Folate
Supplement Forms/Alternate Names:
• Folic acid, folacin
Introduction
Folate is an essential vitamin found in grains, lentils, and spinach. It has been used to improve organ function and blood flow. Folate has also been used to ease symptoms of mental illness. It can be taken as a pill or powder.
Dosages300 to 1000 micrograms daily
What Research Shows
Likely Effective
- Cardiovascular disease (CVD)—likely to prevent stroke when used with standard treatment B1, B2
- Pregnancy support—likely to prevent neural tube defects, congenital heart defects, autism spectrum disorder, preterm birth, and small for gestational age births J1-J11
- Schizophrenia—likely to improve symptoms when used with standard treatment K1
- Stroke—likely to prevent when used with vitamin L1
May Be Effective
- Colorectal cancer—may reduce risk E1-E3
- Diabetes—may ease insulin resistance G1, G2
- Depression—may provide benefit when used with antidepressant medicine F1-F9
May Not Be Effective
- Cognitive function—may not provide benefit in mid and late life D1
Unlikely to Be Effective
- Chronic kidney disease—unlikely to reduce the risk of myocardial infarction or stroke in those with CKDC1
Not Enough Data to Assess
- Cancer riskA1
- Metabolic syndromeH1, H2
- Mild cognitive impairmentI1
Editorial process and description of evidence categories can be found at EBSCO NAT Editorial Process.
Safety Notes
It is likely safe to take folate in small doses for a short time. Large doses may be unsafe and not enough studies have been done to say whether it is safe to use for a long period.
Interactions
Talk to your doctor about any supplements or therapy you would like to use. Some can interfere with treatment or make conditions worse.
References [ + ]
A. Cancer Risk
A1. Qin X, Cui Y, et al. Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials. Int J Cancer. 2013;133(5):1033-1041.
B. Cardiovascular Disease
B1. Li Y, Huang T, et al. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2016;5(8):e003758.
B2. Tian T, Yang KQ, et al. Folic Acid Supplementation for Stroke Prevention in Patients With Cardiovascular Disease. Am J Med Sci. 2017;354(4):379-387.
C. Chronic Kidney Disease
C1. Bravo-Soto GA, Madrid T. Is folic acid supplementation useful for chronic kidney disease? Medwave. 2016 Nov 7;16(Suppl5):e6591.
D. Cognitive Function
D1. Rutjes AW, Denton DA, et al. Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life. Cochrane Database Syst Rev. 2018 Dec 17;12:CD011906.
E. Colorectal Cancer
E1. Liu Y, Yu Q, et al. Vitamin and multiple-vitamin supplement intake and incidence of colorectal cancer: a meta-analysis of cohort studies. Med Oncol. 2015 Jan;32(1):434.
E2. Qin T, Du M, et al. Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials. Sci Rep. 2015 Jul 1;5:12044.
E3. Burr NE, Hull MA, et al. Folic Acid Supplementation May Reduce Colorectal Cancer Risk in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol. 2017 Mar;51(3):247-253.
F. Depression
F1. Taylor MJ, Carney S, et al. Folate for depressive disorders. Cochrane Database Syst Rev. 2003;(2):CD003390.
F2. Venkatasubramanian R, Kumar CN, et al. A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes. J Affect Disord. 2013 Sep 5;150(2):644-648.
F3. Bedson E, Bell D, et al. Folate augmentation of treatment—evaluation for depression (FolATED): randomized trial and economic evaluation. Health Technol Assess. 2014 Jul;18(48):vii-viii, 1-159.
F4. Almeida OP, Ford AH. B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomized, double-blind, placebo-controlled trial. Br J Psychiatry. 2014 Dec;205(6):450-457.
F5. Almeida OP, Ford AH, et al. Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. Int Psychogeriatr. 2015 May;27(5):727-737.
F6. Lopresti AL, Drummond PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J Affect Disord. 2017 Jan 1;207:188-196.
