Hostname: page-component-848d4c4894-4rdrl Total loading time: 0 Render date: 2024-06-17T19:09:10.506Z Has data issue: false hasContentIssue false
  • English
  • Français

Folates and prevention of disease

Published online by Cambridge University Press:  27 September 2007

Anne M Molloy  and
John M Scott
Anne M Molloy
Affiliation:
Department of Clinical Medicine, Trinity College Dublin, Dublin 2, Ireland
John M Scott*
Affiliation:
Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland
*
*Corresponding author: Email jscott@tcd.ie
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Research in the past decade has established that low or inadequate folate status may contribute to congenital malformations and the development of chronic disease in later life. Using an evidence based approach, there are clear guidelines for recommending folic acid supplementation or fortification in certain disease conditions but further proof of its efficacy is required in other circumstances.

There is conclusive evidence that maternal periconceptional supplementation with folic acid prevents the majority of NTDs, probably by overcoming one or more genetically inherited metabolic blocks in folate dependent enzymes. Public health efforts to advise women to increase their folate intake have not been successful. As a result, the U.S. government passed legislation to have all flour fortified with folic acid. This intervention has had a dramatic effect on folate status in the U.S. To date, countries of the EU have not adopted mandatory fortification policies.

The amino acid homocysteine is an essential intermediate in folate metabolism. Substantial evidence indicates that elevated plasma homocysteine is an independent risk factor for heart disease and stroke. Plasma homocysteine levels can be reduced by folic acid supplements. A food fortification policy would probably be an effective population strategy to reduce plasma homocysteine. However, many experts believe that this would be premature without first showing that such reduction would cause a decrease in the prevalence of cardiovascular disease.

The contribution of folate to cancer risk is not well defined although there is reasonable evidence to implicate low folate status in the specific case of colorectal cancer. In particular, long-term folic acid supplementation may reduce risk of colorectal cancer substantially.

Various mental disorders including Alzheimer's Disease have been associated with low folate status or elevated plasma homocysteine. While it is hard to determine if this is cause or effect, there is little doubt that if it were true then low dose folic acid intervention would be highly effective.

Keywords

FolateHomocysteineNeural tube defectsCancerCardiovascular diseaseStrokeAlzheimer's disease
Type
Research Article
Information
Public Health Nutrition , Volume 4 , Issue 2b , April 2001 , pp. 601 - 609
Copyright
Copyright © CABI Publishing 2001

