Drugs that promised to halt Alzheimer’s have all failed. So why is no one testing other options?

By Jerome Burne

Among those most vulnerable to the virus are the 850,000 elderly people in the UK with Alzheimer’s. The official view is that there is nothing that can be done to slow or stop this dreadful disease. There is no evidence to support claims on social media that B vitamins might help, say the experts. Talk to your doctor and eat a ‘healthy balanced diet’.

Actually, it’s not true there’s no evidence, Ten years ago, a study, published in a top medical journal, found that a very high daily dose of B vitamins could reduce shrinkage of the Alzheimer’s areas of the brain by nine times compared to placebo in people with pre-dementia, in just one year. The amounts were folate 80mg, B6 20mg and B 12 50mg, which is 200 times the recommended dose.

What is true is that this high-quality, hopeful research was never followed up with another bigger and longer trial to discover if it could prevent or slow the onset of Alzheimer’s. No money, apparently, was available. Vast sums, however, were available to test drugs, a research program that has been a total failure.

At the time it was widely expected that a type of drug known as a ‘monoclonal antibody’ (MAB) would soon be reducing Alzheimer’s risk. These pills, a triumph of cutting-edge medical science, target and remove damaging proteins, such as those driving cancer, rheumatoid arthritis and the damaged amyloid plaques and tangles that wreak havoc in the brains of Alzheimer’s patients. 

A research project that has totally failed

Fast forward ten years and what has changed in the official treatment and prevention of Alzheimer’s? The short answer is effectively nothing. An estimated 200 billion dollars has been spent on an astonishing number – 300 – of failed trials involving drugs with names like Aducanumab, Gantenerumab or Solanezumab none of which, according to a report in the New York Times in February, prevented Alzheimer’s from progressing. 

Meanwhile nothing serious has been done to find out if B vitamins could really prevent Alzheimer’s in those with early warning signs. Such a trial would cost a trifling (by comparison) £5 million or so. The result has been a lost decade of Alzheimer’s research. But at a grassroots level there has been an enthusiastic response to the idea that various non-drug treatments may help. Over 300,000 people have done tests to assess their risk and many have tried high-dose vitamins other lifestyle changes to reduce it.

‘We still can’t say or be certain that B vitamins can slow or stop Alzheimer’s because the follow up to prove it has never been done’ says lead author Professor David Smith, Director of OPTIMA (Oxford Project to Investigate Memory and Ageing). ‘But for years there has been enough promising evidence to justify testing the idea. It’s shocking that something so desperately needed has been ignored. During that time over a quarter of a million people in the UK alone have developed this horrible disease and there is still nothing to offer them.’ Nutritionist Patrick Holford interviews Professor Smith here.

Drug companies ignore unpatentable non-drug treatments, however promising, so who should research them? Recently a BMJ article suggested that it was no longer acceptable for companies to concentrated on blockbuster drugs with massive sales at the expense of treatments that were far less profitable but were ‘hugely important for public health.’ 

Experts confused about B vitamins

Meanwhile, further analysis of the original study by Smith’s team has made the benefits even clearer. Those in the placebo group lost 3.7 per cent of their grey matter, while those getting the B vitamin lost only 0.5 per cent. (Proceedings of National Academy of Science. May 2013). More recently high levels of omega 3 look like boosting the B benefit.

Official bodies have all ignored this research, so even though everyone knows B vitamins are supposed to benefit the brain, there is a lot of confusion about how much and where to get it from. Secretary for Health Matt Hancock showed how wrong you can be, even when surrounded by medical advisors. 

Two years ago, he was warning that a lack of vitamin B12 raised the risk of dementia, but recommended replacing what was missing with broccoli.  However, there is no B12 at all in broccoli!. It is only in animal food such as eggs, but you’d have to eat 200 eggs to achieve the amount used in this trial. 

The confusion guarantees that many who are deficient will be missed. According to Smith, almost half of people over 70 don’t absorb B12 effectively and many will be on drugs to block stomach acid and/or metformin for diabetes, both can further reduce B12 absorption.  ‘They would have to take 200 times the RDA to get blood levels back to normal,’ he says.

One senior and independent medic who did understand the importance of the research was Professor Sir Christopher Edwards, an endocrinologists and retired Vice-chancellor of Newcastle University. 

How B vitamins protect the brain

‘I was fascinated when I learned about the trial and astonished it hadn’t been followed up,’ he said. ‘The use of brain scans at the beginning and end showed clearly the vitamins were having a dramatic effect.’

