by Jerome Burne
Is putting all our eggs in the drug basket really the best way to beat Alzheimer’s? Just as we can’t rely on drug companies alone to beat antibiotic resistance, so we can’t rely on a pharmaceutical silver bullet for Alzheimer’s. Tackling antibiotic resistance needs heavy investment in drugs that will be used sparingly for a short time. The pharma model prefers drugs for as many people as possible for as long as possible.
An equally unbridgeable strategic mismatch hampers drugs for Alzheimer’s. We need a way to reduce risk right now, preferably cheaply. Drugs can only offer promissory prevention in five to ten years at high cost. But evidence is mounting that taking lifestyle change and high dose vitamin seriously could have an immediate effect. Here’s some evidence why we need a rethink.
Evidence: Last month a big meeting of government and various dementia charities promised an Alzheimer’s treatment by 2020, saying that delaying dementia by five years would cut the number with the disease by one third. That would be great but so far a spend of about £25 billion researching Alzheimer’s drugs has produced virtually nothing useful.
Evidence: That meeting followed the G8 summit on dementia in London last September which was also exclusively about drugs. A statement calling for a shift to prevention signed by over 100 international dementia experts was effectively ignored. It emerged that for every £1000 pounds that UK Research Councils spent on Alzheimer’s just 1p went on studying prevention.
Can a problem as serious and intractable as Alzheimer’s really be tackled by all-too-familiar life-style advice?
Evidence: This week the Lancet published a report by the American Centres for Disease Control and Prevention saying that our epidemic of chronic diseases such as heart disease and diabetes were due to a small number of risk factors that were largely preventable including tobacco, poor diet, lack of exercise alcohol and high blood pressure. All (with the possible exception of alcohol) are also factors linked to Alzheimer’s. When you know what is causing a problem it surely makes sense to spend serious money tackling it.
Evidence: Last week saw the publication of a large analysis based on nearly 200 studies that put some impressive figures the contribution of lifestyle factors to dementia risk. (Epidemiologic studies of modifiable factors associated with cognition and dementia). These included lack of exercise (32%), a low level of education (24%), a low fish consumption (22%) and having a high levels of the amino acid homocysteine in your blood (22%). The only way to lower your level of homocysteine is by taking high doses of vitamin B. The official response to strong evidence that B vitamins may well cut dementia risk has been either ignored or ignorantly attacked (see below).
In an ideal world the government and charities would pick up and run with whatever looked promising as a treatment for Alzheimer’s. But if your agenda was finding a really profitable drug to treat the disease, then a treatment involving a vitamin that costs pennies might seem more of a threat. Sound too conspiracy theorist? Here’s some evidence.
Evidence: Four years ago a big randomised well run trial carried out at Oxford University showed that lowering the level of homocysteine with high levels of B vitamins could reduce the level of brain shrinkage in areas affected by Alzheimer’s by an astonishing 90%.
Evidence: It wasn’t definitive but it was something more specific than the drug companies had come up with so far and it offered something that people could do right away. It certainly deserved a follow up study in the UK. But four years later that has still not been done. In fact the Alzheimer’s charities have not only ignored it but misreported it. A recent review of all the evidence by Alzheimer’s Disease International says that the B vitamin RCTs had found the treatment “effective” but then falsely states in their conclusion that: ‘RCTs targeting elevated homocysteine levels…[have no] significant effect on cognitive function.’
That was bad enough and certainly hard to claim that this was all being done in the interests of patients. This week a study rubbishing the whole idea of using B vitamins to cut the risk of dementia came out. One of the authors was a high profile champion of statins.
Evidence: At first sight it looks like proper science. An analysis (Effects of homocysteine lowering with B vitamins on cognitive aging) of 11 trials involving 22,000 people designed to see if B vitamins could cut their risk of developing Alzheimer’s. Could this be the follow up of the 2010 paper? The conclusion was damming: ‘Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function.’
Evidence: If that study had built on or tested what the original study had found that would have been disappointing but proper science. It might have varied the doses, it would probably have divided patients into high and low homocysteine groups as the study had shown clearly that only those whose homocysteine was high benefited from treatment. To be useful it would have given figures showing the difference between the scores of those in the placebo group and those getting the vitamins.
Evidence: Remarkably it did none of those things. Instead what it actually showed was that if you treat healthy people on a variety of doses of B vitamins, using a measure of memory that can’t detect the small changes you’d expect to find in healthy people and ignore the fact that people with low levels of homocysteine don’t benefit from B vitamins you won’t cut the risk of Alzheimer’s. Hardly surprising. It certainly tells you nothing about the trial done four years ago and certainly doesn’t justify the conclusion that lowering homocysteine with B vitamins has no benefit.
Evidence: From one perspective though it was a roaring success. It attached a prestigious name Professor Sir Rory Collins (recently in the news as an aggressive champion of the benefits of statins (see here: http://healthinsightuk.org/2014/05/22/eminence-based-medicine-defends-the-status-quo-on-statins/) to a report with the conclusion: Dementia. B vitamins. No benefit. Since both doctors and journalists rarely read further than the abstract, the impression that B vitamins don’t work is out there. (More details.)
And that’s not the only piece of evidence that there is a concerted effort to discredit the B vitamin effect by whatever means necessary. An even more shoddy dismissal of B vitamins /Alzheimer’s link was performed about six months ago. Again it plausible to assume that by generating a wholesale condemnation of B vitamins it was a huge success.
Evidence: The study, which involved giving multi vitamins containing a modest amount of B vitamins to 6000 healthy doctors, came with this ringing editorial that provided the scare headlines but which didn’t remotely reflect what the studies actually found .
‘Antioxidants, folic acid, and B vitamins are harmful or ineffective for chronic disease prevention, and further large prevention trials are no longer justified. Most supplements do not prevent chronic disease or death, their use is not justified, and they should be avoided.’(‘Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements’)
Evidence: A finding about multivitamins given to well-educated, well-nourished people not ‘at risk’ of dementia tells you nothing about ‘most’ supplements” and nothing about the benefits of high doses of B vitamins given to people know to be at risk. What happened was that over eight years the cognitive levels of placebo and drug groups stayed almost the same. Again not a surprise.
The fact that those supposedly fighting the scourge of Alzheimer’s can not only ignore good evidence for the effectiveness of prevention but then try very incompetently to discredit the one approach that has a good randomised trial supporting it should make anyone personally involved with Alzheimer’s alarmed and angry.
It also points to one of the serious flaws in our system of evidence based medicine. If the drug approach does yield a pill that shows up in randomised trials to be better than a placebo at slowing the development of Alzheimer’s it will be hailed as a triumph for the evidence-based approach to the problem. The fact that a range of promising, cheaper, most likely far less toxic non-drug approaches were ignored won’t be seen as a failure. But it is.