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Can folate supplements be dangerous? - part 1

Published online by Cambridge University Press:  11 September 2013

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In a nutshell

Concerns have been raised over potential adverse effects of folic acid supplements, particularly in countries where food is fortified with folic acid. The concerns include masking B12 deficiency, increased risk of multiple birth, allergic disease, and the appearance of unmetabolised folic acid in the blood.

At this point in time we lack solid evidence that any of these is a significant practical clinical problem, although neither has it been ruled out that some individuals might be affected.

Type
Brief Report
Information
Arbor Clinical Nutrition Updates , Volume 326 , December 2010 , pp. 1 - 5
Copyright
Copyright © Cambridge University Press 2010

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References

References:

1. Lumley, J. et al. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database Syst Rev. 2001;(3):CD001056.Google Scholar
2. De-Regil, LM. et al. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD007950.CrossRefGoogle ScholarPubMed
3. Johnston, RB Jr. Will increasing folic acid in fortified grain products further reduce neural tube defects without causing harm?: consideration of the evidence. Pediatr Res. 2008 Jan;63(1):2–8.CrossRefGoogle ScholarPubMed
4. Sugden, C. One-carbon metabolism in psychiatric illness. Nutr Res Rev. 2006 Jun;19(1):117–36.CrossRefGoogle ScholarPubMed
5. Miller, AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008 Sep;13(3):216–26.Google ScholarPubMed
6. Mason, JB. Folate, cancer risk, and the Greek god, Proteus: a tale of two chameleons. Nutr Rev. 2009 Apr;67(4):206–12.CrossRefGoogle ScholarPubMed
7. Wright, AJ. et al. Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK. Br J Nutr. 2007 Oct;98(4):667–75.Google Scholar
8. Kim, YI. Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut. 2006 Oct;55(10):1387–9.CrossRefGoogle ScholarPubMed
9. Reynolds, EH. Folic acid and the prevention of neural tube defects. Folate has potential to cause harm. BMJ. 1995 Jul 22;311(6999):257.Google ScholarPubMed
10. Leeming, RJ. et al. Autism: Is there a folate connection? J Inherit Metab Dis. 2009 Jun;32(3):400–2.CrossRefGoogle Scholar
11. Institute of Medicine Food and Nutrition Board. Dietary Reference Intakes for thiamin, riboflavin, niacin, vitamin b6, folate, vitamin b12, pantothenic acid, biotin and choline. National Academy Press, Washington, DC, 1998.Google Scholar
12. Smith, AD. et al. Is folic acid good for everyone? Am J Clin Nutr. 2008 Mar;87(3):517–33.Google Scholar
13. Beaudet, AL. et al. Some, but not complete, reassurance on the safety of folic acid fortification. Am J Clin Nutr. 2010 Dec;92(6):1287–8.CrossRefGoogle ScholarPubMed
14. Stumpf, DA. The neurology of folate and vitamin B12. On line at: http://stumpf.org/pdf/folate-IOM.pdf Google Scholar
15. Wyckoff, KF. et al. Proportion of individuals with low serum vitamin B-12 concentrations without macrocytosis is higher in the post folic acid fortification period than in the pre folic acid fortification period. Am J Clin Nutr. 2007 Oct;86(4):1187–92.Google Scholar
16. Mills, JL. et al. Low vitamin B-12 concentrations in patients without anemia: the effect of folic acid fortification of grain. Am J Clin Nutr. 2003 Jun;77(6):1474–7.CrossRefGoogle ScholarPubMed
17. Butterworth, CE Jr. et al. Folic acid safety and toxicity: a brief review. Am J Clin Nutr. 1989 Aug;50(2):353–8.CrossRefGoogle ScholarPubMed
18. Dickinson, CJ. Does folic acid harm people with vitamin B12 deficiency? QJM. 1995 May;88(5):357–64.Google ScholarPubMed
19. van Amsterdam, JGC. et al. Masking of vitamin B12 deficiency associated neuropathy by folic acid. RIVM report 3402300002, 2005.Google Scholar
20. Carmel, R. Does high folic acid intake affect unrecognized cobalamin deficiency, and how will we know it if we see it? Am J Clin Nutr. 2009 Dec;90(6):1449–50.CrossRefGoogle ScholarPubMed
21. Oakley, GP Jr. Let's increase folic acid fortification and include vitamin B-12. Am J Clin Nutr. 1997 Jun;65(6):1889–90.CrossRefGoogle ScholarPubMed
22. Oakley, GP Jr. Inertia on folic acid fortification: public health malpractice. Teratology. 2002 Jul;66(1):44–54.Google Scholar
23. Reynolds, EH. Benefits and risks of folic acid to the nervous system. J Neurol Neurosurg Psychiatry. 2002 May;72(5):567–71.CrossRefGoogle ScholarPubMed
24. Morris, MC. et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol. 2005 Apr;62(4):641–5.CrossRefGoogle ScholarPubMed
