Vitamin B9 (Folate)
Folate/folic acid is essential for DNA synthesis and pregnancy outcomes. Benefits depend strongly on baseline status and form.
Overview
What is folic acid?
Folic acid or folate are types of vitamin B9. Folic acid is the synthetic form of vitamin B9 found in supplements and is used to fortify foods. It is essential for making and repairing DNA, producing red blood cells, and supporting healthy cell growth. It is especially important during pregnancy to prevent neural tube defects in the developing fetus.
Dosage
The recommended daily allowance of folate is 400 micrograms per day.
The tolerable upper intake level of folic acid is 1 mg per day or 1,000 micrograms although higher doses are sometimes required.
To reduce homocysteine levels, the ideal dose is 800 micrograms (0.8 mg) per day.
Effect graph
Effect heatmap
SupplementDEX Database
59 conditions for , and rated at least stars. All purchase bands. No minimum star filter.
Database Snapshot
Most vitamin b9 (folate) research is concentrated in a handful of conditions.
- Hyperhomocysteinemia accounts for 34 of 252 studies (13%).
- Age-related cognitive decline accounts for 20 of 252 studies (8%).
- Colorectal cancer accounts for 19 of 252 studies (8%).
- Sparse coverage remains for Autism spectrum disorder, Epilepsy, Esophageal cancer risk.
Dietary Sources
Top dietary sources
Ranked by amount per 100 g
Top dietary sources of vitamin B9 include:
Safety
Folic acid is generally safe at the recommended daily allowance.
Dose windows
Long-term
Higher doses in the long term may increase the risk of cancer and cardiovascular risk factors.
Frequently Asked Questions
References
Sources218 references
SupplementDEX uses only high-quality sources to determine supplement effectiveness.
1.SupplementDEX Database: Folate (Vitamin B9) deficiency — Megaloblastic Anemias: Nutritional and Other Causes2017
A study found that management includes identifying any deficiency, establishing its cause, and replenishing B 12 or folate parenterally or orally.
2.SupplementDEX Database: Folate (Vitamin B9) deficiency — Guidelines for the diagnosis and treatment of cobalamin and folate disorders2014
A study found that the clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no 'gold standard' test to define deficiency.
3.SupplementDEX Database: Folate (Vitamin B9) deficiency — Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician1999
A study found that at one time, the diagnosis of a deficiency of vitamin B12 or folate was considered to be relatively straightforward.
SupplementDEX Database · Neural tube defects
7 references4.SupplementDEX Database: Neural tube defects — Folic Acid Supplementation for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement2017
A study in women found that in 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants.
5.SupplementDEX Database: Neural tube defects — The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths2011
A meta-analysis of 18 studies found that pooled results from 13 studies evaluating role of multiple micronutrients supplementation during pregnancy showed no significant effect in reducing stillbirths [RR = 0.98; 95% CI: 0.88 - 1.10] or perinatal mortality [RR = 1.07; 95% CI: 0.92 - 1.25; random model].
6.SupplementDEX Database: Neural tube defects — Folic acid to reduce neonatal mortality from neural tube disorders2010
A meta-analysis found that for NTD primary prevention through folic acid supplementation, combining one RCT with three cohort studies which adjusted for confounding, suggested a reduction of 62% (95% CI: 49-71).
7.SupplementDEX Database: Neural tube defects — Effects and safety of periconceptional folate supplementation for preventing birth defects2010
A meta-analysis of 6105 participants found that the results are consistent in showing a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR).
8.SupplementDEX Database: Neural tube defects — Folic acid, methylation and neural tube closure in humans2009
A meta-analysis found that fourth, the questions whether folate receptor autoantibodies or hampered methylation are mechanisms underlying NTDs are briefly discussed.
9.SupplementDEX Database: Neural tube defects — Folic acid supplementation and neural tube defect recurrence prevention2007
A meta-analysis found that 4 mg/day observational studies report reductions in recurrence risk of 85% to 100% among women taking folic acid prior to subsequent pregnancies.
10.SupplementDEX Database: Neural tube defects — Folate status during pregnancy in women is improved by long-term high vegetable intake compared with the average western diet2001
A prospective study of 109 pregnant women found that long-term high vegetable intake (8+ years) raised plasma and red blood cell folate throughout pregnancy and lowered folate deficiency risk versus an average Western diet.
11.SupplementDEX Database: Age-related cognitive decline — Effects of folic acid supplementation on cognitive function and inflammation in elderly patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials2024
A meta-analysis of 1102 participants found that folic acid supplementation seems to have a positive impact on cognitive function in older adults with mild cognitive impairment, but further evidence of its effectiveness in improving inflammatory cytokines is needed from high-quality studies.
12.SupplementDEX Database: Age-related cognitive decline — Does folic acid supplementation have a positive effect on improving memory? A systematic review and meta-analysis of randomized controlled trials2022
A meta-analysis of 641 participants found that 1 mg/day the overall results of nine trials with 641 participants, revealed that folic acid supplementation did not significantly change memory score compared to placebo (SMD: 0.12; 95% CI: -0.17, 0.40, p = 0.418; I 2 = 62.6%).
13.SupplementDEX Database: Age-related cognitive decline — Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial2021
A randomized trial of 240 older adults found that 800 μg/day for 6 months daily oral FA, DHA and their combined use for 6 months significantly improved the full-scale intelligence quotient (FSIQ) and some subtests of Wechsler Adult Intelligence Scale compared to the placebo.
14.SupplementDEX Database: Age-related cognitive decline — Influences of Folate Supplementation on Homocysteine and Cognition in Patients with Folate Deficiency and Cognitive Impairment2020
A study of 45 patients with alzheimer's disease found that 5 mg/day for 28–63 days the degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not.
15.SupplementDEX Database: Age-related cognitive decline — Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial2019
A randomized trial of 90 adults found that 400 mcg/day observational studies have frequently reported that low blood folate concentrations are associated with poor cognitive performance.
16.SupplementDEX Database: Age-related cognitive decline — Results of 2-year vitamin B treatment on cognitive performance: secondary data from an RCT2014
A randomized trial of 759 older adults found that 400 µg folic acid + 500 µg vitamin B12/day for 2 years hcy concentrations decreased 5.0 (95% confidence interval -5.3 to -4.7) µmol/L in the B-vitamin group and 1.3 (-1.6 to -0.9) µmol/L in the placebo group.
17.SupplementDEX Database: Age-related cognitive decline — Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment2013
A randomized trial in older adults found that 0.8 mg folic acid + 20 mg vitamin B6 + 0.5 mg vitamin B12/day one approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins.
18.SupplementDEX Database: Age-related cognitive decline — Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial2012
A randomized trial of 133 mci patients found that 0.8 mg folic acid + 0.5 mg vitamin B12 + 20 mg vitamin B6/day the mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo.
19.SupplementDEX Database: Age-related cognitive decline — Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials2012
A meta-analysis found that b-vitamin supplementation did not show an improvement in cognitive function for individuals with (SMD = 0.10, 95%CI -0.08 to 0.28) or without (SMD = -0.03, 95%CI -0.1 to 0.04) significant cognitive impairment.
20.SupplementDEX Database: Age-related cognitive decline — Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials2010
A meta-analysis of 2835 participants found that the standardized mean difference in cognitive function test scores was 0.01 (95% confidence interval [95% CI], -0.08 to 0.10), or an increase of 1% (95% CI, -8% to 10%) of 1 standard deviation.
21.SupplementDEX Database: Age-related cognitive decline — Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people2008
A systematic review found that 800 mcg/day in comparing intervention with placebo, weighted mean differences and standardized mean difference or odds ratios were estimated.
22.SupplementDEX Database: Age-related cognitive decline — A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease2008
A randomized trial of 23 dementia patients found that 1 mg folic acid/day there were no significant baseline differences or use of individual ChI between the two arms.
23.SupplementDEX Database: Age-related cognitive decline — Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial2007
A randomized trial of 818 adults found that the 3-year change in memory (difference in Z scores 0.132, 95% CI 0.032 to 0.233), information processing speed (0.087, 0.016 to 0.158) and sensorimotor speed (0.064, -0.001 to 0.129) were significantly better in the folic acid group than in the placebo group.
24.SupplementDEX Database: Age-related cognitive decline — Relation of higher folate intake to lower risk of Alzheimer disease in the elderly2007
An observational study of 192 older adults found that the highest quartile of total folate intake was related to a lower risk of AD (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9; P=.02 for trend) after adjustment for age, sex, education, ethnic group, the epsilon4 allele of apolipoprotein E, diabetes mellitus,.
25.SupplementDEX Database: Age-related cognitive decline — Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons2005
A study of 3718 found that a faster rate of cognitive decline was also associated with high folate intake from food (P for trend = .04) and with folate vitamin supplementation of more than 400 microg/d compared with nonusers (beta = -.03, P<.001).