F7. Schwingshackl L, Boeing H, et al. Dietary Supplements and Risk of Cause-Specific Death, Cardiovascular Disease, and Cancer: A Systematic Review and Meta-Analysis of Primary Prevention Trials. Adv Nutr. 2017 Jan 17;8(1):27-39.
F8. Schefft C, Kilarski LL, et al. Efficacy of adding nutritional supplements in unipolar depression: A systematic review and meta-analysis. Eur Neuropsychopharmacol. 2017 Nov;27(11):1090-1109.
F9. Trincado J, Caneo C, et al. Is augmentation with folate effective for major depressive disorder? Medwave. 2018;18(1):e7156.
G. Diabetes
G1. Sudchada P, Saokaew S, et al. Effect of folic acid supplementation on plasma total homocysteine levels and glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2012;98(1):151-158.
G2. Zhao JV, Schooling CM, et al. The effects of folate supplementation on glucose metabolism and risk of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Ann Epidemiol. 2018 Apr;28(4):249-257.e1.
H. Metabolic Syndrome
H1. Akbari M, Tabrizi R, et al. The Effects of Folate Supplementation on Diabetes Biomarkers Among Patients with Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Horm Metab Res. 2018;50(2):93-105.
H2. Tabrizi R, Lankarani KB, et al. The effects of folate supplementation on lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr. 2018;12(3):423-430.
I. Mild Cognitive Impairment
I1. McCleery J, Abraham RP, et al. Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment. Cochrane Database Syst Rev. 2018 Nov 1;11:CD011905.
J. Pregnancy Support
J1. Hodgetts VA, Morris RK, et al. Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small-for-gestational age neonates: a population study, systematic review and meta-analysis. BJOG. 2015 Mar;122(4):478-490.
J2. De-Regil LM, Peña-Rosas JP, et al. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2015;14(12):CD007950.
J3. Feng Y, Wang S, Chen R, Tong X, Wu Z, Mo X. Maternal folic acid supplementation and the risk of congenital heart defects in offspring: a meta-analysis of epidemiological observational studies. Sci Rep. 2015 Feb 17;5:8506.
J4. Saccone G, Berghella V. Folic acid supplementation in pregnancy to prevent preterm birth: a systematic review and meta-analysis of randomized controlled trials. Eur J Obstet Gynecol Reprod Biol. 2016;199:76-81.
J5. Balogun OO, da Silva Lopes K, et al. Vitamin supplementation for preventing miscarriage. Cochrane Database Syst Rev. 2016 May 6;(5):CD004073.
J6. Hua X, Zhang J, et al. Effect of folic acid supplementation during pregnancy on gestational hypertension/preeclampsia: A systematic review and meta-analysis. Hypertens Pregnancy. 2016 Nov;35(4):447-460.
J7. Xu A, Cao X, Lu Y, Li H, Zhu Q, Chen X, Jiang H, Li X. A Meta-Analysis of the Relationship Between Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects. Int Heart J. 2016 Dec 2;57(6):725-728. Epub 2016 Nov 9. PubMed PMID: 27829639.
J8. Zhang Q, Wang Y, et al. Effect of folic acid supplementation on preterm delivery and small for gestational age births: A systematic review and meta-analysis. Reprod Toxicol. 2017 Jan;67:35-41.
J9. Wang M, Li K, et al. The association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders in children: a meta-analysis. Mol Autism. 2017 Oct 2;8:51.
J10. Bulloch RE, Lovell AL, et al. Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis. Paediatr Perinat Epidemiol. 2018 Jul;32(4):346-357.
J11. Keats EC, Haider BA, et al. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2019 Mar 14;3:CD004905.
K. Schizophrenia
K1. Sakuma K, Matsunaga S, et al. Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis. Psychoparmacology (Berl). 2018;235(8):2303-2314.
L. Stroke
L1. Dong H, Pi F, et al. Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials. PLoS One. 2015 Sep 10;10(9):e0137533.
Last reviewed July 2019 by EBSCO NAT Review Board
Eric Hurwitz, DC
Last Updated: 5/6/2020