Professor Patrick Holford of Teesside University and Head of Science and Education at Biocare has been out and about in the mainstream media, providing the industry response to the Cochrane Review of Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases (pdf). In this, he was joined by assorted other representatives of the supplement industry in an interesting example of manufactroversy or an artificially contrived controversy. Bertrand Russell wrote:
A stupid man’s report of what a clever man says can never be accurate, because he unconsciously translates what he hears into something he can understand.
A disappointing amount of the criticism reflected Russell.[1] Various critics implied that the Cochrane reviewers had been wrong to exclude various studies although the reviewers had followed a transparent, well-specified process and explained their reasoning within the review. They seem to have been criticised for only selecting trials that contained mortality data although mortality was the topic of the review.
Oddly, the reviewers were also responsible for all of the calculations and findings that industry critics accused them of distorting or overlooking. When discussing these findings, the industry spokespeople were careful to ignore the findings that even when you gather together all of the trials, and include those with poor methodology, the results indicate that the vitamins do not show any positive benefit for reducing mortality; the best that can be said is that there is no evidence of harm (the status of selenium is equivocal as the studies that reported reduced mortality were at high risk of bias influencing the outcome).
However, not withstanding the Russell-like misinterpretations, there seemed to be some concerted and purposeful strategy of confusion. Using tactics that are reminiscient of those used by Big Tobacco,[2] the critics were uncritically allowed to muddy the waters as to the quality of the review and were rarely challenged to specify a worked-out and substantiated specific criticism. Amidst the disinformation about the number of participants and the trials included or excluded in various analyses, the critics seemed to have overlooked the reviewers’ helpful elaborations.
More than two thirds of the included trials with more than 180,000 participants fall in the group of low bias risk trials. This highlights the validity of our results…Our estimates of increased mortality in low-bias risk trials increased significantly when we excluded factorial trials as well as other trials with collateral interventions. These trials may all suffer from potential confounding from the collateral interventions. This highlights the potential dramatic public health consequences of our results.
A large number of unpublished trials on supplements may exist. Their results are more likely to have been either neutral or negative than to have shown beneficial effects…Accordingly, our estimates of increased mortality are likely to be conservative. [pg. 10 document; pg. 13 pdf. Emphasis added]
It is all the more remarkable when one considers that one of the most ubiquitous industry spokespeople was Patrick Holford. During the extended coverage on Radio 5, it seems as if Holford criticised the Cochrane Review while solemnly, and with no apparent sense of irony, offering his own anecdote of the benefits of supplements; a short-term ‘study’ with two participants that relied upon self-report. You can not parody this because it defies exaggeration.
Kruger and Dunning explain why it might be too much to expect Holford to form an appropriate assessment of his own level of comparative competence.[3]
Sarah Bosely has put together an overview of the vitamin pill industry faux outrage over the Cochrane Review. She acknowledges the expertise of the Cochrane reviewers and drily observes:
[their] findings have been met with howls of protest from the vitamin and health-food lobby who make a living by promoting supplements. Their denials are likely to give comfort to the large numbers of people who want to think vitamins make them healthier.
Her concluding paragraph is rather miserable but probably more accurate than I care to admit.
And so the debate goes on, with large numbers of people convinced a bit more of what is good for you can’t do you any harm and scientists using methodological techniques that only scientists understand to prove them wrong – only to be disbelieved. In the end, maybe the safest thing is just to eat a better diet.
My outstanding and unanswered question is whether it is possible to have a debate if one side refuses to try and understand why the stats of the other side make sense and constitute a fair test? Along with other industry spokespeople, Holford might have embraced an opportunity to educate the public on the merits of this form of systematic review and the importance of its findings for public health. They might have discussed their plans to upgrade their own education for clients and practitioners. However, none of this happened. Instead, the industry commenters seemed to refuse to accept the demonstrable merits of a systematic review in favour of their own interpretation of it. Beyond this, some of the commenters appeared to question the competence and independence of the Cochrane reviewers although the grounds for this were never made clear.
Yet again, is this an example of what Professor Holford will be teaching to the impressionable minds of students at the University of Teesside? Contriving a controversy and passing it off as informed criticism? Proferring an anecdote in preference to a systematic review that follows careful, agreed, and well-specified procedures?
Update: Added reference to Big Tobacco’s strategy of Doubt is their product and manufactured uncertainty.
Update 2: Effectively, the systematic review process is geared towards evaluating whether or not a particular study was a ‘fair test’. One of the best explanations of ‘fair tests’ is Evans, Thornton and Chalmers’ Testing Treatments (available for free download). We strongly recommend this generalist and entertaining book to interested parties as it explains all the ins-and-outs of what makes a fair test and the fair way in which to interpret the results.
Update 3 (18 April): We should hush our mouths because the celebrities have spoken.
