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Vitamin – DC's Improbable Science

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‘We know little about the effect of diet on health. That’s why so much is written about it’. That is the title of a post in which I advocate the view put by John Ioannidis that remarkably little is known about the health effects if individual nutrients. That ignorance has given rise to a vast industry selling advice that has little evidence to support it.

The 2016 Conference of the so-called "College of Medicine" had the title "Food, the Forgotten Medicine". This post gives some background information about some of the speakers at this event. I’m sorry it appears to be too ad hominem, but the only way to judge the meeting is via the track record of the speakers.

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Quite a lot has been written here about the "College of Medicine". It is the direct successor of the Prince of Wales’ late, unlamented, Foundation for Integrated Health. But unlike the latter, its name is disguises its promotion of quackery. Originally it was going to be called the “College of Integrated Health”, but that wasn’t sufficently deceptive so the name was dropped.

For the history of the organisation, see

The new “College of Medicine” arising from the ashes of the Prince’s Foundation for Integrated Health

Don’t be deceived. The new “College of Medicine” is a fraud and delusion

The College of Medicine is in the pocket of Crapita Capita. Is Graeme Catto selling out?

The conference programme (download pdf) is a masterpiece of bait and switch. It is a mixture of very respectable people, and outright quacks. The former are invited to give legitimacy to the latter. The names may not be familiar to those who don’t follow the antics of the magic medicine community, so here is a bit of information about some of them.

The introduction to the meeting was by Michael Dixon and Catherine Zollman, both veterans of the Prince of Wales Foundation, and both devoted enthusiasts for magic medicne. Zollman even believes in the battiest of all forms of magic medicine, homeopathy (download pdf), for which she totally misrepresents the evidence. Zollman works now at the Penny Brohn centre in Bristol. She’s also linked to the "Portland Centre for integrative medicine" which is run by Elizabeth Thompson, another advocate of homeopathy. It came into being after NHS Bristol shut down the Bristol Homeopathic Hospital, on the very good grounds that it doesn’t work.

Now, like most magic medicine it is privatised. The Penny Brohn shop will sell you a wide range of expensive and useless "supplements". For example, Biocare Antioxidant capsules at £37 for 90. Biocare make several unjustified claims for their benefits. Among other unnecessary ingredients, they contain a very small amount of green tea. That’s a favourite of "health food addicts", and it was the subject of a recent paper that contains one of the daftest statistical solecisms I’ve ever encountered

"To protect against type II errors, no corrections were applied for multiple comparisons".

If you don’t understand that, try this paper.
The results are almost certainly false positives, despite the fact that it appeared in Lancet Neurology. It’s yet another example of broken peer review.

It’s been know for decades now that “antioxidant” is no more than a marketing term, There is no evidence of benefit and large doses can be harmful. This obviously doesn’t worry the College of Medicine.

Margaret Rayman was the next speaker. She’s a real nutritionist. Mixing the real with the crackpots is a standard bait and switch tactic.

Eleni Tsiompanou, came next. She runs yet another private "wellness" clinic, which makes all the usual exaggerated claims. She seems to have an obsession with Hippocrates (hint: medicine has moved on since then). Dr Eleni’s Joy Biscuits may or may not taste good, but their health-giving properties are make-believe.

Andrew Weil, from the University of Arizona
gave the keynote address. He’s described as "one of the world’s leading authorities on Nutrition and Health". That description alone is sufficient to show the fantasy land in which the College of Medicine exists. He’s a typical supplement salesman, presumably very rich. There is no excuse for not knowing about him. It was 1988 when Arnold Relman (who was editor of the New England Journal of Medicine) wrote A Trip to Stonesville: Some Notes on Andrew Weil, M.D..

“Like so many of the other gurus of alternative medicine, Weil is not bothered by logical contradictions in his argument, or encumbered by a need to search for objective evidence.”

This blog has mentioned his more recent activities, many times.