26.SupplementDEX Database: Age-related cognitive decline — Reduced risk of Alzheimer's disease with high folate intake: the Baltimore Longitudinal Study of Aging2005
A study of 57 older adults found that when these 3 vitamins were analyzed together, only total intake of folate at or above the RDA (RR, 0.45; 95% CI, 0.21 to 0.97) was associated with a significant decreased risk of AD.
27.SupplementDEX Database: Age-related cognitive decline — A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly2004
A meta-analysis found that all three case control studies found that serum total homocysteine was significantly higher in cases when compared with controls, and there was wide variation for both serum vitamin B(12) and folate in both groups of participants.
28.SupplementDEX Database: Age-related cognitive decline — Folic acid supplementation in dementia: a preliminary report2003
A study of 11 dementia patients found that 10 mg/day however, there was a trend for the folate group to perform worse on two specific cognitive measures, suggesting a possible trend toward worsening of some cognitive abilities after the folic acid.
29.SupplementDEX Database: Age-related cognitive decline — Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits1998
A randomized trial in older adults found that our results from this preliminary study demonstrated that patients treated with folic acid for 60 days showed a significant improvement on both memory and attention efficiency when compared with a placebo group.
30.SupplementDEX Database: Age-related cognitive decline — Folate and amine metabolites in senile dementia: a combined trial and biochemical study1971
A study found that folate and amine metabolites in senile dementia: a combined trial and biochemical study..
SupplementDEX Database · Depression
12 references31.SupplementDEX Database: Depression — Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
32.SupplementDEX Database: Depression — Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults2022
A randomized trial of 586 women found that the same analysis for the negative control, cyanocobalamin, found no association with suicide attempt (HR, 1.01; 95% CI, 0.80-1.27).
33.SupplementDEX Database: Depression — Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis2021
A meta-analysis of 5 studies found that adjunct therapy with l-Methylfolate or folic acid improves depression scale scores, patient response, and remission rates.
34.SupplementDEX Database: Depression — Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial2014
A randomized trial of 112 (ages 14–24) found that 2.5 mg/day for 14–24 years although long term folic acid supplementation was well tolerated, with high levels of adherence, there was no evidence that it reduced the incidence of mood disorder compared to those taking placebo.
35.SupplementDEX Database: Depression — Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity2007
A meta-analysis of 315 studies found that this relationship remained after adjustment for potential confounding (OR)(pooled adjusted) = 1.42; 95% CI 1.10 to 1.83).
36.SupplementDEX Database: Depression — Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample2005
An observational study in older adults found that being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level.
37.SupplementDEX Database: Depression — Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification2004
An observational study of 627 older adults found that the adjusted OR for high CES-D score in women in the lowest tertile of folate was 2.04 (95% CI: 1.38, 3.02), which was significantly different from that in women in the highest tertile of folate (P < 0.001).
38.SupplementDEX Database: Depression — Folate for depressive disorders2003
A systematic review of 247 studies found that fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at ten weeks (relative risk (RR) 0.47, 95% CI 0.24 to 0.92) The number needed to treat with folate for one additional person to experience a 50% reduction on this scale was 5 (95%.
39.SupplementDEX Database: Depression — Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial2000
A randomized trial of 127 patients with major depressive disorder found that 500 µg folic acid/day plasma homocysteine was significantly decreased in women by 20.6%, but there was no significant change in men.
40.SupplementDEX Database: Depression — Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study1993
A randomized trial of 49 older adults found that 50 mg/day for 4 weeks 5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic.
41.SupplementDEX Database: Depression — Enhancement of recovery from psychiatric illness by methylfolate1990
A randomized trial of 123 patients with major depressive disorder found that 15 mg/day for 6 months among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery.
42.SupplementDEX Database: Depression — Folic acid enhances lithium prophylaxis1986
A study of 75 patients with mood disorders found that patients who had their plasma folate increased to 13 ng/ml or above had a 40% reduction in their affective morbidity.
SupplementDEX Database · Hyperhomocysteinemia
34 references43.SupplementDEX Database: Hyperhomocysteinemia — Vitamin B Supplementation and Homocysteine Reduction in Nigerian Children with Nephrotic Syndrome: A Randomized Controlled Trial2025
A randomized trial in children/adolescents found that 5 mg folic acid + 50 mg vitamin B6 + 1 mg vitamin B12/day vitamin B supplementation significantly reduced plasma homocysteine and improved lipid profiles in children with NS.
44.SupplementDEX Database: Hyperhomocysteinemia — Effect of Vitamin B6, B9, and B12 Supplementation on Homocysteine Level and Cardiovascular Outcomes in Stroke Patients: A Meta-Analysis of Randomized Controlled Trials2021
A meta-analysis of 8513 participants found that risk ratio (RR) was calculated for determining the risk of stroke, major cardiovascular disorder, and vascular death by using a fixed-effect model.
45.SupplementDEX Database: Hyperhomocysteinemia — Homocysteine-lowering interventions for preventing cardiovascular events2017
A meta-analysis of 3929 participants found that compared with placebo, homocysteine-lowering interventions were associated with reduced stroke outcome (homocysteine-lowering = 4.3% versus comparator = 5.1%, RR 0.90, 95% CI 0.82 to 0.99, I 2 = 8%, 10 trials, N = 44,224; high-quality evidence).
46.SupplementDEX Database: Hyperhomocysteinemia — Folic Acid Supplementation for Stroke Prevention in Patients With Cardiovascular Disease2017
A meta-analysis of 65790 participants found that folic acid supplementation was associated with a significant benefit in reducing the risk of stroke in patients with CVD (RR = 0.90; 95% CI: 0.84-0.97; P = 0.005).
47.SupplementDEX Database: Hyperhomocysteinemia — Effects of 2-year vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly on arterial stiffness and cardiovascular outcomes within the B-PROOF trial2015
A randomized trial of 569 older adults found that 500 µg vitamin B12 + 400 µg folic acid/day for 2 years analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline.
48.SupplementDEX Database: Hyperhomocysteinemia — Effect of folic acid supplementation on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials2012
A meta-analysis of 2052 participants found that consistently, a greater beneficial effect was seen in those trials with baseline CIMT levels ≥0.8 mm (WMD: -0.14 mm; 95%CI: -0.19, -0.08; P<0.0001), and a reduction in the homocysteine concentration ≥30% (WMD: -0.22 mm; 95%CI: -0.38, -0.06; P=0.009).
49.SupplementDEX Database: Hyperhomocysteinemia — Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials2012
A meta-analysis of 58804 participants found that pooling the RRs showed that folic acid supplementation was not associated with any significant change in the risk of CVD (RR 0.98, 0.95 to 1.02; p=0.36), CHD (RR 1.03, 0.98 to 1.08; p=0.23), and all-cause mortality (RR 1.00, 0.96 to 1.04; p=0.92), but was linked to a.
50.SupplementDEX Database: Hyperhomocysteinemia — Reconciling the evidence on serum homocysteine and ischaemic heart disease: a meta-analysis2011
A meta-analysis of 39597 participants found that meta-analysis of the MTHFR studies showed a statistically significantly increased risk of ischaemic heart disease in TT compared with CC homozygotes; odds ratio 1.16 (1.04 to 1.29) for a 1.9 µmol/L homocysteine difference (TT minus CC).
51.SupplementDEX Database: Hyperhomocysteinemia — Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals2010
A meta-analysis of 485 studies found that there was no significant effect on the rate ratios (95% confidence intervals) for overall cancer incidence (1.05 [0.98-1.13]), cancer mortality (1.00 [0.85-1.18]) or all-cause mortality (1.02 [0.97-1.08]) during the whole scheduled treatment period or during the later years.
52.SupplementDEX Database: Hyperhomocysteinemia — Homocysteine lowering and cardiovascular events after acute myocardial infarction2006
A randomized trial of 3749 adults found that 0.8 mg folic acid + 0.4 mg vitamin B12 + 40 mg vitamin B6/day the mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31).
53.SupplementDEX Database: Hyperhomocysteinemia — Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials2005
A meta-analysis of 2596 participants found that after standardization for sex and to pretreatment plasma concentrations of 12 micromol homocysteine/L and 12 nmol folate/L, daily doses of 0.2, 0.4, 0.8, 2.0, and 5.0 mg folic acid were associated with reductions in homocysteine of 13% (95% CI: 10%, 16%), 20% (17%, 22%), 23%.
54.SupplementDEX Database: Hyperhomocysteinemia — Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial2004
A randomized trial of 1853 adults found that 2.5 mg folic acid + 25 mg vitamin B6 + 0.5 mg vitamin B12/day for 2 years a 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose gro
55.SupplementDEX Database: Hyperhomocysteinemia — The challenge of stroke prevention2004
A study found that the challenge of stroke prevention..
