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Can folate supplements be dangerous? - part 2

In a nutshell

Whilst adequate folate is protective against cancer, there are theoretical grounds and some clinical evidence to suggest that, in people with existing pre-cancerous or cancer cells, folate supplements could stimulate their growth.

However, more studies have failed to show this than have reported it, and so the hypothesis remains neither confirmed nor refuted. Until this matter is resolved, some caution is appropriate, particularly in those who may already have early stage tumour.



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1. Helman, A. Can folate supplements be dangerous? - part 1. Arb Clin Nutr Upd. 2010 Dec;326:15.
2. Fossey, A. Epigenetics: beyond genes. Southern Forests. 2009 Jun;71(2):121124.
3. Dolinoy, DC. et al. Epigenetic gene regulation: linking early developmental environment to adult disease. Reprod Toxicol. 2007 Apr-May;23(3):297307.
4. Kim, YI. Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr. 2005 Nov;135(11):2703–9.
5. Wolffe, AP. et al. Epigenetics: regulation through repression. Science. 1999 Oct 15;286(5439):481–6.
6. Mason, JB. Folate, cancer risk, and the Greek god, Proteus: a tale of two chameleons. Nutr Rev. 2009 Apr;67(4):206–12.
7. Kim, YI. Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut. 2006 Oct;55(10):1387–9.
8. Mason, JB. et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1325–9.
9. Kim, YI. Will mandatory folic acid fortification prevent or promote cancer? Am J Clin Nutr. 2004 Nov;80(5):1123–8.
10. Hubner, RA. et al. Should folic acid fortification be mandatory? No. BMJ. 2007 Jun 16;334(7606):1253.
11. Luebeck, EG. et al. Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions. Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1360–7.
12. Wald, NJ. et al. Should folic acid fortification be mandatory? Yes. BMJ. 2007 Jun 16;334(7606):1252.
13. Mathers, JC. Reversal of DNA hypomethylation by folic acid supplements: possible role in colorectal cancer prevention. Gut. 2005 May;54(5):579–81.
14. Choi, SW. et al. Folate and carcinogenesis: an integrated scheme. J Nutr. 2000 Feb;130(2):129–32.
15. Lindzon, GM. et al. Effect of folic acid supplementation on the progression of colorectal aberrant crypt foci. Carcinogenesis. 2009 Sep;30(9):1536–43.
16. Sanderson, P. et al. Folate and colo-rectal cancer risk. Br J Nutr. 2007 Dec;98(6):1299–304.
17. Kim, YI. Role of folate in colon cancer development and progression. J Nutr. 2003 Nov;133(11 Suppl 1):3731S3739S.
18. Du, W. et al. Folate and fiber in the prevention of colorectal cancer: between shadows and the light. World J Gastroenterol. 2010 Feb 28;16(8):921–6.
19. Pellis, L. et al. High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells. Br J Nutr. 2008 Apr;99(4):703–8.
20. Novakovic, P. et al. Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis. 2006 May;27(5):916–24.
21. Duthie, SJ. et al. Folate deficiency in vitro induces uracil misincorporation and DNA hypomethylation and inhibits DNA excision repair in immortalized normal human colon epithelial cells. Nutr Cancer. 2000;37(2):245–51.
22. Huang, J. et al. Cancer chemoprevention by targeting the epigenome. Curr Drug Targets. 2010 Dec 15. [Epub ahead of print]
23. McGuire, JJ. Anticancer antifolates: current status and future directions. Curr Pharm Des. 2003;9(31):2593–613.
24. Aune, D. et al. Dietary folate intake and the risk of 11 types of cancer: a case-control study in Uruguay. Ann Oncol. 2010 Jul 19. [Epub ahead of print].
25. Oaks, BM. et al. Folate intake, post-folic acid grain fortification, and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr. 2010 Feb;91(2):449–55.
26. Guerreiro, CS. et al. Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients. Am J Clin Nutr. 2008 Nov;88(5):1413–8.
27. Rossi, E. et al. Folate levels and cancer morbidity and mortality: prospective cohort study from Busselton, Western Australia. Ann Epidemiol. 2006 Mar;16(3):206–12.
28. Stolzenberg-Solomon, RZ. et al. Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr. 2006 Apr;83(4):895904.
29. Van Guelpen, B. et al. Low folate levels may protect against colorectal cancer. Gut. 2006 Oct;55(10):1461–6.
30. Keszei, AP. et al. Dietary folate and folate vitamers and the risk of pancreatic cancer in the Netherlands cohort study. Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1785–91.
31. Larsson, SC. et al. Folate intake and risk of breast cancer by estrogen and progesterone receptor status in a Swedish cohort. Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3444–9.
32. Johansson, M. et al. Circulating concentrations of folate and vitamin B12 in relation to prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition study. Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):279–85.
33. Skinner, HG. et al. A prospective study of folate intake and the risk of pancreatic cancer in men and women. Am J Epidemiol. 2004 Aug 1;160(3):248–58.