But why are B vitamins so effective at protecting the brain? The connection is an amino acid called homocysteine, which had been suspected of causing damage for years because many dementia patients had a high level. The trial was the first time the link had been proved because the only way to lower it is with B vitamins.

Your homocysteine level (over 11 raises your risk) is one of the best blood markers for Alzheimer’s risk and can be measured by any GP. However, it too is still being largely ignored by GPs and gerontologists.

 The homocysteine connection was the reason Professor Edwards quickly understood why Smith’s trial made sense. As an endocrinologist, he treated diabetic patients and knew that those with high homocysteine were more likely to suffer nerve damage to the feet and eyes because it is toxic to nerves. ‘I could see why lowering it worked,’ he said.

Professor Edwards was sufficiently impressed to have his own homocysteine level tested and discovered it was over 11. ‘I didn’t have any obvious cognitive impairment,’ he says, ‘but I started taking the B vitamins because there seemed a good case for it and, although the amount was unusually high, the safety data was reassuring.’

Charity warns about non-drug options

Within a few months it was down to a safe level and he stopped taking them preferring, he explained, to rely on ‘omega 3, physical and mental exercise and a holiday in the sun to stave off the disease.’ It’s a protective strategy that many others in the UK have taken up, despite official disapproval. 

The website of the main charity, Alzheimer’s Research UK, warns against any: ‘herbal’, ‘alternative’ or ‘complementary’ products that claim to benefit people with dementia, or to improve memory.’ It explains that: ‘There has been little high-quality research into these products, and some may not be safe for people with dementia.’ 

What the charity doesn’t explain is why there has been no research. Could it be that that relying on commercial companies for the bulk of research, guarantees that promising but unpatentable approaches are ignored?  The charity, with its close links to the industry, did not believe it had any responsibility to investigate.

When asked why there had been no follow up of Professor Smith’s original promising RCT, Dr Rosa Sancho, Head of Research at the charity explained: ‘To find out if B vitamins can slow or prevent the development of Alzheimer’s disease, scientists would need to carry out further clinical trials’. Well quite, and the problem with that is…..?

Testing programme is underway

There is one charity, however, which took David Smith’s research seriously. The Food for the Brain Foundation set up a free, online Cognitive Function Test, a digital version of the one used in memory clinics along with a short diet and lifestyle questionnaire. 

Over 300,000 people have now filled in the test and the questionnaire and researchers at University College London are currently analysing the data. Results, originally due in June, have been delayed.

This project, the only one in the UK, highlights the failure of the charities and NHS England to live up to their repeated claims that they are working hard to find ways to spot Alzheimer’s early and prevent it. Smith’s research not only offers a plausible treatment, it also suggests a blood test (homocysteine level) that could act as an early warning. 

In 2017 it looked as if non-drug approaches might get a boost. A Lancet article found that primary prevention had the largest effect on reducing the development of the disease. It calculated the risk reduction from various strategies; 22 per cent from eating more fatty fish or taking omega 3 supplements, getting adult education, (24 per cent), exercise (32 per cent). 

Diet and lifestyle can help

The Conservatives made an election promise to double funding for Alzheimer’s research and the leading charity warned that without new ways to prevent and treat this invisible pandemic ‘one in three people born today will develop dementia.’ 

So, faced with a stark warning of impending economic disaster, did funding switch to researching ways to make the best use of diet and lifestyle? Hardly. Begging bowls for drug money were rattled even harder to support a strategy that had already chalked up a failure rate of 99.6% between 2002 and 2010 (Economist August 29 2020).

So if World Alzheimer’s Day on September 21st is going to actually achieve anything, one resolution would be to stop collecting funds to continue researching the plaque busting drugs that have failed again and again. Another would be to properly fund research into the many other possibilities that have been ignored for too long.

For instance, as well as homocysteine, check out the benefits of omega 3. Despite shoestring budgets, Smith and a few other mavericks have been uncovering new ways to boost the benefit of B vitamins. Recently a few small studies found that combining them with omega 3 could dramatically improve their effect. 

A follow-up reanalysis of the blood samples taken during Smith’s original trial revealed that patients with really low omega 3 levels had gained no benefit from the vitamins. But those with the highest omega 3 levels, who also got the vitamins, suffered virtually no brain shrinkage at all. Their brains and memory were like those of a healthy person.  By the end of the trial, almost a third of the group no longer met the diagnosis of Alzheimer’s. 