56.SupplementDEX Database: Hyperhomocysteinemia — Secondary prevention with folic acid: effects on clinical outcomes2003
A randomized trial of 593 found that 0.5 mg/day the primary end point (all-cause mortality and a composite of vascular events) was encountered in 31 (10.3%) patients in the folic acid group and in 28 (9.6%) patients in the control group (relative risk 1.05; 95% confidence interval: 0.63 to 1.75).
57.SupplementDEX Database: Hyperhomocysteinemia — Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study2003
A randomized trial in adults found that in older adults, daily supplementation with folic acid effectively lowers plasma homocysteine concentrations, and a daily dose of approximately 400 micro g is the minimum dose required for adequate homocysteine reduction.
58.SupplementDEX Database: Hyperhomocysteinemia — Dietary intake of folate and risk of stroke in US men and women: NHANES I Epidemiologic Follow-up Study. National Health and Nutrition Examination Survey2002
An observational study in adults found that incidence data for stroke and CVD were obtained from medical records and death certificates.
59.SupplementDEX Database: Hyperhomocysteinemia — Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation2002
A study of 29 healthy adults found that 10 mg/day for 1 year flow-mediated dilation also improved significantly, from 7.4% +/- 2.0% to 8.9% +/- 1.5% (P <0.0001), but there was no change in nitroglycerin-induced (endothelium-independent) responses.
60.SupplementDEX Database: Hyperhomocysteinemia — Effect of low doses of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C-->T polymorphism of methylenetetrahydrofolate reductase2002
A randomized trial in healthy adults found that 400 µg/day folic acid or 5-methyltetrahydrofolate for 7 weeks after folic acid for 3 and 7 weeks, values fell from 12.6 +/- 3.3 to 9.2 +/- 2.9 and 9.2 +/- 2.7 (P < 0.005) and from 15.6 +/- 4.9 to 11.7 +/- 3.9 and 9.1 +/- 2.4 mumol L-1, mean +/- SD (P < 0.005) in wild-type and homozygous subjects, respectively.
61.SupplementDEX Database: Hyperhomocysteinemia — Randomized trial of folic acid supplementation and serum homocysteine levels2001
A randomized trial of 151 adults found that 1 mg/day for 3 months serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid).
62.SupplementDEX Database: Hyperhomocysteinemia — Power Shortage: clinical trials testing the "homocysteine hypothesis" against a background of folic acid-fortified cereal grain flour2001
A randomized trial in women found that large randomized, controlled trials of total homocysteine-lowering therapy for the potential reduction of cardiovascular disease outcomes are ongoing in the United States and Canada.
63.SupplementDEX Database: Hyperhomocysteinemia — Diagnosis and treatment of hyperhomocysteinemia2001
A study found that vitamin therapy, particularly with folic acid, reduces plasma homocysteine significantly and improves other surrogate markers of cardiovascular risk such as endothelial function.
64.SupplementDEX Database: Hyperhomocysteinemia — 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 disease2001
A randomized trial of 90 patients with coronary artery disease found that 5 mg folic acid/day for 12 weeks at the end of the study, plasma homocysteine was lower in the folic acid group compared with the placebo group (mean [95% confidence interval] 9.3 (8.5 to 10.1) vs. 12.3 [11.3 to 13.4] micromol/l, p < 0.001).
65.SupplementDEX Database: Hyperhomocysteinemia — Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements2000
An observational study found that after standardization for a pretreatment homocysteine concentration of 12 micromol/L and folate concentration of 12 nmol/L (approximate average concentrations for western populations), dietary folic acid reduced homocysteine levels by 25% (95% confidence interval [CI]: 23 to.
66.SupplementDEX Database: Hyperhomocysteinemia — Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification2000
An observational study found that prevalence of stenosis > or = 25% was 43% in men and 34% in women, with an odds ratio of 2.0 for individuals in the highest homocysteine quartile (> or = 14.4 mumol/L) compared with those in the lowest quartile ( 13 mumol/L) decreased from 18.7 to 9.8% (P < 0.001) between.
67.SupplementDEX Database: Hyperhomocysteinemia — Dietary strategies for lowering homocysteine concentrations2000
A randomized trial found that the reduction in tHcy was significantly negatively correlated with the increase in serum folate, which may be a useful marker for measuring dietary change.
68.SupplementDEX Database: Hyperhomocysteinemia — The effect of different treatment regimens in reducing fasting and postmethionine-load homocysteine concentrations2000
A randomized trial found that 5 mg/day all regimens, except pyridoxine 200 mg, significantly reduced fasting tHcy without differences in the percentage reduction (32-38%).
69.SupplementDEX Database: Hyperhomocysteinemia — Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial2000
A randomized trial of 10 patients with premature atherothrombotic disease found that 5 mg folic acid + 250 mg vitamin B6/day for 2 years it was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035).
70.SupplementDEX Database: Hyperhomocysteinemia — Endpoints for homocysteine-lowering trials2000
A study found that endpoints for homocysteine-lowering trials..
71.SupplementDEX Database: Hyperhomocysteinemia — Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease2000
A randomized trial of 75 patients with coronary artery disease found that folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FMD from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo.
72.SupplementDEX Database: Hyperhomocysteinemia — Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients1999
A randomized trial of 29 found that 50 mg/day for 12 weeks moreover, a chi(2) analysis of participants with pretreatment tHcy levels >/=15 micromol/L (n=29) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels <12 micromol/L: group 1, 5 of 10 (50%); group 2, 1 of 11 (9%); and group 3, 0.
73.SupplementDEX Database: Hyperhomocysteinemia — Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid1999
A study in healthy adults found that 0.1 g/kg recent evidence demonstrates that hyperhomocyst(e)inaemia is a novel risk factor for cardiovascular diseases.
74.SupplementDEX Database: Hyperhomocysteinemia — Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration1998
A meta-analysis of 1114 participants found that 16.5 mg/day typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 mumol/l to 8-9 mumol/l).
75.SupplementDEX Database: Hyperhomocysteinemia — Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women1998
A randomized trial of 150 women found that the effect observed with the combination of folic acid + 400 microg vitamin B-12 (total homocysteine, -18%) was significantly larger than that with a supplement containing folic acid alone (total homocysteine, -11%) (P < 0.05).
76.SupplementDEX Database: Hyperhomocysteinemia — Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial1997
A randomized trial of 8 found that 50 mg/day these results occurred after adjustment for age; sex; and pretreatment levels of total homocysteine, B vitamins, and creatinine.
SupplementDEX Database · Stroke
13 references77.SupplementDEX Database: Stroke — Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide2024
A meta-analysis of 21 RCTs (115,559 participants) found folic acid supplementation reduced stroke risk by 10%, with greater benefit in regions without grain fortification.
78.SupplementDEX Database: Stroke — The effect of folic acid in patients with cardiovascular disease: A systematic review and meta-analysis2019
A meta-analysis of 47523 participants found that our meta-analysis showed that cardiovascular patients who received folic acid therapy had significantly decreased risk of stroke (RR = 0.85, 95% CI = 0.77-0.94, Pheterogeneity = .347, I = 10.6%) compared with patients who received control treatment.
79.SupplementDEX Database: Stroke — Supplemental Vitamins and Minerals for CVD Prevention and Treatment2018
A systematic review found moderate evidence for folic acid/B-vitamin cardiovascular benefits but no clear preventive benefit from calcium, vitamin D, multivitamins, or selenium on CVD or all-cause mortality.
80.SupplementDEX Database: Stroke — Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers2017
A meta-analysis of 22 trials (82,723 participants) found folic acid reduced stroke risk 11% overall, with stronger effects in low-folate regions without fortification.
81.SupplementDEX Database: Stroke — B vitamins in stroke prevention: time to reconsider2017
A meta-analysis found that the potential benefits of B vitamin therapy with folic acid and methylcobalamin or hydroxycobalamin, instead of cyanocobalamin, to lower homocysteine concentrations in people at high risk of stroke warrant further investigation.
82.SupplementDEX Database: Stroke — Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials2016
A meta-analysis of 334 studies found that the pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84-0.96; P=0.002) for stroke, 1.04 (95% CI 0.99-1.09; P=0.16) for coronary heart disease, and 0.96 (95% CI 0.92-0.99; P=0.02) for overall CVD.
83.SupplementDEX Database: Stroke — Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients2016
A CSPPT subgroup analysis in hypertensive adults found folic acid plus enalapril reduced first stroke risk 31% among those with total cholesterol ≥200 mg/dL.
84.SupplementDEX Database: Stroke — Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial2015
The CSPPT in 20,702 hypertensive Chinese adults found enalapril plus 0.8 mg/day folic acid reduced first stroke versus enalapril alone over 4.5 years (HR 0.79).
85.SupplementDEX Database: Stroke — Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis2012
A meta-analysis of 55,764 participants found folic acid reduced stroke risk 8% overall and 11% in populations without folic acid fortification.
86.SupplementDEX Database: Stroke — 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 trial2012
A VITATOPS post-hoc analysis of 8,164 stroke/TIA patients found B vitamins (folic acid, B6, B12) reduced vascular events only in those not on antiplatelet therapy (HR 0.76).
