ArticlesEffect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial
Introduction
Cognitive function declines with ageing, especially cognitive domains related to memory and information processing speed.1 Changes in cognitive performance, especially memory function, have been linked to risk of dementia in old age.2, 3 Modifiable risk factors for age-related cognitive decline have been identified, but their causality has not yet been established.4 Poor folate status is one such suspected risk factor.5, 6
A longitudinal study,7 undertaken in the USA when folic acid fortification of foods was routine, showed greater cognitive decline in people with a high folic acid intake than in those with low intakes. A systematic review of supplementation with folic acid alone or in combination with other B vitamins showed that no beneficial effect on cognitive performance was conferred.8 Many of the trials have used small study populations, supplemented for a short duration, or used tests such as the Mini-Mental State Examination,9 which are unable to detect subtle changes in cognitive function (table 1).10, 11, 12, 13, 14, 15, 16, 17, 18, 19
We investigated whether 800 μg daily oral folic acid supplementation for 3 years improved cognitive performance compared with placebo in older adults. Cognitive performance was assessed with tests that probe cognitive domains that decline in the ageing process.
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Participants
Participants were men and post-menopausal women aged 50–70 years, from the Gelderland region in the Netherlands who participated in the Folic Acid and Carotid Intima-media Thickness (FACIT) trial (unpublished), a study investigating the effect of folic acid supplementation on atherosclerotic progression. Additional outcomes of the trial were age-related decline in cognitive function and hearing. Here we present data for the effect of folic acid on the cognitive performance aspect of the study.
Results
Patients were randomised between November, 1999, and April, 2001, and the study was undertaken from September, 2000, to December, 2004. The figure shows the trial profile. Five participants allocated folic acid treatment reported adverse events: forgetfulness, sun allergies, weight gain, tinnitus, and dark urine. Adverse effects reported in the placebo group (n=7) were muscle aches, headaches, weight gain, queasiness, bitter taste in mouth, and skin irritations. The participant with headache
Discussion
In 818 older adults, daily oral folic acid supplementation for 3 years beneficially affected global cognitive function, and specifically memory, and information processing: functions that are sensitive to ageing.1 The decline in memory seen with ageing is generally preceded, and might be affected, by a decline in speed functions.32 Nonetheless, folic acid supplementation might beneficially affect both memory and speed simultaneously, since high concentrations of homocysteine have been
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