34. Alberg, AJ. et al. The risk of cervical cancer in relation to serum concentrations of folate, vitamin B12, and homocysteine. Cancer Epidemiol Biomarkers Prev. 2000 Jul;9(7):761–4.
35. Eichholzer, M. et al. Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence. Swiss Med Wkly. 2001 Sep 22;131(37–38):539–49.
36. Lewis, SJ. et al. Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst. 2006 Nov 15;98(22):1607–22.
37. Larsson, SC. et al. Folate and risk of breast cancer: a meta-analysis. J Natl Cancer Inst. 2007 Jan 3;99(1):6476.
38. Sanjoaquin, MA. et al. Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer. 2005 Feb 20;113(5):825–8.
39. Larsson, SC. et al. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology. 2006 Oct;131(4):1271–83.
40. Collin, SM. et al. Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1632–42.
41. Choi, SW. et al. Folate status: effects on pathways of colorectal carcinogenesis. J Nutr. 2002 Aug;132(8 Suppl):2413S2418S.
42. Ericson, UC. et al. Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele. Am J Clin Nutr. 2009 Nov;90(5):1380–9.
43. Collin, SM. et al. Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2528–39.
44. Lightfoot, TJ. et al. Methylene tetrahydrofolate reductase genotype modifies the chemopreventive effect of folate in colorectal adenoma, but not colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2008 Sep;17(9):2421–30.
45. Kono, S. et al. Genetic polymorphisms of methylenetetrahydrofolate reductase and colorectal cancer and adenoma. Cancer Sci. 2005 Sep;96(9):535–42.
46. Bailey, LB. Folate, methyl-related nutrients, alcohol, and the MTHFR 677C-->T polymorphism affect cancer risk: intake recommendations. J Nutr. 2003 Nov;133(11 Suppl 1):3748S3753S.
47. Ma, J. et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res. 1997 Mar 15;57(6):1098–102.
48. Chen, J. et al. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res. 1996 Nov 1;56(21):4862–4.
49. Boccia, S. et al. Meta- and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: a huge-GSEC review. Am J Epidemiol. 2008 Mar 1;167(5):505–16.
50. Plazar, N. et al. Hyperhomocysteinemia and the role of B vitamins in cancer. Radiol Oncol 2010; 44(2): 7985.
51. Jaszewski, R. et al. Folic acid supplementation inhibits recurrence of colorectal adenomas: a randomized chemoprevention trial. World J Gastroenterol. 2008 Jul 28;14(28):4492–8.
52. Logan, RF. et al. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology. 2008 Jan;134(1):2938.
53. Anon. Folic acid: an update on scientific developments. Conference report, EFSA, Uppsala, Sweden, 21-22 January 2009.
54. Levine, AJ. et al. MTHFR genotype and colorectal adenoma recurrence: data from a double-blind placebo-controlled clinical trial. Cancer Epidemiol Biomarkers Prev. 2008 Sep;17(9):2409–15.
55. Cole, BF. et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351–9.
56. 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(6):432–5.
57. Zhang, SM. et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA. 2008 Nov 5;300(17):2012–21.
58. Lonn, E. et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006 Apr 13;354(15):1567–77.
59. Zhu, S. et al. The effect of folic acid on the development of stomach and other gastrointestinal cancers. Chin Med J (Engl). 2003 Jan;116(1):15–9.
60. Cooper, K. et al. Chemoprevention of colorectal cancer: systematic review and economic evaluation. Health Technol Assess. 2010 Jun;14(32):1206.
61. Paspatis, GA. et al. Folate supplementation and adenomatous colonic polyps. Dis Colon Rectum. 1994 Dec;37(12):1340–1.
62. Figueiredo, JC. et al. Colorectal adenomas in a randomized folate trial: the role of baseline dietary and circulating folate levels. Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2625–31.
63. Ebbing, M. et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009 Nov 18;302(19):2119–26.
64. 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):7382.
65. Zarcone, R. et al. [Folic acid and cervix dysplasia]. Minerva Ginecol. 1996 Oct;48(10):397400.
66. Childers, JM. et al. Chemoprevention of cervical cancer with folic acid: a phase III Southwest Oncology Group Intergroup study. Cancer Epidemiol Biomarkers Prev. 1995 Mar;4(2):155–9.
67. Butterworth, CE Jr. et al. Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial. Am J Obstet Gynecol. 1992 Mar;166(3):803–9.
68. Oakley, GP Jr. Let's increase folic acid fortification and include vitamin B-12. Am J Clin Nutr. 1997 Jun;65(6):1889–90.
69. Oakley, GP Jr. Inertia on folic acid fortification: public health malpractice. Teratology. 2002 Jul;66(1):4454.
70. Smith, AD. et al. Is folic acid good for everyone? Am J Clin Nutr. 2008 Mar;87(3):517–33.
71. Anon. Opinion of the scientific committee on food on the tolerable upper intake level of folate. EFSA report 28 November 2008
72. Osterhues, A. et al. Shall we put the world on folate? Lancet. 2009 Sep 19;374(9694):959–61.

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Can folate supplements be dangerous? - part 2


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