The article in today’s Daily Mail about B vitamins and Alzheimer’s is the story of the triumph of dogged scientific persistence – do read it first if you can because this blog would become impossibly long if I repeated all the details.
But behind it is another story of indifference and prejudice that is preventing people getting access to a treatment that could be effective and safe.
For years researchers have known that there is a link between Alzheimer’s and an amino acid called homocysteine; studies regularly found these patients had high levels. So could homocysteine be contributing to the disease or was it an innocent bystander? It’s also well known that the only way to reduce homocysteine is to increase your intake of B vitamins, so some nutritionists suggested taking B vitamins as a prophylactic.
Scientific sceptics condemned this as foolish and irrational because there was no randomised controlled trial (RCT) evidence to support it. Fair enough. But then an Oxford Professor of pharmacology, David Smith, did a top quality RCT on the idea that ticked all the boxes: it was a reasonable size and lasted for two years. This was premium grade research.
B vitamins cut brain shrinkage
The result was impressive and surprising. Those who took a very high combination of B vitamins saw a significant drop in brain shrinkage measured by a brain scan compared to those getting a placebo. Their score on memory and thinking tests stopped getting worse too.
This is where the indifference and prejudice kicked in. You might think Alzheimer’s charities would welcome the result, not least because the drug approach of targeting plaque had proved a total failure and there was little to offer patients.
However all one leading charity had to say was that the best way to protect yourself was to get B vitamins from a healthy diet. This is inadequate in so many ways; not least the fact that there is no evidence that a healthy balanced diet (leaving aside the question of what that is) is actually protective.
As for getting your B vitamins from food, quite apart from the fact that it would be impossible to get the high levels used in the trial, elderly people, the ones most at risk, are often deficient in B vitamins. This is partly because old people living alone often don’t eat so well and meals in hospitals and care homes are rarely nutrient rich. It is also because the drugs many are on such as acid blockers and the diabetes drug metformin are known to reduce availability of B12. There was simply no attempt to take any serious notice at all of what Professor Smith had discovered.
B vitamins are fraudulent
A tougher line was taken by one of the most aggressive champions of RCTs (his identity is unimportant because he speaks for a lot of people who believe they are supporting a scientific approach to medicine by ridiculing nutrition and use of vitamins).
When faced with evidence from a “gold standard” RCT did he say “OK, interesting let’s investigate”? Absolutely not. Instead he began his blog responding to the research by asserting: “B vitamins are a favourite of the fraudulent supplements industry. One of their pet propositions is that they will prevent dementia.” So not much science there either.
Even so it was a properly conducted study, with results which, if replicated, could quite possibly cut the rate people progressed to Alzheimer’s – the stated aim of most of the drug trials. Even the charity had said more research needs to be done. So did any of the funding bodies concerned about Alzheimer’s pick up on it?
Again, absolutely not. For two years Professor Smith took his academic begging bowl to top funders in the States and the UK without any success. Now it could be that the research was really flawed – as some academics hinted to me – or simply that it is a tough game, lots of promising research doesn’t get followed up on. There is no hidden agenda I was assured.
Good quality research
And so we come to the trial that that prompted today’s article (it’s important but it’s not the trial that Professor Smith was seeking funds for to show that B vitamins can actually slow or prevent the development of Alzheimer’s). It is top quality science – published in a leading journal) with a lead author who works at the Functional Magnetic Resonance Imaging Centre at Oxford. Still fraudulent?
It was part-funded by the Medical Research council. It found the reduction in brain shrinkage was better than 50% – it was 90%. It tied down the link between brain shrinkage and cognitive decline and supported the idea that homocysteine could actively damage the brain
So how has it been received? Remarkably the response of Alzheimer’s Research UK was almost identical to the first time round. First it said more research was needed, which was obvious two years ago but nothing has been done.
And the healthy diet advice was rolled out yet again along with keeping weight down and exercise. It’s the standard basic advice to deal with any chronic disease. It’s been promoted as the solution to obesity and diabetes for the last 20 years and look how well that has worked.