Sir Cliff Richard, Gloria Hunniford, Jenny Seagrove and Carole Caplin have joined health industry experts in rejecting the widely publicised antioxidant review and reassuring consumers that concerns over these supplements are unfounded.
So, that should be that then. What do you mean they’re speaking a load of nonsense about the number of trials and that they are obviously reading someone else’s crib notes rather than read the paper for themselves?
Update 27 April: A Holford canard about the excluded studies is gaining surprising popularity: Are supplements harmful?
In this review, which is a rehash of their paper published last year in the Journal of American Medical Association (JAMA), they first excluded over 400 trials, many of which had positive outcomes, but had no deaths. They then decided which trials they liked (low risk bias) and did not like (high risk bias), a factor that has received criticism in mainstream medical journals
We responded earlier and a very patient Professor Gluud corrected Holford in the course of a Radio 5 item.
Essentially, Bjelakovic et al discuss their exclusion of 405 trials. These trials involved 40,000 participants: they were mostly small Phase I or II trials and short-term with little or no follow-up and no clinical outcome measures (pg. 8 (pdf), pg. 5 document). Bjelakovic et al contacted all of the authors to enquire whether there were any deaths. Around 20% of the authors replied and reported that there were no deaths in either arm of their studies. The authors did not exclude studies that were positive for the supplement arm but negative for the placebo or control arm.
Several people have expressed concern that eliminating the 405 studies “create[s] a bias in which the therapy on trial appears to be associated with deaths?”. However, these trials were, as the authors described above and only involved 40,000 rather than the 232,550 participants in the 67 trials that were assessed: 164,439 of these participants were healthy. You can read about the characteristics of the excluded studies in the review (pp. 118-42 (pdf), pg. 115-39 document).
The authors did take account of the 405 trials by performing a sensitivity analysis.
Therefore we performed exploratory analyses adding an imagined trial with 1 death and 20000 participants in each intervention group. The influence of zero events trials on our final result was not noticeable.
Their findings didn’t change.
Notes
[1] Some of the criticism might be more thoughtful but not as reported to date. Both selective7 and Woobegone direct our attention to Bernadine Healy’s remarks about the 2007 JAMA review. She mischaracterises the reviewers’ careful work as “blenderizing” and this has been adopted by others who have use it as a glib dismissal without explaining it further. And without explaining why such a criticism is sufficient grounds to dismiss the findings of this review.
Oddly enough, one of the recurrent criticisms of this review is that it concentrated on randomised controlled trials and did not include observational studies. There are some commenters such as Truswell who question whether the Cochrane Review process is appropriate for assessing what are essentially observational and cohort studies. These are legitimate issues that are soberly and thoughtfully discussed. On the other hand, we have Holford and other industry spokespeople, criticising the authors on the basis of their understanding or interpretation of this review.
[2] The Paranoid Style in American Science: Doubt is their product. Daniel Engber discusses Big Tobacco’s skilful use of the corporate strategy of “manufactured uncertainty” to deny that “scientific evidence has ever been produced, presented or submitted to prove conclusively that cigarette smoking causes cancer”.
[3] You may be interested to read an overview of the Justin Kruger and David Dunning paper that discusses how difficulties in understanding one’s own incompetence can lead to inflated self-assessments.
What’s even more amazing is that when they then shared the performance of other participants with the people who performed poorly (hoping that they would then adjust their self-perception downward) people who scored poorly failed to adjust their self-perception of their performance. In other words, they are completely unaware of their own [in]competence, and can’t detect competence in others.
It really it a very helpful paper that explains many otherwise inexplicable actions.
A Photon in the Darkness likewise offers a helpful discussion of this paper: The Arrogance of Ignorance
People taking a cocktail of drugs are, presumably, extremely ill so it is hardly surprising many of them die.
Perhaps we could do an experiment to see whether – as Patrick Holford – puts it “food is better medicine than drugs.” We take several thousand people taking drugs for managing chronic conditions. Half of them stop taking their medication for eighteen months and start eating copious amounts of Holford endorsed super foods and supplements. The other half continue following the advice of their doctor.
Any volunteers?
The only reason these people are ill in the first place is because the are in a state of imbalance. Doctors drugs never have and never will correct any of these imbalances. What do you think a chronic condition is Lee. Have they reached that stage of health because they are defeicient in some sort of drug. I dont think so
*cough* – Type 1 diabetes is chronic; while it can not be cured at present (albeit some interesting therapies are under investigation), it can be managed.
What do you mean that people become ill through “a state of imbalance”?
What is this cough thing you arrogant [edited for obscenity]?
By chronic i am refering to long term health conditions which the majority are not gentic and cannot be sorted out by drugs.
Is type 1 diabetes not an imbalance? There was me thinking that insulin is not produced, thus there is an imbalance of insulin production, blood sugar, glucose in cells etc etc.Note this is a hormone not a drug
You will not find holford reccomending anyone coming of insulin for type 1 D.