Boost the brain with omega 3

This was extraordinary. Vitamin B plus omega 3 blocks the destruction of brain cells! Yet still, there is no sign that any of the promised £83 million of extra funding for dementia is available for testing it. 

But this is not the only promising prevention strategy that is being studiously ignored by those holding the purse-strings. Years of eating the high carbohydrate, high sugar diet that can lead to obesity and diabetes, may also be damaging brain cells according to Professor Stephen Cunnane of Sherbrooke University in Canada, an expert on fatty acid metabolism in the brain.

A way to rescue the brain cells is to supply them with a different sort of fuel, called ketones, that your body makes when you cut most carbohydrates out of your diet. ‘It works for diabetics,’ says Cunnane ‘and it’s safe and scientifically founded to treat a cognitive deficiency with ketones.’

Maybe more government funding will arrive. Maybe the government will push drug companies to test promising but unprofitable treatments. This was proposed in the BMJ recently by Professor Mariana Marzacotto, an economist at University College London. She argues that companies which didn’t agree to test such treatment could be banned from benefiting from the 40 per cent of UK medical R&D that comes from public and charitable sources.

We know a privatised approach to public health doesn’t work.That’s why fresh solutions for antibiotics resistance are being explored to provide the urgently needed new antibiotics that companies ignore because they fail to produce the required revenue stream. 

Ignoring B vitamins when there isn’t a plan B is no longer an option.

Jerome Burne

Jerome Burne

Jerome Burne is the editor of HealthInsightUK. He is an award-winning journalist who has been specialising in medicine and health for the last 10 years and now works mainly for the Daily Mail. His most recent book “The Hybrid Diet” was written with nutritionist Patrick Holford, published 2018. Award: 2015: Finalist for 'Blogger of the Year' Medical Journalists' Association.


  • Interesting. My husband has been diagnosed with Altzheimers. I had him on B vitamins, Onega 3, uridine & MCT oil. Plus brain clear tabletsthevNeurologist said it was rubbish and I should stop them as his b levels were through the roof. I was given a drink like Danacol, Souvenaid & told to stop the vitamins. Within 2 months he was disappearing . I’m no doctor but I am with him 24/7 & the difference was awful. Stopped the drink &!went back to the vitamins … it’s been a month. He still has the attention span of a gnat but he is much more ‘present’
    Any advice or recommendations would be most welcome . Thankyou

  • It’s pointless to wish that the pharmaceutical industry will conduct research into therapies that do not offer a return on the investment, if for no other reason that the directors would be in breach of their fiduciary duty to act in the best interests of shareholders. They’re businesses not charities. Nor should this research be left to the charities, too many of which are just shills for Big Pharma and Big Medicine anyway (eg the Alzheimer’s, Diabetes and Heart associations to name a few).

    Also Pharma and Big Medicine have no interest in actually curing disease since that means you’re no longer a source of revenue for them. Their interest is in keeping you a customer for life. Hence the focus on treating symptoms of disease not the causes and the mantra that diseases like Alzheimer’s, diabetes and heart disease are irreversible and progressive. They certainly are if you rely on your doctor’s advice!

    This situation is an example of what economists term market failure – no-one is motivated to undertake beneficial activity because they are unable to benefit from doing so. This is precisely where the government’s role should be: to fund the research that private industry can’t or won’t, not to subsidise Big Pharma by funding drug trials. Governments have far more money and resources to undertake this research than any charity can hope to provide. In fact the richest charities are those that are Pharma-funded and thus precisely the ones least likely to fund cheap therapies that would undercut their benefactors’ profits. We should be demanding that our governments switch their research funding to these alternative therapies. It’s in their interest as well as ours as taxpayers to prevent and/or reverse these diseases and put the brakes to the galloping rate of increase in the health budget.

    • Editorial

      Absolutely agree and i’ve suggested in several posts that, while the relationship between the NHS and pharma is supposed to be a public/private partnership, the NHS side is very much the sleeping partner. Leaving the research of all promising non-profitable treatments to pharma is clearly not a good idea.
      However there are a few promising signs that this could be changing. An example is the concern over antibiotic resistance and the refusal of drug companies to research new antibiotics without large compensation. An article in the NEJM earlier this year proposed a not-for-profit to develop new antibiotics was needed. (can supply link if you are interested)
      The Alzheimer’s post was another example of why something like that is desperately needed. It also illustrated the highly compromised position of the charities who pursuade people to contribute to beating cancer/Alazheimers/ diabetes. What is never made clear is their involvment with drug companies means that the only treatment your money will go to is a drug one. My recent post on the Mail on Sunday and its attacks on independents doctors and researchers challenging the official line made it clear how compromised Diabetes UK is on this point, going as far as not declaring thier pharma funding.

