regimen.
- Vitamin B12 Supplementation in Addition to Folic Acid and Iron Improves Hematological and Biochemical Markers in Pregnancy: A Randomized Controlled Trial
PubMed ID: 32302504
Pregnancy trial adding B12 to IFA modestly improved hematologic markers; folic acid present as part of regimen (indirect folate support).
- 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
Weekly higher‑dose folic acid raised RBC folate and greatly increased the proportion above a protective threshold—strong evidence of improving RBC folate status.
- Multi-Micronutrient Fortified Rice Improved Serum Zinc and Folate Concentrations of Cambodian School Children. A Double-Blinded Cluster-Randomized Controlled Trial
PubMed ID: 31756911
Fortified rice in school meals increased serum folate and eliminated deficiency—population‑level improvement in folate status that supports RBC health.
- Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial
PubMed ID: 31425504
Infant RCT: L‑5‑MTHF formula produced higher red‑cell folate vs folic‑acid formula—direct biomarker evidence linked to erythropoiesis potential.
- A Pilot Randomized Controlled Double-Blind Trial of High- Versus Low-Dose Weekly Folic Acid in People With Rheumatoid Arthritis Receiving Methotrexate
PubMed ID: 30001258
High weekly folic acid markedly increased RBC folate concentrations in RA patients, demonstrating impact on red cell folate status relevant to erythropoiesis.
- Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial
PubMed ID: 31036337
Preoperative regimen including oral folic acid (with other agents) reduced perioperative transfusions and raised early postoperative hemoglobin; folic acid was one component.
- 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 supervised iron-plus-folic-acid modestly raised hemoglobin, consistent with improved RBC parameters in a supplementation program (folic acid part of regimen).
- Response of Red Blood Cell Folate to Supplementation in Nonpregnant Women is Predictable: A Proposal for Personalized Supplementation
PubMed ID: 29143484
Dose/time models show predictable RBC‑folate rises with folic acid dosing — biologically relevant to RBC production and folate sufficiency.
- 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 folate raised RBC‑folate substantially and got many women to protective RBC levels — supports erythropoiesis/folate‑dependent RBC synthesis.
- Randomized control trial comparing effectiveness of weekly versus daily antenatal oral iron supplementation in preventing anemia during pregnancy
PubMed ID: 29271022
Trial showed weekly iron+folate prevented third‑trimester anemia as effectively as daily dosing, implicating folate as part of antenatal anemia prevention.
- 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
Fortified milk RCT substantially raised red-cell folate and plasma folate — folate status improvements support erythropoiesis and NTD prevention thresholds.
- Impact of weekly iron folic acid supplementation with and without vitamin B12 on anaemic adolescent girls: a randomised clinical trial
PubMed ID: 26695724
Weekly supervised iron+folic acid (with added B12) cured anemia and improved iron stores in adolescent girls (clear hematologic benefit).
- Multivitamin and iron supplementation to prevent periconceptional anemia in rural tanzanian women: a randomized, controlled trial
PubMed ID: 25905863
Large randomized trial: iron+folic acid reduced hypochromic microcytic anemia vs folic acid alone (direct anemia endpoint though effect largely due to iron).
- Pregnancy-induced changes in the long-term pharmacokinetics of 1.1 mg vs. 5 mg folic acid: a randomized clinical trial
PubMed ID: 25167960
Higher folic acid dose produced earlier and larger rises in RBC folate during pregnancy, supporting erythropoiesis and prevention of megaloblastic changes.
- The effect of folic acid supplementation with ferrous sulfate on the linear and ponderal growth of children aged 6-24 months: a randomized controlled trial
PubMed ID: 25335446
Folic acid supplementation in infants increased weight gain and improved weight‑for‑age; folate is important for cell replication and erythropoiesis in growing children.
- Weekly iron folate supplementation in adolescent girls--an effective nutritional measure for the management of iron deficiency anaemia
PubMed ID: 23618489
Weekly or daily iron–folic acid capsules raised hemoglobin and reduced anemia in adolescent girls (clear hematologic benefit though iron is primary).
- 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
400 µg folic acid significantly increased RBC folate — supports red‑cell folate status and indirectly red‑cell health.
- 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‑folate regimens raised hemoglobin and reduced anemia in anemic children — folate part of effective regimens (iron main driver).
- Micronutrient supplementation and pregnancy outcomes: double-blind randomized controlled trial in China
PubMed ID: 23303315
Large trial including iron+folic acid reduced anemia prevalence in pregnant women—hematologic benefit observed (iron major driver).
- 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
1 mg/day folate increased erythrocyte folate (biomarker related to folate stores important for erythropoiesis).
- Addition of cobalamin to iron and folic acid improves hemoglobin rise in nutritional anemia
PubMed ID: 22415494
In children with nutritional anemia, iron+folic acid plus cobalamin produced larger hemoglobin increases than iron+folic acid alone; folate was included in baseline therapy.
- 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 folic acid status and reduced anemia risk compared with IFA alone in adolescent girls, implying improved RBC production risk profile.
- Long-term effect of low-dose folic acid intake: potential effect of mandatory fortification on the prevention of neural tube defects
PubMed ID: 21593499
Randomized intervention showed chronic low‑dose folic acid steadily raises RBC folate and model predicts meaningful RBC folate increases — supports erythropoiesis nutrient status.
- Randomized controlled trial of 2 prenatal iron supplements: is there a dose-response relation with maternal hemoglobin?
PubMed ID: 21367950
Pregnancy trial: iron+folate and MMN raised hemoglobin in women who were anemic at baseline — improved erythropoiesis in anemic subgroup.
- 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
Dose‑response trial produced large RBC folate increases and reduced prevalence of RBC folate below protective threshold — direct RBC biomarker effect.
- 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
Twice-weekly MMN improved hemoglobin and RBC folic acid more than twice-weekly iron+folic acid in anemic girls—direct red-cell production/folate-status effects.
- 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
Programmatic iron–folic acid delivery produced a measurable increase in population haemoglobin and lower anaemia prevalence.
- Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma
PubMed ID: 37068377
Similar strong evidence: folic acid supplementation reduced hematologic toxicity in mesothelioma patients receiving pemetrexed+cisplatin, demonstrating a clinically important hematologic protective effect.
- Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy
PubMed ID: 37196429
Strong clinical evidence: folic acid + B12 given with pemetrexed dramatically reduced severe hematologic toxicity (including neutropenia) and related complications—supports role in protecting bone‑marrow/hematopoiesis during chemo.
- 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
Iron regimen combined with folinic acid significantly improved hemoglobin and ferritin in iron‑deficient pregnant women.
- Improving Micronutrient Status of Children and Women in Rural Communities in India Using Crystal Salt Enriched with Multiple Micronutrients
PubMed ID: 33952731
Salt fortified with folic acid (plus other micronutrients) produced a large reduction in anaemia and rises in hemoglobin/ferritin — strong supportive evidence.
- 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
Intervention (probiotic + low-dose iron and folic acid) led to smaller declines in ferritin and Hb in pregnancy versus placebo; folic acid was a component though not isolated.
- 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 containing iron and folic acid reduced anemia prevalence and improved iron-status markers in children vs baseline, demonstrating impact on hematologic outcomes.
- The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT
PubMed ID: 31776782
After sleeve gastrectomy, an enhanced multivitamin raised serum folate and substantially reduced anemia rates (per‑protocol), directly supporting RBC-related outcomes.
- 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
Leucovorin (reduced folate) rescue at 18h reduced severe neutropenia/thrombocytopenia versus 24h; demonstrates folate form supports hematologic recovery/less cytopenia in MTX context.
- 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
Green‑MED diet increased serum folate and hemoglobin/iron-related measures — direct evidence that dietary folate supports hematologic status.
- Optimizing Vitamin and Trace Element Profiles in Blood after Gastrointestinal Tract Surgery by a New Parenteral Nutrition Formula
PubMed ID: 30799392
PN formula with increased folic acid raised plasma folate in surgical patients — folate is essential for erythropoiesis and preventing macrocytic anemia.
- 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
Randomized RYGB limb length trial showed longer limb increased folic acid deficiency risk, implicating folate's role in RBC maintenance and need for supplementation.
- 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
Trials of prenatal/postnatal LNS/MNP/IFA (which included folic acid) produced substantial reductions in childhood anemia and iron‑deficiency anemia at 18 months—direct evidence supporting hematologic effects in children.
- 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
Fortified prenatal supplement (includes folate) reduced late‑pregnancy anemia — direct evidence of hematologic benefit.
- Prenatal Hemoglobin Levels and Early Cognitive and Motor Functions of One-Year-Old Children
PubMed ID: 26055847
Iron + folic acid supplementation raised maternal hemoglobin and reduced anemia at delivery—direct evidence implicating folate‑containing antenatal supplements in supporting erythropoiesis.
- Impact of multiple micronutrient supplementation ("sprinkles") on iron deficiency anemia in Bedouin Arab and Jewish infants
PubMed ID: 25167690
Home fortification 'Sprinkles' that included folic acid (plus iron and other micronutrients) significantly reduced markers of iron‑deficiency and anemia in infants — strong evidence of improved red cell indices in the combined supplementation context, though folic acid was not the sole active.
- [Efficacy and toxicity of pemetrexed or gemcitabine combined with cisplatin in the treatment of patients with advanced non-small cell lung cancer]
PubMed ID: 23075680
Folic acid and B12 were co‑administered with pemetrexed to reduce hematologic toxicity; trial showed reduced leukopenia, supporting a role in blood cell health during chemotherapy.
- Once a week (200 mg) elemental iron: an effective option for prophylaxis in non-anaemic pregnant women
PubMed ID: 22480099
Pregnancy study showed significant increases in hemoglobin/PCV; folic acid was present but iron was the main driver — still indicates relevance to hematologic status in pregnancy.
- Efficacy of different strategies to treat anemia in children: a randomized clinical trial
PubMed ID: 20863398
Randomized trial in anemic children: iron+folic acid produced marked hemoglobin increases and greater anemia reduction vs fortified food — direct clinical evidence for RBC support.
- The effects of iron and/or zinc supplementation on maternal reports of sleep in infants from Nepal and Zanzibar
PubMed ID: 19322104
Infant iron–folic acid supplementation is directly relevant to anemia prevention and red blood cell formation in infants.
- Sustainable effect of Ayurvedic formulations in the treatment of nutritional anemia in adolescent students
PubMed ID: 20180694
Indian adolescents: iron+folic acid produced a modest sustained hemoglobin rise—supportive of correcting anemia when combined with iron.
- 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
Iron–folic acid supplementation during pregnancy improved neonatal outcomes and reduced early neonatal mortality compared with folic acid alone; while RBC indices were not the primary reported outcomes, iron+folate is a standard intervention to prevent maternal/neonatal anemia (moderate support).
- Micronutrient Sprinkles reduce anemia among 9- to 24-mo-old children when delivered through an integrated health and nutrition program in rural Haiti
PubMed ID: 17374671
Micronutrient Sprinkles (including folic acid and iron) produced large, significant increases in hemoglobin and reduced anemia prevalence in young children — strong evidence that the program improved RBC parameters (though folate was not isolated).
Brain health (76)
- 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
Fortified milk RCT raised red-cell/plasma folate to levels associated with low neural-tube-defect risk — strong relevance to fetal brain/neuraxis development.