87.SupplementDEX Database: Stroke — Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials2011
A genetic meta-analysis of 59,995 individuals found MTHFR-stroke associations were stronger in low-folate Asia; homocysteine-lowering trials showed no benefit in fortified populations.
88.SupplementDEX Database: Stroke — Efficacy of homocysteine-lowering therapy with folic Acid in stroke prevention: a meta-analysis2010
A meta-analysis of 13 RCTs (39,005 participants) found folic acid trended toward stroke benefit overall; significant 11% reduction in primary prevention trials (RR 0.89).
89.SupplementDEX Database: Stroke — Efficacy of folic acid supplementation in stroke prevention: a meta-analysis2007
A meta-analysis of 8 folic acid RCTs found supplementation reduced stroke risk 18%, with greater benefit over 36 months and without grain fortification.
SupplementDEX Database · Vitiligo
3 references90.SupplementDEX Database: Vitiligo — Serum homocysteine, folate, and vitamin B12 levels in patients with vitiligo and their potential roles as disease activity biomarkers: A systematic review and meta-analysis2019
A meta-analysis of 22 studies (1,448 vitiligo patients) found higher serum homocysteine and lower vitamin B12 versus controls; folate levels did not differ significantly.
91.SupplementDEX Database: Vitiligo — Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure1997
In 100 vitiligo patients, oral folic acid and vitamin B12 plus sun exposure led to repigmentation in 52 and stopped spread in 64% over up to 2 years.
92.SupplementDEX Database: Vitiligo — Folic acid and vitamin B12 in vitiligo: a nutritional approach1992
In 15 vitiligo patients with low folate, combined folic acid, vitamin B12, and ascorbic acid treatment produced definite repigmentation in 8 without side effects.
SupplementDEX Database · Anemia
3 references93.SupplementDEX Database: Anemia — The Inclusion of Folic Acid in Weekly Iron-Folic Acid Supplements Confers no Additional Benefit on Anemia Reduction in Nonpregnant Women: A Randomized Controlled Trial in Malaysia2021
A randomized trial of 311 women found that 60 mg/day for 16 weeks among all women, the risks of anemia [risk ratio (RR): 0.65; 95% CI: 0.45, 0.96; P = 0.03] and iron deficiency based on ferritin (RR: 0.30; 95% CI: 0.20, 0.44; P < 0.001) were lower at 16 wk than at baseline.
94.SupplementDEX Database: Anemia — A randomized controlled trial examining the addition of folic acid to iron supplementation in the treatment of postpartum anemia2014
A randomized trial of 112 women found that 600 mg/day for 4 weeks the addition of folic acid to iron supplementation is not beneficial in women with postpartum anemia, as it has no effect on hematologic or health status parameters.
95.SupplementDEX Database: Anemia — Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes2013
A meta-analysis of 17771 participants found that this review found that folic acid supplementation has no impact on pregnancy outcomes such as preterm birth (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.38; three studies, 2959 participants), and stillbirths/neonatal deaths (RR 1.33, 95% CI 0.96 to 1.85;.
SupplementDEX Database · Cataracts
1 reference96.SupplementDEX Database: Cataracts — Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-Related Cataract in a Randomized Trial of Women2016
A randomized trial of 3925 women found that 2.5 mg/day for the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04).
SupplementDEX Database · Diarrhea
1 reference97.SupplementDEX Database: Diarrhea — Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial2013
A randomized trial in children/adolescents found that in comparison with placebo, children treated with folic acid alone or in combination with vitamin B-12 had a significantly higher risk of persistent diarrhea (OR: 2.1; 95% CI: 1.1, 3.8).
98.SupplementDEX Database: Elderly physical function — A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study2016
A randomized trial of 2919 older adults found that 600 IU/day for 2 years moreover, time to first fall was not significantly different (HR: 1.0, 95% CI 0.9-1.2).
SupplementDEX Database · High blood pressure
4 references99.SupplementDEX Database: High blood pressure — A Meta-Analysis of Folic Acid in Combination with Anti-Hypertension Drugs in Patients with Hypertension and Hyperhomocysteinemia2017
A meta-analysis of 7887 participants found that in addition, folic acid supplementation obviously reduced the risk of cardiovascular and cerebrovascular events (CVCE) by 12.9% compared with control groups.
100.SupplementDEX Database: High blood pressure — Folic acid therapy reduces the risk of mortality associated with heavy proteinuria among hypertensive patients2017
A randomized trial of 10 hypertensive patients found that however, eGFR levels did not significantly modify the effect of folic acid supplementation in reducing the risk of all-cause mortality (P for interaction = 0.228).
101.SupplementDEX Database: High blood pressure — High-dose folic acid supplementation effects on endothelial function and blood pressure in hypertensive patients: a meta-analysis of randomized controlled clinical trials2009
A meta-analysis of 12 studies found that the pooled estimate of effect of folic acid supplementation on systolic and diastolic blood pressure was -2.03 mm Hg (95% confidence interval [CI], -3.63 to -0.43; P = .04) and 0.01 mm Hg (95% CI, -1.12 to 1.13; not significant), respectively.
102.SupplementDEX Database: High blood pressure — Efficacy of folic acid and enalapril combined therapy on reduction of blood pressure and plasma glucose: a multicenter, randomized, double-blind, parallel-controlled, clinical trial2008
A randomized trial of 80 women found that 0.4–0.8 mg folic acid + 10 mg enalapril/day for 8 weeks there was no significant difference in BP or FPG reduction among the three treatment groups.
SupplementDEX Database · Infant mortality
1 reference103.SupplementDEX Database: Infant mortality — Effects and safety of periconceptional oral folate supplementation for preventing birth defects2015
A meta-analysis of 7391 participants found that folic acid had a significant protective effect for reoccurrence (RR 0.34, 95% CI 0.18 to 0.64); four studies; 1846 births).
SupplementDEX Database · Leukemia
1 reference104.SupplementDEX Database: Leukemia — Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study2007
A meta-analysis of 97 studies found that combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8-1.1).
SupplementDEX Database · Male infertility
5 references106.SupplementDEX Database: Male infertility — The Role and Place of Antioxidants in the Treatment of Male Infertility Caused by Varicocele2022
In 163 men with idiopathic or varicocele-related infertility, 6 months of an antioxidant formula containing 3,450 mg/day L-carnitine plus acetyl-L-carnitine improved sperm count, concentration, and motility, with greatest benefit in grade III varicocele.
105.SupplementDEX Database: Male infertility — The Effect of Daily Intake of Selenium, Vitamin E and Folic Acid on Sperm Parameters in Males with Idiopathic Infertility: A Single-Blind Randomized Controlled Clinical Trial2021
A randomized trial of 35 men found that 200 μg/day according to between-group analysis, no significant difference was found in mean semen volume (P=0.610), sperm concentration (P=0.126), total sperm motility (P=0.765), progressive sperm motility (P=0.767), normal sperm morph (P=0.403), SMI (P=0.556) or FSC (P=0.706) between.
107.SupplementDEX Database: Male infertility — Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial2020
A randomized trial of 1185 pregnant women found that 5 mg folic acid + 30 mg zinc/day for 6 months among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates.
108.SupplementDEX Database: Male infertility — Effects of supplement therapy on sperm parameters, protamine content and acrosomal integrity of varicocelectomized subjects2013
A randomized trial in men found that we may conclude that co-administration of zinc and folic acid significantly improved sperm parameters and increased varicocelectomy outcomes.
109.SupplementDEX Database: Male infertility — Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial2002
A randomized trial in subfertile men found that 5 mg/day for 26 weeks pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men.
SupplementDEX Database · Osteoporosis
3 references110.SupplementDEX Database: Osteoporosis — Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: Extended follow-up of the B-PROOF trial2020
A randomized trial of 662 older adults found that 400 μg for 5–7 years no effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR:.
111.SupplementDEX Database: Osteoporosis — Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial2014
A randomized trial of 2919 adults found that 600 IU/day osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21).
112.SupplementDEX Database: Osteoporosis — The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial2013
A randomized trial of 8164 patients with cerebrovascular disease found that 2 mg folic acid + 25 mg vitamin B6 + 500 µg vitamin B12/day for 2.8 years participants had a mean age of 62.6 years (SD 12.5 years) and 64% were male, 42% of Western European descent and 75% were functionally independent (Oxford Handicap Scale of two or less).
SupplementDEX Database · Preeclampsia
6 references113.SupplementDEX Database: Preeclampsia — Folic Acid and Risk of Preterm Birth, Preeclampsia, and Fetal Growth Restriction Among Women With Epilepsy: A Prospective Cohort Study2022
An observational study of 64 women found that aSM-treated women with epilepsy starting folic acid after the first trimester had a higher risk compared with women without epilepsy with similar timing of folic acid (aOR 2.6, 95% CI 1.1-6.5), and even higher if not using folic acid (aOR 9.4, 95% CI 2.6-34.8).