The majority of chronic complaints that drugs are prescribed for are also just imbalances that do not need drugs
throw up some complaints and i will explain
You have amply demonstrated your ability to sustain a decent argument, Teel. I would imagine that you explanations would be on a similar level. I, for one, shall resist your invitation to “throw up”.
As someone pithily expressed the matter,
“I have an inherent dislike of the sewer and the language it produces, I can only doff my cap in admiration at your existence in such a place, which you obviously feel so at home in”.
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“Note this is a hormone not a drug”
insulin, is ineed, a hormone (and knowing this is part of the GCSE science syllabus).
Teel, would you consider insulin, as prepared and sold for injection by, say Novo Nordisk (a big farmer supplier of insulin listed in the BNF) a drug?
“You will not find holford reccomending anyone coming of insulin for type 1 D.”
No, but you will find him flogging cinnamon and chromium for type ii diabetes. Perhaps HW can provide a link to the predicatable consequences of Professor Holford going toe-to-toe on GMTV with someone with a meaningful science qualification.
Would that be the entertaining Dr Sarah Jarvis?
I suppose one might describe illness as an unbalanced state. Death, for me at least, would be totally unbalanced. No one of sound mind is ever forced to take prescription drugs. If you don’t want to that is up to you and, ultimately, no one is going to force you to.
Have to confess to never having read Mr Holford’s “Food is Better Medicine” than drugs. Is there anyone out there who could explain it to me to save me the trouble of having to read it?
You lot seem to be obsessed with a short clip of a doctor who is denying that holford has completely reversed her type 2 d.
Although holford looks like a smug [edited] he has got the result.
This is an example of where drugs are not needed yet prescribed. Again just a breakdown in homeostasis like every other illness symptom disease due to environment.
Hence change the cellular environment which you cannot do with drugs.
Isn’t it the case that if diabetes is diagnosed early enough blood sugar levels can often be managed without the need for drugs? Could this possibly be the case with the woman Mr Holford paraded on GMTV making it a bit dishonest for his supporters to claim he has reversed her diabetes?
The major problem, as I understand it, is that many people go for years without having their diabetes diagnosed. Can Mr Holford cure them as well?
Fear not the path of truth
for the lack of people walking on it.
Yes Diabetes can be prevented and treated without the need for drugs (except for once you are on insulin there is no turning back unfortunately). Have you looked into the potentials of grapefruit for one example? I doubt it…
They have been using it in India for the last thousand years, now theres a trial for you.
Oh and LeeT the thing that jumped out at me most from the article that you posted about Holford and his funding is that the lawyers of the parents of the afflicted children are so convinced about Holfords argument they are prepared to put their money where their mouth is………
and what is this massive misconception that supplements, herbs etc have not been ‘clinically tried’
They have been on trial ever since they were first began to be discovered in 1905, check out the American Journal of Medical science if you want some clinical trials on supplements (I know you like that sort of publication)
And herbs, herbs………
Now they have been tested and tried for thousands of years just try and say that they haven’t and you will just unveil your purposeful ignorance.
Together, Hopkins and Funk formulated the vitamin hypothesis of deficiency disease – that a lack of vitamins could make you sick.
The food the majority of people eat in the Western world is deficient in vitamins and minerals due to modern farming methods, junk foods etc. This is the argument for supplements and people like Holford.
Modern medicine wants to put a plaster on the problem in the form of inadequate drugs that cause damage to other areas of the body. Nutritionalists such as Holford look for the cause….
Nice work Teel, except no need to operate on their level (swearing etc) although tempting I know
Diabetes can’t be cured nutritionally you people are so myopic.
Sorry been busy hope you didn’t miss me too much
Dominutrix
Do you really have no idea about how a state of imbalance can make you ill really?
I do hope you are not a practicing doctor because you clearly do not have a clue
Teel
sorry just read your book recommendation sounds really interesting thanks for the tip :0)
and to the group of people who think nature is bad for your health…
Would anyone be up for a discussion about the bad science behind coke putting vitamins and antioxidants in their caffeinated drink.
I’ll kick it off
It is a fact that caffeine interfears with the bodies absorption of vitamins:
‘Caffeine has a diuretic action and causes nutrient depletion of several important nutrients vital for optimum psychological health, like vitamin B6. The tannin interferes with nutrient absorption of essential minerals including calcium, iron and magnesium and B group vitamins’
1. Bruce M.S. et al (1989) Caffeine Abstension in the Management of Anxiety Disorders, Psychol. Med. 19 pp 211 – 214, mentioned in Snaith P. (1991) Clinical Neurosis, 2nd edition, Oxford Medical Publications.
Now this is terrible misconduct and misinformation on a grand scale, it is making a sadly unaware public believe they are getting their vitally needed vitamins where in fact they are depleteing their nutrients.
and you want to attack Holford ever even considered that you were barking up the wrong tree here…………………………………………..