- Enhancement of recovery from psychiatric illness by methylfolate
PubMed ID: 1974941
Methylfolate improved psychiatric outcomes in folate‑deficient patients — supports brain/mental health where folate deficiency is present.
- 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 + B12 substantially lowered homocysteine—potentially relevant to secondary brain vascular risk.
- Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia
PubMed ID: 12823643
Folic acid+B12 lowered homocysteine ~30% in people at high dementia risk—biochemical change relevant to brain health though short-term cognition unchanged.
- Exclusive breast-feeding for 6 months, with iron supplementation, maintains adequate micronutrient status among term, low-birthweight, breast-fed infants in Honduras
PubMed ID: 15113951
Exclusive breastfeeding maintained infant folate — adequate infant folate supports early brain development though direct neuro outcomes not reported.
- Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities
PubMed ID: 15523663
Periconceptional multivitamin with folic acid strongly reduced neural tube defects and some congenital cardiac malformations—direct prevention of neural development defects.
- Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women
PubMed ID: 14985695
Daily folic acid raised RBC folate to levels associated with neural-tube defect risk reduction (relevant to brain/neuronal development).
- Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia
PubMed ID: 16412989
Crossover trial in schizophrenia showed cognitive improvements with B‑vitamin therapy including folic acid.
- 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 RCT: folic acid markedly raised folate/lowered homocysteine and produced small but significant cognitive improvements over 3 years.
- A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease
PubMed ID: 17600848
In Alzheimer’s patients folic acid (1 mg) plus cholinesterase inhibitor improved functional/social measures and responder rates.
- 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
Prenatal multimicronutrient (including folate) maternal supplementation produced small but significant improvements in infant mental development at 1 year.
- Impact of a multiple-micronutrient fortified salt on the nutritional status and memory of schoolchildren
PubMed ID: 20533221
Schoolchildren given salt fortified with multiple vitamins (including folic acid) showed improved memory—cognitive/brain benefit in a nutritional program.
- Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal
PubMed ID: 21177506
Prenatal iron+folic acid produced modest improvements in later child cognitive and motor outcomes—supports neurodevelopmental benefits of maternal folate.
- 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
Folic acid + B12 improved global, immediate and delayed memory scores over 2 years in older adults with distress.
- Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
PubMed ID: 21780182
B‑vitamin regimen including folic acid lowered homocysteine and slowed cognitive decline in MCI participants — direct brain health benefit.
- The effect of maternal multiple micronutrient supplementation on cognition and mood during pregnancy and postpartum in Indonesia: a randomized trial
PubMed ID: 22427850
Large randomized substudy: maternal MMN (including folic acid) produced modest overall cognitive and reading efficiency benefits, especially in undernourished/anemic women.
- Effects of a multivitamin, mineral and herbal supplement on cognition and blood biomarkers in older men: a randomised, placebo-controlled trial
PubMed ID: 22711385
Short RCT of multivitamin improved a measure of episodic memory alongside folate/B12 increases and homocysteine lowering.
- Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia
PubMed ID: 23467813
Folate+B12 improved negative symptoms in schizophrenia — supports some aspects of brain/mental health.
- A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes
PubMed ID: 23507369
Folate augmentation improved depressive symptoms — neuropsychiatric/brain health relevance.
- Effect of iron deficiency anemia in pregnancy on child mental development in rural China
PubMed ID: 23400604
Prenatal iron/folate supplementation protected child mental development vs prenatal iron‑deficiency anemia (folate part of antenatal regimen).
- 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 offspring executive attention and altered brain activation years later (direct developmental brain benefit).
- 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
RCT in MCI: folic acid improved multiple cognitive tests and biomarkers (strong direct evidence for cognitive benefit in MCI).
- 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
Young children receiving folic acid±B12 showed improved gross motor and problem-solving scores (direct neurodevelopmental benefit).
- Folic Acid Supplementation Mitigates Alzheimer's Disease by Reducing Inflammation: A Randomized Controlled Trial
PubMed ID: 27340344
RCT in AD: folic acid + donepezil improved MMSE and reduced TNF‑α/Aβ40 over 6 months.
- 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
Folic acid and DHA alone and combined improved cognitive scores and lowered oxidative DNA damage/increased mtDNA in MCI—strong, direct brain-health trial evidence.
- Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
PubMed ID: 29255930
Randomized 24‑month folic acid supplementation in MCI improved multiple cognitive test scores and reduced Aβ biomarkers—direct brain‑health evidence.
- 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 iron+folic acid improved child linear growth and fine motor development at age 2, supporting early brain/neuromotor development.
- Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial
PubMed ID: 28289280
L‑methylfolate RCT showed biochemical, symptomatic and convergent MRI changes in schizophrenia, indicating direct brain effects.
- Maternal multiple micronutrient supplementation and other biomedical and socioenvironmental influences on children's cognition at age 9-12 years in Indonesia: follow-up of the SUMMIT randomised trial
PubMed ID: 28104188
Long‑term follow‑up of maternal MMN (including folate) produced small persistent cognitive benefits in children at 9–12 years.
- B-Vitamin Therapy for Kidney Transplant Recipients Lowers Homocysteine and Improves Selective Cognitive Outcomes in the Randomized FAVORIT Ancillary Cognitive Trial
PubMed ID: 29182708
Modest improvements in specific cognitive domains (processing speed, delayed recall) observed with high‑dose B‑vitamin therapy that included folic acid.
- Folic Acid Supplementation throughout pregnancy: psychological developmental benefits for children
PubMed ID: 29469926
Small randomized trial: continued maternal folic acid associated with higher emotional intelligence/resilience in children, indicating developmental brain effects.
- 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 lowered homocysteine/inflammation and produced small but significant cognitive gains in older adults with MCI.
- 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
RCT continuing folic acid in pregnancy produced small but significant improvement in offspring verbal reasoning at age 7 and large increases in maternal/cord folate.
- 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 RCT in AD (non‑fortified population) gave modest cognitive improvement and lowered Hcy/TNFα — supports brain effects in adults.
- 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 (trimesters 2–3) RCT produced sustained cognitive and neural differences in children at 11 y — strong brain‑development evidence.
- Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment
PubMed ID: 33935094
RCT in MCI: B‑vitamins including folic acid lowered tHcy and reduced cognitive decline and brain atrophy associations — strong brain benefit.
- 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
Folic acid improved cognition and processing speed over 3 years in older adults with low omega‑3 status (subgroup effect).
- B Vitamin Supplementation Slows Cognitive Decline in Mild Cognitive Impairment Patients with Frontal Lobe Atrophy
PubMed ID: 36057827
B‑vitamin trial in MCI lowered homocysteine and slowed decline in a subgroup — suggests brain‑health benefit in selected patients.
- Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults
PubMed ID: 36169979
Large observational association between folic‑acid prescriptions and reduced suicide attempts implies central nervous system/mental‑health relevance.
- Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms
PubMed ID: 35578268
Randomized maternal folic acid continuation altered cord‑blood DNA methylation at brain‑expressed genes — plausible mechanistic effect on offspring brain development.
- Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial
PubMed ID: 39243316
Randomized folinic‑acid trial in children with ASD improved autism severity and behaviors—direct clinical evidence of benefit to neurodevelopment/brain-related outcomes.
- Cognitive benefits of folic acid supplementation during pregnancy track with epigenetic changes at an imprint regulator
PubMed ID: 39681839
Pregnancy folic acid RCT altered cord‑blood imprint methylation and mitigated genotype‑linked processing‑speed/MEG deficits in offspring—supports neurodevelopmental protection.
- Prognostic Impact of Serum Homocysteine-Lowering Therapy on Patients with Hemorrhagic Stroke and Its Influence on National Institutes of Health Stroke Scale and China Stroke Scale Scores
PubMed ID: 37793337
High‑dose homocysteine‑lowering B‑vitamin therapy in hemorrhagic stroke associated with better neurological scores (NIHSS/CSS); folate likely contributed though multi‑vitamin regimen used.
- 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 RCT in young children with autism produced a statistically significant improvement in social reciprocity—direct brain/behavior effect.
- 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
Adjunctive folate reduced mania and improved MMSE scores, indicating beneficial effects on brain function in psychiatric patients.
- Prenatal and preschool micronutrient supplementation and behavioral outcomes in school-aged children in Nepal-a cohort study
PubMed ID: 41092983
Prenatal iron‑folate exposure associated with modest reductions in child hyperactivity/inattention scores on follow‑up — developmental brain effects.
- Folic acid supplementation improves cognitive function in participants with cerebral small vascular disease-related cognitive impairment: a randomized controlled trial
PubMed ID: 40945966
RCT in CSVD-related cognitive impairment: folic acid lowered homocysteine and produced significant improvements in MoCA and MMSE.
- Prevention of congenital abnormalities by periconceptional multivitamin supplementation
PubMed ID: 8324432
Large randomized trial of periconceptional multivitamin with 0.8 mg folic acid showed strong reduction in neural-tube and major congenital CNS defects (neural development/brain health relevance).
- Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study
PubMed ID: 8257478
5'-MTHF improved depression scores in elderly demented patients, implying central nervous system/brain effect.
- Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy--a Pediatric Oncology Group study
PubMed ID: 9586883
Shows that lower folinic‑acid rescue relative to methotrexate exposure is associated with increased acute neurotoxicity and leukoencephalopathy — direct neuroprotection implication for folate rescue.
- VITATOPS, the VITAmins TO prevent stroke trial: rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke (NCT00097669) (ISRCTN74743444)
PubMed ID: 18705976
VITATOPS targeted recurrent stroke prevention with folic acid+B vitamins — directly relevant to cerebrovascular/brain outcomes (design paper only).
- The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability
PubMed ID: 19384265
B‑vitamin therapy including folic acid produced clinical benefit (halved migraine disability) and large homocysteine reductions — direct CNS clinical signal in this dataset.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
Strong RCT evidence: B9 (with B12/B6) lowered homocysteine and markedly slowed brain atrophy in older adults with MCI.
- B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial
PubMed ID: 20976769
Long-term B‑vitamin supplementation reduced post-stroke major depression — indicates neuropsychiatric/brain benefits.
- Effect of leucovorin (folinic acid) on the developmental quotient of children with Down's syndrome (trisomy 21) and influence of thyroid status
PubMed ID: 20084109
Randomized, double-blind trial of folinic acid in young children with Down syndrome showing per-protocol improvements in global developmental age and coordination — direct CNS/developmental evidence.
- L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials
PubMed ID: 23212058
L‑methylfolate improved depressive symptoms when added to SSRIs—indirect evidence that bioavailable folate can benefit brain function in depression.
- 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 improved depression outcomes (brain-related clinical endpoint) in a randomized trial — supports brain health relevance.
- Prenatal Hemoglobin Levels and Early Cognitive and Motor Functions of One-Year-Old Children
PubMed ID: 26055847
All mothers received iron+folic acid and maternal Hb related to infant motor scores; supports an association between maternal folate-containing supplementation and early neurodevelopment (moderate indirect evidence).
- Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial
PubMed ID: 27752075
Randomized, placebo‑controlled trial: high‑dose folinic acid produced clinically meaningful improvements in verbal communication and behavior in children with autism, direct strong evidence for neurological benefit.
