folic acid; folate; vitamin B9
Jump to navigation
Jump to search
Introduction
Body stores: generally 5-10 mg.
Indications
- prevention & treatment of folate deficiency[15]
- treatment of megaloblastic anemia
- treatment of hyperhomocysteinemia (see Folgard Rx)
- pregnancy*
- lactating mother[15]
- prevention of hypertension (women)
- prevention of stroke in patients with hypertension[18][20] (2.7% vs. 3.4%) especially among those with low serum folate
- adjunct for treatment of depression[12]
- all persons planning to or who could become pregnant*[22]
* folic acid fortification of cereal grains prevents > 1300 neural tube defects annually[16]
* folic acid supplementation in high-risk pregnancy is only 37%[17]
* daily supplement containing 0.4 to 0.8 mg[22]
Contraindications
- NOT useful for secondary prevention of:[3]
- NOT useful for prevention of Alzheimer's disease or vascular demenia[23]
Dosage
- RDA (male) 0.15-0.2 mg/day, female 0.15-0.18 mg/day or 400 ug/day
- pregnancy: 0.4-1 mg PO QD (begin 1 month before conception, continue for 2-3 months after delivery)[4][11]
- alcoholics 1 mg PO QD
Tablets: 400 ug, 800 ug, 1 mg.
Adverse effects
- doses > 1 mg/day may obscure hematologic manifestations of pernicious anemia (vit B12 deficiency)
- supplementation may increase risk of prostate cancer (RR=1.24)[6]
- supplementation may increase risk of colorectal cancer (RR=1.28)[19]
- supplementation of folic acid 0.8 mg, vit B12 0.4 mg & vit B6 40 mg QD increases
- risk of cancer overall (RR=1.07)
- risk of dying of cancer
- all cause mortality
- hazzard ratio 1.2-1.4, number needed to harm 40-90[8]
- folic acid impairs immune surveillance of cancer cells & might stimulate the growth of established cancers
- supplementation of up to 2.0 mg/day for 5 years not associated with increased risk of cancer of any type[13]
- folic acid supplementation alone was associated with an increased risk of Alzheimer's disease (RR=1.34) & vascular dementia (RR=1.61)[23]
- corresponding reductions in volumes of hippocampus & amygdala noted[23]
- these adverse effects not observed when folic acid was combined with with other B vitamins[23]
Drug interactions
- 5-aminosalicylic acid, oral contraceptives, phenytoin, & sulfasalazine may decrease folate levels
Mechanism of action
- 0.5 mg folate QD decreases serum homocysteine 18%
More general terms
More specific terms
Additional terms
- folate antagonist; folic acid analog; folic acid antagonist
- folate deficiency
- folate in serum/plasma
- folate metabolism
- folate receptor or folate-binding protein
- N5-formyltetrahydrofolate (folinic acid, citrovorum factor, Fusilev)
Component of
- folic acid/lactobacillus casei
- cholecalciferol/folic acid
- calcium ascorbate/calcium threonate/cobalamin/ferrous asparto glycinate/ferrous fumarate/folic acid/succinate
- ascorbate/biotin/folic acid/methylcobalamin/nicotinamide/pantothenate/pyridoxine/riboflavin/thiamine/zinc citrate
- ascorbate/biotin/folic acid/methylcobalamin/nicotinamide/pantothenate/pyridoxine/riboflavin/thiamine
- alpha tocopheryl acetate/ascorbate/beta carotene/cobalamin/ergocalciferol/folic acid/nicotinic acid/pantothenate/pyridoxine/retinol/riboflavin/thiamine
- alpha tocopherol/ascorbate/calcium phosphate/docosahexaenoate/ferrous fumarate/folic acid/pyridoxine/sodium docusate
- folic acid/nicotinamide/zinc oxide
- folic acid/nicotinamide/zinc/zinc oxide
- folic acid/methylcobalamin/pyridoxine
- folic acid/inositol
- folic acid/heme
- ferrous sulfate/folic acid
- docosahexaenoate/eicosapentaenoate/folic acid/hypericum perforatum
- cobalamin/folic acid/polysaccharide iron complex
- cobalamin/folic acid/iron/polysaccharide iron complex