Professor Smith has provided good evidence for a new, specific and radical promising treatment and its implications are simply being ignored. Could it be because drugs are simply preferred to vitamins whatever the evidence? Hard to prove but a news item I found on the Alzheimer’s Research UK website lends support to the idea.
Two million for drug brain shrinkage trial
It was a report of a two million pound trial of blood pressure drug call Losartan, due to start later this year to see if it can reduce brain shrinkage and improve memory in Alzheimer’s patients. The researchers will be using brain scans and memory tests.
It’s being done at Bristol University and the researchers describe Losartan as “well tolerated” (Side effects listed on the medical site WebMD include diarrhoea, muscle cramps, dizziness, insomnia, and nasal congestion).
The proposal goes on to say that the drug could improve brain/blood flow, that brain shrinkage is known to be “strongly linked with reduced memory function” and that the “the beauty of this drug is that if it works it is already available and cheap.” Funding for the study was announced in December last year as part of the Prime Minister’s boost for Alzheimer’s research funding.
If the evidence is all that matters it is very hard to understand why two million needs to be spent on Losartan when we already have RCT evidence for treatment with a vitamin that has virtually no side effects, has been shown to reduce brain shrinkage dramatically and is available and far cheaper? Would patients really prefer to take Losartan for years rather than B vitamins which have a range of other benefits?
If this is scientific medicine it needs a radical overhaul, starting with the trial everyone agrees, theoretically, needs to be done.
Body of Evidence 
Can you tell us more about this? I’d love to find out some additional information.
Have a look at the website – Food for the Brain the have a test and possibly more up to date information
Hi every one, here every one is sharing these familiarity, therefore it’s nice
to read this blog, and I used to pay a visit this weblog daily.
Peroxynitrite is the principal oxidant in Alzheimer’s disease. Peroxynitrites inhibit the synthesis and release of neurotransmitters involved in short-term memory, sleep, smell, mood, social recognition and alertness. They contribute to vascular damage in the brain. And they inhibit the regeneration of neurons in the hippocampus and trigger the death of brain cells.
B vitamins lower homocysteine levels and the subsequent production of peroxynitrites. Vitamin B12 is also a peroxynitrite scavenger.
The best peroxynitrite scavengers are methoxyphenols. They include eugenol in rosemary essential oil, eugenol and ferulic acid in lemon balm essential oil (Melissa officinalis), and ferulic acid (and vanillic acid and syringic acid) in heat-processed ginseng. Eugenol and ferulic acid improve cognition in patients with mild to moderate Alzheimer’s disease (and to a lesser degree in some other forms of dementia) and ferulic acid has a positive on behavior in Alzheimer’s disease. dementia with lewy bodies, and frontotemporal lobe dementia.
http://www.ncbi.nlm.nih.gov/pubmed/20377818
http://www.ncbi.nlm.nih.gov/pubmed/12810768
http://www.ncbi.nlm.nih.gov/pubmed/22780999
http://www.ncbi.nlm.nih.gov/pubmed/21272180
The failure of scientists, research institutes, and Alzheimer’s organizations to follow-up on these highly promising studies is one of the great hidden tragedies in the history of Alzheimer’s disease.
Many thanks for that information – totally new field for me – very interested to know more
This is what really concerns me is the fear of charities to accept ‘gold standard’ evidence and sadly yes, it appears most people have been brainwashed into believing medication to be the only cure. So disheartening!
The income from most medical charities comes from Big Pharma and they are tied in to the medical establishment…..so they are not interested in other evidence or ways of helping people……suggest you try to read their accounts – it makes for disheartening reading. Many of the familiar names have effectively become fronts for Big Pharma. We have gold standard evidence that plant medicine helps people with or prevent the onset of Alzheimers but none of this is ever mentioned and personally I was refused the opportunity of talking to sufferers to make them aware of other options.