114.SupplementDEX Database: Preeclampsia — Effect of high-dose folic acid supplementation on the prevention of preeclampsia in twin pregnancy2022
A secondary analysis of 428 twin pregnancies in the FACT trial found high-dose folic acid (4–5.1 mg/day) did not significantly prevent preeclampsia versus placebo.
115.SupplementDEX Database: Preeclampsia — Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial2018
The FACT trial in 2,301 high-risk pregnant women found 4 mg/day folic acid did not reduce preeclampsia versus placebo (14.8% vs 13.5%; RR 1.10).
116.SupplementDEX Database: Preeclampsia — Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis2018
A meta-analysis of 8 observational studies found maternal folic acid supplementation associated with 22% lower preeclampsia odds (OR 0.78), though evidence quality was low.
117.SupplementDEX Database: Preeclampsia — Effect of folic acid supplementation during pregnancy on gestational hypertension/preeclampsia: A systematic review and meta-analysis2016
A meta-analysis of 13 studies found folic acid reduced gestational hypertension/preeclampsia in RCTs (RR 0.62) but not in cohort studies; overall benefit remains uncertain.
118.SupplementDEX Database: Preeclampsia — Folic acid supplementation during early pregnancy and the risk of gestational hypertension and preeclampsia2013
In 193,554 Chinese pregnant women, daily 400 µg folic acid alone in early pregnancy did not prevent gestational hypertension or preeclampsia and may have slightly increased risk.
SupplementDEX Database · Pregnancy outcomes
2 references119.SupplementDEX Database: Pregnancy outcomes — Folic acid supplementation in pregnancy to prevent preterm birth: a systematic review and meta-analysis of randomized controlled trials2016
A meta-analysis of 5 RCTs in 5,332 women found folic acid supplementation did not reduce preterm birth before 37 weeks versus control (22.6% vs 22.9%).
120.SupplementDEX Database: Pregnancy outcomes — Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation2012
A meta-analysis of 10 RCTs found each two-fold increase in folate intake associated with ~2% higher birth weight; no effect on placental weight or gestational length.
SupplementDEX Database · Weight loss
1 reference121.SupplementDEX Database: Weight loss — The effect of folic acid supplementation on body weight and body mass index: A systematic review and meta-analysis of randomized controlled trials2022
A meta-analysis of 9 RCTs found folic acid did not change body weight or BMI overall but lowered BMI in women with PCOS and those with homocysteine ≥15 µmol/L.
SupplementDEX Database · Colorectal adenoma
12 references122.SupplementDEX Database: Colorectal adenoma — Folic acid prevents the initial occurrence of sporadic colorectal adenoma in Chinese older than 50 years of age: a randomized clinical trial2013
A randomized trial in adults found that 1 mg/day cRA occurred in 64 (14.88%) participants in the folic acid group and 132 (30.70%) in the control group [unadjusted risk ratio (RR), 0.49; 95% confidence interval (CI), 0.37-0.63; P < 0.01]; left-sided adenoma (unadjusted RR, 0.54; 95% CI, 0.38-0.76; P = 0.001) and advanced.
123.SupplementDEX Database: Colorectal adenoma — Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma2012
A randomized trial of 1470 women found that 2.5 mg the risk of colorectal adenoma was similar among participants receiving treatment (24.3%, 180 of 741 participants) vs placebo (24.0%, 175 of 729 participants) (multivariable adjusted relative risk = 1.00, 95% confidence interval = 0.83 to 1.20).
124.SupplementDEX Database: Colorectal adenoma — [Folic acid supplementation and colorectal adenoma recurrence: systematic review]2012
A meta-analysis found that observational studies show that folate levels may be associated with the development of adenomas and colorectal cancer, suggesting that folic acid supplementation may have a preventive effect.
125.SupplementDEX Database: Colorectal adenoma — Folic acid supplementation and colorectal cancer risk: a meta-analysis2011
A meta-analysis found that the risk associated with treatment was the highest for the occurrence of an advanced lesion (odds ratio 1.50, 95% confidence interval 1.06-2.10).
126.SupplementDEX Database: Colorectal adenoma — Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials2011
An observational study of 2632 adults found that 1.0 mg/day for 6–42 months the RR comparing folic acid versus placebo was 0.98 (95% CI = 0.82-1.17) for all adenomas and 1.06 (95% CI = 0.81-1.39) for advanced lesions.
127.SupplementDEX Database: Colorectal adenoma — Folic acid supplementation for the prevention of recurrence of colorectal adenomas: metaanalysis of interventional trials2010
A meta-analysis of 775 participants found that 1 mg/day however, the overall effect for all included studies was not significant [odds ratio = 0.78 (95% CI; 0.49, 1.24; P = 0.30)].
128.SupplementDEX Database: Colorectal adenoma — Meta-analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancer2010
A meta-analysis found that there is no evidence that folic acid is effective in the chemoprevention of colorectal adenomas or colorectal cancer for any population.
129.SupplementDEX Database: Colorectal adenoma — Chemoprevention of colorectal cancer: systematic review and economic evaluation2010
A UK systematic review of chemoprevention trials concluded calcium can reduce adenomatous polyps but noted limited direct CRC endpoint data and mixed evidence across micronutrients.
130.SupplementDEX Database: Colorectal adenoma — Aspirin and folic acid for the prevention of recurrent colorectal adenomas2008
A randomized trial of 945 patients with prior polyps found that 300 mg/day folate supplementation was found to have no effect on adenoma recurrence (relative risk, 1.07; 95% CI, 0.85-1.34).
131.SupplementDEX Database: Colorectal adenoma — Folic acid for the prevention of colorectal adenomas: a randomized clinical trial2007
A randomized trial of 516 adults found that 1 mg/day during the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI],.
132.SupplementDEX Database: Colorectal adenoma — Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas1998
A study in patients with at least one recent large-bowel adenoma found that alcohol intake (seven or more drinks/week) was associated with increased risk (odds ratio = 2.04; 95% confidence interval = 1.28-3.26).
133.SupplementDEX Database: Colorectal adenoma — Micronutrients and the risk of colorectal adenomas1996
An observational study of 236 found that folate appeared to be most protective, with women in the highest quartile only 40% as likely to develop adenomas compared with women in the lowest (odds ratio = 0.39, 95% confidence interval 0.15-1.01).
SupplementDEX Database · Acne
1 reference134.SupplementDEX Database: Acne — Inflammatory acne management with a novel prescription dietary supplement2012
A study of 235 women found that at week 8, 88% of the patients experienced a visible reduction in inflammatory lesions, and 81% of the patients rated their appearance as much or moderately better compared with baseline.
135.SupplementDEX Database: Age-related macular degeneration (AMD) — Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study2009
A randomized trial of 55 women found that 2.5 mg/day for visually significant AMD, there were 26 cases in the combination treatment group and 44 in the placebo group (relative risk, 0.59; 95% confidence interval, 0.36-0.95 [P = .03]).
SupplementDEX Database · All-cause mortality
1 reference136.SupplementDEX Database: All-cause mortality — Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to All-Cause and Cause-Specific Mortality: A National Population-Based Cohort2022
An observational study of 55569 adults found that higher dietary intakes of folate and vitamin B6 were significantly associated with lower all-cause and cardiovascular mortality.
SupplementDEX Database · Alzheimer's disease
2 references137.SupplementDEX Database: Alzheimer's disease — 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 Trial2021
A randomized trial of 120 dementia patients found that 1.2 mg/day moreover, supplementation significantly increased plasma SAM (P<0.001) and SAM/SAH (P<0.001), and significantly decreased the levels of serum Hcy (P<0.001), plasma SAH (P<0.001), and serum TNFα (P<0.001) compared to in the control subjects.
138.SupplementDEX Database: Alzheimer's disease — High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial2008
A randomized trial of 340 dementia patients found that 5 mg/day for 18 months prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.
139.SupplementDEX Database: Autism spectrum disorder — Prenatal Folic Acid Supplements and Offspring's Autism Spectrum Disorder: A Meta-analysis and Meta-regression2022
A meta-analysis of 10 studies found that the consumption of a daily amount of at least 400 μg folic acid from dietary sources and supplements, was associated with a reduced risk of offspring ASD [OR 0.55, 95% CI 0.36-0.83].
140.SupplementDEX Database: Autism spectrum disorder — Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children2013
A study of 85176 pregnant women found that the adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90).
SupplementDEX Database · Beta-thalassemia
1 reference141.SupplementDEX Database: Beta-thalassemia — Determining and surveying the role of carnitine and folic acid to decrease fatigue in β-thalassemia minor subjects2013
In β-thalassemia minor patients, carnitine plus folic acid for 3 months reduced fatigue severity versus baseline in a clinical evaluation.