- cobalamin/folic acid
- cobalamin/fatty acid omega 3/folic acid/phytosterol/pyridoxine
- cobalamin/docosahexaenoate/eicosapentaenoate/folic acid/phytosterol/policosanol/pyridoxine
- cholecalciferol/cobalamin/folic acid/pyridoxine/riboflavin
- cholecalciferol/cobalamin/fatty acid omega 3/folic acid/phytosterol/pyridoxine
- calcium carbonate/folic acid/magnesium carbonate
- calcium carbonate/cobalamin/folic acid/pyridoxine
- calcium carbonate/cholecalciferol/cyanokit/folic acid
- azelaic acid/folic acid/nicotinamide/pyridoxine/zinc oxide
- ascorbate/folic acid/iron/polysaccharide iron complex
- ascorbate/folic acid
- ascorbate/ferrous fumarate/folic acid/nicotinic acid/polysaccharide iron complex
- ascorbate/cobalamin/folic acid/nicotinic acid/pyridoxine/riboflavin/sodium fluoride/thiamine/vitamin a/vitamin d/vitamin e
- ascorbate/cobalamin/copper sulfate/ferrous fumarate/folic acid/manganese sulfate/nicotinamide/pantothenate/polysaccharide iron complex/pyridoxine/riboflavin/thiamine/zinc sulfate
- ascorbate/cobalamin/copper sulfate/ferrous fumarate/folic acid/magnesium sulfate/manganese sulfate/nicotinamide/pantothenate/pyridoxine/riboflavin/thiamine/zinc sulfate
- ascorbate/cobalamin/copper sulfate/ferrous fumarate/folic acid/magnesium sulfate/manganese sulfate/nicotinamide/pantothenate/polysaccharide iron complex/pyridoxine/riboflavin/thiamine/zinc sulfate
- ascorbate/cobalamin/copper/copper sulfate/ferrous fumarate/folic acid/magnesium sulfate/manganese/manganese sulfate/nicotinamide/pantothenate/pyridoxine/riboflavin/thiamine/zinc sulfate
- ascorbate/cholecalciferol/cobalamin/folic acid/magnesium oxide/nicotinic acid/polysaccharide iron complex/potassium iodide/pyridoxine/riboflavin/thiamine/vitamin a/vitamin e/zinc oxide
- ascorbate/cholecalciferol/cobalamin/copper sulfate/ferrous fumarate/folic acid/kelp/magnesium oxide/magnesium sulfate/nicotinamide/pyridoxine/riboflavin/vitamin a/zinc sulfate
- ascorbate/carbonyl iron/cobalamin/folic acid/sodium docusate
- ascorbate/carbonyl iron/cobalamin/folic acid
- ascorbate/calcium citrate/carbonyl iron/cholecalciferol/folic acid/pyridoxine
- ascorbate/calcium carbonate/cholecalciferol/fatty acid omega 3/folic acid/linoleate/pyridoxine/vitamin e
- ascorbate/calcium carbonate/cholecalciferol/choline bitartrate/cobalamin/docosahexaenoate/eicosapentaenoate/ferrous fumarate/folic acid/nicotinic acid/potassium iodide/pyridoxine/riboflavin/thiamine/vitamin e/zinc oxide
- ascorbate/ca+2/cobalamin/folic acid/iron/polysaccharide iron complex
- ascorbate/biotin/ferrous fumarate/folic acid/iron/methylcobalamin/nicotinamide/pantothenate/pyridoxine/riboflavin/thiamine
- ascorbate/biotin/cobalamin/folic acid/nicotinamide/pantothenate/pyridoxine/riboflavin/thiamine
- ascorbate/biotin/cobalamin/copper sulfate/ferrous fumarate/folic acid/magnesium sulfate/manganese sulfate/nicotinic acid/pantothenate/polysaccharide iron complex/pyridoxine/riboflavin/thiamine/zinc sulfate
- ascorbate/biotin/cholecalciferol/cobalamin/folic acid/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine
- ascorbate/biotin/calcium carbonate/cobalamin/ferrous fumarate/folic acid/magnesium oxide/nicotinamide/pantothenate/pyridoxine/riboflavin/thiamine/vitamin a/vitamin e/zinc oxide
- ascorbate/biotin/calcium carbonate/cobalamin/ferrous fumarate/folic acid/magnesium oxide/nicotinamide/pantothenate/pyridoxine/riboflavin/thiamine/vitamin a/vitamin e/zinc/zinc oxide
- ascorbate/biotin/calcium carbonate/cobalamin/dextran/folic acid/iron dextran/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine
- ascorbate/beta carotene/calcium carbonate/carbonyl iron/cholecalciferol/cobalamin/folic acid/magnesium oxide/nicotinamide/pyridoxine/riboflavin/sodium docusate/thiamine/zinc oxide
