B Vitamins and Cognitive Performance in Older Adults: Review

A copious amount of scientific scrutiny has been dedicated to documenting typical and atypical human ageing, with a substantial body of work focusing upon the impact of lifestyle choices. One such lifestyle choice is that of diet and, in particular, micronutrient ingestion. Epidemiological studies have reported positive associations between B vitamin status and cognitive function, including negative associations between biological markers (i.e., homocysteine) of dysregulated one-carbon metabolism and cognitive function. This has led to a surge of randomised control trials (RCTs) investigations into B vitamin therapy. However, results have continuingly failed to show beneficial behavioural effects. Despite this, results reliably show treatment-related increases in B vitamin level and decreases in homocysteine level—both of which have been identified as risk factors for atypical ageing. In this paper we argue that it would be premature to conclude that B vitamin therapy has no potential and that more research is needed to systematically investigate the optimal dose, the therapeutic “window,” and individual differences in therapy responders and nonresponders. We start with a brief look at one-carbon metabolism and then consider the evidence from epidemiological studies and RCTs in relation to three specific B vitamins: folic acid (B9), pyridoxine (B6), and cobamides (B12). 1. Mechanism of Action In 1992, two papers suggested that elevated levels of homocysteine may be a biological marker of abnormal one-carbon metabolism and that this may play a role in the aetiology of Alzheimer’s disease (AD) [1, 2]. Behavioural support for this hypothesis comes from epidemiological work in healthy adults and patient populations, which demonstrates a negative association between homocysteine levels and cognitive function. In addition, it has been reported that elevated homocysteine levels are an independent risk factor for AD (see [3]). One-carbon metabolism refers to the generation of one-carbon units, normally from serine, through association with a folic acid derivative; tetrahydrofolate (THF), to form 5, 10-methylenetetrahydrofolate and then 5-methyltetrahydrofolate. This, in turn, is used to methylate homocysteine, in a reaction catalysed by B12, and is used in the synthesis of methionine. Smith [3] outlines twelve biologically plausible mechanisms to explain the association between B vitamins, homocysteine, and dementia. However, Selhub et al. [4] state that the evidence for such mechanisms relies on animal and cell culture models and that there is “no supportive