Many thanks for your comment absolutely agree would be very interested to see charity accounts if you have some I think we should get a campaign going
In 2002 in the UK I examined a number of them as part of my dissertation. The Daily Express (?) or Mail (?) shortly thereafter ran a piece on this. In 2007 I tried to look at a Canadian breast cancer charity and found the same pattern. All accounts have to be made public and you can request a copy. Note where the actually income comes from and also the where the money is spent excluding admin – grants to MD’s etc. None of the accounts I looked at were what you might describe as clear and a forensic accountant would be helpful. In Canada I learnt that that particular charity spend less than 0.5% on prevention and to quote Prof B Agarwhal of MD Anderson Houston Texas…Cancer is a preventable disease….it requires a lifestyle change. ( see Pubmed for exact wording ). Earlier this year I met with him at a conference and he re inforced this point in a private discussion. Anything that might trigger a reduction in conventional medicine in the interests of patients is blocked where ever possible. See the latest on Pubmed on colon cancer showing the clear relationship to diet and the onset of the disease and the work done in the Planck institute Freiburg recently released for MS, Fibromyalgia, Cancer, Alzheimers, Parkinsons.
Do send me some more data on this
The research I did in 2002/3 is long binned but you can get the data yourself by either looking up the accounts on line or requesting copies of annual accounts from the charities themselves and then if necessary Companies House. Even short form accounts reveal a lot.
am planning piece along those lines just thought you might add to the background. watch this space.
Great article Jermone, wish more people paid attention to it though!
Sally M Pacholok and her hubbie wrote about B12 and Alzheimer’s http://www.amazon.co.uk/Could-be-B12-Epidemic-Misdiagnoses/dp/1884995691.
The http://www.pernicious-anaemia-society.org/ know about it and their chairman wrote about his own decline into memory loss in http://www.amazon.co.uk/Pernicious-Anaemia-Forgotten-Consequences-Deficiency/dp/1781610045
My mother died of it, my youngest sister has it and I have PA so I KNOW what low B12 levels cause ….but everyone ignores the simple solution=B12 jabs at a cost on the NHS of LESS than 75p a shot. Shame:(
I just got a leaflet from the Alzheimer’s Society pleading for money for research to find a ‘cure’ for Alzheimer’s. The examples given are genetic research (despite only 1% of Alzheimer’s being caused by genes) and drug research on what causes t’au proteins in the brain to accumulate (current research says it’s homocysteine). Not a mention of B vitamins. Shame!
The key to Alzheimer’s prevention is early screening, followed by homocysteine testing and B vitamins, plus other preventive measures. The free on-line Cognitive Function Test at foodforthebrain.org takes 15 minutes to do and picks up the earliest signs of cognitive decline. That’s why we are pushing for everyone over 50 to take the test annually. it then tells you what to do.
Thank you Patrick for your common sense reply and co incidentally confirmation of my earlier reply to this blog about the activities of Big Pharma. I would add that those concerned about Alzheimers could benefit from going to a Medical Herbalist ( NIMH or CPP are the professional bodies to find a local practitioner ) because plants have been shown to inhibit Tau proteins and Alzheimers (eg. Sehgal N, Gupta A, Valli RK, Joshi SD, Mills JT, Hamel E, Khanna P, Jain SC, Thakur SS, Ravindranath V.Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3510-5. Epub 2012 Jan 30.PMID: 22308347)
In addition, the fabulous work coming out of the Max Planck Institute in Freiburg has shown quite clearly that the origin of many of the chronic auto immune diseases such as Alzheimers’ arise in the gut through diet, bacterial change and viruses ie almost totally preventable. K Berer has done outstanding work on MS replicating it in mouse models.
RE your comments on heart disease I made the point it was a marker rather than a treatment objective. High levels is a well known risk factor for cardiac disease ( Mayo clin Proc 2008 83(11) 1203-1212. atherosclerosis 158 (2001) 425-430 However if you look at the actions of statins, the most ubiquitous heart drug handed out, and the consequences of the mitochondrial / liver/ pancreatic dysfunction it causes, you will see that it inhibits and dysregulates these key compounds for bodily function. Initial symptoms of a lack of B12 for example can be confused with early angina or stroke onset. For cancer and homocysteine indicates poor methylation and increased likelihood of aberrant DNA replication not to mention the destruction of significant amounts of cardiac tissue by chemo drugs. ( Top Chem Curr 2012 29 2175-81 ). Incidentally some of the B12 etc work has also been done in Bologna and the US (?2008, 2001, 2005 )
You’ve got an impressive grip on it. Given the range of metabolic side-effects of statins the way they have been doled out to primary care patients is going to seem highly irresponsible by the next generation of doctors.