- alpha tocopheryl acetate/ascorbate/calcium carbonate/cobalamin/copper sulfate/ferrous fumarate/folic acid/magnesium oxide/nicotinamide/potassium iodide/pyridoxine/retinol/riboflavin/thiamine/vitamin d/zinc sulfate
- alpha tocopheryl acetate/ascorbate/biotin/carbonyl iron/cobalamin/folic acid/sodium docusate
- alpha tocopheryl acetate/ascorbate/biotin/carbonyl iron/cobalamin/copper sulfate/folic acid/sodium docusate
- alpha tocopherol/cyanokit/folic acid/magnesium oxide/pyridoxine
- alpha tocopherol/ascorbate/cholecalciferol/docosahexaenoate/ferrous fumarate/folic acid/pyridoxine/sodium docusate
- alpha tocopherol/ascorbate/carbonyl iron/cholecalciferol/cobalamin/folic acid/nicotinamide/pyridoxine/riboflavin/thiamine
- alpha tocopherol/ascorbate/calcium phosphate/cholecalciferol/docosahexaenoate/ferrous fumarate/folic acid/pyridoxine/sodium docusate
- alpha tocopherol/ascorbate/calcium citrate/carbonyl iron/cholecalciferol/folic acid/nicotinamide/potassium iodide/pyridoxine/riboflavin/sodium docusate/thiamine/zinc oxide
- alpha tocopherol/ascorbate/calcium citrate/carbonyl iron/cholecalciferol/docosahexaenoate/folic acid/nicotinamide/potassium iodide/pyridoxine/riboflavin/sodium docusate/thiamine/zinc oxide
- alpha tocopherol/ascorbate/calcium carbonate/carbonyl iron/cholecalciferol/cobalamin/cupric oxide/folic acid/magnesium oxide/nicotinamide/pyridoxine/riboflavin/sodium docusate/thiamine/zinc oxide
- alpha tocopherol/ascorbate/biotin/cholecalciferol/cobalamin/folic acid/nicotinamide/panthenol/pyridoxine/riboflavin/thiamine/vitamin a/vitamin k
- alpha tocopherol/ascorbate/biotin/biotin/cobalamin/ergocalciferol/folic acid/multivitamin/nicotinamide/panthenol/pyridoxine/riboflavin/thiamine/vitamin a/vitamin k
- alpha tocopherol/ascorbate/beta carotene/calcium carbonate/cholecalciferol/cobalamin/folic acid/magnesium oxide/nicotinamide/pyridoxine/riboflavin/thiamine/zinc oxide
- alpha tocopherol/ascorbate/beta carotene/calcium carbonate/cholecalciferol/cobalamin/ferrous fumarate/folic acid/nicotinamide/pantothenate/pyridoxine/riboflavin/sodium docusate/thiamine/zinc oxide
- alpha tocopherol/ascorbate/beta carotene/calcium carbonate/cholecalciferol/cobalamin/docosahexaenoate/folic acid/magnesium oxide/nicotinamide/pyridoxine/riboflavin/thiamine/zinc oxide
- acetylcysteine/folic acid/methylcobalamin
- ferrous fumarate/folic acid/polysaccharide/polysaccharide iron complex
- ferrous fumarate/folic acid
- cobalamin/folic acid/heme/heme iron polypeptide/polypeptide/polysaccharide iron complex
- ascorbate/ferrous fumarate/folic acid/nicotinamide/polysaccharide iron complex
- ascorbate/cobalamin/folic acid/iron carbonyl/sodium docusate
- ascorbate/cobalamin/ferrous fumarate/folic acid/liver stomach concentrate
- ascorbate/cobalamin/ferrous fumarate/folic acid
- alpha tocopherol/ascorbate/calcium phosphate/docosahexaenoate/eicosapentaenoate/ferrous fumarate/folic acid/pyridoxine
- cobalamin/folic acid/pyridoxine
- cobalamin/folic acid/heme/heme iron polypeptide/polysaccharide/polysaccharide iron complex
- folic acid/proto oncogene tyrosine kinase fer
- folic acid/polysaccharide/polysaccharide iron complex
- cobalamin/docosahexaenoate/eicosapentaenoate/folic acid/phytosterol/pyridoxine
- ascorbate/ferrous sulfate/folic acid
- ascorbate/folic acid/nicotinamide/polysaccharide/polysaccharide iron complex
- ascorbate/cobalamin/folic acid
- ascorbate/cobalamin/folic acid/sodium docusate
- ascorbate/biotin/cobalamin/folic acid/nicotinic acid/pantothenate/pyridoxine/riboflavin/thiamine
- alpha tocopherol/ascorbate/calcium phosphate/docosahexaenoate/eicosapentaenoate/folic acid/pyridoxine
