In the news: B vitamins and Alzheimer’s disease
A new analysis of several clinical trials has drawn a conclusion that will dismay many: taking B vitamins does not slow the decline in memory and thinking skills that comes with age. The results suggest that B vitamins are unlikely to prevent Alzheimer’s disease. The news is the opposite of what we, and the hundreds of thousands of families affected by the disease, had hoped for – but it does give us new knowledge to help people make more informed decisions about these supplements.
Where has the news come from?
The researchers, led by a team at the University of Oxford, drew their conclusions after pulling together data from 11 separate clinical trials of B vitamins, involving a total of 22,000 people. In each of these trials, the people taking part were randomly assigned to either take B vitamins or a placebo, and tests of the participants’ memory and thinking skills were carried out. The trials varied in size – ranging from just 108 people to 8,891 participants – and in duration, with the shortest lasting around three and a half months, and the longest running for seven years.
Each of the trials also looked at the effects of B vitamins on levels of an amino acid called homocysteine. High homocysteine has been linked to Alzheimer’s disease, and since B vitamins are known to reduce homocysteine levels, researchers have been keen to explore whether the supplements could also prevent or reduce the risk of Alzheimer’s.
However, when they pooled the results of all the trials, the researchers found that – although people taking B vitamins did see a reduction in homocysteine – there were no strong differences in memory and thinking scores between those who took B vitamins, and those who took the dummy pills.
Updating the evidence
These findings appear to be at odds with the VITACOG study from 2010, which involved 168 people and was widely reported in the media when it was first published. That two-year trial, which was part-funded by Alzheimer’s Research UK, showed that people with mild memory problems and high homocysteine had a slower rate of brain shrinkage when they took B vitamins, compared to people who took a placebo. Further analysis of the same trial, published a year later, suggested that B vitamins could also slow declining memory, at least in people with high homocysteine. So why are these new results so different?
When the VITACOG study was first published, both the researchers and Alzheimer’s Research UK highlighted the need for much larger, longer trials to be carried out, in order to confirm the findings and understand the implications for Alzheimer’s. While the VITACOG trial was well run, its small sample size meant that no firm conclusions could be drawn from the results at that stage. As one of the VITACOG researchers warned when the findings were first announced: “I wouldn’t yet recommend that anyone getting a bit older and beginning to be worried about memory lapses should rush out and buy vitamin B supplements without seeing a doctor.”
The need for large studies is explored further in our March blog post on dementia headlines, and it’s an important point in this case. Although this wide-ranging review is not a new trial, by pulling together data from many thousands of people, it gives the most up-to-date, comprehensive picture we have so far of the effects of B vitamins on cognition.
It’s always disappointing when potential preventative treatments fail. At Alzheimer’s Research UK, we’re striving to find treatments that people so desperately need, but to recommend a treatment, we have to have robust evidence that it works.
This analysis does suggest some future avenues for research – for example, the authors suggest that instead of being a cause of Alzheimer’s disease, high homocysteine could potentially be a marker of underlying problems. Research to further investigate exactly why high homocysteine levels and Alzheimer’s are linked could help us to better understand the disease and how to treat it.
The research also further underlines the urgent need for preventions for Alzheimer’s. Research into prevention has dominated the news this week, with one new study suggesting that as many as a third of Alzheimer’s cases could be avoided with simple lifestyle changes – but there’s much we still need to know about how to stave off the condition. It’s one reason we’ve committed to set up a prevention fund as part of our Defeat Dementia campaign, and it’s why we’ve signed up to the Blackfriars Prevention Consensus, which calls for action on risk reduction as well as continued research into preventions.
You can help us support our research into dementia prevention by donating online.
- This post was updated on 13 October 2014 to add clarity on some points.
About the author
Very disappointing… I thought the VITACOG results looked promising, including the reduced atrophy shown in this paper (which I don’t think you linked above)
By the way, unless I missed it, neither the blog nor the ARUK news item actually link to the paper; it’s here:
Thanks for your comments Ged, and thank you for including a link to the papers.
I wish I had seen this blog earlier.
A few points are important to mention here. Then, people can decide for themselves whether this meta-analysis actually contradict the successful VITACOG results (Plos One 2010, Int J Geriatr Psychiatry 2012, PNAS 2013 – for which I am the corresponding author).
First and foremost, this meta-analysis excluded trials on mild cognitive impairment (MCI) and Alzheimer’s disease. As a possible consequence, most of the trials included in this meta-analysis either did not see any significant cognitive change (between the start and the end of the trial) in the placebo group, or did not look at such change.
In other words, people included in these trials included in the meta-analysis were healthy and did not show any cognitive decline, whether they received B-vitamin treatment or not. So B-vitamin could hardly prevent or slow down something not happening in the first place.
In the VITACOG trial on the other hand, people given B-vitamins for 2 years actually had mild cognitive impairment, and were at risk for developing Alzheimer’s disease (http://users.fmrib.ox.ac.uk/~douaud/FAQs.pdf).
So: this meta-analysis did not include people with MCI or cognitive decline; our study did. Yet, the authors of this meta-analysis state that their results do not support the “claims” (their word) made in ours. Indeed, how could they, when these are not even the same populations involved in the first place?
Also, we and others (FACIT, Lancet 2007) have shown something quite easy to grasp: B-vitamin treatment seem to only benefit a subgroup of the participants, those who have high levels of homocysteine to start with.
It is thus quite surprising that the meta-analysis did not look in each individual trial at the effect of B-vitamins in this specific subgroup that is more likely to benefit from the treatment.
The list of points of contention goes on, but it is rather specialised. [For more details on our latest VITACOG results and why it might differ from some other trials, please see the FAQs: http://users.fmrib.ox.ac.uk/~douaud/FAQs.pdf%5D.
To conclude, this perhaps shows the perils of making blanket statement such as “Taking B vitamins won’t prevent Alzheimer’s disease”, as written by the authors of this meta-analysis in their press release. If such a sweeping message really has to be written for this meta-analysis, it should read more accurately: “Taking B vitamins won’t prevent cognitive decline for those who, overall, do not show cognitive decline anyway”.
There are so many flaws in the Clarke et al meta-analysis which we dissected in detail at http://www.foodforthebrain.org. The one I find most suspicious, given that the indiividual homocysteine scores of the participants were known, was the failure to investigate any differences for those who started with raised homocysteine levels, eg comparing the top quarter with the bottom quarter homocysteine scorers and any differences in cognition between those on placebo and B vitamins. Another obvious obvious weakness is that the main memory test, MMSE, is too insensitive to pick up small changes, which is all one could hope for in otherwise healthy people over an average of five years. I am surprised this study made it through peer-review into publication. This research question is completely different to that asked by the Vitacog studies. It certainly does not invalidate these studies, which showed a clear benefit on memory and reduced rate of brain shrinkage in those with raised homocysteine and mild cognitive impairment. The substantial weaknesses and omissions in the Clarke et al paper make it close to meaningless in its conclusions.
Thanks for sharing! It’s disappointing that b-vitamins don’t aid in slowing down the progression of Alzheimer’s disease.