Monitoring homocysteine is a very important marker for all chronic auto immune disease ( Alzheimers, cancer MS etc ) as well more familiarlly used for cardiac conditions. High levels are predictive for these diseases ( see Pubmed ) High levels of B12 B6 Folate and methionine all reduce these abnormal levels. One of the principal reasons is that these diseases start in the gut ( see Pubmed microbiome project K Berer ).
Sadly most of the so called medical charities are funded by Big Pharma with close links to academia to control and promote research where a patentable outcome can be demonstrated. The Alzheimers charity along with many others is a political and PR front. Thus the disiinterest in a cheap and effective remedy. The Publicly available accounts are less than clear.
Many publications specialist or not are also affected by this bias as Big Pharma spends a lot on Advertising. Another part of the problem is that most medics over the age of 45yrs have virtually no training in nutrition, biochemistry and pharmacology so they cannot understand the basics of the human condition.
Hi – certainly agree that high homocysteine is linked with a number of chronic conditions and that vested interests push treatments towards drugs. Not heard about the gut link with homocysteine, sounds v. interesting, thanks, intend to chase it up.
But on the link between homocysteine and heart disease, the finding a few years ago was that lowering it in heart patients didn’t bring added benefit to the usual treatment. Professor David Smiths team (who did the Alzheimer’s study) analysed this study (don’t have reference off top of my head but can dig it out if you are interested) and suggested that what it actually showed was that adding B vitamins to the cocktail of heart drugs the patients were already on wasn’t beneficial. However they did discover that the study had found a reduction in stroke risk, but it wasn’t reported in the main text of the article; instead it was only available on line and you had to look pretty hard to find it. I don’t think any big study has been done on effect of homocysteine lowering on patients at raised risk of heart disease who haven’t yet developed it.
I do agree with you Jerome about coconut oil and another thing to research is ketogenic diet/life style (this works for diabetes type 2 and obesity), if providing the brain with a different fuel ketones improves not only Alzheimer’s but also other neurodegenerative diseases, wouldn’t that be a great thing.
Very keen on ketogenic approach seems to make a lot of sense. There is some very sensible research into links with cancer too going on in the States at the moment. Am planning to write about it soon
Totally agree – thanks for shining a light on the real trouble with treating Alzheimer’s. I recently finished reading Patrick Holford’s New Optimum Nutrition for the Mind – and similar problems surround pretty much all types of mental illness from ADHD/ADD to schizophrenia. I’d highly recommend checking out the Brain Bio Center at foodforthebrain.org for anyone who is interested in this topic, it’s a fantastic resource
Thank you for this very welcome article. The widespread downplaying of the benefits of vitamins and good nutrition and the favouring of iffy, usually expensive and frequently harmful, drug therapies instead is a great shame.
excellent
Excellent article. Thank you!
I find the same problem with Agnus Castus and PMT – when I contacted the National Association for Premenstrual Syndrome (NAPS) to find out if any research was being conducted, they didn’t even bother to reply and on the treatment forum there is no mention of this herb (and the response to my raising it was quite hostile). I, for years, believed herbs and vitamins were no better than placebo, but since ‘curing’ my own PMT with agnus castus six years ago, my eyes are open and I realise I have been brainwashed. There is a place for medicines, herbs, vitamins and other treatments such as CBT, but of course, there is only big profit in patented medicines. Pharma companies are predominantly concerned with profit, and it seems doctors, patients and even governments assume their advice is unbiased (naively). As my nan and great aunt developed dementia (one in her late 40’s) I will be following the vitamin B research closely, but now herbal remedies need licenses, restricting the dosage (for Agnus Castus this means a reduction from 20mg to 4mg) I do worry for the future.