SupplementDEX Database · Bipolar disorder
3 references142.SupplementDEX Database: Bipolar disorder — Short-Term Effects of Folate Supplementation in Combination With Vitamin B6 for Treating Acute Manic Episodes in Bipolar I Disorder: A Randomized Controlled Trial2025
A randomized trial of 43 patients with bipolar disorder found that 5 mg/day all groups demonstrated significant clinical improvements after the treatment period; however, the trends in MMSE scores showed no significant differences (p = 0.068).
143.SupplementDEX Database: Bipolar disorder — Causal relationship between B vitamins and neuropsychiatric disorders: A systematic review and meta-analysis2025
A meta-analysis found that this complexity underscores the importance of personalized supplementation in developing future therapeutic approaches for NPDs.
144.SupplementDEX Database: Bipolar disorder — 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 trial2009
A randomized trial in patients with bipolar disorder found that based on our findings, folic acid seems to be an effective adjuvant to sodium valproate in the treatment of the acute phase of mania in patients with bipolar disorder.
SupplementDEX Database · Breast cancer risk
4 references145.SupplementDEX Database: Breast cancer risk — Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis2014
A meta-analysis of 5924 participants found that 153–400 μg increased dietary folate intake reduced breast cancer risk for women with higher alcohol intake level, but not for those with lower alcohol intake.
146.SupplementDEX Database: Breast cancer risk — Folate and risk of breast cancer: a meta-analysis2007
A meta-analysis of 306209 participants found that high blood folate levels versus low levels were not statistically significantly associated with the risk of breast cancer in prospective studies (OR = 0.81, 95% CI = 0.59 to 1.10 [three studies]) or in case-control studies (OR = 0.41, 95% CI = 0.15 to 1.10 [two studies]).
147.SupplementDEX Database: Breast cancer risk — Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk2006
A meta-analysis of 13 studies found that we found no difference in breast cancer risk between MTHFR 677 TT homozygotes and CC homozygotes (OR = 1.05, 95% CI = 0.88 to 1.25), and there was no evidence of an interaction between folate intake and MTHFR genotype on breast cancer risk.
148.SupplementDEX Database: Breast cancer risk — Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study2001
An observational study of 1321 women found that unconditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (95% CIs) after adjusting for potential confounding factors.
SupplementDEX Database · Cancer risk
3 references149.SupplementDEX Database: Cancer risk — Benefits and Risks of Periconceptional Folic Acid Supplementation2023
A study found that benefits and Risks of Periconceptional Folic Acid Supplementation..
150.SupplementDEX Database: Cancer risk — Benefits and Risks of Periconceptional Folic Acid Supplementation-Reply2023
A study found that benefits and Risks of Periconceptional Folic Acid Supplementation-Reply..
151.SupplementDEX Database: Cancer risk — Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy2022
An observational study of 784 pregnant women found that 1 mg/day cox proportional hazards models were used to calculate adjusted hazard ratios with corresponding 95% CIs, adjusted for potential confounders.
SupplementDEX Database · Cardiovascular disease
6 references152.SupplementDEX Database: Cardiovascular disease — Association of folate intake with cardiovascular-disease mortality and all-cause mortality among people at high risk of cardiovascular-disease2022
A study of 14234 adults found that after multivariate adjustment, a J shaped association was found: modest intake of TFE and DFE was associated with lower risk of CVD-mortality and all-cause mortality, whereas higher intake did not persistently reduce these risks.
153.SupplementDEX Database: Cardiovascular disease — Homocysteine-lowering therapy with folic acid is effective in cardiovascular disease prevention in patients with kidney disease: a meta-analysis of randomized controlled trials2013
A meta-analysis of 11032 participants found that when pooling the nine randomized trials, folic acid therapy reduced the risk of CVD by 10%（RR = 0.90; 95% CI:0.81-1.00, P = 0.046).
154.SupplementDEX Database: Cardiovascular disease — The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis2012
A meta-analysis of 10951 participants found that folic acid based homocysteine therapy did not prevent cardiovascular events (relative risk 0.97, 95% confidence interval 0.92 to 1.03, P = 0.326) or any of the secondary outcomes.
155.SupplementDEX Database: Cardiovascular disease — Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials2012
A meta-analysis found that the estimated RR were not significantly different for any outcomes, including CHD (RR 1·00, 95 % CI 0·75, 1·31, P = 0·97), CVD (RR 0·94, 95 % CI 0·84, 1·05, P = 0·30), stroke (RR 0·83, 95 % CI 0·57, 1·19, P = 0·31) and all-cause mortality (RR 1·00, 95 % CI 0·92, 1·09, P = 0·98).
156.SupplementDEX Database: Cardiovascular disease — Folic acid therapy and cardiovascular disease in ESRD or advanced chronic kidney disease: a meta-analysis2011
A meta-analysis of 3886 participants found that a greater beneficial effect was observed among those trials with a treatment duration >24 months (RR, 0.84; 95% CI, 0.72 to 0.98; P = 0.02), a decrease in Hcy level >20% (RR, 0.83; 95% CI, 0.73 to 0.95; P = 0.007), and no or partial folic acid fortification (RR, 0.80; 95% CI,.
157.SupplementDEX Database: Cardiovascular disease — Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?2000
A randomized trial of 100 patients with chronic renal failure found that 5 mg folic acid/day for 12 weeks at the end of the study, both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [mean (95% CI) 39.0 (29.8 to 51.0) versus 7.7 (6.6 to 8.9) microg/L and 739 (613 to 891) versus 220 (184 to 262) microg/L, respectively; both.
SupplementDEX Database · Child development
3 references158.SupplementDEX Database: Child development — Association between the Use of Folic Acid Supplements during Pregnancy and Children's Cognitive Function at 7-9 Years of Age in the INMA Cohort Study2022
An observational study in pregnant women found that 400 μg/day for 7–9 years a high FAs use throughout the two periods of pregnancy was associated with a better N-back Task performance only in girls (d' number 2-back (β = 0.28; 95% CI: 0.01; 0.56) and d' number 3-back (β = 0.32; 95% CI: 0.08; 0.56)).
159.SupplementDEX Database: Child development — 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 trial2021
A randomized trial of 68 pregnant women found that 400 μg/day for 26 weeks of 119 mother-child pairs in the FASSTT trial, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018).
160.SupplementDEX Database: Child development — 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)2019
A randomized trial of 70 pregnant women found that 400 μg/day for 26 weeks at 7 years, the children of folic acid treated mothers scored significantly higher than the placebo group in word reasoning: mean 13.3 (95% CI 12.4-14.2) versus 11.9 (95% CI 11.0-12.8); p = 0.027; at 3 years, they scored significantly higher in cognition: 10.3 (95% CI.
SupplementDEX Database · Chronic kidney disease
3 references161.SupplementDEX Database: Chronic kidney disease — Efficacy of Folic Acid Therapy on the Progression of Chronic Kidney Disease: The Renal Substudy of the China Stroke Primary Prevention Trial2016
A randomized trial of 7559 adults found that 0.8 mg folic acid + 10 mg enalapril/day compared with the enalapril group, the enalapril-folic acid group had a 21% reduction in the odds of the primary event (odds ratio [OR], 0.79; 95% CI, 0.62-1.00) and a slower rate of eGFR decline (1.28% vs 1.42% per year; P = .02).
162.SupplementDEX Database: Chronic kidney disease — Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial2010
A randomized trial of 238 patients with diabetic nephropathy found that 2.5 mg/day plasma total homocysteine decreased by a mean (SE) of 2.2 (0.4) micromol/L at 36 months in the B-vitamin group compared with a mean (SE) increase of 2.6 (0.4) micromol/L in the placebo group (mean difference, -4.8; 95% CI, -6.1 to -3.7; P < .001, in favor of B vitamins).
163.SupplementDEX Database: Chronic kidney disease — Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial2007
A randomized trial of 2056 hemodialysis patients found that 40 mg folic acid + 2 mg vitamin B12 + 25 mg vitamin B6/day no significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60
164.SupplementDEX Database: Cleft lip & cleft palate — Folate intake, markers of folate status and oral clefts: An updated set of systematic reviews and meta-analyses2020
A meta-analysis found that the prevalence of CL/P showed a small decline post-folic acid fortification in seven studies (OR 0.94, 95% CI 0.86-1.02).
165.SupplementDEX Database: Cleft lip & cleft palate — High dosage folic acid supplementation, oral cleft recurrence and fetal growth2013
A randomized trial of 2508 women found that 4 mg/day the recurrence rates in the two folic acid groups both separately and combined were significantly different from the 6.3% historic recurrence rate post the folic acid fortification program for this population (p = 0.0009 when combining the two folic acid groups).
166.SupplementDEX Database: Cleft lip & cleft palate — Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis2007
A meta-analysis found that in aggregate, our results support the hypothesis of a protective effect of folic acid-containing supplement intake during pregnancy on the risk for oral clefts, although this conclusion is tempered by the potential for bias and uncontrolled confounding.