  • The government doesn’t need to partner with Pharma in order to conduct trials of nutritional therapies. They could do it today if there was the political will. We need Health Ministers who see their job as acting for the benefit of the citizens and not as the care and feeding of the lobby groups – pharma, the doctors and the nursing unions. These groups cry crocodile tears about the ever-increasing medical costs while constantly working to increase the size of the trough and jumping in with all four trotters to maximise their share. Nutritional therapies threaten their incomes by actually making people healthier. And it’s not just the medical lobbies that stand to lose. The farmers and the food companies on the commercial side, then there are the ideological lobbies like the 7DA church, the dietitians and the fanatical vegans. It’s going to take a real commitment right at the top to make this happen.

    In order to develop new antibiotics the government needs to harness the knowledge that already exists in the large pharmaceutical companies. I’ve read that the major companies have data on massive numbers of compounds they’ve screened for efficacy but for various reasons have decided not to proceed with. Access to that data will shorten the development time, no need to reinvent the wheel. However I don’t agree that Govt should enter joint venture partnerships with pharmaceutical companies for two reasons:

    1) the pharmaceutical company’s interest is in charging the highest possible price for the new drugs, the govt as the consumer in being charged the lowest price. If pharma is allowed to set the price the govt (ie you and me as taxpayers) will end up paying twice – once for the research and secondly for the ongoing supply. Note that this already happens with publicly funded research, any other researchers wanting to access the results have to pay journal publishers like Elsevier (with our money!).

    2) the pharma company’s interest is in maximising sales of the product. As a result far more antibiotics are given to farm animals than humans, frequently in animal feed to promote weight gain or as a prophylactic (and so farmers can be lax about sanitation and infection control) This is by far the major factor driving antibiotic resistance. This practice has to be banned, but if the pharma company owns the patent rights it’ll be impossible to prevent them doing this.

    This solution as I see it is that the government should subcontract the research to the pharmaceutical industry, paying for the research and development on a cost-plus basis and including a reasonable price for access to their compound databases. A key condition is the government owns the intellectual property and the patent rights. On successful development of the drug the govt licences the product to multiple companies (to promote competition), setting maximum prices and a clause prohibiting use in animals. Note that this model is already used in defence contracting, the govt issues research contracts for new weapon systems to industry and actual production is priced on a cost-plus basis.

    While I’m generally not in favour of government-run enterprises (since the incentives are for less efficiency not more) there are times when only the government can perform certain functions eg would you really want a for-profit fire brigade and have to bargain with them while your house was burning down? I suspect this proposal in the NEJM for a nonprofit to develop new drugs is just another American refusal to accept that sometimes there is a role for government. Just where is this nonprofit going to come up with the 100s of millions of $ required? It can only come from either government or industry, and if from industry they’re going take over the nonprofit for their own ends just as they’ve done with the Diabetes, Heart and other charities. So we’re back to government funding.

    • Editorial

      Totally agree new improved funding along with genuinely independent licencing body is needed (some interesting work on the absurdly pharma friendly approach to cancer drugs, that I have written about).

      Interesting – though not surprising, that drug companies have lots of data on promising antibiotics to start the process of non-pharma antibiotic research.

      You might be interested in a few of the specific details of the NEJM proposal that I picked up on:
      Link here:
      Proposal began: ‘We believe the current entrepreneurial development model for antibiotics is broken and needs to be fundamentally transformed.’

      This class of drugs don’t make enough, it continued, partly because of campaigns to get doctors to dish them out less freely and partly because they are usually effective. Patients generally only need a short course. Both factors cut sales.

      Other benefits of a non-profit include:
      ‘No pressure to generate continuous revenue growth to drive up shareholder value.’
      Greater flexibility: ‘A drug with annual sales of tens of millions of dollars is a catastrophic failure for many (corporations) but would be a lifeline for non-profits which could reinvest revenue …to sustain research and development efforts.’

      Getting pharma business practices under control obvious essential, if hugely challenging. Was surprised that you suggested defence spending provides a model. Not my field, but I thought it was famously uncontrolled. USA stories of $500 toilet seats and runaway spending on new weapons systems. All things of the past??

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