Folic Acid Supplements — Finally Here to Stay?
Folic Acid Supplements — Finally Here to Stay?
Abstract & Commentary
By Harold L. Karpman, MD, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.
Synopsis: Three years of folic acid supplementation improves information processing speed in older adults with raised total homocysteine blood levels.
Source: Durga J, et al. Lancet. 369:208-216.
It has been clearly demonstrated that cognitive function, especially in the domains related to memory and information processing speed, decline significantly with aging1 and that these changes have been linked to the risk of developing dementia in older age.2, 3 Modifiable risk factors for age-related cognitive decline have previously been identified4 and, interestingly enough, an inadequate folic acid intake has long been suspected to be one of these risk factors.5, 6
Because previous studies7, 8 yielded mixed results (possibly due to such factors as small study populations, short duration of folic acid supplementation, and/or inadequate cognitive function testing) as to the benefits of folic acid supplementation, Durga and his colleagues organized and performed the FACIT trial.9 This randomized, double-blind, placebo-controlled study took place between November, 1999 and December, 2004. The 818 participants who were aged 50-70 years were randomly assigned to receive 800 mcg oral folic acid or placebo daily for 3 years. The effect on cognitive performance was measured as the difference between the two groups with respect to the three-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency using five separate tests which have been previously described.10, 11 At the end of the three-year study period, serum folate concentrations increased by 576%, plasma total homocysteine concentration decreased by 26%, and both information processing speed, and sensorimotor speed had improved and were significantly better in the folic acid group than in the placebo group.
Commentary
Being able to avoid the usual decline in cognitive function which occurs with aging is obviously an important goal for each and every one of us. The FACIT trial9 is a very well designed randomized, double-blind, controlled trial which has yielded extremely important results. However, the possibly significant limitations of the trial deserve exploration. First, assuming that high plasma total homocysteine concentrations might be a causal risk factor for cognitive decline, 3044 out of 4200 participants were excluded from the study because of low total plasma homocysteine concentrations. Thus, the observed effect of folic acid supplementation on cognitive function might have been greater than would be expected in populations with lower plasma total homocysteine concentrations, for example, as in countries such as the USA where overall homocysteine levels are generally lower than they are in other countries (probably because fortification of flour with folic acid is mandated in the USA). It is important to also note that even though the prevalence of dementia was not measured at baseline, it is unlikely that the study population included many cognitively impaired or demented participants since the general performance on the dementia screening test (ie, the Mini-Mental State Examination) was quite high both at the beginning and at the end of the trial.
In summary, the basic question is whether or not folic acid supplementation will lead to a reduced incidence of cognitive decline and/or dementia. Some have argued that age-related cognitive decline is the beginning of a continuum leading to dementia12 and others have argued that13 it is not an early stage of dementia.2 These quite complex issues and other factors such as the confounding effects of vitamin B12 deficiency and/or the clinical relevance of folic acid supplementation in populations already afflicted with mild cognitive impairment and dementia will have to be evaluated. However, at this time, it would appear safe to say that three years of folic acid supplementation improves information processing speed and memory in older adults with raised total homocysteine concentration and that, at this time, there appears to be little reason not to prescribe 800 mcg of folic acid orally for individuals over 50 years of age with elevated homocysteine levels.
References
1. van Boxtel MPJ, et al. J Geront A Biol Sci Med Sci. 1998;53:M147-154.
2. Lovden M, et al. Psych. Aging. 2005;20:303-316.
3. Peterson RC, et al. Arch Neurol. 1999; 56:303-308.
4. Fillit HM, et al. Mayo Clin Proc. 2002; 77:681-696.
5. Calvaresee E, et al. J.Geront B Psychol Sci Soc Sci. 2001;56:327-339.
6. Mattson MP, et al. Trends Neurosci. 2003;26:137-146.
7. Morris MC, et al. Arch Neuro. 2005;62:641-645.
8. Malouf M, et al. Sys Review. 2003;4:CD 004514.
9. Durga J, et al. Lancet. 369:208-216.
10. Jolles J, et al. Maastricht: Neuropsych publishers, 1995.
11. Durga J, et al. Neurobiol aging. 2006;27:334-343.
12. Brayne C, et al. Lancet. 1988;331:1265-1267.
13. Morrison JH, et al. Science. 1997;278:412-419.
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