Oh and vampires of the chemical abyss have you ever tried to think independently instead of being fed all this nonsense?
It might be a bit painful at first but you do get used to it and it really is quite liberating.
Don’t turn your backs on what has sustained the human race for thousands of years thinking pharms with their short and troubled history of trials and misadventure is the solution.
Its you that has got it wrong and back to fount.
Noticed none of you picked me up on the aspartame I wonder why……
Isnt it obvious that the bodies job (or the cells that makes us) is to keep every thing in balance. Thats all it does.
It does this by our cells communicating with each other via binding of membrane receptors, changing of gene expression and working of the cell according to need.
The working of the cell (and the whole organism) is then reliant on the environement outside the cell. If the environemt is disrupted and the wrong receptors are being frequently engaged, then gene expression and the working of the cell will be disrupted. There is then an imbalance of secretions of proteins that inturn will engage other protein receptors.
An inflammatory mediator viscous cycle is agreat example of this. Cytokine sickness syndrome or the NO/ONOO cycle.
Anyway the point to this is that illness comes from imbalance of engagement of protein rececptors and gene expression. Drugs that you seem to think are so important will only add to the wrong cellular environment. Lets try and put our cells (That are more intelligent than the organism it creates) back in the environment it recognises.
koo, you really are remarkably deluded.
Type 1 (classic “insulin dependent” diabetics) have to take insulin. Otherwise they die. Full stop.
In Type 1 the insulin-producing cells (pancreatic Beta cells) have been destroyed. Type 1 is typically not detected until more than 90% of these cells are gone, because that is the point where blood glucose starts to rise (hyperglycaemia). Therapy for type 1 almost always means replacing insulin by injections.
Before injectable insulin was developed (in the 1920s and 1930s) type 1 diabetes – which mostly happens young – was universally FATAL before people reached their late teens. They had to starve themselves to anorexic proportions even to make it that far. You can look it up.
Type 2 diabetes is different, as it is not caused by insulin lack per se (like type 1) – it is caused by the body’s systems being or becoming “insensitive” to what insulin is there. This causes the body to “push” insulin release (increase it). Eventually this usually means insulin production cannot cope with demand, at which point the people need treatment because otherwise they get dangerously hyperglycaemic.
Mild and/or early stage type 2 diabetes can sometimes be treated by dietary control, and especially by losing weight (the majority of type 2 patients are overweight). People are typically told to exercise more and watch their food to try and drop some weight, as even 7-10 pounds can make a big difference. However, sadly many people find it difficult or impossible to lose the weight. If they can’t achieve decent blood glucose control this way then they need drugs. The drugs may include insulin if the body is not managing to produce enough to meet the increased demand.
There are, it goes without saying, NO “magic foodstuffs” which will fix type 2 diabetes. Another Alt Health urban legend. It is largely a matter of a “sensible balanced diet” (again) – all that stuff like “Eat regular meals, reduce high sugar foods and eat less fat, five portions of fruit and veg a day, less salt, moderate drinking”. All, it goes without saying, mainstream dietary advice you get from nurses, doctors, dietitians etc etc.
Anyway, if you think eating grapefruit is going to make a difference to diabetes, you are a nutjob (but we knew that anyway). Eating grapefruit can, however, interact with various prescription drugs in ways that can be quite dangerous. These drugs include statins (for treating high cholesterol) and some anti-high blood pressure drugs. Anyone taking these medications should avoid grapefruit like the plague.
Because, as ever, every sensible person is aware that the aspartame scare has been exploded long ago except for conspiracy theorists with a diploma from Google U.
Are either of you ever going to come up with references for the majority of your assertions?
And, a paper from 1989, you really need to update your ‘knowledge’. Even newspapers know that caffeine really isn’t a powerful diuretic for most people as it was thought to be. Doesn’t mean that this negates the pharmacalogical effect of caffeine on someone with a nervous disorder or anxiety but, really, not that powerful a diuretic.
Teel, I think some of the issue is, normally, when commenters like you start talking about ‘imbalance’, you normally turn into ‘germ-theory deniers’. tbh – that’s the way that I thought you were going. I was waiting for the whole Beauchamp-Pasteur schtick.
However, looking at your other stuff, such as, “change the cellular environment which you cannot do with drugs”, it looks like new schtick is similar to other schtick.
“Cytokine sickness syndrome” – almost, but not quite, had a Googlewhack, but Teel’s comment was one of only 2 internet uses. It doesn’t appear in the whole of PubMed, and there was only 1, unhelpful, reference in Google Scholar which was concerned with IL-6 – however, it points to a couple of other references.
Having broadened the search, doesn’t really seem germane to a discussion of manufacturing controversy about the Cochrane review of antioxidant supplements.