There are many published articles on Agnus castus (also known as Vitex) Your best bet is to work with a qualitifed herbalist, though it sounds like you’ve managed it well yourself. The pharma industry cannot patent herbal preparations and supplements, so it’s in their best financial interests to debunk them at every turn. As most Continuing Professional Education (required of all GPs) is funded by big pharma, that bias naturally extends to physicians.
This is an excellent, eye-opening, post. Many thanks.
Thanks for your comments. I looked at evidence for herbal approaches to PMT and menopause some years ago and results seemed mixed. Obvious problem with gathering evidence but has there been any convincing trials recently?
Here are a few found on quick perusal. As a practitioner, I see consistent benefit, especially with low mood and irritability.
http://www.bmj.com/content/322/7279/134
Click to access 20208.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22791378
Impressive – thanks
Re your comments on PMT trials etc. A Medical Herbalist prescribes and prepares the herbal compound ( tincture ) for a patient on an individual basis ie every bottle is different. You cannot conduct trials for this approach to medicine as the purpose of a trial is to mass produce a patentable drug. However what is done and which is why Medical Herbalists understand the plants is that there is a great deal of data on plant constituents and actions biomedically and biochemically which is then allied to the known pathological processes of the condition being treated both in vivo and in vitro. In otherwords truly evidenced based personalised medicine. It is also extremely effective otherwise we would not have patients! The whole purpose, when trials were introduced at the end of the 60’s, was to limit the liability of governments after the Thalidomide disaster – it was not designed to provide evidence of how it worked or that it was % better than placebo or to show potential interactions. The clinical trial process and proceedings have barely improved since the 1960’s. Recent exceptions include the fact now they must be registered, objectives and outcomes reported in full within 5 yrs of the ending of the trial and any financial interests by the reporting authors. Any trial withdrawn does not have to declare any thing.
Anything bought over the counter is not a drug nor herbal medicine nor does it have to go through trials. It is a product concocted by a manufacturer which must provide evidence for some of the claims made in marketing literature submitted to the EU. Most of the these manufacturers are owned by Big Pharma.. I declare I am a Medical Herbalist treating a variety of diseases and Pubmed is my daily newspaper! I have no commercial associations to manufacturers or other bodies.
Very much agree about impossibility of doing RCTs (randomised controlled trials) on individualised treatments and also agree that the widespread medical assumption that RCTs are the best and only way to evaluate treatments is very misleading, in fact my last two posts pointed out some of the problems with the basic design of RCTs, over and above pharmaceutical fiddling which is now widely accepted as a fact.
However having a way of distinguishing more effective from less effective treatments is obviously desirable and this is something that I’n interested in finding more about. Intriguingly cancer treatments which are being increasingly driven by variations in genetic mutations, are moving in an individualised direction and my sense is that a lot of the drug use tied to gene patterns doesn’t have a clear RCT base.
Without trials such as Schellenberg 2001, 2012, I wouldn’t have heard about the benefits of agnus castus – and although I am sure you are right about the patient centred approach, I don’t think conducting trials on the effectiveness or not of herbal treatments, diminishes this holistic treatment option. Is there not a place for RCT’s in developing an evidence base for the alternatives to the medical monopoly? I didn’t see a herbalist, but if I had, I would have expected them to support the therapy they were offering me with evidence of its effectiveness. I am hugely supportive of choice and evidence based information. I took the dose found to be effective in the trials (20mg standardised extract), and it worked for me, without the need to visit a herbalist. Fine tuning herbal doses on an individual basis, I am sure, is the best way to get maximum benefit, but I don’t agree you cannot (should not) conduct trials on herbal medicines at all. The scientific method may result in over-generalisation, but it does allow for replication, with replication comes reliability. The validity comes from the qualitative experience of herbalists and patients – both types of evidence have their place.
Yes. Seems that what is needed is to remove RCTs from position as only arbiter of what is proper medicine and have other types of trials that can be agreed on to provide reliable data – observationa? …at this point I need help from someone with proper grip on statistics but there must be a number of options out there.
