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Food fortification with Folic Acid– Risks vs Benefits
- Dhruvashree Somasundara (6 March 2007)
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Mandatory folic acid fortification - more than a 'theoretical' risk less than a panacea
- Mark A. Lawrence, Sharleen L. O'Reilly and Lynette Riddell (7 March 2007)
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Dhruvashree Somasundara, Ex- PRHO, Bangalore Medical College, Bangalore-560001, India
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Folic acid deficiency during pregnancy is a well-known, preventable cause of Neural Tube Defects (NTD). Attempts to prevent this have been on for more than a decade. The Health Education Authority (HEA) (1995-98), by rigorous activity, increased awareness for the need for folic acid supplementation during pregnancy, but compliance was less than one-third, most of which was postconceptional. But the most important phase of requirement of folic acid is during conception, that is, during Embryogenesis(1). Therefore supplementation in postconceptional period proved to be less effective in preventing NTD. Another benefit of Folic acid given in the periconceptional period is that it prevents childhood leukaemia. Research(2) conducted between 1992 and 1998, led by Professor Mel Greaves at The Institute of Cancer Research, UK, suggests that children exposed to higher levels of folic acid in the womb have a significantly lower risk of developing leukaemia. According to a Health Food Manufacturers’ Association (HFMA) Report, the average intake of folic acid per day per person in the UK is 200 Microgram(3). But periconceptional requirement of folic acid per day is 400 Microgram. The strategies of dietary intake and supplementation in the form of pills to meet this requirement, as mentioned by the authors, have not shown much success. The third strategy, Food fortification brings in the practical debate of whether to increase folic acid intake in the entire population and weighing benefits to newborns against the adverse effects it can cause in the more vulnerable group of people. The people at risk of adverse effects due to additional folic acid are the elderly and people on antifolates. Elderly are at risk primarily because they are commonly deficient in Vitamin B12 as well, implying, they not only required the additional folic acid, but they also required additional Vitamin B12. So it would be more appropriate to fortify food with both folic acid and Vitamin B12, which, even if not useful to a certain section of population, would not prove harmful. For people on antifolates, it would be the duty of the doctor prescribing the medication to warn the patients about their dietary restrictions while on the medication. In addition to the benefits of folic acid in the periconceptional period, the article also mentions its effects in decreasing the incidence of Coronary Heart Disease and Stroke. A study(1) conducted in the United States on the effect of decrease in plasma homocysteine levels, showed a decrease in deaths due to stroke and Ischemic heart disease by 3.4%. There is also some evidence that levels of folate and Vitamin B12 are low in patients of depression and that the efficacy of treatment is enhanced when both these vitamins were given (4). Since food-fortification is a large scale measure, one must consider the expenditure involved. Once fortification infrastructure is in place, the cost of adding it to the flour is less than £0.01/kg of flour(5). Hence, this is more cost-effective than screening of women in the periconceptional period. Though there is the argument of inappropriate mass medication, there is little chance of harm by food fortification, especially if folic acid and B12 are given together. Also, since it has been shown to be beneficial in various other conditions, food fortification would be an appropriate measure to ensure nutritional well-being of women and thus of newborns. REFERENCES: 1. www.rcog.org.uk, Periconceptional Folic Acid and Food Fortification in the Prevention of Neural Tube Defects, Scientific Advisory Committee, Opinion Paper 4 2. Institute of Cancer Research, Press Release, 23 April, 2003. 3. www.hfma.co.uk/PositionPaperFolicAcid 4. Treatment of depression: time to consider folic acid and vitamin B12, Journal of Psychopharmacology, Vol. 19, No. 1, 59-65 (2005) 5. www.mrc.ac.uk/YourHealth/StoriesDiscovery/FolicAcid Competing interests: None declared |
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Mark A. Lawrence, Associate Professor School of Exercise and Nutrition Sciences, Deakin University, Victoria 3125, Australia, Sharleen L. O'Reilly and Lynette Riddell
