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Folic acid – should we take supplements?

A GP friend recently asked me about taking folic acid supplements. He said that in a discussion about supplements with a knowledgeable medical colleague, he'd been told that "there is good evidence to show that we should all be taking ... folic acid." The friend apparently takes 800mcg/day.

This is an interesting issue and, as with much of medicine, the answer isn't cut and dried. A few years ago there was particularly public enthusiasm for folic acid in a number of key medical journals. In 1998, an editorial entitled "Eat right and take a multivitamin" in the much respected New England Journal of Medicine (Oakley 1998) stated "The evidence that increased consumption of folic acid would prevent cardiovascular disease is strong and we should recommend consumption of at least 400 micrograms of folic acid daily (to all adults)." In the same year - 1998 - compulsory fortification of flour with folic acid was introduced in North America. More recently an article appeared in the British Medical Journal with the title "Is folic acid the ultimate functional food component for disease prevention?" (Lucock 2004), and in a recent report, "Folate and Disease Prevention" (see below) the UK Standing Advisory Committee on Nutrition (SACN) has recommended that mandatory fortification of flour with folic acid should be introduced, with certain conditions, in the United Kingdom.

The SACN report was published in December of 2006. The major reason they give for recommending compulsory fortification with folic acid is to reduce neural tube defects in babies. Mothers-to-be with low folate levels are more likely to have babies with spina bifida and anencephaly. SACN commented that, by 2006, there wasn't adequate evidence to recommend folate fortification for its possible cardiovascular benefits. Meta-analysis of relevant research underlines this suspicion that the 1998 New England Journal of Medicine editorial was making premature claims for the value of folic acid in reducing cardiovascular disease (Bazzano, Reynolds et al. 2006). Recent work provides greater support for supplementation reducing death from strokes (Wang, Qin et al. 2007), but even this more limited benefit of supplementation is still questioned (Ntaios, Savopoulos et al. 2008).

Folic acid supplementation reduces neural tube defects. Despite initial hopes, supplementation does not seem to reduce deaths from cardiovascular disease. It's effects on stroke are still not entirely clear although the situation here is more encouraging. What about other diseases? A search on PubMed using ‘folic acid' as the keyword yields nearly 22,000 research articles. It's a big field! Areas of interest include effects on cancer, on dementia, and on mood. With cancer, folic acid appears to have dual action - reducing the risk of some new cancers but increasing the progression of some early, undiagnosed pre- and established cancers (Ulrich 2007). This kind of dual action also seems to occur with supplementation effects on dementia. For older people with adequate vitamin B12 status, folic acid appears to help maintain cognitive function. For those with poor vitamin B12 status, folic acid supplementation seems to worsen their situation both for cognitive function and for anaemia (Smith 2007). It also looks likely that whether or not subjects take adequate physical exercise may be more important than folic acid status for protection against dementia - and may at times confuse the supplementation picture, presumably because regular exercisers are also likely to eat a healthier diet and take supplements (Middleton, Kirkland et al. 2007). Our understanding of folic acid's effects on mood are still developing. It may well be that better folate status protects, to some extent against, the development of depression (Gilbody, Lightfoot et al. 2007). Supplementation may also improve the effectiveness of antidepressants (Fava 2007). Research is currently underway to explore these issues further (Roberts, Bedson et al. 2007).

I did warn at the start of this post that the situation with folic acid supplementation isn't cut and dried. My current personal opinion is that the benefits of mandatory supplementation of a major food source like flour outweighs the potential damage that this supplementation may produce. If one is taking extra folic acid either via fortified food sources or dietary supplements or both, it seems important to make sure that one is getting enough vitamin B12, be mindful of possible cancer risks, and realise that more is not necessarily better (Smith, Kim et al. 2008). Someone once said that giving someone dietary supplements without paying attention to the overall quality of the food they eat, is like stealing an old lady's handbag and then tossing her a few coins from it before making off. A good healthy diet and adequate exercise are going to be much more helpful than just taking supplements. Good diet, adequate exercise and supplements are probably even better. In answer to my friend's query - I take 400 mcg of folic acid as a daily supplement along with good diet, adequate vitamin B12, and plenty of exercise. With the current upper limit on safe folate intake suggested to be 1 mg daily, I would tend not to take 800 mcg of supplement but there isn't currently strong evidence either way.

Bazzano, L. A., K. Reynolds, et al. (2006). "Effect of Folic Acid Supplementation on Risk of Cardiovascular Diseases: A Meta-analysis of Randomized Controlled Trials." JAMA 296(22): 2720-2726. [Abstract/Full Text]
Fava, M. (2007). "Augmenting antidepressants with folate: a clinical perspective." J Clin Psychiatry 68 Suppl 10: 4-7. [PubMed]
Gilbody, S., T. Lightfoot, et al. (2007). "Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity." J Epidemiol Community Health 61(7): 631-7. [PubMed]
Lucock, M. (2004). "Is folic acid the ultimate functional food component for disease prevention?" BMJ 328(7433): 211-214. [Abstract/Full Text]
Middleton, L. E., S. A. Kirkland, et al. (2007). "Exercise: a potential contributing factor to the relationship between folate and dementia." J Am Geriatr Soc 55(7): 1095-8. [PubMed]
Ntaios, G. C., C. G. Savopoulos, et al. (2008). "Vitamins and stroke: the homocysteine hypothesis still in doubt." Neurologist 14(1): 2-4. [PubMed]
Oakley, G. P. (1998). "Eat right and take a multivitamin." New England Journal of Medicine 338(15): 1060-1. [Abstract/Full Text]
Roberts, S. H., E. Bedson, et al. (2007). "Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial." BMC Psychiatry 7: 65. [PubMed]
Smith, A. D. (2007). "Folic acid fortification: the good, the bad, and the puzzle of vitamin B-12." Am J Clin Nutr 85(1): 3-5. [Free Full Text]
Smith, A. D., Y.-I. Kim, et al. (2008). "Is folic acid good for everyone?" Am J Clin Nutr 87(3): 517-533. [Free Full Text]
Standing Advisory Committee on Nutrition. Folate and disease prevention. Norwich: The Stationery Office, 2006. http://www.sacn.gov.uk/pdfs/folate_and_disease_prevention_report.pdf Accessed April 19, 2008.
Ulrich, C. M. (2007). "Folate and cancer prevention: a closer look at a complex picture." Am J Clin Nutr 86(2): 271-3. [Free Full Text]
Wang, X., X. Qin, et al. (2007). "Efficacy of folic acid supplementation in stroke prevention: a meta-analysis." Lancet 369(9576): 1876-82. [PubMed]

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