- Home fortification during the first 1000 d improves child development in Bangladesh: a cluster-randomized effectiveness trial
PubMed ID: 28275128
Large cluster‑RCT of prenatal/postnatal supplementation (programs including folic acid) showed modest improvements in motor and language development—relevant to early brain health, though folic acid not isolated.
- 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
Randomized folinic acid adjunct improved core behavioral features in children with ASD — directly relevant to brain/behavioral health.
- Preconception micronutrient supplementation positively affects child intellectual functioning at 6 y of age: A randomized controlled trial in Vietnam
PubMed ID: 33668050
Preconception MMS (including folic acid) produced small but significant improvements in children's IQ, working memory and processing speed at age 6–7.
- 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
Trial in pregnant women used folinic acid and showed improved maternal iron markers and higher newborn weight — relevant to fetal brain development (direct folate role).
- 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 trials (including folic acid) showed slowed cognitive decline and reduced brain atrophy in MCI — direct evidence for brain‑protective effects in that population.
- Long-Chain Polyunsaturated Fatty Acids, Homocysteine at Birth and Fatty Acid Desaturase Gene Cluster Polymorphisms are Associated with Children's Processing Speed up to Age 9 Years
PubMed ID: 33396458
Maternal folate status and lower tHcy during pregnancy associated with better child processing speed and some improved neurodevelopment measures.
- Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers
PubMed ID: 18270369
Higher dietary folate associated with ~20% lower ischemic stroke risk (protects cerebrovascular health).
- [Clinical studies on fifty-seven Chinese patients with combined methylmalonic aciduria and homocysteinemia]
PubMed ID: 17953808
Patients with methylmalonic aciduria/homocysteinemia receiving B12+folic acid regimens had clinical neurological recovery in a subset.
- Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children
PubMed ID: 17704033
Fortified salt with folic acid was associated with improvements in several cognitive/attention tests in children.
- Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women
PubMed ID: 17302515
Folic‑acid fortified water in pregnant women substantially raised maternal folate (important for fetal brain development) — indirect support for cognitive outcomes.
- Trial using multiple micronutrient food supplement and its effect on cognition
PubMed ID: 18716734
School food supplement including folic acid improved blood indices and several memory/attention measures after one year.
- 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
Methylfolate (5‑MTHF) given with fish‑oil modestly increased maternal DHA; maternal/cord DHA relevant to fetal/infant brain development.
- 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‑vitamins including folate slowed MRI-measured brain atrophy in MCI subjects with high ω‑3 levels—direct brain-structure benefit.
- Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment
PubMed ID: 26757190
B‑vitamin regimen (including folic acid) improved global cognition and episodic memory in MCI patients with high ω‑3 status—direct cognitive-function benefit.
- 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 randomized trial: folic acid (800 µg/d) ± DHA improved global cognition and reduced inflammatory markers in elderly with MCI—direct brain health evidence.
- 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
Folic acid (0.8 mg) improved specific cognitive tests, increased SAM and lowered homocysteine and blood Aβ in MCI—biochemical and cognitive brain benefits.
- DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial
PubMed ID: 35704085
Folic acid + B12 slowed cognitive decline only in participants with higher baseline DHA—subgroup benefit for cognition/brain health.
Cell health (129)
- Actinomycin d versus methotrexate-folinic acid as the treatment of stage I, low-risk gestational trophoblastic neoplasia: a randomized controlled trial
PubMed ID: 19574798
Folinic acid (reduced folate) was used as part of MTX regimens/rescue — folinate participates in nucleotide synthesis pathways and is mechanistically linked to DNA synthesis.
- Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid
PubMed ID: 12421850
Large increases in red cell folate indicate sufficient substrate for DNA synthesis and mitosis.
- Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial
PubMed ID: 12637400
Pregnancy supplements including folic acid with iron/multiple micronutrients modestly increased newborn weight—evidence of enhanced fetal growth when folate is part of a regimen.
- The effect of folic acid and folinic acid supplements on purine metabolism in methotrexate-treated rheumatoid arthritis
PubMed ID: 15476202
Folinic acid (reduced folate) corrected MTX‑induced accumulation of AICA, directly reversing MTX interference in purine (DNA) metabolism — strong mechanistic evidence.
- Effect of folic Acid supplementation on the folate status of buccal mucosa and lymphocytes
PubMed ID: 15247137
Raised lymphocyte folate and plasma 5‑MeTHF indicate improved intracellular folate availability for growth-related pathways.
- Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities
PubMed ID: 15523663
Prevention of NTDs by periconceptional folate implies support for embryonic cell growth and morphogenesis.
- 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
In vitro lymphocyte cultures showed folate deficiency increased genomic damage and cell death, indicating folate is needed for faithful cell division.
- Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma
PubMed ID: 15831910
Folic acid supplementation increased serum/erythrocyte folate and raised genomic DNA methylation in blood and colon tissue (mechanistic).
- Folic acid fortified milk increases blood folate and lowers homocysteine concentration in women of childbearing age
PubMed ID: 15927936
Large RBC folate increases in women of childbearing age support folate's role in DNA synthesis and cell division (periconceptional relevance).
- 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 with fewer micronuclei (chromosome stability); short‑term supplementation did not change markers.
- Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers
PubMed ID: 16736000
Folic acid increased SAM and significantly reduced uracil misincorporation into DNA—direct evidence of improved DNA synthesis/stability.
- 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
Reduction in anemia with iron+folic acid suggests improved hematopoietic cell growth.
- 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 anemia recovery with folic acid+iron indicates enhanced erythropoiesis (cell growth).
- [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 preserved and increased RBC folate during lactation — supports one‑carbon metabolism used in DNA synthesis.
- 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
Active folate ([6S]‑5‑MTHF) raised RBC and plasma folate more than folic acid — biochemical support for DNA synthesis capacity.
- Folic acid and vitamin B-12 supplementation does not favorably influence uracil incorporation and promoter methylation in rectal mucosa DNA of subjects with previous colorectal adenomas
PubMed ID: 17709451
High‑dose folic acid+B12 altered molecular markers (increased uracil misincorporation and trends to altered methylation), directly implicating folate in DNA metabolism (but showing possible adverse changes).
- 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
Short‑term folic acid supplementation raised plasma and colonic mucosal 5‑methyl THF, increasing substrate for DNA synthesis in target tissue.
- Folic acid does not improve endothelial function in obese children and adolescents
PubMed ID: 17519435
Large increase in red‑cell folate after supplementation supports folate’s role in cell division (erythropoiesis example).
- 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 RBC/plasma folate support availability for cell division.
- Colorectal adenomas in a randomized folate trial: the role of baseline dietary and circulating folate levels
PubMed ID: 18843003
Large RCT: 1 mg/day folic acid produced major increases in circulating folate (biochemical substrate for DNA synthesis/methylation).
- 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
RBC/serum folate increases indicate improved one‑carbon metabolism needed for cell growth and division (mechanistic link).
- Antenatal micronutrient supplementation reduces metabolic syndrome in 6- to 8-year-old children in rural Nepal
PubMed ID: 19549749
Antenatal folic acid linked to healthier child metabolic/kidney outcomes—consistent with supporting fetal cell growth during gestation.
- 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
Raised RBC folate supports folate‑dependent cell division processes, particularly in pregnancy.
- Modeling mechanisms of in vivo variability in methotrexate accumulation and folate pathway inhibition in acute lymphoblastic leukemia cells
PubMed ID: 21152005
Mechanistic study showing folate-pathway enzyme differences and polyglutamation govern folate-dependent DNA synthesis and thus cell division—strong mechanistic relevance.
- 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
RBC folate increases at protective levels are directly relevant to one‑carbon metabolism needed for healthy cell division, particularly in early pregnancy.
- 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
Dose/genotype study demonstrated folate and homocysteine responses influenced by MTHFR genotype — directly tied to one‑carbon metabolism relevant to DNA synthesis.
- Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age
PubMed ID: 22163281
Randomized folic acid dosing showed dose‑dependent increases in folate and sample‑type changes in global DNA methylation — direct one‑carbon/epigenetic effect relevant to DNA synthesis/repair.
- Associations between genes in the one-carbon metabolism pathway and advanced colorectal adenoma risk in individuals with low folate intake
PubMed ID: 22253295
Epidemiologic data show low folate intake interacts with one‑carbon metabolism genotypes to raise advanced colorectal adenoma risk — consistent with folate's role in DNA synthesis/repair and carcinogenesis prevention.
- 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
Erythrocyte folate increases after 1 mg/day indicate improved folate supply for DNA synthesis and cell division.
- 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
Daily folic acid (1 mg) substantially reduced incident colorectal adenomas — implicates folate's role in DNA synthesis/repair and neoplasia prevention.
- The effect of folic acid supplementation with ferrous sulfate on the linear and ponderal growth of children aged 6-24 months: a randomized controlled trial
PubMed ID: 25335446
Folic acid supplementation in infants increased weight gain and weight‑for‑age, reflecting enhanced somatic growth in early childhood.
- 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 increases in RBC folate during pregnancy support one‑carbon metabolism required for cell division during fetal development.
- 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) with folic acid in arsenic‑exposed adults—supports DNA protection/synthesis.
- 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
Folic acid increased CIN1 regression indicating favorable effects on abnormal cervical epithelial cell division.
- 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
400 μg folic acid in pregnancy increased fetal/cord folate forms — supports substrate availability for fetal DNA synthesis and methylation.
- 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 IFA improved child linear growth and motor outcomes, consistent with nutrient support for early cell/tissue growth.
- Unmetabolized Folic Acid, Tetrahydrofolate, and Colorectal Adenoma Risk
PubMed ID: 28600398
Higher methylated folate associated with increased advanced/multiple adenoma risk, consistent with folate facilitating cell division/proliferation.
- 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
Marked increases in RBC‑folate with 800 µg/day support folate‑dependent one‑carbon metabolism required for DNA synthesis and cell division.
- Response of Red Blood Cell Folate to Supplementation in Nonpregnant Women is Predictable: A Proposal for Personalized Supplementation
PubMed ID: 29143484
Dose/time modeling of RBC folate supports predictable attainment of folate levels needed for proper cell division preconception/pregnancy.
- Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock
PubMed ID: 30350398
Folic acid + B12 changed DNA methylation patterns and reduced epigenetic age in women — direct molecular evidence linking folate to DNA methylation dynamics.
- A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57
PubMed ID: 30777123
Pregnancy RCT showed robust increases in maternal/cord folate and changes in offspring DNA methylation—evidence folate availability affects one‑carbon biology and DNA methylation.
- Folic acid supplementation and risk of colorectal neoplasia during long-term follow-up of a randomized clinical trial
PubMed ID: 31401653
RCT found increased risk of sessile serrated lesions with prolonged folic acid — a clinical signal that folate can promote proliferation of certain colonic cell populations.
- Efficacy of 4.0 mg versus 0.4 mg Folic Acid Supplementation on the Reproductive Outcomes: A Randomized Controlled Trial
PubMed ID: 34959975
Higher-dose folic acid (4 mg) increased birthweight and reduced composite adverse outcomes, supporting fetal growth effects.
- 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 and oxidative markers, and trended to lower CIN2/3 recurrence — consistent with roles in DNA synthesis/repair.
- Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomised controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA)
PubMed ID: 36632790
Cord‑blood gene expression changes enriched for G2/M transition and chromosome segregation after preconception micronutrient intervention (including folate) indicate influence on cell proliferation pathways.
- 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 markedly amplified risk of CIN3+ in presence of high HPV/host methylation—supports folate's role in one‑carbon metabolism, DNA methylation and genomic stability.
- Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial
PubMed ID: 38342693
Folic acid produced histological improvement in gastric precancerous lesions—suggests folate influences mucosal DNA/repair processes relevant to carcinogenesis.
- Modulation of the antitumor effect of methotrexate by low-dose leucovorin in squamous cell head and neck cancer: a randomized placebo-controlled clinical trial
PubMed ID: 2405105
Leucovorin (folinic acid) rescue altered tumor response and toxicity by interacting with folate-dependent pathways required for DNA synthesis/cell division.
- Sequential combination of methotrexate (MTX), 5-fluorouracil (FU), and high-dose folinic acid (FA) in advanced colorectal cancer: double biochemical modulation?
PubMed ID: 1951176
Combination sequence including folinic acid produced meaningful tumor responses; demonstrates clinical activity of a folate-derivative-containing regimen though folinic acid was part of a multi‑drug sequence.
- Retrospective analysis of late intensification therapy with high-dose methotrexate for standard-risk acute lymphoblastic leukemia in childhood (CCLSG-S811 study). The Children's Cancer and Leukemia Study Group
PubMed ID: 1777605
Early intensification with high-dose MTX and leucovorin rescue correlated with substantially higher EFS in childhood ALL — clinical relevance to cell growth control via folate-pathway modulation in chemotherapy regimens.
- Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer
PubMed ID: 1941055
Large randomized trial showing leucovorin (a B9 derivative) added to 5-FU improved response and survival versus a comparator regimen — clinically important effect consistent with folate’s biochemical role in nucleotide metabolism that modulates fluoropyrimidine activity.
- Randomised comparison of weekly bolus 5-fluorouracil with or without leucovorin in metastatic colorectal carcinoma
PubMed ID: 1389519
Leucovorin (folinic acid) modulates 5-FU activity by stabilizing thymidylate synthase complexes — this randomized trial showed increased tumor response, reflecting folate pathway pharmacology.
- Intravenous 6-thioguanine or cisplatin, fluorouracil and leucovorin for advanced non-small cell lung cancer: a randomized phase II study of the cancer and leukemia group B
PubMed ID: 1333267
Oral leucovorin included in multi-agent chemo increased response and survival in NSCLC — consistent with folate modulation of antimetabolite effect (DNA synthesis relevance).
- Fluorouracil versus folinic acid/fluorouracil in advanced colorectal cancer--preliminary results of a randomized trial
PubMed ID: 1557640
Addition of folinic acid to 5-FU substantially prolonged time to progression and increased responses — clinical demonstration of folate-related effects on nucleotide synthesis in chemo modulation.
- [Fluorouracil as monotherapy or combined with folinic acid in the treatment of metastasizing colorectal carcinoma]
PubMed ID: 1618109
Combining folinic acid with 5-FU significantly increased tumor responses and nearly doubled median survival — strong clinical signal of folinate's biochemical role in pyrimidine metabolism relevant to DNA synthesis.
- Weekly regimen of 5-FU vs 5-FU + intermediate dose folinic acid in the treatment of advanced colorectal cancer
PubMed ID: 1622115
Weekly 5-FU plus folinic acid greatly increased objective responses versus 5-FU alone — consistent with folate pathway involvement in nucleic acid metabolism.
- 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 folinic acid after weekly methotrexate markedly reduced toxicity and withdrawals without reducing efficacy — consistent with rescue of normal-cell division from antifolate toxicity.
- Folinic acid does improve 5-fluorouracil activity in vivo. Results of a phase III study comparing 5-fluorouracil to 5-fluorouracil and folinic acid in advanced colon cancer patients
PubMed ID: 8459266
Randomized phase III: folinic acid roughly tripled tumor response vs 5-FU alone — clinical evidence of folinate affecting thymidylate synthase/DNA synthesis balance.
- Prevention of congenital abnormalities by periconceptional multivitamin supplementation
PubMed ID: 8324432
Periconceptional folic acid supports proper embryonic cell proliferation and neural-tube closure — relevant to normal cell growth in fetal development.
- Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer
PubMed ID: 7683942
Small randomized trial where leucovorin-containing chemotherapy doubled median survival; leucovorin's role is modulation of 5-FU's DNA-synthesis effects.
- The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03
PubMed ID: 8410113
Large randomized adjuvant trial: leucovorin-modulated 5-FU significantly improved disease-free and overall survival—direct clinical effect of folinic acid in 5-FU modulation (DNA synthesis).
- Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer
PubMed ID: 8143995
Randomized trial: adding folinic acid to 5-FU reduced recurrence and improved survival in colon cancer—strong clinical evidence of folinate's role when paired with DNA-targeting 5-FU.
- Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators
PubMed ID: 7715291
Large pooled adjuvant trials: high-dose folinic acid + 5-FU reduced recurrence/mortality; mechanistically folinate participates in one-carbon metabolism and thymidylate synthesis (moderate direct mechanistic/clinical linkage).
- Treatment of advanced colorectal cancer with high-dose intensity folinic acid and 5-fluorouracil plus supportive care
PubMed ID: 8562173
Randomized study: high-intensity folinic acid + 5-FU increased response and survival vs 5-FU alone — clinical evidence consistent with folinate's role in DNA synthesis modulation.
- Combined intraperitoneal plus intravenous chemotherapy after curative resection for colonic adenocarcinoma
PubMed ID: 8562152
Adjuvant intraperitoneal/IV 5-FU + leucovorin improved survival/recurrence vs observation — supports folinate's clinical impact tied to nucleic acid synthesis pathways in chemotherapy modulation.
- [Early phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal cancer. l-Leucovorin and 5-FU Study Group]
PubMed ID: 7717714
Dose/schedule study where higher-dose/weekly leucovorin increased 5-FU response rates — clinical support for folinate's role in pathways related to DNA synthesis and chemo modulation.
- [Clinical evaluation of leucovorin and 5-fluorouracil]
PubMed ID: 7611750
Randomized trial showed dose‑dependent effects of leucovorin (a reduced folate) on 5‑FU modulation; leucovorin’s biochemical role is directly tied to thymidylate synthase/one‑carbon transfer and DNA synthesis, though here used to modulate cytotoxic therapy.
- Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation
PubMed ID: 8882400
Periconceptional folic acid significantly reduced congenital malformations, consistent with essential folate role in embryonic cell division.
- 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
Duplicate listed: high‑dose folinic acid benefit described above.
- Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with weekly high-dose 48-hour continuous-infusion fluorouracil for advanced colorectal cancer: a Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD) study
PubMed ID: 9739438
Duplicate: infusion vs bolus leucovorin context.
- Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy--a Pediatric Oncology Group study
PubMed ID: 9586883
Study shows MTX neurotoxicity risk is related to MTX:leucovorin ratios and timing — leucovorin rescue is used to protect dividing normal cells during antifolate chemotherapy.
- Effective biomodulation by leucovorin of high-dose infusion fluorouracil given as a weekly 24-hour infusion: results of a randomized trial in patients with advanced colorectal cancer
PubMed ID: 9469324
Duplicate listed: see earlier entry (leucovorin modulation improves DNA‑related chemo 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
Duplicate listed: see first entry (strong evidence of leucovorin modulating DNA synthesis with clinical endpoints).
- 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
Duplicate noted earlier: MTHF as folate modulator with clinical effects.
- Combined intravenous and intraperitoneal chemotherapy with fluorouracil + leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon carcinoma
PubMed ID: 9579845
Intraperitoneal + IV 5‑FU + leucovorin significantly improved DFS and OS vs FU/levamisole — leucovorin's role modulating 5‑FU is mechanistically tied to thymidylate synthase/DNA synthesis.
- Long-term somatic and mental development of children after periconceptional multivitamin supplementation
PubMed ID: 9776529
Periconceptional folic-acid–containing multivitamin use during early embryogenesis relates to nucleotide supply and DNA synthesis important for development; evidence supports biological plausibility and safety.
- Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02
PubMed ID: 10699069
Leucovorin-modulated 5-FU showed subgroup DFS benefit; leucovorin (folinate) acts on folate-dependent DNA synthesis pathways — moderate direct relevance.
- 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 adjuvant colon cancer trial showing clinically important survival benefit when 5-FU was modulated with folinic acid (direct mechanistic role of folate in thymidylate synthase stabilization/DNA synthesis).
- Thymidylate synthase expression in colorectal cancer: a prognostic and predictive marker of benefit from adjuvant fluorouracil-based chemotherapy
PubMed ID: 11919227
Thymidylate synthase is central to folate‑dependent DNA synthesis and cell division; the study links TS biology to treatment response, providing an indirect mechanistic tie to folate's role in cell division.
- Increase of survival benefit in advanced resectable colon cancer by extent of adjuvant treatment: results of a randomized trial comparing modulation of 5-FU + levamisole with folinic acid or with interferon-alpha
PubMed ID: 16041207
Large RCT showed clinically important benefit when folinic acid (a B9 derivative) was used with 5‑FU — folinic acid’s mechanism directly involves one‑carbon metabolism and thymidylate synthesis relevant to DNA synthesis.
- A randomised phase II trial of weekly high-dose 5-fluorouracil with and without folinic acid and cisplatin in patients with advanced biliary tract carcinoma: results of the 40955 EORTC trial
PubMed ID: 15691639
Folinic acid included in a regimen that increased tumor responses and survival in biliary tract cancer — supports a role in nucleotide metabolism/chemosensitization (mechanistic relevance to DNA synthesis).
- Weekly infusional high-dose fluorouracil (HD-FU), HD-FU plus folinic acid (HD-FU/FA), or HD-FU/FA plus biweekly cisplatin in advanced gastric cancer: randomized phase II trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie
PubMed ID: 17577037
Adding folinic acid (a reduced folate) to fluorouracil increased tumor response rates — mechanistically consistent with folate's role in nucleotide metabolism/DNA synthesis that modulates 5‑FU efficacy.
- Sulfadoxine-pyrimethamine, chlorproguanil-dapsone, or chloroquine for the treatment of Plasmodium vivax malaria in Afghanistan and Pakistan: a randomized controlled trial
PubMed ID: 17519409
Antifolate antimalarial trial demonstrates the essential role of the folate pathway for parasite DNA synthesis — provides biologic evidence that folate is central to nucleotide/replication pathways.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
Marked increases in plasma folate in trial support folate availability for one-carbon reactions needed for cell maintenance/growth; brain atrophy results imply tissue preservation.
- 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
Folinic acid (active folate) added to 5-FU chemoradiotherapy reduced local recurrence and improved stage‑specific survival — mechanistic role of folate in nucleotide synthesis underlies this benefit.
- Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer
PubMed ID: 20940718
See above; repeated evidence of folinic acid in FOLFOX4 improving anti-tumor activity (mechanistic relevance to DNA synthesis).
