Last month I reported on a small study that purported to show that supplementation with the B-vitamins – B12, B6 and folate, were associated in a small study with a decrease in the amount of brain atrophy over a two year period. There were some problems with this study, but it is plausible that a subset of the population, if they are functionally low in one or more of these B vitamins, may neurologically benefit from correction through supplementation.

I, and others, pointed out, however, that the study did not look at cognitive function, which is a more relevant clinical outcome. It only looked at brain atrophy as measured with an MRI scan, and it is not clear if the results are clinically significant. I suggested the need for further research with more clinically relevant outcomes.

Well, I did not have to wait long. A couple of weeks later a study was published in Neurology by Ford et al that looked at cognitive function and risk of developing Alzheimer’s disease (AD). Here are the methods from the abstract:

The investigators recruited 299 community-representative hypertensive men 75 years and older to a randomized, double-blind controlled clinical trial of folic acid, vitamin B6, and B12 supplementation vs placebo over 2 years. The primary outcome of interest was the change in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog). A secondary aim of the study was to determine if supplementation with vitamins decreased the risk of cognitive impairment and dementia over 8 years.

The results were completely negative – no statistically significant effects on either cognitive function or on the risk of developing AD, at least in hypertensive men 75 and over.

We see this situation often in clinical research – apparently conflicting results depending on how you look at a question. In general, directly relevant clinical outcomes (like cognitive function and risk of AD) are considered to trump indirect outcome measures (like brain atrophy). You also have to consider the size of the study and the magnitude of the resultant effect.  Taking all this into account it seems that this more recent negative study has greater implications for the relationship between B-vitamin supplementation and dementia than does the prior positive study.

I had concluded that at present the research is inconclusive, but there is plausibility to benefit for B-vitamin supplementation, at least in a subset of people who are relatively deficient. Even after this more recent study this is still true, but this study makes it more likely that there may be no cognitive benefit to supplementation, and any potential benefit is likely to be modest.

There is still room for further research and I doubt this will be the last word on this particular question. But it does signal the need for caution before claiming any specific benefits for B-vitamins and dementia.