References

1Scott, JM, Weir, DG. Folate/Vitamin B12 inter-relationships. In: Tipton, KF, ed. Essays in Biochemistry. Vol 28. London: Portland Press, 1994: 63–72.Google Scholar
2Scott, JM. Folate and vitamin B12. Proc. Nutr. Soc. 1999; 58: 441–8.CrossRefGoogle ScholarPubMed
3Scott, JM, Weir, DG, Molloy, A, McPartlin, J, Daly, L, Kirke, P. Folic acid metabolism and mechanisms of neural tube defects. In: Bock, G, Marsh, J, eds. Ciba Foundation Symposium 181, Neural Tube Defects. Chichester: John Wiley and Sons, 1994: 180–91.Google ScholarPubMed
4Elwood, JM, Little, J, Elwood, JH. Epidemiology and control of neural tube defects. Oxford: Oxford University Press, 1992.Google Scholar
5EUROCAT Working Group. Prevalence of neural tube defects in 20 regions of Europe and the impact of prenatal diagnosis, 1980–1986. J. Epidemiol. Community Health 1991; 45: 52–8.CrossRefGoogle Scholar
6MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991; 338: 131–7.CrossRefGoogle Scholar
7Czeizel, AF, Dudas, J.Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. New Engl. J. Med. 1992; 327: 1832–5.Google Scholar
8Cuskelly, CJ, McNulty, H, Scott, JM. Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects. Lancet 1996; 347: 657–9.Google Scholar
9Scott, JM, Weir, DG, Kirke, PN. ‘Prevention of neural tube defects with folic acid a success but…’. Q. J. Med. 1994; 87: 705–7.CrossRefGoogle ScholarPubMed
10Daly, S, Scott, JM. The prevention of neural tube defects. Curr. Opin. Obstet. Gynecol. 1998; 10: 85–9.Google Scholar
11Daly, S, Mills, JL, Molloy, AM, Conley, M, Lee, YJ, Kirke, PN, Weir, DG, Scott, JM. Minimum effective dose of folic acid for food fortification to prevent neural-tube defects. Lancet 1997; 350: 1666–9.CrossRefGoogle ScholarPubMed
12Jacques, PF, Selhub, J, Bostom, AG, Wilson, PW, Rosenberg, IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. New. Engl. J. Med. 1999; 340: 1449–54.CrossRefGoogle ScholarPubMed
13Schneider, JA, Rees, DC, Liu, YT, Clegg, JB. Worldwide distribution of a common methylenetetrahydrofolate reductase mutation [letter]. Am. J. Hum. Genet. 1998; 62: 1258–60.Google Scholar
14Shields, DC, Kirke, PN, Mills, JL, Ramsbottom, D, Molloy, AM, Burke, H, Weir, DG, Scott, JM, Whitehead, AS. The ‘thermolabile’ variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother. Am. J. Hum. Genet. 1999; 64: 1045–55.Google Scholar
15Bestor, T.Methylation patterns in the vertebrate genome. J. Natl. Inst. Health Res. 1993; 5: 57–60.Google Scholar
16Smithells, RW, Sheppard, S, Schorah, CJ, Seller, MJ, Nevin, NC, Harris, R, Read, AP. Possible prevention of neural tube defects by periconceptional vitamin supplementation. Lancet 1980; i: 339–40.Google Scholar
17Smithells, RW, Nevin, NC, Seller, MJ, Sheppard, S, Harris, R, Read, AP, Fielding, DW, Walker, S, Schorah, CJ, Wild, J.Further experience of vitamin supplementation for prevention of neural tube defect recurrences. Lancet 1983; i: 1027–31.CrossRefGoogle Scholar
18Daly, LE, Kirke, PM, Molloy, A, Weir, DG, Scott, JM. Folate levels and neural tube defects. Implication for prevention. JAMA 1995; 274: 1698–702.Google Scholar
19Laurence, KM, James, N, Miller, MH, Tennant, GB, Campbell, H.Double blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects. Br. Med. J. 1981; 282: 1509–11.CrossRefGoogle ScholarPubMed
20Expert Advisory Group. Folic acid and the prevention of neural tube defects. London: Department of Health, 1992.Google Scholar
21Centers for Disease Control. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR 1992; 41: 1–7.Google Scholar
22Scott, JM, Weir, DG, Kirke, PN. Folate and neural tube defects. In: Bailey, LB, ed. Folate in Health and Disease. New York: Marcel Dekker, Inc., 1995: 329–60.Google Scholar
23Weir, DG, Scott, JM. Homocysteine as a risk factor for cardiovascular disease: nutritional implications. Nutr. Res. Rev. 1998; 11: 311–38.Google Scholar
24McCully, KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am. J. Pathol. 1969; 56: 111–28.Google Scholar
25Boushey, CJ, Beresford, SA, Omenn, GS, Motulsky, AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intake. JAMA 1995; 274: 1049–57.Google Scholar
26Eikelboom, JW, Lonn, E, Genest, J, Hankey, G, Yusuf, S.Homocysteine and cardiovascular disease: A critical review of the epidemiologic evidence. Ann. Intern. Med. 1999; 131: 363–75.Google Scholar
27Perry, IJ, Refsum, H, Morris, RW, Ebrahim, SB, Ueland, PM, Shaper, AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995; 346: 1395–8.CrossRefGoogle ScholarPubMed
28Selhub, J, Jacques, PF, Bostom, AG, D'Agostino, RB, Wilson, PW, Belanger, AJ, O'Leary, DH, Wolf, PA, Schaefer, EJ, Rosenberg, IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N. Engl. J. Med. 1995; 332: 286–91.CrossRefGoogle ScholarPubMed
29Malinow, MR, Nieto, FJ, Szklo, M, Chambless, LE, Bond, G.Carotid artery intimal-medial wall thickening and plasma homocyst(e)ine in asymptomatic adults: The Atherosclerosis Risk in Communities Study. Circulation 1993; 87: 1107–13.Google Scholar
30Green, R, Jacobsen, DW. Clinical implications of hyperhomocysteinaemia. In: Bailey, LB, ed. Folate in Health and Disease. New York: Marcel Dekker, Inc., 1995: 75–122.Google Scholar
31Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. BMJ 1998; 316: 894–8.CrossRefGoogle Scholar
32Blount, BC, Mack, MM, Wehr, CM, MacGregor, JT, Hiatt, RA, Wang, G, Wickramasinghe, SN, Everson, RB, Ames, BN. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc. Natl. Acad. Sci. USA 1997; 94: 3290–5.Google Scholar
33Choi, SW, Mason, JB. Folate and carcinogenesis. J. Nutr. 2000; 130: 129–32.Google Scholar
34Mason, JB. Folate Status: Effects on Carcinogenisis. In: Bailey, LB, ed. Folate in Health and Disease. New York: Marcel Dekker, Inc., 1995: 361–78.Google Scholar
35Giovannucci, E, Stampfer, MJ, Colditz, GA, Hunter, DJ, Fuchs, C, Rosner, BA, Speizer, FE, Willett, WC. Multivitamin use, folate and colon cancer in women in the Nurses' Health Study. Ann. Intern. Med. 1998; 129: 517–24.Google Scholar
36Bottiglieri, T, Crellin, RF, Reynolds, EH. Folates and Neuropsychiatry. In: Bailey, LB, ed. Folate in Health and Disease. New York: Marcel Dekker, Inc., 1995: 435–62.Google Scholar
37Clarke, R, Smith, AD, Jobst, KA, Refsum, H, Sutton, L, Ueland, PM. Folate, vitamin B12 and serum total homocysteine levels in confirmed Alzheimer Disease. Arch. Neurol. 1998; 55: 1449–55.CrossRefGoogle ScholarPubMed