Alex Richardson, of Oxford Food and Behaviour Research (a charity, not part of the university) is an enthusiast for omega-3, a favourite of the supplement industry, She has published several papers that show little evidence of effectiveness. That looks entirely honest. On the other hand, their News section contains many links to the notorious supplement industry lobby site, Nutraingredients, one of the least reliable sources of information on the web (I get their newsletter, a constant source of hilarity and raised eyebrows). I find this worrying for someone who claims to be evidence-based. I’m told that her charity is funded largely by the supplement industry (though I can’t find any mention of that on the web site).

Stephen Devries was a new name to me. You can infer what he’s like from the fact that he has been endorsed byt Andrew Weil, and that his address is "Institute for Integrative Cardiology" ("Integrative" is the latest euphemism for quackery). Never trust any talk with a title that contains "The truth about". His was called "The scientific truth about fats and sugars," In a video, he claims that diet has been shown to reduce heart disease by 70%. which gives you a good idea of his ability to assess evidence. But the claim doubtless helps to sell his books.

Prof Tim Spector, of Kings College London, was next. As far as I know he’s a perfectly respectable scientist, albeit one with books to sell, But his talk is now online, and it was a bit like a born-again microbiome enthusiast. He seemed to be too impressed by the PREDIMED study, despite it’s statistical unsoundness, which was pointed out by Ioannidis. Little evidence was presented, though at least he was more sensible than the audience about the uselessness of multivitamin tablets.

Simon Mills talked on “Herbs and spices. Using Mother Nature’s pharmacy to maintain health and cure illness”. He’s a herbalist who has featured here many times. I can recommend especially his video about Hot and Cold herbs as a superb example of fantasy science.

Annie Anderson, is Professor of Public Health Nutrition and
Founder of the Scottish Cancer Prevention Network. She’s a respectable nutritionist and public health person, albeit with their customary disregard of problems of causality.

Patrick Holden is chair of the Sustainable Food Trust. He promotes "organic farming". Much though I dislike the cruelty of factory farms, the "organic" industry is largely a way of making food more expensive with no health benefits.

The Michael Pittilo 2016 Student Essay Prize was awarded after lunch. Pittilo has featured frequently on this blog as a result of his execrable promotion of quackery -see, in particular, A very bad report: gamma minus for the vice-chancellor.

Nutritional advice for patients with cancer. This discussion involved three people.
Professor Robert Thomas, Consultant Oncologist, Addenbrookes and Bedford Hospitals, Dr Clare Shaw, Consultant Dietitian, Royal Marsden Hospital and Dr Catherine Zollman, GP and Clinical Lead, Penny Brohn UK.

Robert Thomas came to my attention when I noticed that he, as a regular cancer consultant had spoken at a meeting of the quack charity, “YestoLife”. When I saw he was scheduled tp speak at another quack conference. After I’d written to him to point out the track records of some of the people at the meeting, he withdrew from one of them. See The exploitation of cancer patients is wicked. Carrot juice for lunch, then die destitute. The influence seems to have been temporary though. He continues to lend respectability to many dodgy meetings. He edits the Cancernet web site. This site lends credence to bizarre treatments like homeopathy and crystal healing. It used to sell hair mineral analysis, a well-known phony diagnostic method the main purpose of which is to sell you expensive “supplements”. They still sell the “Cancer Risk Nutritional Profile”. for £295.00, despite the fact that it provides no proven benefits.

Robert Thomas designed a food "supplement", Pomi-T: capsules that contain Pomegranate, Green tea, Broccoli and Curcumin. Oddly, he seems still to subscribe to the antioxidant myth. Even the supplement industry admits that that’s a lost cause, but that doesn’t stop its use in marketing. The one randomised trial of these pills for prostate cancer was inconclusive. Prostate Cancer UK says "We would not encourage any man with prostate cancer to start taking Pomi-T food supplements on the basis of this research". Nevertheless it’s promoted on Cancernet.co.uk and widely sold. The Pomi-T site boasts about the (inconclusive) trial, but says "Pomi-T® is not a medicinal product".

There was a cookery demonstration by Dale Pinnock "The medicinal chef" The programme does not tell us whether he made is signature dish "the Famous Flu Fighting Soup". Needless to say, there isn’t the slightest reason to believe that his soup has the slightest effect on flu.