- polypill (Polycap)
- Souvenaid; Fortasyn Connect
- Folgard Rx 2.2 (folate, B12, B6)
References
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 3.0 3.1 Journal Watch 23(17):134, 2003 Liem A et al Secondary prevention with folic acid: effects on clinical outcomes. Coll Cardiol 41:2105, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12821232
- ↑ 4.0 4.1 Journal Watch 24(10):82, 2004 Cleves MA, Hobbs CA, Collins HB, Andrews N, Smith LN, Robbins JM. Folic acid use by women receiving routine gynecologic care. Obstet Gynecol. 2004 Apr;103(4):746-53. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15051568
- ↑ Journal Watch 25(11):87-88, 2005 Botto LD, Lisi A, Robert-Gnansia E, Erickson JD, Vollset SE, Mastroiacovo P, Botting B, Cocchi G, de Vigan C, de Walle H, Feijoo M, Irgens LM, McDonnell B, Merlob P, Ritvanen A, Scarano G, Siffel C, Metneki J, Stoll C, Smithells R, Goujard J. International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ. 2005 Mar 12;330(7491):571. Epub 2005 Feb 18. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15722368 <Internet> http://bmj.bmjjournals.com/cgi/content/full/330/7491/571
- ↑ 6.0 6.1 Figueiredo JC et al Folic acid and risk of prostate cancer: Results from a randomized clinical trial. J Natl Cancer Inst 2009 Mar 18; 101:432. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19276452
- ↑ 7.0 7.1 Ionescu-Ittu R et al, Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada BMJ 2009;338:b1673 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19436079 <Internet> http://www.bmj.com/cgi/content/full/338/may12_2/b1673
- ↑ 8.0 8.1 Ebbing M et al Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009 Nov 18; 302:2119. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19920236
Drake BF and Colditz GA Assessing cancer prevention studies - A matter of time. JAMA 2009 Nov 18; 302:2152 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19920243 - ↑ Department of Veterans Affairs, VA National Formulary
- ↑ Prescriber's Letter 17(1): 2010 Folic Acid and Cancer Risk Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260109&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 11.0 11.1 11.2 Wolff T et al Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2009 May 5;150(9):632-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19414843 U.S. Preventive Services Task Force. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009 May 5;150(9):626-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19414842
corresponding NGC guideline withdrawn Dec 2014 - ↑ 12.0 12.1 Prescriber's Letter 18(10): 2011 Folate for Depression Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=271003&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 13.0 13.1 Vollset SE et al Effects of folic acid supplementation on overall and site- specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. The Lancet, Early Online Publication, 25 January 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23352552 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)62001-7/abstract
Miller JW and Ulrich CM. Folic acid and cancer - Where are we today? Lancet 2013 Jan 25 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23352551 - ↑ 14.0 14.1 Suren P et al Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children JAMA. 2013;309(6):570-577. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23403681 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1570279
Berry RJ et al Periconceptional Folic Acid and Risk of Autism Spectrum Disorders. JAMA. 2013;309(6):611-613 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23403688 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1570262 - ↑ 15.0 15.1 15.2 Deprecated Reference
