The last few weeks have produced yet another example of how selective reporting can give a very misleading impression.
As usual, the reluctance of the media to report important negative results is, in part, to blame..
The B vitamins are a favourite of the fraudulent supplements industry. One of theit pet propositions is that they will prevent dementia. The likes of Patrick Holford were, no doubt, delighted when a study from Oxford University, published on September 8th, seemed to confirm their ideas. The paper was Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. (Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al. (2010)).
The main problem with this paper was that it did not measure dementia at all, but a surrogate outcome, brain shrinkage. There are other problems too. They were quickly pointed out in blogs, particularly by the excellent Carl Heneghan of the Oxford Centre for Evidence Based Medicine, at Vitamin B and slowing the rate of Brain Atrophy: the numbers don’t add up. Some detailed comments on this post were posted at Evidence Matters, David Smith, B vitamins and Alzheimer’s Disease.
This paper was reported very widely indeed. A Google search for ‘Vitamin B Alzheimer’s Smith 2010’ gives over 90,000 hits at the time of posting. Most of those I’ve checked report this paper uncritically. The Daily Mail headline was 10p pill to beat Alzheimer’s disease: Vitamin B halts memory loss in breakthrough British trial, though in fairness to Fiona MacRae, she did include at the end
“The Alzheimer’s Society gave the research a cautious welcome. Professor Clive Ballard said: ‘This could change the lives of thousands of people at risk of dementia. However, previous studies looking at B vitamins have been very disappointing and we wouldn’t want to raise people’s expectations yet.’ “
That caution was justified because a mere two weeks later, on September 22nd, another paper appeared, in the journal Neurology.. The paper is Vitamins B12, B6, and folic acid for cognition in older men, by Ford et al. It appears to contradict directly Smith et al. but it didn’t measure the same thing. This one measured what actually matters.
“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 conclusion was negative.
“Conclusions: The daily supplementation of vitamins B12, B6, and folic acid does not benefit cognitive function in older men, nor does it reduce the risk of cognitive impairment or dementia.”
Disgracefully, this paper has hardly been reported at all.
It is an excellent example of how the public is misled because of the reluctance of the media to publish negative results. Sadly that reluctance is sometimes also shown by academic journals, but not in this case.
Two things went wrong, The first was near-universal failure to evaluate critically the Smith et al paper. The second was to ignore the paper that measured what actually matters.
It isn’t as though there wasn’t a bit of relevant history, Prof Smith was one of the scientific advisors for Patrick Holford’s Food for the Brain survey. This survey was, quie rightly, criticised for being uninterpretable. When asked about this, Smith admitted as much, as recounted in Food for the Brain: Child Survey. A proper job?.
Plenty has been written about Patrick Holford, here and elsewhere. There is even a web site that is largely devoted to dispelling his myths, Holford Watch. He merited an enture chapter in Ben Goldacre’s book, Bad Science. He is an archetypal pill salesman and the sciencey talk seems to be largely used as a sales tool.
It might have been relevant too, to notice that the Smith et al. paper stated
Competing interests: Dr. A. D. Smith is named as an inventor on two patents held by the University of Oxford on the use of folic acid to treat Alzheimer’s disease (US6008221; US6127370); under the University’s rules he could benefit financially if the patent is exploited.
There is, of course, no reason to think that the interpretation of the data was influenced by he fact that the first author had a financial interest in the outcome. In fact university managers encourage that sort of thing strongly.
Personally, I’m more in sympathy with the view expressed by Strohman (1997)
“academic biologists and corporate researchers have become indistinguishable, and special awards are given for collaborations between these two sectors for behaviour that used to be cited as a conflict of interest”.
When it comes to vitamin pills, caveat emptor.
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Carl’s writeup was uncharacteristically obtuse. Apparent drop-outs of that magnitude in MRI studies are common since it is difficult to get everyone to agree to undergo an MRI. This in no way calls into question the intent-to-treat population. That being said, a < 1% reduction in brain volume apparent on an MRI is unlikely to be clinically significant.
Your point about the media response to this is well taken.
I’ve only had a quick glance at the papers but whereas the first study examined 70 year old subjects (male and female) the second recruited men aged 75 years or greater and treated them for two years. Since the probablity of AD increases with age perhaps the second group were too far advanced for the vitamins to work. Furthermore the vitamin doses were not the same in the 2 studies[ Folic acid 2mg vs 0.8 mg; B12, 0.4 mg vs 0.5 mg; B6 25 mg vs 20 mg]. And one study excuded patients already taking vitamin B supplements whereas the other included them if they were below a certain dosage. (If my reading is correct this must surely have been pointed out). A journalist being aware of this would be inclined to stick with the headline grabbing story.
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