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Sir, We read with interest the editorial by Bille et al (‘Folic acid and birth malformations’, BMJ, 334, 433-434)(1) questioning why the introduction of mandatory folic acid fortification was being delayed in Europe. The authors have taken the opportunity provided by findings of one retrospective case-control study that indicates 40% of cleft lip cases might be prevented by periconceptional folic acid supplementation, to argue for mandatory folic acid fortification. However, the focus of the authors’ argument for this intervention is the prevention of neural tube defects (NTDs). The authors refer both to the ‘large proportion’ of NTDs that would be prevented - later inferring that all 4500 annual cases in Europe might be prevented. At the same time, the authors dismiss reasons for not introducing mandatory folic acid fortification as being based on ‘theoretical concerns’ about safety and the ‘common argument’ that there are ethical concerns with exposing the population as a whole for the benefit of a relatively small group. While we agree with the authors regarding the importance of preventing NTDs, we challenge the authors’ statements that for mandatory folic acid fortification the safety risks are theoretical and that the intervention would somehow be a panacea for NTD prevention. There is now a substantial number of evidence-based concerns about the safety implications of mandatory folic acid fortification. These concerns include possible increased risk of cancer particularly colorectal cancer,(2) decreased cognitive function,(3) increased risk of compromised immunity (4) and lack of evidence of protection against coronary heart disease.(5-8) Concern has also been raised regarding an increased proportion of methylenetetrahydrofolate reducatase homozygote births in women using folic acid supplements to prevent NTDs.(9) This could be a possible negative outcome for future generations as this genotype is reliant on a high intake of folate to maintain health and is negatively associated with increased risk of several chronic diseases if diet quality is not maintained. We have also yet to see if folic acid supplementation in utero may result in phenotypic changes in offspring as recently seen in the agouti gene murine experiments,(10) and whether they could result in increased risk of disease later in life. In contrast to claims about the substantial protective effect of folic acid on NTD prevalence, evidence from those countries where mandatory folic acid fortification has been introduced indicates that for most countries in Europe, it might be hoped that 20-30% of cases might be prevented, leaving 70-80% that will not. Clearly, any NTD case prevented is a benefit, however, this must by weighed against all potential risks and benefits for all children, teenagers, adults and older adults who would be exposed to raised levels of synthetic folic acid. Finally, the author’s primary argument for dismissing ethical considerations associated with this debate is based on a speculative statement that if fortification could also reduce the burden of chronic diseases that have a population-wide prevalence then it would be justified. This argument has been presented and investigated for over a decade and the results of several secondary prevention trials have failed to find evidence to demonstrate a protective relationship between folic acid and chronic disease.(5-8, 11) Certainly, if substantial evidence were to be found, then this would significantly affect the ethical perspective to this debate. However, until that time, our group believes the evidence associated with mandatory folic acid fortification raises a substantial number of safety concerns and indicates that its effectiveness will not be a panacea. A.Prof. Mark Lawrence, Dr. Sharleen O’Reilly and Dr. Lynnette Riddell References 1. Bille C, Murray JC, Olsen SF. Folic acid and birth malformations. BMJ 2007; 334: 433-434. 2. Cole B, Baron J, Sandler R, Haile R. A randomised trial of folic acid to prevent colorectal adenomas. Proceedings of the American Association of Cancer Research 2005; 46: 4399. 3. McMahon J, Green T, Skeaff C, Knight R, Mann J, Williams S. A controlled trial of homocystine lowering and congitive performance. N Engl J Med 2006; 354: 2764-2772. 4. Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B, Selhub J, McTiernan A, Yasui Y, Oral E, Potter JD, Ulrich CM. Unmetabolized Folic Acid in Plasma Is Associated with Reduced Natural Killer Cell Cytotoxicity among Postmenopausal Women. J. Nutr. 2006; 136: 189-194. 5. Loscalzo J. Homocysteine trials--clear outcomes for complex reasons. N Engl J Med 2006; 354: 1629-32. 6. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J, Jr. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006; 354: 1567-77. 7. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, Sides EG, Wang CH, Stampfer M. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. Jama 2004; 291: 565-75. 8. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354: 1578-88. 9. Munoz-Moran E, Dieguez-Lucena JL, Fernandez-Arcas N, Peran-Mesa S, Reyes-Engel A. Genetic selection and folate intake during pregnancy. Lancet 1998; 352: 1120-1. 10. Pennisi E. Environmental epigenomics meeting. Supplements restore gene function via methylation. Science 2005; 310: 1761. 11. The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease. N Engl J Med 2006; 354: 1567-1577. Competing interests: None declared |
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