- 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
Folinic acid (leucovorin) added to 5‑FU improved long‑term survival in colon cancer; leucovorin directly interacts with thymidylate synthase/folate pathways relevant to DNA synthesis.
- 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
Direct dose–response study of leucovorin (folinic acid) showing large increases in tumour and plasma folate and upregulation of folate-pathway genes — strong mechanistic evidence for folate's role in nucleotide synthesis.
- Optimizing Vitamin and Trace Element Profiles in Blood after Gastrointestinal Tract Surgery by a New Parenteral Nutrition Formula
PubMed ID: 30799392
Increased plasma folate after PN supports folate's role in cell proliferation and repair in postoperative patients.
- Sex-Related Differences in Impact on Safety of Pharmacogenetic Profile for Colon Cancer Patients Treated with FOLFOX-4 or XELOX Adjuvant Chemotherapy
PubMed ID: 31395900
Pharmacogenetic analysis includes MTHFR and other folate‑pathway genes affecting fluoropyrimidine/leucovorin toxicity — mechanistically tied to folate-mediated nucleotide metabolism.
- Higher baseline global leukocyte DNA methylation is associated with MTX non-response in early RA patients
PubMed ID: 31242943
Study links leukocyte one‑carbon (folate-dependent) methylation to treatment response — directly implicates folate pathways and DNA methylation/synthesis.
- 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
Timing of leucovorin rescue influenced rates of severe cytopenias after high‑dose MTX, consistent with folate's role in supporting DNA synthesis and healthy cell division in normal tissues.
- Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy
PubMed ID: 37196429
Folic acid + B12 given with an antifolate chemo (pemetrexed) decreased marrow toxicity, consistent with supporting healthy cell division under cytotoxic stress.
- Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma
PubMed ID: 37068377
Same rationale as above: folate supplementation reduced chemotherapy‑related marrow toxicity indicating support for cell division recovery.
- Comparison of two doses of leucovorin in severe low-dose methotrexate toxicity - a randomized controlled trial
PubMed ID: 37208770
Strong mechanistic/clinical evidence: leucovorin (reduced folate) rescue in methotrexate toxicity shows folate supports DNA synthesis and healthy cell division in proliferating tissues.
- A Randomized Double-blind Clinical Trial of Weierkang Pills for the Treatment of Chronic Atrophic Gastritis
PubMed ID: 35050943
Clinical comparator trial used folic acid + teprenone; histologic measures (atrophy/intestinal metaplasia scores) were assessed and folic‑acid–containing arm showed effects as a comparator—supports a role in mucosal cell health though folate was not isolated as the single active.
- Fluorouracil modulation in colorectal cancer: lack of improvement with N -phosphonoacetyl- l -aspartic acid or oral leucovorin or interferon, but enhanced therapeutic index with weekly 24-hour infusion schedule--an Eastern Cooperative Oncology Group/Cancer and Leukemia Group B Study
PubMed ID: 11331320
Trials of leucovorin (folinic acid) as a 5‑FU modulator show pharmacologic effects on outcomes/toxicity—supporting folate's role in DNA synthesis modulation.
- Traditional Korean diet high in one-carbon nutrients increases global DNA methylation: implication for epigenetic diet
PubMed ID: 38867083
Dietary folate increased plasma 5‑MTHF and global DNA methylation — direct mechanistic evidence linking folate to one‑carbon/epigenetic processes.
- Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children's Oncology Group AALL0434 Methotrexate Randomization
PubMed ID: 30138085
Leucovorin use in MTX regimens underscores folate's central role in nucleotide synthesis and cell division (clinical oncology context).
- Adverse Event Profile by Folate Receptor Status for Vintafolide and Pegylated Liposomal Doxorubicin in Combination, Versus Pegylated Liposomal Doxorubicin Alone, in Platinum-Resistant Ovarian Cancer: Exploratory Analysis of the Phase II PRECEDENT Trial
PubMed ID: 27654255
Exploratory study looked at folate-receptor expression and a folate-targeted drug; connects folate pathway to tumor cell growth biology (indirect).
- A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours
PubMed ID: 16940981
Folate+B12 coadministration reduced chemotherapy‑related hematologic toxicity, implying protection of dividing normal cells.
- Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis
PubMed ID: 12695153
RCT evidence that folate modifies methotrexate toxicity and dosing—consistent with folate's role in supporting normal cell division during exposure to antimetabolites.
- Molecular determinants of folate levels after leucovorin administration in colorectal cancer
PubMed ID: 19636555
Leucovorin (reduced folate) study measured tissue folate distribution and gene expression related to folate metabolism — directly relevant to folate supply for DNA synthesis.
- 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 strongly associated with lower micronucleus frequency — evidence folate supports healthy cell division/genomic stability.
- Vitamin supplementation of HIV-infected women improves postnatal child growth
PubMed ID: 15817867
Maternal multivitamin (including folic acid) supplementation improved child weight and weight‑for‑age/length z‑scores at 24 months (supports growth outcomes).
- 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
Correcting marginal folate status preconception/early pregnancy supports rapid cell division in early embryogenesis (biological rationale and trial evidence of status change).
- Functionality of endogenous folates from rye and orange juice using human in vivo model
PubMed ID: 12474071
Dietary folates increased serum and RBC folate — providing substrate for DNA synthesis and cell division.
- Plasma homocysteine concentration is decreased by dietary intervention
PubMed ID: 12696562
Large increases in serum folate after dietary changes provide substrate for methylation and nucleotide synthesis — relevant to DNA synthesis.
- Multicentric study of efficacy of periconceptional folic acid containing vitamin supplementation in prevention of open neural tube defects from India
PubMed ID: 11247198
Strong preventive effect on neural tube defect recurrence underscores folate's role in DNA synthesis and proper cell division during early embryogenesis.
- Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women
PubMed ID: 17302515
Pregnancy folic‑acid fortification increased maternal folate stores strongly—supports fetal cell growth processes.
- 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
Equivalent increases in plasma and RBC folate from folic acid or L‑5‑MTHF after fortification — shows improved folate availability needed for DNA synthesis and repair (biomarker evidence).
- Folate levels measured by LC-MS/MS in patients with colorectal cancer treated with different leucovorin dosages
PubMed ID: 25238909
Perioperative leucovorin (folinic acid) dose‑dependently raised tissue methyleneTHF (active folate) in tumour/mucosa — direct pharmacologic evidence of substrate for one‑carbon reactions and DNA synthesis.
- One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans
PubMed ID: 25283139
Sustained folic acid supplementation elevated circulating 5‑methylTHF providing substrate necessary for normal cell division (indirect 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
Randomized folate dosing raised active folate markedly — strong biomarker evidence supporting availability for one‑carbon metabolism and DNA synthesis.
- Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation
PubMed ID: 1307234
Folic acid prevents neural‑tube defects by supporting DNA synthesis and cell division in early embryogenesis — direct strong evidence.
- [Prevention of the first occurrence of anencephaly and spina bifida with periconceptional multivitamin supplementation (conclusion)]
PubMed ID: 7970646
Replication of strong RCT evidence linking folate to normal embryonic cell division and neural tube closure.
- Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions
PubMed ID: 15786529
High‑dose folic acid increased gastric mucosal folate and changed apoptosis/p53/Bcl-2 expression in premalignant lesions, indicating effects on cellular proliferation and DNA-related pathways.
- The effect of docosahexaenoic acid and folic acid supplementation on placental apoptosis and proliferation
PubMed ID: 16870008
Significant increase in placental PCNA with 5‑MTHF + DHA — direct evidence of increased placental cell proliferation.
- 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
Folic acid increased SAM and lowered homocysteine and Aβ biomarkers—changes in one‑carbon metabolism support methylation/DNA synthesis pathways.
- 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
Folic acid ± DHA reduced oxidative DNA damage (8‑OHdG) and increased mtDNA copy number—biomarkers consistent with improved DNA integrity/synthesis/mitochondrial genome maintenance.
- Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects
PubMed ID: 2296932
High‑dose folic acid sharply increased folate biomarkers and markedly decreased deoxyuridine suppression test (dUST), a functional assay of folate‑dependent DNA synthesis — strong direct evidence.
- Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group
PubMed ID: 1677062
NTD prevention by periconceptional folic acid reflects restoration of folate‑dependent cell proliferation during embryogenesis (mechanistic linkage).
- Chemoprevention effects on bronchial squamous metaplasia by folate and vitamin B12 in heavy smokers
PubMed ID: 7774326
Reduction of bronchial epithelial atypia with folate+B12 indicates an effect on epithelial cell turnover/aberrant growth (small trial).
- Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial
PubMed ID: 7978695
Folic acid reduced methotrexate toxicity in RA while preserving efficacy—directly relevant to supporting normal folate‑dependent cell processes during antiproliferative therapy.
- Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults
PubMed ID: 9683174
Folate/B12 supplementation lowered homocysteine and reduced a DNA‑damage marker in high‑baseline subjects.
- Folate status of elderly women following moderate folate depletion responds only to a higher folate intake
PubMed ID: 10827214
Repletion restored folate biomarkers and reversed tHcy only at higher dose, consistent with supporting normal cell division through one‑carbon metabolism.
- Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial
PubMed ID: 11339442
Dose‑dependent RBC and plasma folate increases indicate substrate availability for nucleotide synthesis and cell division.
- Genomic DNA methylation decreases in response to moderate folate depletion in elderly women
PubMed ID: 11010943
Controlled folate depletion–repletion in older women caused measurable reductions in leukocyte DNA methylation — direct mechanistic evidence on DNA one‑carbon metabolism.
- 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
Dose‑related folate increases with fortified cereal support nucleotide synthesis capacity.
Mood balance (26)
- Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial
PubMed ID: 28289280
High‑dose L‑methylfolate produced modest but measurable symptomatic and brain‑imaging improvements in schizophrenia, implying CNS/affect modulation potential.
- Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults
PubMed ID: 36169979
Very large within‑person pharmacoepidemiology: months on folic acid prescriptions were associated with substantially lower suicide attempts/self‑harm (strong observational signal).
- Association of serum homocysteine, folate, and vitamin B(12) and mood following the Swank and Wahls elimination dietary interventions in relapsing-remitting multiple sclerosis: Secondary analysis of the WAVES trial
PubMed ID: 37148578
Diet interventions that included methylfolate improved mood in people with MS, though multiple components confounded attribution to folate alone.
- Associations between folate intake and knee pain, inflammation mediators and comorbid conditions in patients with symptomatic knee osteoarthritis
PubMed ID: 39604894
Observational association between higher dietary folate and fewer depressive symptoms (PHQ‑9) in osteoarthritis cohort—associational evidence linking folate intake and mood.
- 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: adjunctive folate (5 mg/day) produced large, clinically meaningful reductions in manic symptoms—strong direct evidence for mood effects.
- Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study
PubMed ID: 8257478
5'-MTHF reduced depressive symptoms in elderly/demented patients versus baseline and comparable to trazodone.
- Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials
PubMed ID: 15260915
Meta‑analysis found adding folate to depression treatment produced a modest but significant antidepressant effect; strong direct evidence for mood benefit.
- B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial
PubMed ID: 20976769
Randomized double‑blind trial: folic acid (2 mg) with B6/B12 reduced post-stroke major depression hazard substantially.