- ↑ 16.0 16.1 Williams J et al Updated Estimates of Neural Tube Defects Prevented by Mandatory Folic Acid Fortification - United States, 1995-2011. MMWR Weekly. January 16, 2015 / 64(01);1-5 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6401a2.htm
- ↑ 17.0 17.1 Arth A et al Supplement Use and Other Characteristics Among Pregnant Women with a Previous Pregnancy Affected by a Neural Tube Defect - United States, 1997-2009 MMWR Weekly. January 16, 2015 / 64(01);6-9 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6401a3.htm
- ↑ 18.0 18.1 Huo Y et al Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in ChinaThe CSPPT Randomized Clinical Trial. JAMA. Published online March 15, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25771069 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2205876
Stampfer M, Willett W Folate Supplements for Stroke Prevention. Targeted Trial Trumps the Rest. JAMA. Published online March 15, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25770867 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2205875 - ↑ 19.0 19.1 Wien TN, Pike E, Wisloff T, Staff A, Smeland S, Klemp M. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open. 2012;2:e000653. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22240654
- ↑ 20.0 20.1 Reuters Staff Folic Acid Cuts Stroke Risk in Hypertensive Patients With High Total Cholesterol. Medscape. Nov 02, 2016. http://www.medscape.com/viewarticle/871281
Qin X, Li J, Spence JD, Zhang Y et al Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients. Stroke. 2016 Nov;47(11):2805-2812. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27729579 - ↑ 21.0 21.1 US Preventive Services Task Force Folic Acid Supplementation for the Prevention of Neural Tube Defects. US Preventive Services Task Force Recommendation Statement. JAMA. 2017;317(2):183-189. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28097362 <Internet> http://jamanetwork.com/journals/jama/fullarticle/2596300
Mills JL Strategies for Preventing Folate-Related Neural Tube Defects. Supplements, Fortified Foods, or Both? JAMA. 2017;317(2):144-145 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28097344 <Internet> http://jamanetwork.com/journals/jama/fullarticle/2596 - ↑ 22.0 22.1 22.2 US Preventive Services Task Force Folic Acid Supplementation to Prevent Neural Tube Defects. US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2023;330(5):454-459 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37526713 https://jamanetwork.com/journals/jama/fullarticle/2807739
Viswanathan M, Urrutia RP, Hudson KN et al Folic Acid Supplementation to Prevent Neural Tube Defects. Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2023;330(5):460-466 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37526714 https://jamanetwork.com/journals/jama/fullarticle/2807740 - ↑ 23.0 23.1 23.2 23.3 23.4 Ling Y, Yan S, Huang X et al Associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure: evidence from 466,224 UK Biobank participants. J Gerontol A Biol Sci Med Sci. 2023 Nov 29:glad266. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38029284 https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glad266/7455295
Patient information
folic acid patient information
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5280354
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3405
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6037
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5317366
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=86481
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- Kegg: http://www.genome.jp/dbget-bin/www_bget?