Thanks for the links, Deborah, two of those research studies were new to me. What i really don’t understand is why anti-depressants are the first line treatment for PMT (after pill, mirena coil, etc). Surely trying agnus castus (with minimal documented side effects) before resorting to prozac (which has been shown to reduce libido in 80% of women who take it – and believe me PMT already wreaks havoc on your sex life) has to be a better response? Sadly new restrictions to the selling of herbal products has led to the dosage of agnus castus being reduced to a level where it is unlikely to be effective. I was seriously contemplating a hysterectomy at 37 because my periods were so painful. I was prescribed morphine (which didn’t work and left me unable to drive or work). Agnus castus transformed my life. It disheartens me that even if women find out about agnus castus, they will be buying tablets in a dosage that is unlikely to work.
Absolutely and if you are talking about good RCT evidence the data supporting the SSRI antidepressants is not at all impressive – see work by David Healy on risks/side-effects and Irving Kirsch on effectiveness.
Juliet, Do see a herbalist if things get difficult. Doctors aren’t trained to use them and often dismiss them out of hand. If you Google NIMH, the organization governing medical herblists in the UK, you should find a qualified herbalist who can give you personalized care. I, too, dispair at the removal of many herbal medicines from the general public. It is the people’s medicine, after all!
Sadly the drugs lobby will always have the upper hand. Anything more natural will always be ‘rubbished’ and efforts made to make it more difficult to obtain by the masses. Alzheimer’s is a time bomb and when it goes off the drugs companies celebrate and familes everywhere mourn the diminishing capacity of their loved one. We all have to get wise to the more natural alternatives that will support our ongoing health and try to minimise the ongoing damage of dis-ease.
Absolutely but maybe we are getting to a point where enough people need channel that movie Network and open their windows and yell: “We won’t take it any more!”
Charities are dependent on public support and government run trials use taxpayers money and since many of the public are obviously happy to use more natural approaches that desire should be reflected in research they fund. What about requiring them to allocate 25% of funding to researching non-drug treatments. Could be called something like: The Healthy Slice.
Great idea, Jerome, The Healthy Slice of the research budget for more natural ways to fight disease. I am sure many of the more enlightened would go along with that idea. It is such a shame that you have to experience Alzheimer’s ‘very close to home’ to realise how it is treated, progresses, and how other ways need to be found to try and slow down its progress or if possible reverse its march on the brain.
Thanks for your support Barbara. As well as being in favour of following up on the excellent evidence for the benefit of B vitamins in possibly reducing the risk of Alzheimer’s, I also think there is a case for starting research on another approach which might help Alzheimer’s patients. It sounds ridiculous at first hearing – coconut oil. I wrote about it in the Daily Mail in on Jan 8 2013 and followed it up with a post giving called “Coconut out-takes – what the Mail didn’t say.” If you’ve a personal interest you might find it useful.The post has a link to the Mail article
Syphon off 25 percent of public funding to investigate possible non-pharma solutions to a variety of problems? Hey, now that is something I’d wholeheartedly support. Back in the day I think it was called thinking outside the box…. And I was under the impression that it was part of what research and researchers ‘did’. Must be getting old, eh?
I understand that these days you have to not only know what your project is going to discover but to know what the return is going to be during they first two years of the business you start up as a result
What really concerns me is the apparent fear of charities to accept ‘gold standard’ evidence and sadly yes, it appears most people have been brainwashed into believing medication to be the only cure. So disheartening!
Very interesting read. Thank you!
I always knew Marmite was essential! 🙂
There are hidden MSGs in Marmite created during the manufacturing process so if you’re MSG sensitive you’d be better off with good quality B vitamin supplements
Didn’t know that about Marmite and I’m sure its worth taking but not if you are trying to follow the evidence gathered by Professor Smith and cut rate of brain shrinkage with mild congnitive impairment who found that amounts of vitamin B12 you needed was several thousand times the amount in a regular Marmite serving.
Very good reading, thank you.
Great stuff.
My version of a Google translation of this is:
“Research by Oxford pharmacologist David Smith has established that vitamin B may be able to help in cases of mild dementia. But the widespread benefits this could bring is in danger of being lost because he has been unable to get funds to do the necessary follow up studies.” Apologies in advance if it is wildly wrong.