In summary, the whole meeting was devoted to exaggerating vastly the effect of particular foods. It also acted as advertising for people with something to sell. Much of it was outright quackery, with a leavening of more respectable people, a standard part of the bait-and-switch methods used by all quacks in their attempts to make themselves sound respectable. I find it impossible to tell how much the participants actually believe what they say, and how much it’s a simple commercial drive.

The thing that really worries me is why someone like Phil Hammond supports this sort of thing by chairing their meetings (as he did for the "College of Medicine’s" direct predecessor, the Prince’s Foundation for Integrated Health. His defence of the NHS has made him something of a hero to me. He assured me that he’d asked people to stick to evidence. In that he clearly failed. I guess they must pay well.

Follow-up

Jump to follow-up

[This an update of a 2006 post on my old blog]

The New York Times (17 January 2006) published a beautiful spoof that illustrates only too clearly some of the bad practices that have developed in real science (as well as in quackery). It shows that competition, when taken to excess, leads to dishonesty.

More to the point, it shows that the public is well aware of the dishonesty that has resulted from the publish or perish culture, which has been inflicted on science by numbskull senior administrators (many of them scientists, or at least ex-scientists). Part of the blame must attach to "bibliometricians" who have armed administrators with simple-minded tools the usefulness is entirely unverified. Bibliometricians are truly the quacks of academia. They care little about evidence as long as they can sell the product.

The spoof also illustrates the folly of allowing the hegemony of a handful of glamour journals to hold scientists in thrall. This self-inflicted wound adds to the pressure to produce trendy novelties rather than solid long term work.

It also shows the only-too-frequent failure of peer review to detect problems.

The future lies on publication on the web, with post-publication peer review. It has been shown by sites like PubPeer that anonymous post-publication review can work very well indeed. This would be far cheaper, and a good deal better than the present extortion practised on universities by publishers. All it needs is for a few more eminent people like mathematician Tim Gowers to speak out (see Elsevier – my part in its downfall).

Recent Nobel-prizewinner Randy Schekman has helped with his recent declaration that "his lab will no longer send papers to Nature, Cell and Science as they distort scientific process"

The spoof is based on the fraudulent papers by Korean cloner, Woo Suk Hwang, which were published in Science, in 2005.  As well as the original fraud, this sad episode exposed the practice of ‘guest authorship’, putting your name on a paper when you have done little or no work, and cannot vouch for the results.  The last (‘senior’) author on the 2005 paper, was Gerald Schatten, Director of the Pittsburgh Development Center. It turns out that Schatten had not seen any of the original data and had contributed very little to the paper, beyond lobbying  Scienceto accept it. A University of Pittsburgh panel declared Schatten guilty of “research misbehavior”, though he was, amazingly, exonerated of “research misconduct”. He still has his job. Click here for an interesting commentary.

The New York Times carried a mock editorial to introduce the spoof..

One Last Question: Who Did the Work?

By NICHOLAS WADE

In the wake of the two fraudulent articles on embryonic stem cells published in Science by the South Korean researcher Hwang Woo Suk, Donald Kennedy, the journal’s editor, said last week that he would consider adding new requirements that authors “detail their specific contributions to the research submitted,” and sign statements that they agree with the conclusions of their article.

A statement of authors’ contributions has long been championed by Drummond Rennie, deputy editor of The Journal of the American Medical Association,
and is already required by that and other medical journals. But as innocuous as Science‘s proposed procedures may seem, they could seriously subvert some traditional scientific practices, such as honorary authorship.

Explicit statements about the conclusions could bring to light many reservations that individual authors would not otherwise think worth mentioning. The article shown [below] from a future issue of the Journal of imaginary Genomics, annotated in the manner required by Science‘s proposed reforms, has been released ahead of its embargo date.

The old-fashioned typography makes it obvious that the spoof is intended to mock a paper in Science.

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The problem with this spoof is its only too accurate description of what can happen at the worst end of science.