SupplementDEX Database · Colorectal cancer
17 references167.SupplementDEX Database: Colorectal cancer — Folate intake and risk of colorectal cancer: a systematic review and up-to-date meta-analysis of prospective studies2023
A meta-analysis of 280 studies found that the combined relative risk (RR) for the highest intake compared with the lowest was 0.88 [95% confidence interval (CI), 0.83-0.92, P = 10 -4 ).
168.SupplementDEX Database: Colorectal cancer — Association of folate intake and colorectal cancer risk in the postfortification era in US women2021
An observational study of 86320 women found that in the postfortification period (1998-2016), intake of total or specific forms of folate was not associated with CRC risk, even among multivitamin users.
169.SupplementDEX Database: Colorectal cancer — Folic Acid Supplementation May Reduce Colorectal Cancer Risk in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis2017
A meta-analysis of 4517 participants found that we found an overall protective effect for folic acid supplementation on the development of CRC, pooled hazard ratio=0.58 (95% confidence interval, 0.37-0.80).
170.SupplementDEX Database: Colorectal cancer — High levels of folate from supplements and fortification are not associated with increased risk of colorectal cancer2011
An observational study of 56011 found that intake of high levels of natural folate (RRQ5vsQ1=0.86; 95% CI: 0.70-1.06; P trend=.12) or folic acid (RRQ5vsQ1=0.84; 95% CI: 0.68-1.03; P trend=.06) were not significantly associated with risk of colorectal cancer.
171.SupplementDEX Database: Colorectal cancer — Pre- and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States2011
An observational study of 6484 adults found that 200 μg/day in the postfortification analysis (6484 cases), a higher total folate intake was associated with a decreased colorectal cancer risk (HR for ≥900 compared with <200 μg/d: 0.70; 95% CI: 0.58, 0.84).
172.SupplementDEX Database: Colorectal cancer — Folate intake and the risk of colorectal cancer: a systematic review and meta-analysis2011
A meta-analysis of 27 studies found that similarly, for cohort studies, the resulting summary risk estimate for high versus low dietary folate intake was 0.92 (CI 95% 0.81-1.05) with no significant heterogeneity.
173.SupplementDEX Database: Colorectal cancer — Micronutrient intake and risk of colon and rectal cancer in a Danish cohort2010
An observational study of 56332 (ages 50–64) found that rectal cancer did not seem associated with any micronutrient.
174.SupplementDEX Database: Colorectal cancer — Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer2010
A meta-analysis of 725134 participants found that 100 μg/day results for total folate intake were similar in analyses using absolute intake cutpoints (pooled multivariate RR = 0.87, 95% CI 0.78-0.98, comparing ≥ 560 mcg/days vs. <240 mcg/days, p-value, test for trend = 0.009).
175.SupplementDEX Database: Colorectal cancer — Folate and vitamin B6 intake and risk of colon cancer in relation to p53 expression2008
An observational study of 399 women found that similarly, high vitamin B(6) intake conferred a protective effect on p53-overexpressing cancers (top versus bottom quintile: RR, 0.57; 95% CI, 0.35-0.94; P(heterogeneity) = .01) but had no effect on p53 wild-type tumors.
176.SupplementDEX Database: Colorectal cancer — Folate intake and colorectal cancer risk: a meta-analytical approach2005
A meta-analysis found that these results offer some support for the hypothesis that folate has a small protective effect against colorectal cancer but confounding by other dietary factors cannot be ruled out.
177.SupplementDEX Database: Colorectal cancer — The influence of folate and multivitamin use on the familial risk of colon cancer in women2002
A prospective cohort of 88,758 women found high folate and methionine intake and multivitamin use reduced excess colon cancer risk associated with a family history of colorectal cancer.
178.SupplementDEX Database: Colorectal cancer — Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study2001
An analysis of 14,407 NHANES I participants found high folate intake was inversely associated with colon cancer in men, and low folate plus low methionine with high alcohol increased risk.
179.SupplementDEX Database: Colorectal cancer — Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study1998
An observational study of 88756 women found that multivariate relative risk (RR) and 95% CIs for colon cancer in relation to energy-adjusted folate intake.
180.SupplementDEX Database: Colorectal cancer — Are dietary factors involved in DNA methylation associated with colon cancer?1997
An observational study of 1 found that this trend was modest and most marked in those diagnosed at a younger age [odds ratio (OR) for men = 1.3, 95% confidence interval (CI) = 0.9-1.9; OR for women = 1.6, 95% CI = 1.0-2.6].
181.SupplementDEX Database: Colorectal cancer — The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis1997
An observational study of 98 uc patients found that 0.4–1.0 mg folic acid/day folate use also varied with the degree of dysplasia (RR for cancer, 0.45; RR for high-grade dysplasia, 0.52; RR for low-grade dysplasia, 0.75 compared with patients with no dysplasia) (P = 0.08).
182.SupplementDEX Database: Colorectal cancer — Intake of selected micronutrients and risk of colorectal cancer1997
An observational study found that our results provide further support for a protective effect of several micronutrients on colorectal cancer risk and some indications for a specific and stronger effect of selected anti-oxidants.
183.SupplementDEX Database: Colorectal cancer — Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis1993
An observational study of 67 uc patients found that adjusting for confounding effects of age, sex, race, disease duration, and folate supplementation, the risk of dysplasia or cancer was significantly decreased by 18% for each 10 ng/ml increase in red blood cell folate (odds ratio 0.82, 95% confidence interval 0.68-0.99).
184.SupplementDEX Database: Congenital heart disease — A Meta-Analysis of the Relationship Between Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects2016
A meta-analysis found that odds ratios (ORs) and 95% confidence interval (CIs) were merged using STATA 12.0.
SupplementDEX Database · Diabetic neuropathy
1 reference185.SupplementDEX Database: Diabetic neuropathy — Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial2013
A randomized trial of 214 diabetic patients found that 3 mg L-methylfolate + 2 mg methylcobalamin + 35 mg pyridoxal-5'-phosphate/day for 24 weeks lMF-MC-PLP appears to be a safe and effective therapy for alleviation of peripheral neuropathy symptoms, at least in the short term.
SupplementDEX Database · Eczema
1 reference186.SupplementDEX Database: Eczema — Pre-natal folic acid and iron supplementation and atopic dermatitis in the first 6 years of life2019
An observational study of 395 pregnant women found that children in which mothers used both iron and folic acid supplementation had a fourfold decreased risk of developing atopic dermatitis [OR = 0.22; 95% confidence interval (CI) 0.06-0.79, p = 0.02], after adjusting for possible confounding factors.
SupplementDEX Database · Epilepsy
2 references187.SupplementDEX Database: Epilepsy — Effect of Folic Acid Supplementation on Seizure Control in Epileptic Children Receiving Long Term Antiepileptic Therapy2018
A study of 140 children/adolescents found that on 3 mo follow up, children supplemented with folic acid (Group A) had significant fall in mean seizure frequency while in non-supplemented children (Group B), no significant change was seen (p value <0.05).
188.SupplementDEX Database: Epilepsy — Vitamins for epilepsy2005
A meta-analysis of 331 studies found that one study (226 participants) found a significantly higher bone mineral content (BMC) among patients with epilepsy taking AEDs with vitamin D supplementation compared to controls who were not given supplementation (OR 3.6; 95% CI 2.48 to 4.72; p < 0.00001).
189.SupplementDEX Database: Erectile dysfunction — Positive effects of dietary supplementation with nutraceuticals on male subclinical hypogonadism: a pilot study2023
In 15 overweight men with subclinical hypogonadism, a nutraceutical containing myoinositol, alpha-lipoic acid, and folic acid added to lifestyle changes for 3 months improved BMI, insulin sensitivity, and testosterone versus baseline.
SupplementDEX Database · Esophageal cancer risk
2 references190.SupplementDEX Database: Esophageal cancer risk — Folate intake, serum folate, and risk of esophageal cancer: a systematic review and dose-response meta-analysis2019
A meta-analysis of 3886 participants found that 50 μg/day the pooled odds ratios for EC in the highest versus the lowest levels of folate intake and serum folate were 0.64 (0.54-0.76, P<0.001) and 0.45 (0.19-1.07, P=0.071), respectively.
191.SupplementDEX Database: Esophageal cancer risk — Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis2006
A meta-analysis found that these findings support the hypothesis that folate may play a role in carcinogenesis of the esophagus, stomach, and pancreas.
SupplementDEX Database · Gout
1 reference192.SupplementDEX Database: Gout — Risk factors for gout and prevention: a systematic review of the literature2011
A systematic review of 53 studies found that hypertension, renal insufficiency, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, diabetes, obesity, and early menopause were each associated with a higher risk of incident gout and/or gout flares.
