Wednesday, October 20, 2010

B vitamins and dementia -- time to start taking them yet?

So, the latest story about vitamin B12 protecting against dementia is making the rounds this week. The original paper is published in PLoS One, and describes the randomized, double-blind placebo-controlled two-year trial of high-dose folic acid and vitamins B6 and B12 in 271 older individuals.  These people underwent MRI at the beginning and end of the study to assess change in brain size that could be attributable to treatment, and the study concludes that brain atrophy in older people with mild dementia can be slowed by lowering homocysteine levels with B vitamins. And thus, presumably, the development of dementia can be slowed.

The BBC story says:
Certain B vitamins - folic acid, vitamin B6 and B12 - control levels of a substance known as homocysteine in the blood. High levels of homocysteine are associated with faster brain shrinkage and Alzheimer's disease.
The study authors believe it was the B vitamins' effect on levels of homocysteine that helped slow the rate of brain shrinkage.
And the size of the effect surprised the authors of the paper. 
"It's a bigger effect than anyone could have predicted," he said, "and it's telling us something biological.
"These vitamins are doing something to the brain structure - they're protecting it, and that's very important because we need to protect the brain to prevent Alzheimer's."
It's nice to see the focus being taken off genes, and put on environmental risk factors that may lead to this devastating disease.  This was a small and fairly short-term study, and of course the authors say that more research is needed, but it does sound promising, and perhaps we should all think about taking B vitamins with our cereal.

But hold on. 

A paper that seems to have gotten a lot less notice (we wonder why!?) is one that appeared online ahead of print in Neurology on Sept 22. This is a report of another double-blind controlled study of 299 men over 75 given either folic acid and vitamins B6 and B12, or placebo, and who were assessed for signs of dementia initially, at 2 and at 8 years. This study found that treatment had no effect on cognitive function in men, even while lowering homocysteine levels by 22.5%.

They point out that high homocysteine levels (tHcy) have been associated with dementia, and that levels have been shown by other studies to be lowered by 20% or so with B vitamins, as the PLoS paper describes, but that it's not clear whether this link is causal.  They also point out that this link has been studied before, but it has not been successfully demonstrated that B vitamins can affect risk of dementia.  Why not? 
Observational studies have consistently linked high tHcy to cognitive impairment, but the results of randomized trials have thus far failed to show any obvious benefits associated with tHcy-lowering therapy. These conflicting findings may be due to bias and confounding in observational studies, inclusion of prevalent cases of cognitive impairment in some trials, lack of power to measure small but important treatment effects, insufficient treatment duration,and recruitment of excessively healthy volunteers.
Ah, our old friends bias and confounding.

And, outcome measures differ between studies, which may affect conclusions.  In just these two studies alone, one used a measure of cognitive impairment and the other brain size (though the authors state that they will publish on their cognitive results at a later time).  The paper in Neurology concludes by suggesting that "elevated plasma homocysteine is not a risk factor but merely a marker that reflects underlying common processes responsible for both dementia and high tHcy, and that homocysteine-lowering treatment with B-vitamins does not affect the long-term cognitive function of people at risk."

We will certainly be hearing more on this subject.  But we wouldn't buy stock in B vitamins yet.


JKW said...

I haven't read the actual studies yet, but I am curious if the researchers controlled broadly for diet. Vitamin B12 is really the only vitamin that is hard to get from a vegetarian diet (and before anyone thinks it - no, we don't have any problems getting enough protein or calcium). I would think that any studies not accounting for this big difference between vegetarians and non-vegetarians would confound any results from studies trying to measure the "protective" effects of B12 doses (since regular dietary intake of the vitamin during the course of the study would be so variable).

Ken Weiss said...

To me this raises another question which is the lack of accuracy of past (let alone present) dietary intake, and whether deep past diet has an effect on late-age disease (it probably does, at least to some extent).

If people respond to news stories, at least in the middle class, then their diets will change a lot, food companies will change their products, etc. This may even filter down to the underprivileged and what their dietary options are.

But who can remember in enough detail what they ate, etc.?

Anne Buchanan said...

As far as I can tell, the people in these studies were given far more of these vitamins than people normally get in their diets -- even carnivore diets. So the issue you raise may not be relevant to these particular studies. But of course that doesn't mean it may not be relevant to real life!

occamseraser said...

PLoS1, the public library of s_ _ _
(fill in the blanks)

I am beyond being surprised by anything that gets published in that e-rag. But this fits the Mermaid mantra of hype all too often misleading and trumping substance in media friendly "journals".

Anne Buchanan said...

Yes, there's a wide range of quality in PLoS One. But, you get what you pay for. Or rather, what the authors pay for.

Ken Weiss said...

Yes, PLoS One has a purpose, to avoid censorship of the innovative. There are some good things published there. But with more than 4000 papers published per year, they aren't all gems. And because authors pay to play, and the only review is for 'technical' quality rather than importance, which sometimes seems rather cursory, this is largely a vanity press journal. It's a way for students, for example, to get into 'print' quickly (if their mentor has the money to pay the fee).

Still, that doesn't by itself mean that the papers are poor, and much that's good has appeared in PLoS One.

health quotes said...

If people respond to news stories, at least in the middle class, then their diets will change a lot, food companies will change their products, etc.I haven't read the actual studies yet, but I am curious if the researchers controlled broadly for diet.

occamseraser said...

A very generous assessment IMO. Much, if not most, wouldn't get into properly reviewed journals -- and they're permitting/promoting nonscientific crap that can claim "peer-reviewed" credibility that simply isn't earned. p<.05
Name one innovative paper that makes your/their point re: censorship:
fellatio in bats?
masturbation in squirrels?
parting of the Red Sea?
acupuncture clinical trials?


Ken Weiss said...

I'd say 3 papers in which Mark Stoneking was an author in the last couple of years. And there are others. But that doesn't undermine the ProblemOne with PLoS One