Something must be done if we are to justify the money we get and and we are to retain the confidence of the public

My suggestions are as follows

  • Nature Science and Cell should become news magazines only. Their glamour value distorts science and encourages dishonesty
  • All print journals are outdated. We need cheap publishing on the web, with open access and post-publication peer review. The old publishers would go the same way as the handloom weavers. Their time has past.
  • Publish or perish has proved counterproductive. You’d get better science if you didn’t have any performance management at all. All that’s needed is peer review of grant applications.
  • It’s better to have many small grants than fewer big ones. The ‘celebrity scientist’, running a huge group funded by many grants has not worked well. It’s led to poor mentoring and exploitation of junior scientists.
  • There is a good case for limiting the number of original papers that an individual can publish per year, and/or total grant funding. Fewer but more complete papers would benefit everyone.
  • Everyone should read, learn and inwardly digest Peter Lawrence’s The Mismeasurement of Science.

Follow-up

3 January 2014.

Yet another good example of hype was in the news. “Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease“. It was published in the Journal of the American Medical Association. The study hit the newspapers on January 1st with headlines like Vitamin E may slow Alzheimer’s Disease (see the excellent analyis by Gary Schwitzer). The supplement industry was ecstatic. But the paper was behind a paywall. It’s unlikely that many of the tweeters (or journalists) had actually read it.

The trial was a well-designed randomised controlled trial that compared four treatments: placebo, vitamin E, memantine and Vitamin E + memantine.

Reading the paper gives a rather different impression from the press release. Look at the pre-specified primary outcome of the trial.

1ry utcome

The primary outcome measure was

" . . the Alzheimer’s Disease Cooperative Study/Activities of Daily Living (ADCSADL) Inventory.12 The ADCS-ADL Inventory is designed to assess functional abilities to perform activities of daily living in Alzheimer patients with a broad range of dementia severity. The total score ranges from 0 to 78 with lower scores indicating worse function."

It looks as though any difference that might exist between the four treaments is trivial in size. In fact the mean difference between Vitamin E and placebos was only 3.15 (on a 78 point scale) with 95% confidence limits from 0.9 to 5.4. This gave a modest P = 0.03 (when properly corrected for multiple comparisons), a result that will impress only those people who regard P = 0.05 as a sort of magic number. Since the mean effect is so trivial in size that it doesn’t really matter if the effect is real anyway.

It is not mentioned in the coverage that none of the four secondary outcomes achieved even a modest P = 0.05 There was no detectable effect of Vitamin E on

  • Mean annual rate of cognitive decline (Alzheimer Disease Assessment Scale–Cognitive Subscale)
  • Mean annual rate of cognitive decline (Mini-Mental State Examination)
  • Mean annual rate of increased symptoms
  • Mean annual rate of increased caregiver time,

The only graph that appeared to show much effect was The Dependence Scale. This scale

“assesses 6 levels of functional dependence. Time to event is the time to loss of 1 dependence level (increase in dependence). We used an interval-censored model assuming a Weibull distribution because the time of the event was known only at the end of a discrete interval of time (every 6 months).”

It’s presented as a survival (Kaplan-Meier) plot. And it is this somewhat obscure secondary outcome that was used by the Journal of the American Medical Assocciation for its publicity.

JAMA

Note also that memantine + Vitamin E was indistinguishable from placebo. There are two ways to explain this: either Vitamin E has no effect, or memantine is an antagonist of Vitamin E. There are no data on the latter, but it’s certainly implausible.

The trial used a high dose of Vitamin E (2000 IU/day). No toxic effects of Vitamin E were reported, though a 2005 meta-analysis concluded that doses greater than 400 IU/d "may increase all-cause mortality and should be avoided".

In my opinion, the outcome of this trial should have been something like “Vitamin E has, at most, trivial effects on the progress of Alzheimer’s disease”.

Both the journal and the authors are guilty of disgraceful hype. This continual raising of false hopes does nothing to help patients. But it does damage the reputation of the journal and of the authors.

This paper constitutes yet another failure of altmetrics. (see more examples on this blog). Not surprisingly, given the title, It was retweeted widely, but utterly uncritically. Bad science was promoted. And JAMA must take much of the blame for publishing it and promoting it.

altm

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.