SupplementDEX Database · Hair growth
1 reference193.SupplementDEX Database: Hair growth — A Randomized, Placebo-controlled Clinical Study Evaluating a Dietary Supplement for Hair Growth2024
In 65 women with thinning hair, 6 months of B-vitamin/zinc/botanical gummies increased hair density by 10.1% and improved self-reported shedding and appearance versus placebo, with no adverse events.
194.SupplementDEX Database: Head and neck cancer risk — Association between folate intake and risk of head and neck squamous cell carcinoma: An overall and dose-response PRISMA meta-analysis2017
A meta-analysis of 9 studies found that the linearity model of dose-response analysis indicated that with increased 100 μg/d folate intake, the risk of HNSCC decreased 4.3% degree (OR 0.957, 95% CI 0.935-0.980).These results indicate that folate is a protective nutrient against HNSCC carcinogenesis.
SupplementDEX Database · Infertility
1 reference195.SupplementDEX Database: Infertility — 5-Methyltetrahydrofolate and Vitamin B12 Supplementation Is Associated with Clinical Pregnancy and Live Birth in Women Undergoing Assisted Reproductive Technology2021
A study in women found that 400 mcg vitamin B complex supplementation remained independently associated, after multivariable adjustment, with clinical pregnancy (OR 2.03, p = 0.008) and live birth (OR 1.83, p = 0.03).
SupplementDEX Database · Kidney failure
2 references196.SupplementDEX Database: Kidney failure — Supplementation with Folic Acid and Cardiovascular Outcomes in End-Stage Kidney Disease: A Multi-Institution Cohort Study2022
An observational study in patients with eskd found that the mean follow-up time was 5.8 years, and the event rates of arteriovenous access thrombosis were 17.0% and 23.6% in the daily and weekly folic acid supplementation groups (sub-distribution hazard ratio = 0.69, 95% confidence interval = 0.61 to 0.77), respectively.
197.SupplementDEX Database: Kidney failure — A pilot study of thiamin and folic acid in hemodialysis patients with cognitive impairment2021
A randomized trial of 25 mci patients found that 90 mg/day for 96 weeks the proportion of adverse events in treatment group was significantly lower than that in control group.
SupplementDEX Database · Low birth weight
3 references198.SupplementDEX Database: Low birth weight — Maternal Folic Acid Supplementation, Dietary Folate Intake, and Low Birth Weight: A Birth Cohort Study2022
An observational study of 10542 women found that compared with non-users, folic acid supplementation was associated with a reduced risk of LBW ( OR : 0.80, 95% CI : 0.66-0.97), and the reduced risk was mainly seen for term-LBW ( OR : 0.59, 95% CI : 0.41-0.85), and multiparous-LBW ( OR : 0.72, 95% CI : 0.54-0.94).
199.SupplementDEX Database: Low birth weight — Maternal folic acid supplementation and more prominent birth weight gain in twin birth compared with singleton birth: a cross-sectional study in northwest China2020
An observational study in women found that 4 mg/day the present study suggests the association of periconceptional 0·4 mg/d FA supplementation with increased birth weight and reduced risk of SGA and LBW in both singletons and twins, and this association may be more prominent in twins.
200.SupplementDEX Database: Low birth weight — Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small-for-gestational age neonates: a population study, systematic review and meta-analysis2015
A meta-analysis found that preconception commencement of FA supplementation was associated with reduced risk of SGA <10th centile (aOR 0.80, 95% CI 0.71-0.90, P < 0.01) and SGA <5th centile (aOR 0.78, 95% CI 0.66-0.91, P < 0.01).
SupplementDEX Database · Lung cancer
2 references201.SupplementDEX Database: Lung cancer — Dietary folate intake and lung cancer risk in former smokers: a case-control analysis2003
An observational study found that dietary folate intake from natural food was significantly higher among the controls than among the cases (P < 0.001), and folate intake above the control median value was associated with a 40% decreased risk of lung cancer (adjusted OR, 0.60; 95% CI, 0.45-0.79).
202.SupplementDEX Database: Lung cancer — Association of the B-vitamins pyridoxal 5'-phosphate (B(6)), B(12), and folate with lung cancer risk in older men2001
A randomized trial in men found that adjusting for any of the other serum factors (folate, B(12), and homocysteine) either alone or jointly did not significantly alter these estimates.
SupplementDEX Database · Melanoma
1 reference203.SupplementDEX Database: Melanoma — Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials2013
A meta-analysis of 49 studies found that however, a significantly reduced risk was observed for melanoma (three trials, n = 19,128, 0.47; 0.23-0.94, p = 0.03).
204.SupplementDEX Database: Nonalcoholic fatty liver disease (NAFLD) — Association between folate and non-alcoholic fatty liver disease among US adults: a nationwide cross-sectional analysis2023
A cross-sectional analysis of 2,261 US adults (ages 20+) examined how folate status is associated with non-alcoholic fatty liver disease prevalence.
205.SupplementDEX Database: Oropharyngeal cancer — Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium2015
A pooled analysis of 5,127 oral/pharyngeal cancer cases and 13,249 controls found higher total folate intake associated with lower overall OPC risk (OR 0.65, highest vs lowest quintile).
SupplementDEX Database · Pancreatic cancer risk
2 references206.SupplementDEX Database: Pancreatic cancer risk — Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies2011
A pooled analysis of 14 cohorts with 862,664 adults followed 7–20 years found no association between dietary or total folate intake and pancreatic cancer risk.
207.SupplementDEX Database: Pancreatic cancer risk — Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers2001
In 27,101 male smokers aged 50–69, highest vs lowest dietary folate quintile was associated with 48% lower pancreatic cancer risk over up to 13 years (HR 0.52).
208.SupplementDEX Database: Peripheral neuropathy — Effect of the combination of uridine nucleotides, folic acid and vitamin B12 on the clinical expression of peripheral neuropathies2014
An open-label study of 212 patients with peripheral neuropathy found UMP plus folic acid and vitamin B12 for 2 months significantly reduced neuropathic pain scores.
209.SupplementDEX Database: Polycystic ovary syndrome — Metabolic response to folate supplementation in overweight women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial2014
An RCT in 81 obese women with PCOS found 5 mg/day folate for 8 weeks lowered homocysteine, insulin resistance, and cholesterol versus 1 mg/day or placebo.
210.SupplementDEX Database: Polycystic ovary syndrome — Effects of metformin with or without supplementation with folate on homocysteine levels and vascular endothelium of women with polycystic ovary syndrome2010
In 50 women with PCOS on metformin 1,700 mg/day, adding 400 µg/day folic acid offset metformin-induced homocysteine rise and improved vascular endothelial function.
SupplementDEX Database · Schizophrenia
2 references211.SupplementDEX Database: Schizophrenia — Folate and vitamin B12 supplementation in patients with schizophrenia and low serum folate level: A 24-week randomized, double-blind, placebo-controlled study2024
An RCT in 36 schizophrenia patients with low folate found 5 mg folate plus 500 µg B12 daily for 24 weeks did not improve PANSS symptoms or cognition versus placebo.
212.SupplementDEX Database: Schizophrenia — Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis2018
A meta-analysis of 7 RCTs (340 patients) found folic acid plus antipsychotics modestly improved negative symptoms (SMD −0.25) but not total psychopathology in schizophrenia.
SupplementDEX Database · Stomach cancer risk
1 reference213.SupplementDEX Database: Stomach cancer risk — Use of folic acid supplementation to halt and even reverse the progression of gastric precancerous conditions: a meta-analysis2022
A meta-analysis of 13 studies in 1,252 patients found folic acid 20–30 mg/day for 3–6 months may improve gastric precancerous lesions and symptom rates.
SupplementDEX Database · Type 2 diabetes
5 references214.SupplementDEX Database: Type 2 diabetes — Dietary Folate, Vitamin B6, and Vitamin B12 and Risk of Cardiovascular Diseases among Individuals with Type 2 Diabetes: A Case-Control Study2023
A case-control study of 419 Chinese adults with type 2 diabetes found highest-quartile folate intake associated with lower CVD risk (OR 0.32) versus lowest quartile.
215.SupplementDEX Database: Type 2 diabetes — The Influence of Maternal Folate Status on Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis2023
A systematic review found higher serum and red blood cell folate in pregnancy associated with increased gestational diabetes risk, especially in the second trimester.
216.SupplementDEX Database: Type 2 diabetes — Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials2021
A meta-analysis of 24 RCTs found folic acid modestly lowered fasting glucose, fasting insulin, and HOMA-IR in adults; HbA1c was unchanged.
217.SupplementDEX Database: Type 2 diabetes — Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial2020
An RCT in 80 type 2 diabetes patients found add-on methylcobalamin (with or without folic acid) improved HbA1c and insulin resistance over 8 weeks versus standard therapy.
218.SupplementDEX Database: Type 2 diabetes — Effect of folic acid supplementation on plasma total homocysteine levels and glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis2012
A meta-analysis of 4 RCTs in 183 type 2 diabetes patients found folic acid lowered homocysteine but did not significantly reduce HbA1c versus placebo.