25. Morris, MS. et al. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr. 2007 Jan;85(1):193–200.CrossRefGoogle ScholarPubMed
26. Rosenberg, IH. Effects of folate and vitamin B12 on cognitive function in adults and the elderly. Food Nutr Bull. 2008 Jun;29(2 Suppl):S132–42.CrossRefGoogle ScholarPubMed
27. Malouf, R. et al. Vitamin B12 for cognition. Cochrane Database Syst Rev. 2003;(3):CD004326.Google Scholar
28. Herbert, V. et al. Call for endorsement of a petition to the Food and Drug Administration to always add vitamin B-12 to any folate fortification or supplement. Am J Clin Nutr. 1997 Feb;65(2):572–3.CrossRefGoogle ScholarPubMed
29. van Amsterdam, JGC. et al. Neurotoxicity of folic acid. RIVM report 340230001, 2004.Google Scholar
30. Eros, E. et al. Epileptogenic activity of folic acid after drug induces SLE (folic acid and epilepsy) Eur J Obstet Gynecol Reprod Biol. 1998 Sep;80(1):75–8.CrossRefGoogle ScholarPubMed
31. Butterworth, CE Jr. et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr. 1982 Jan;35(1):73–82.CrossRefGoogle ScholarPubMed
32. Norris, JW. Folate and vitamin B12 in epilepsy. Br Med J. 1970 Oct 10;4(5727):119.Google Scholar
33. Snaith, RP. Folate and vitamin B12 in epilepsy. Br Med J. 1970 Jul 18;3(5715):165.Google Scholar
34. Signore, C. et al. Effects of folic acid fortification on twin gestation rates. Obstet Gynecol. 2005 Apr;105(4):757–62.Google Scholar
35. Vollset, SE. et al. Folate supplementation and twin pregnancies. Epidemiology. 2005 Mar;16(2):201–5.CrossRefGoogle ScholarPubMed
36. Muggli, EE. et al. Folic acid and risk of twinning: a systematic review of the recent literature, July 1994 to July 2006. Med J Aust. 2007 Mar 5;186(5):243–8.CrossRefGoogle ScholarPubMed
37. Kabesch, M. et al. Epigenetic mechanisms and the relationship to childhood asthma. Eur Respir J. 2010 Oct;36(4):950–61.Google Scholar
38. Ownby, DR. Has mandatory folic acid supplementation of foods increased the risk of asthma and allergic disease? J Allergy Clin Immunol. 2009 Jun;123(6):1260–1.CrossRefGoogle ScholarPubMed
39. Håberg, SE. et al. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child. 2009 Mar;94(3):180–4. Epub 2008 Dec 3.CrossRefGoogle ScholarPubMed
40. Miyake, Y. et al. Maternal B vitamin intake during pregnancy and wheeze and eczema in Japanese infants aged 16-24 months: The Osaka Maternal and Child Health Study. Pediatr Allergy Immunol. 2010 Jun 14.Google Scholar
41. Thuesen, BH. et al. Atopy, asthma, and lung function in relation to folate and vitamin B12 in adults. Allergy. 2010 Nov;65(11):1446–54.CrossRefGoogle ScholarPubMed
42. Björkstén, B. The hygiene hypothesis: do we still believe in it? Nestle Nutr Workshop Ser Pediatr Program. 2009;64:11–8.CrossRefGoogle ScholarPubMed
43. Matsui, EC. et al. Higher serum folate levels are associated with a lower risk of atopy and wheeze. J Allergy Clin Immunol. 2009 Jun;123(6):1253–9.Google Scholar
44. Ulrich, CM. et al. Folate supplementation: too much of a good thing? Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):189–93.CrossRefGoogle ScholarPubMed
45. Nijhout, HF. et al. A mathematical model of the folate cycle: new insights into folate homeostasis. J Biol Chem. 2004 Dec 31;279(53):55008–16.CrossRefGoogle ScholarPubMed
46. Sweeney, MR. et al. Folic acid fortification and public health: report on threshold doses above which unmetabolised folic acid appear in serum. BMC Public Health. 2007 Mar 22;7:41.CrossRefGoogle Scholar
47. Kalmbach, RD. et al. Circulating folic acid in plasma: relation to folic acid fortification. Am J Clin Nutr. 2008 Sep;88(3):763–8.CrossRefGoogle ScholarPubMed
48. Kelly, P. et al. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr. 1997 Jun;65(6):1790–5.Google Scholar
49. Troen, AM. et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr. 2006 Jan;136(1):189–94.CrossRefGoogle ScholarPubMed
50. Anon. Opinion of the scientific committee on food on the tolerable upper intake level of folate. EFSA report 28 November 2008 Google Scholar
51. Anon. Folic acid: an update on scientific developments. Conference report, EFSA, Uppsala, Sweden, 21-22 January 2009.Google Scholar
52. Kauwell, GP. et al. Zinc status is not adversely affected by folic acid supplementation and zinc intake does not impair folate utilization in human subjects. J Nutr. 1995 Jan;125(1):66–72.Google Scholar
53. Milne, DB. et al. Effect of oral folic acid supplements on zinc, copper, and iron absorption and excretion. Am J Clin Nutr. 1984 Apr;39(4):535–9.CrossRefGoogle ScholarPubMed