- L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials
PubMed ID: 23212058
Randomized trial: L‑methylfolate (bioactive B9) 15 mg/day significantly augmented SSRI antidepressant response (improved symptom scores and response rate) — strong direct evidence for mood benefit.
- 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 (15 mg) adjunct to SSRI produced significantly larger reductions in depression scores in RCT subgroups — strong direct evidence for mood benefit in selected patients.
- Impact of a Specific Amino Acid Composition with Micronutrients on Well-Being in Subjects with Chronic Psychological Stress and Exhaustion Conditions: A Pilot Study
PubMed ID: 29710825
Randomized trial of an amino-acid plus micronutrient formula (included folate) produced significant reductions in perceived stress; folate may have contributed but product was combined so attribution is limited.
- 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
Folinic acid adjunct to risperidone improved behavioral subscales in ASD, supporting neurobehavioral/mood effects.
- Enhancement of recovery from psychiatric illness by methylfolate
PubMed ID: 1974941
Randomized trial: methylfolate improved psychiatric symptoms and social functioning in folate‑deficient psychiatric patients — strong direct support for mood benefit in deficient patients.
- Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial
PubMed ID: 10967371
Randomized trial: adding 500 µg folic acid to fluoxetine significantly improved depression scores in women and lowered homocysteine.
- Evaluation of Nutritional Status of Patients with Depression
PubMed ID: 26413529
Case–control: people with major depression had lower serum folate and B12 (associative evidence linking folate status to depression).
- Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet
PubMed ID: 19154566
B‑vitamin supplementation including folic acid in coeliac patients lowered homocysteine and improved psychological well‑being scores.
- 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
Adding folic acid to valproate improved mania symptoms more than valproate alone in hospitalized manic patients.
- Micronutrient supplementation may reduce symptoms of depression in Guatemalan women
PubMed ID: 19886513
Supplementation containing folic acid associated with reduced depressive symptoms and baseline low RBC folate correlated with higher depression scores.
- Longitudinal relationship of diet and oxidative stress with depressive symptoms in patients with metabolic syndrome after following a weight loss treatment: the RESMENA project
PubMed ID: 24314875
In metabolic‑syndrome weight‑loss trial, higher folate intake associated with reduced depressive symptoms (observational/associative evidence).
- Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia
PubMed ID: 23467813
Folate+B12 produced modest genotype‑dependent improvement in negative symptoms of schizophrenia (psychiatric symptom benefit).
- 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) augmentation with fluoxetine produced substantially better depression scores and remission rates vs lower dose.
- 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
Adjunct B‑vitamin (including folic acid) improved sustained antidepressant response and lowered relapse risk over 1 year; folate may contribute.
- Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression
PubMed ID: 15323594
Observational trial: low baseline folate strongly predicted very poor antidepressant treatment response — links folate status to mood outcomes.
- 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 depression cohort: low serum folate predicted much higher relapse risk on continuation fluoxetine (strong association with mood stability).
- 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 scores.
- Effects of dietary supplements on depressive symptoms in older patients: a randomised double-blind placebo-controlled trial
PubMed ID: 17662509
Large RCT of a multi‑nutrient supplement (including folate) in older patients showed fewer depressive symptoms at 6 months.
Energy & Fatigue (32)
- 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
School MMS (includes folate) lowered moderate/severe anemia prevalence — potential to improve energy via correcting anemia.
- The potential adding therapeutic effect of pentoxifylline and/or folic acid for chronic kidney disease patients: randomized controlled trial
PubMed ID: 40826392
CKD trial: folic acid (500 µg/day) associated with higher hemoglobin and reduced fatigue scores over 6 months — direct clinical fatigue improvement.
- Comparative effectiveness of daily therapeutic supplementation with multiple micronutrients and iron-folic acid versus iron-folic acid alone in children with mild-to-moderate anaemia in rural India: an open-label, randomised controlled trial
PubMed ID: 40021307
Iron‑folic acid raised hemoglobin in anemic children (clinical RBC improvement) which can support energy levels.
- 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 B12) cured anemia in adolescents—correcting anemia is likely to reduce fatigue.
- Randomized controlled trial of 2 prenatal iron supplements: is there a dose-response relation with maternal hemoglobin?
PubMed ID: 21367950
Pregnant women receiving iron + folate (or MMN including folate) had improved hemoglobin if anemic, which may alleviate fatigue associated with anemia.
- 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, adding folic acid (in combination) improved hemoglobin and iron markers—hematologic improvement can reduce fatigue.
- 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 physical work capacity and recovery time in schoolgirls; improved hematologic status plausibly reduces fatigue.
- 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 in severely anemic children produced clinically meaningful anemia responses—likely to reduce fatigue.
- Providing iron/folic acid tablets free of charge improves compliance in pregnant women in Senegal
PubMed ID: 19203773
Free provision of iron+folic acid in pregnancy doubled use and substantially reduced anemia—direct implication for reducing fatigue from anemia.
- Impact of a multiple-micronutrient fortified salt on the nutritional status and memory of schoolchildren
PubMed ID: 20533221
Salt fortified with folic acid (and other nutrients) raised hemoglobin by ~0.67 g/dL in children—supports reduced fatigue.
- 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
Adding folic acid to iron therapy in young children greatly reduced anemia and increased hemoglobin—relevant to reducing anemia‑related fatigue.
- 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 effectively corrected infant anemia (reducing anemia-related fatigue), though GI side effects occurred without other micronutrients.
- 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
Iron+folic acid in preschool children reduced anemia prevalence — anemia correction plausibly reduces fatigue.
- 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
Daily sprinkles with iron+folic acid improved anemia recovery in infants — likely to reduce fatigue from anemia.
- 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
Folic acid ± DHA increased mtDNA copy number and reduced oxidative DNA damage—mitochondrial effects that plausibly support cellular energy production.
- Maternal folate status during extended lactation and the effect of supplemental folic acid
PubMed ID: 9989694
1 mg folic acid in lactating women increased erythrocyte folate and hemoglobin vs no supplement — improved hematologic status can reduce fatigue.
- 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 after infection treatment produced large hemoglobin increases in children (likely to reduce fatigue from anemia).
- Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls
PubMed ID: 11814373
Iron with folic acid greatly reduced anemia in adolescents, a common cause of fatigue.
- 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
Adding folate to iron accelerated hemoglobin recovery in anaemic pregnant women—likely to reduce fatigue through anemia correction.
- Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women
PubMed ID: 12495257
Iron+folate raised haemoglobin in pregnant women; potential to reduce fatigue.
- A micronutrient-fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women
PubMed ID: 12730420
A multi‑micronutrient drink (including folate) raised hemoglobin and reduced anemia risk in pregnant women—consistent with fatigue improvement potential.
- Anemia prophylaxis in adolescent school girls by weekly or daily iron-folate supplementation
PubMed ID: 12736400
Weekly or daily iron–folate supplementation raised iron stores and helped prevent anemia in adolescent girls—treating anemia commonly reduces fatigue.
- Intermittent iron supplementation regimens are able to maintain safe maternal hemoglobin concentrations during pregnancy in Venezuela
PubMed ID: 15113952
Intermittent iron with small folic acid doses maintained acceptable maternal hemoglobin in most pregnant women; maintaining Hb can reduce fatigue.
- 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 increased hemoglobin and iron stores vs comparator—likely to reduce anemia-related fatigue (hematologic benefit observed).
- Efficacy of twice-weekly multiple micronutrient supplementation for improving the hemoglobin and micronutrient status of anemic adolescent schoolgirls in Bangladesh
PubMed ID: 16210713
Twice‑weekly iron+folic acid raised hemoglobin in anemic adolescent girls—improved anemia can reduce fatigue.
- 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
In premature infants, added B12+folate increased RBC counts and helped maintain hemoglobin—physiologic basis to reduce fatigue.
- Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers
PubMed ID: 16736000
Folic acid increased SAM (key methyl donor) and improved nucleotide stability—supports one‑carbon metabolism/energy‑related methylation pathways.
- 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
Iron–folic acid program reduced anaemia prevalence; anemia correction commonly reduces fatigue.
- Improving Micronutrient Status of Children and Women in Rural Communities in India Using Crystal Salt Enriched with Multiple Micronutrients
PubMed ID: 33952731
Fortification markedly reduced anaemia prevalence — improved hemoglobin plausibly reduces fatigue.
- 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 containing folic acid performed comparably to iron+folic acid drops in reducing anemia in children — anemia improvement commonly reduces fatigue.
- The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT
PubMed ID: 31776782
Optimized multivitamin after sleeve gastrectomy raised folate and markedly reduced anemia rates—reduced anemia can plausibly reduce fatigue.
- [Primary prophylaxis against cerebral toxoplasmosis. Efficacy of folinic acid in the prevention of hematologic toxicity of pyrimethamine]
PubMed ID: 8029191
Randomized trial in HIV patients showed folate given with pyrimethamine modestly preserved hemoglobin vs no folate; improved hemoglobin can reduce fatigue (indirect but clinically relevant).
Healthy aging (31)
- Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock
PubMed ID: 30350398
Folic acid + B12 altered DNA methylation and reduced epigenetic (biological) age in a subgroup of women — direct molecular evidence relevant to ageing.
- 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) in arsenic‑exposed adults—mechanistic anti‑aging signal.
- 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 incident colorectal adenomas in older adults — clinically meaningful prevention outcome relevant to healthy aging.
- Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
PubMed ID: 21780182
B‑vitamin supplementation (includes folic acid) lowered homocysteine ~30% and slowed cognitive decline in older adults with MCI, supporting aspects of healthy aging.
- 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
2‑year low‑dose folic acid + B12 modestly improved memory scores in older adults with psychological distress — supports cognitive aging.
- 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 in women: folic acid with B6/B12 reduced risk of age‑related macular degeneration, an age‑related outcome.
- 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
Three‑year folic acid raised folate, lowered homocysteine and produced small improvements in memory/processing speed in older adults.
- Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial
PubMed ID: 17200216
800 µg folic acid for 3 years modestly slowed low‑frequency (speech) hearing decline in older adults.
- Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers
PubMed ID: 16736000
Folic acid increased SAM and reduced uracil misincorporation—improves DNA stability mechanisms linked to healthy aging.
- Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women
PubMed ID: 16339055
Higher dietary folate associated with ~50% lower colorectal cancer risk in a large female cohort (observational).
- Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study
PubMed ID: 15777680
Low dietary folate (with other B-vitamins) associated with lower BMD in MTHFR TT women, linking folate status to age-related bone health.
- Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial
PubMed ID: 15741530
In elderly stroke patients folic acid+B12 markedly reduced hip fractures over 2 yrs (clinically important outcome relevant to healthy aging).
- 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
Improvements in endothelial function, insulin resistance and ADMA with folate+B12 suggest benefits to metabolic and vascular aging processes.
- Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study
PubMed ID: 12716688
Dose‑response trial in older adults showed ~22% homocysteine lowering at ~400 µg/day—homocysteine reduction is plausibly relevant to healthy aging.
- Genomic DNA methylation decreases in response to moderate folate depletion in elderly women
PubMed ID: 11010943
Folate depletion in older women caused leukocyte DNA undermethylation, a mechanism relevant to aging and genomic stability.
- 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 folic acid raised B‑vitamin status and lowered homocysteine in older adults — relevant to aging biology.
- Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults
PubMed ID: 9683174
Folate/B12 reduced homocysteine and a DNA‑damage marker in high‑baseline subjects—mechanisms relevant to healthy aging.
- 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
Folic acid and DHA (especially combined) improved cognition, reduced oxidative DNA damage (8‑OHdG) and increased mtDNA copy number in MCI—mechanistic aging-relevant benefits.
- 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
Folic acid (with/without DHA) increased SAM, lowered homocysteine and improved some cognitive measures and blood Aβ over 6 months—biomarkers linked to aging brain health.
- 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) slowed brain atrophy ~40% in MCI patients with high omega‑3 status—supports a neuroprotective/aging-related outcome.
- Effect of adding B-vitamins to vitamin D and calcium supplementation on CpG methylation of epigenetic aging markers
PubMed ID: 29395637
Addition of B9/B6/B12 produced small changes in epigenetic aging methylation markers vs control over 1 year (biological aging signal).
- 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 −33% micronucleus frequency (less genome damage), a mechanism relevant to aging.
- One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation
PubMed ID: 27379829
Small randomized supplementation study found correlations between folate/one‑carbon metabolites and telomere length, suggesting an aging-related link.
- Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations
PubMed ID: 7603218
Large trial in elderly: injections normalized homocysteine/MMA and other deficiency markers rapidly—biochemical correction relevant to healthier aging biology.
- 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
Pooled RCTs of folic‑acid‑containing B‑vitamin supplements slowed cognitive decline and brain atrophy in MCI patients (genotype‑dependent), consistent with a role in aspects of healthy brain aging.
- Folate administration decreases oxidative status and blood pressure in postmenopausal women
PubMed ID: 24906471
High‑dose methylfolate reduced oxidative stress markers in RCT — plausible contribution to healthy aging mechanisms.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
High-quality RCT: folic acid+B12+B6 reduced whole-brain atrophy rate in MCI over 2 years — supports a healthy-aging brain effect.
- Folic acid supplementation improves cognitive function in participants with cerebral small vascular disease-related cognitive impairment: a randomized controlled trial
PubMed ID: 40945966
Folic acid improved cognition (MoCA/MMSE) and lowered homocysteine in small vessel disease patients—relevant to cognitive aspects of 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
3‑year folic acid improved global cognition and processing speed in older adults with low omega‑3 status (subgroup benefit).
- Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment
PubMed ID: 33935094
B‑vitamin RCT (including folic acid) in MCI reduced homocysteine and prevented some cognitive decline over 2 years — relevant to healthy aging.
- Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
PubMed ID: 29255930
24‑month folic acid RCT in MCI improved some cognitive scores and Aβ biomarkers, suggesting an effect relevant to healthy brain aging.
Focus & concentration (32)
- B-Vitamin Therapy for Kidney Transplant Recipients Lowers Homocysteine and Improves Selective Cognitive Outcomes in the Randomized FAVORIT Ancillary Cognitive Trial
PubMed ID: 29182708
RCT (high‑dose B vitamins incl. folic acid) showed small but significant improvements in processing speed (Digit Symbol) and delayed recall.
- 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
Small cognitive test score improvements seen with folic acid+B12 in MCI, consistent with modest memory/focus benefit.
- 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
Cognitive test improvement in AD with folic acid+B12 over 6 months — supports memory/cognitive domains modestly.
- 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
Long‑term offspring cognitive tests (processing speed, attention) improved after maternal folic acid — direct memory/focus support.
- Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment
PubMed ID: 33935094
Demonstrated prevention of cognitive decline in MCI with B‑vitamin treatment (includes folic acid) over 2 years.
- 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 speed (attention/ executive function).
- 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
Improved global cognition and processing speed in a subgroup with low omega‑3 when supplemented with folic acid.
- Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms
PubMed ID: 35578268
Maternal folic acid influenced cord‑blood methylation at brain genes; prior reports link continued folic acid to improved child cognitive outcomes.
- Cognitive benefits of folic acid supplementation during pregnancy track with epigenetic changes at an imprint regulator
PubMed ID: 39681839
Maternal folic acid mitigated genotype‑related reduced processing speed in children at age 11 (WISC subtests), indicating benefits for certain aspects of attention/processing.
- Folic acid supplementation improves cognitive function in participants with cerebral small vascular disease-related cognitive impairment: a randomized controlled trial
PubMed ID: 40945966
Improved MoCA and MMSE scores in CSVD patients after folic acid, consistent with better memory/attention and global cognition.
- Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial
PubMed ID: 20838622
Slower brain atrophy with B9+B12+B6 in MCI implies preservation of memory-related brain tissue and potential cognitive benefits.
- Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial
PubMed ID: 27752075
Folinic acid improved communication and some cognitive/behavioral outcomes in ASD, supporting benefits on certain cognitive domains (moderate evidence).
- Preconception micronutrient supplementation positively affects child intellectual functioning at 6 y of age: A randomized controlled trial in Vietnam
PubMed ID: 33668050
Trial reported improvements in working memory and processing speed in children after preconception MMS that contained folic acid.
- 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
Supplementation with folic‑acid‑containing B‑vitamins improved cognitive measures (executive function and global CDR scores) in MCI subgroups, supporting memory/focus benefits.
- 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 MCI improved Digit Span and other cognitive measures (direct evidence for memory/attention improvements).
- Long-Chain Polyunsaturated Fatty Acids, Homocysteine at Birth and Fatty Acid Desaturase Gene Cluster Polymorphisms are Associated with Children's Processing Speed up to Age 9 Years
PubMed ID: 33396458
Maternal folate/homocysteine and fatty‑acid balance related to better child processing speed (a facet of cognitive performance).
- Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children
PubMed ID: 17704033
Multiple memory and an attention test improved after 1 year of micronutrient‑fortified salt that included folic acid.
- Trial using multiple micronutrient food supplement and its effect on cognition
PubMed ID: 18716734
A school food supplement containing folic acid (among others) showed improvements in several memory tests and attention.
- Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment
PubMed ID: 26757190
B‑vitamin regimen including folic acid improved episodic memory (HVLT‑DR) and global cognition in MCI patients with high ω‑3 status—specific memory benefit.
- 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
Folic acid ± DHA improved arithmetic and digit span (attention/working memory) and increased SAM/lowered homocysteine in MCI—memory/attention gains.
- 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
Folic acid (±DHA) produced statistically significant improvements in full-IQ/cognitive scores in MCI—relevant to memory and focus.
- Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia
PubMed ID: 16412989
Improved neuropsychological performance (WCST) in schizophrenia with B‑vitamin therapy including folic acid.
- 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
Three‑year folic acid supplementation produced small but statistically significant improvements in memory and information processing speed.
- Impact of a multiple-micronutrient fortified salt on the nutritional status and memory of schoolchildren
PubMed ID: 20533221
Fortified salt (multi‑micronutrient incl. folic acid) improved memory scores in schoolchildren.
- 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
Direct RCT evidence: folic acid + B12 produced modest but significant improvements in immediate and delayed recall and overall cognitive score.
- Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
PubMed ID: 21780182
B‑vitamin supplementation preserved some memory and executive measures, especially in those with higher baseline homocysteine.
- The effect of maternal multiple micronutrient supplementation on cognition and mood during pregnancy and postpartum in Indonesia: a randomized trial
PubMed ID: 22427850
Maternal MMN (including folic acid) improved overall cognition and reading efficiency, indicating memory/attention benefits in nutritionally vulnerable women.
- 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, lowered homocysteine) improved one episodic/contextual memory measure in older men (small RCT).
- 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
Child supplementation with folic acid±B12 improved problem-solving (attention/executive function domain).
- Folic Acid Supplementation Mitigates Alzheimer's Disease by Reducing Inflammation: A Randomized Controlled Trial
PubMed ID: 27340344
MMSE (global cognition) improved with folic acid adjunct in early AD (pilot RCT evidence).
- Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
PubMed ID: 29255930
MCI trial reported improvements in full‑scale/verbal IQ and Information/Digit Span subtests with folic acid supplementation.
- Maternal multiple micronutrient supplementation and other biomedical and socioenvironmental influences on children's cognition at age 9-12 years in Indonesia: follow-up of the SUMMIT randomised trial
PubMed ID: 28104188
Maternal MMN (including folate) produced modest long‑term cognitive test benefits in offspring, relevant to memory and school‑age function.
Nerve health (21)
- Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial
PubMed ID: 23218892
L‑methylfolate+B12/B6 produced clinically meaningful improvement in neuropathy symptoms and lowered homocysteine over 24 weeks — direct evidence for nerve‑symptom benefit in neuropathy patients.
- [Clinical studies on fifty-seven Chinese patients with combined methylmalonic aciduria and homocysteinemia]
PubMed ID: 17953808
Patients with combined MMA/homocysteinemia receiving B12+folic acid regimens had clinical neurological recovery in a subset (supports nerve function).
- Treatment of alcoholic polyneuropathy with vitamin B complex: a randomised controlled trial
PubMed ID: 16926172
A B‑vitamin complex (including folic acid) improved measures of alcoholic polyneuropathy vs placebo over 12 weeks; effects cannot be attributed solely to folic acid but support a role for B vitamins in nerve function.
- Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation
PubMed ID: 8882400
Periconceptional folic acid lowers neural tube/related defects and supports neural development—relevant to nerve formation/function in the fetus.
- Effect of folic acid supplementation on nerve conduction velocity in diabetic polyneuropathy patients
PubMed ID: 30730785
16‑week RCT in diabetic polyneuropathy: 1 mg/day folic acid raised folate, lowered homocysteine, and significantly improved multiple nerve conduction measures.
- Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial
PubMed ID: 28289280
L‑methylfolate produced symptomatic improvement and MRI changes (mPFC thickness/connectivity) in schizophrenia, supporting neuronal/brain functional effects.
- Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
PubMed ID: 29255930
Cognitive improvements and biomarker changes in MCI after folic acid suggest preservation/improvement of brain/nerve function.
- 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
Fortified-milk trial raised maternal folate to levels associated with low NTD risk — directly relevant to neural-tube/nerve development in fetus.
- 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
Maternal folic acid (400 μg) increased cord-blood 5-MTHF and total folate — supports fetal neural support and nerve development substrate.
- FDA drug approval summaries: pemetrexed (Alimta)
PubMed ID: 15477632
Folic acid and B12 are recommended during pemetrexed therapy to reduce severe toxicity (including neurologic/myelosuppressive effects), supporting nerve/neurologic protection.
- Effect of iron deficiency anemia in pregnancy on child mental development in rural China
PubMed ID: 23400604
Prenatal iron/folate supplementation protected child mental development vs prenatal iron‑deficiency anemia — relevant to neurodevelopment/nervous system outcomes.
- High dosage folic acid supplementation, oral cleft recurrence and fetal growth
PubMed ID: 23380913
Periconceptional folic acid reduced oral‑cleft recurrence (neural/craniofacial development relevance) and reflects neural‑development effects of folate.
- Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
PubMed ID: 21780182
B‑vitamin regimen (including folic acid) stabilized executive function and improved some cognitive domains in those with elevated homocysteine — supportive for neural function.
- 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
Folic acid + B12 improved memory measures over 2 years — supports aspects of neural function in older adults.
- Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia
PubMed ID: 16412989
B‑vitamin therapy (including folic acid) improved clinical and cognitive/neuropsychological measures in schizophrenia — relevant to neural function.
- Vitamins and entacapone in levodopa-induced hyperhomocysteinemia: a randomized controlled study
PubMed ID: 16801668
Folate+B12 lowered levodopa‑related homocysteine in Parkinson’s patients—relevant to peripheral/central nerve health.
- Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities
PubMed ID: 15523663
Periconceptional folic acid strongly prevented neural tube defects (directly related to neural/nerve development).
- 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 in RYGB increased folic acid deficiency requirements — folate deficiency is a recognized risk factor for neuropathy and impaired nerve function.
- [Prevention of the first occurrence of anencephaly and spina bifida with periconceptional multivitamin supplementation (conclusion)]
PubMed ID: 7970646
Same strong RCT evidence for neural development (nerve structures) with periconceptional folic acid.
- Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy--a Pediatric Oncology Group study
PubMed ID: 9586883
Strong, direct clinical association: higher cumulative MTX and lower folinic‑acid rescue were linked to increased acute neurotoxicity and leukoencephalopathy.
- Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation
PubMed ID: 1307234
Prevention of neural‑tube defects by periconceptional folic acid demonstrates a critical role in neural development and by extension nerve health in the developing fetus.
Detoxification (25)
- Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh
PubMed ID: 30590411
Large RCT in arsenic‑exposed adults: folic acid (400–800 μg/d) accelerated arsenic methylation (more DMA, less MMA/InAs) and enhanced arsenic excretion — strong direct evidence for detoxification role.
- Modulation of the antitumor effect of methotrexate by low-dose leucovorin in squamous cell head and neck cancer: a randomized placebo-controlled clinical trial
PubMed ID: 2405105
Leucovorin (folinic acid) reduced methotrexate toxicity (rescue therapy) — direct evidence of folate-related mitigation of drug toxicity.
- Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children
PubMed ID: 38728816
Randomized folic acid+B12 in children increased arsenic methylation (DMAs) and altered arsenic species in blood/urine—strong evidence folate enhances arsenic detoxification via one‑carbon metabolism.
- 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
Folic acid reduced protein carbonyls (marker of protein oxidation) in pregnancy, indicating reduced oxidative stress/detoxification benefit.
- Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial
PubMed ID: 26559255
In arsenic‑exposed adults, folic acid produced dose‑dependent reductions in urinary 8‑OHdG, supporting detox-related DNA protection.
- Effect of folic acid supplementation on homocysteine, serum total antioxidant capacity, and malondialdehyde in patients with type 2 diabetes mellitus
PubMed ID: 21896879
High‑dose folic acid increased total antioxidant capacity and decreased MDA (lipid peroxidation), indicating improved oxidative‑stress/ detoxification markers.
- 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
Folate 5 mg increased total antioxidant capacity in hypercholesterolemic subjects—supports antioxidant/detox pathways.
- Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial
PubMed ID: 18714059
Folic acid+B12 markedly lowered homocysteine in a large trial—direct effect on homocysteine detox/metabolism.
- Lowering homocysteine with B vitamins has no effect on blood pressure in older adults
PubMed ID: 17449579
B‑vitamin supplementation lowered homocysteine (a toxic intermediate), supporting detoxification of one‑carbon metabolites.
- [Effects of intervention therapy of methylcobalamin and folic acid on plasma homocysteine concentration and homocysteine thiolactonases/paraoxonase activity in patients with type 2 diabetes mellitus]
PubMed ID: 17425871
Folic acid increased paraoxonase (PON) activity in T2D patients—PON has antioxidant/detoxifying roles.
- Folic acid supplementation lowers blood arsenic
PubMed ID: 17921403
Randomized folic acid (400 µg/day) improved arsenic methylation and lowered blood arsenic substantially — direct evidence folate supports detoxification via methylation.
- Reduction of the efficacy of methotrexate by the use of folic acid: post hoc analysis from two randomized controlled studies
PubMed ID: 16200612
Post-hoc pooled analysis: folic acid use in RA trials associated with reduced some methotrexate toxicities, consistent with a protective effect against drug-related adverse events.
- Economic evaluation of folate supplementation during methotrexate treatment in rheumatoid arthritis
PubMed ID: 15124248
Adding folic or folinic acid to methotrexate therapy reduced drug discontinuation (folate rescue reduces methotrexate toxicity)—direct mitigation of drug toxicity.
- Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia
PubMed ID: 12823643
In the same trial folic acid/B12 lowered isoprostane excretion (~26%), indicating a reduction in oxidative stress markers linked to detox processes.
- Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults
PubMed ID: 9683174
Lowered homocysteine and DNA damage with folate/B12 suggests improved methylation and detoxification capacity.
- Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers
PubMed ID: 9514403
Folic acid lowered homocysteine, a metabolite whose accumulation reflects impaired one‑carbon/clearance pathways.
- 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 RCT showing marked, dose‑dependent improvements in arsenic methylation indices and blood arsenic metabolites with folic acid (400–800 μg) — highest-quality evidence for folate aiding arsenic detoxification.
- Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A Randomized Controlled Trial
PubMed ID: 25978852
RCT: high‑dose folic acid (800 μg/d) modestly lowered blood arsenic over 24 weeks, consistent with enhanced arsenic methylation (detoxification).
- Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh
PubMed ID: 17093162
Randomized folic acid (400 μg/day) in folate‑deficient adults increased arsenic methylation (%DMA +5.9) and reduced toxic urinary arsenic species — clear evidence folate aids arsenic detoxification via one‑carbon metabolism.
- Metabolic Signature of Arsenic Exposure and Metabolism: The Folic Acid and Creatine Trial
PubMed ID: 40668877
Large RCT in arsenic‑exposed adults: folic acid improved arsenic methylation, lowered blood arsenic and produced one‑carbon metabolite changes — direct detoxification evidence.
- 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
Well‑powered RCT showed folic acid improved arsenic methylation patterns (increased %DMAs, decreased %MMAs/%InAs) — direct detoxification evidence.
- 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
In arsenic-exposed adults folic acid prevented declines in choline and markedly changed DMG/betaine consistent with improved arsenic methylation/detox pathways.
- Plasma trimethylamine-N-oxide following supplementation with vitamin D or D plus B vitamins
PubMed ID: 27569255
B‑vitamin supplementation (including folic acid) lowered plasma TMAO compared with control—suggests an effect on metabolic/detox pathways.
- Comparison of efficacy of folic acid and silymarin in the management of antiepileptic drug induced liver injury: a randomized clinical trial
PubMed ID: 28603098
Randomized trial in children with drug‑related liver injury: daily folic acid improved ALT/AST/GGT and normalized enzymes more often than silymarin.
- Effect of folic acid intervention on ALT concentration in hypertensives without known hepatic disease: a randomized, double-blind, controlled trial
PubMed ID: 22085872
Randomized, double‑blind trial in hypertensive adults: 0.8 mg/day folic acid modestly but significantly lowered serum ALT over 8 weeks (hepatic benefit).
Immune support (18)
- Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly
PubMed ID: 15449576
Multinutrient formula that included folic acid increased NK activity, maintained IL‑2 and was associated with fewer infections; folate contribution cannot be separated but trial shows immune benefit in presence of folic acid.
- Impact of nutritional supplementation during pregnancy on antibody responses to diphtheria-tetanus-pertussis vaccination in infants: A randomised trial in The Gambia
PubMed ID: 31386660
Maternal MMN (vs iron‑folate) improved some infant vaccine antibody responses — folic acid was part of comparator and intervention arms.
- Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial
PubMed ID: 30773140
Infant LNS with multiple micronutrients (including folate) increased thymic index at 1 year — surrogate for immune development.
- Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy
PubMed ID: 37196429
Direct clinical evidence: routine folic acid + B12 given with pemetrexed markedly reduced severe hematologic toxicity (neutropenia), reflecting preserved bone‑marrow/immune cell production.
- Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma
PubMed ID: 37068377
Direct clinical evidence: folic acid (with B12) was used to reduce pemetrexed toxicity and was associated with much lower hematologic complications vs historical expectations.
- 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 food (including folic acid) reduced respiratory and diarrheal illness incidence/duration in preschoolers (confounded but relevant).
- [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
Randomized trial of a multivitamin (included folic acid) showed modest improvement in common cold symptom scores and fewer absences in a subgroup.
- 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
Folate‑rich intervention reduced inflammatory cytokines (TNF‑α, IL‑6, IL‑1β), indicating an anti‑inflammatory effect.
- 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 product including folic acid reduced hs‑CRP (inflammatory marker) in cardiac rehab patients.
- 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
Multi-nutrient supplement including folic acid upregulated antiviral/interferon-signaling genes in overweight women—transcriptomic immune signal though folate-specific contribution uncertain.
- 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
In RA patients on methotrexate, continuing folic acid reduced neutropenia and treatment withdrawal (direct immune/cell‑count benefit).
- 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
Adding folic/folinic acid to MTX reduced toxicity and treatment discontinuation, indirectly preserving immune/hematologic function.
- Folic acid supplementation reduces the development of some blood cell abnormalities in children receiving carbamazepine
PubMed ID: 16380297
Folic acid reduced leukopenia and neutropenia incidence in children on carbamazepine (blood/immune cell preservation).
- Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects
PubMed ID: 16491109
12‑week folic acid reduced homocysteine and some inflammatory markers (CRP, MCP‑1, IL‑8) — plausible immune benefit.
- Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural Nepal
PubMed ID: 19368922
Prenatal folic acid+iron was associated with lower puerperal sepsis and postpartum infection risk in a large trial setting.
- 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, arms containing folic acid (with retinol and iron) produced larger increases in lymphocyte IL‑2/proliferation than iron alone—immune marker improvement.
- Multiple micronutrient supplementation improves vitamin B₁₂ and folate concentrations of HIV infected children in Uganda: a randomized controlled trial
PubMed ID: 21600005
Twice‑RDA multiple-micronutrient powder (including folate) raised serum folate and B12 in HIV-infected children—supports micronutrient repletion important for immune competence.
- Micronutrients decrease incidence of common infections in type 2 diabetic outpatients
PubMed ID: 21859655
Multinutrient supplement (including folate) raised folate and reduced common infections and altered immune markers in T2D outpatients.
Appetite regulation (2)
- Acceptability of multiple micronutrient powders and iron syrup in Bihar, India
PubMed ID: 29210507
Caregivers reported perceived increases in child appetite/food consumption after iron‑and‑folic‑acid syrup or MNP use—subjective but directly relevant.
- Effects of folic acid on preschool children's appetite: randomized triple-blind clinical trial
PubMed ID: 17875076
Randomized trial in underweight children: 1 mg folic acid produced a small, short‑term increase in reported appetite.
Hair & Nails (1)
- Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children
PubMed ID: 17704033
Fortified salt eliminated angular stomatitis (a mucocutaneous lesion) in schoolchildren, suggesting skin/mucosal benefit related to micronutrient repletion including folate.
Similar by evidence
Supplements the same benefits carry qualifying findings for — a fact about the evidence graph, not a recommendation to swap.
Products with Vitamin B9
Search all715 products whose verified label declares Vitamin B9 — not every bottle that mentions it in a title.
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.