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This is a follow-up of the poat on BBC2 and the Open University on Alternative Medicine.

Following the article by Simon Singh in the Guardian (25 March 2006), two letters appeared on April 1, 2006. The first, from Prof. Edzard Ernst, confirmed that he felt the BBC had ignored and misrepresented his advice.

 In its response to our criticism of the Alternative Medicine series, the BBC says “it is extremely unusual that Professor Ernst should make these comments so long after the series was aired” (Report, March 25). I made my criticism in writing two months before the programme was broadcast. The reason why I reiterated them when I did was simply because Simon Singh interviewed me in my capacity as adviser to the BBC. Extremely unusual? Long after? I don’t think so.
Prof Edzard Ernst
Peninsula Medical School, Exeter

The second letter defended the BBC. It was unequivocal in its support of the entire series of programmes, and its appearence surprised me.  In the light of all that has been written, one might have hoped that the BBC would listen and learn from its mistakes. The letter has ten signatories.

We are all scientists involved as consultants or contributors to the BBC2 series, Alternative Medicine. We do not in any way recognise the experience of working on the series as described in your article (Was this proof of acupuncture’s power … or a sensationalised TV stunt?, Science, March 25), nor do we share the views of those scientists you have quoted in it. In all its dealings with us, the BBC asked for advice and input where needed, took on board our feedback and incorporated our comments into the final edit of the programme as transmitted, where appropriate. Far from feeling dissatisfied with the final outcome, we feel the series seemed well balanced and informative, doing full justice to the subject matter it addressed.

Dr Jack Tinker
Royal Society of Medicine

Prof Brian Berman
University of Maryland

Prof Liz Williamson
Reading University

Dr Andrew Vickers
Memorial Sloane-Kettering Cancer Center, New York

Dr James Warner
Imperial College London

Dr Mike Cummings
British Medical Acupuncture Society

Prof Gary Green
York University

Dr Carl Albrecht
University of Johannesburg

Dr Jen Cleland
University of Aberdeen

Professor Irving Kirsch
University of Plymouth

But all is not what it seems. Contrary to appearances, this letter was actually written by the BBC who also compiled the signatories (it seems to have been the responsibility of Kim Creed, of BBC Factual Publicity).

    • One of the signatories. Dr James Warner, had never seen the letter until after it was published, and tells me that “[I] substantially do not agree with the sentiments expressed therein. Indeed, we had to resist attempts by the programme makers to sensationalise our work”.
      The Guardian has published a correction.
  • Six other signatories tell me that their approval was limited to the way their own contribution was treated, and was not intended as approval of the whole series. One commented ” I’ve obviously been naïve, and I am very fed up with this whole thing”. Another says ” I suppose I (foolishly by the sounds of things) extrapolated from my own programme and experience, without considering the wider implications of the concluding sentence”.
  • Only one of the eight signatories whom I’ve asked has actually seen all three programmes, as they were transmitted. This makes it rather odd that they should appear to endorse so unequivocally the whole series.
  • One of the signatories, Carl Albrecht, gives his address as “University of Johannesburg”, but oddly the BBC forgot to mention that Dr Albrecht is co-owner (at least until very recently) of the South African Company, Phyto Nova, that makes, promotes and sells the untested herb, Sutherlandia, for treatment of AIDS (see, for example, here).
    He is, therefore, highly biassed. He is also exceedingly controversial. One of his strongest critics has been Stuart Thomson, Director of the Gaia Research Institute,
    hardly an organisation that is biassed against “natural medicines”. Albrecht is indeed a very curious choice of advisor for a programme about science.
  • Three of the signatories (Berman, Cummings and Albrecht) are heavily committed to CAM, and so unlikely to be critical of anything that favours it, even apart from financial interests in the outcome. Brian Berman even has is own an entry in Quackwatch. So several of the signatories are pretty much committed in advance. Asking them if they endorse the programmes is about as informative as asking a group of priests if the endorse god.
  • It gets worse. This morning, 6th April, I heard from Andrew Vickers, of the Memorial Sloan-Kettering Cancer Center, New York. This is what he says.

    “I didn’t sign this letter ”
    “I was shown the text of the letter but didn’t fully agree with it and told them so. I said something along the lines that the series didn’t do ‘full justice to the subject matter’ (how could it possibly?) but that what they did was fair and reasonable within the constraints set by the medium. You are also right to point out that my comments only go so far as the acupuncture episodes (which I saw) rather than the other two shows (which I did not). No doubt had I been shown a final version for signature I would have also pointed this out.”

The BBC brought us superb programmes like Life on Earth and Planet Earth.  They bring us superb news (I’m listening to the incomparable John Humphrys on the Today Programme right now). They have suffered unjustly at the hands of spin-meisters like Alastair Campbell and the execrable Hutton Report (If the Hutton Report had been an undergraduate essay, it would have scored alpha-plus for collection of evidence and gamma-minus for ability to connect evidence to conclusions).

How ironic it is, then, to see the BBC behaving in this case like spin artists.  Deny everything, and, if necessary, falsify the evidence.

Jump to Open University course K221

Jump to follow-up

BBC2 TV showed a much-advertised series on alternative medicine, in February 2006. The programmes seem to be linked with a dubious Open University course.

The programmes are presented by Kathy Sykes, who is professor of the public understanding of science at Bristol University. She has done some excellent work in that area, for example, in the Rough Science TV series.

The first programme: acupuncture

The first programme, on acupuncture, was shown on 24th January, 2006. The programme did not start
in a very promising way. Just lots of testimonials from happy patients, the staple diet of all snake oil salesmen.
They are watchable, of course, but don’t do anything at all to promote public understanding of what constitutes evidence.

There is, of course, little doubt that sticking needles into your body can produce physiological responses. Two things remain uncertain.

  • Just how useful are these responses in helping particular conditions?
  • Is there anything at all in the mumbo jumbo of meridians and chi?.

With a big flourish we were shown “a 21-year-old Shanghai factory worker undergoing open-heart surgery with only the needles to control her pain”. It turns out that this was a sham. The patient was doped on opiates and local anaesthetics. The needles were merely cosmetic. Why were we not told?

The apparently contradictory trials suggested that, at least the alleged principles of acupuncture are nonsense. The programme concentrated on a trial by Berman (Ann Intern Med. 2004,
141, 901-10 ) which used ‘sham acupuncture’, with ‘stage dagger needles’, on osteoarthritis of the knees. In this sort of trial there is no actual penetration, and the sham needles are placed on the places dictated by the mumbo jumbo. This procedure was justly criticised by a subsequent letters in the same journal (Ann
Intern Med
2005, 142, 871

Another large study was ignored by the TV programme altogether. This was by Linde et al. (Journal of the American Medical Association. 2005 293(17):2118-25). This study concluded

“Acupuncture was no more effective than sham acupuncture in reducing migraine headaches although both interventions were more effective than a waiting list control.”

As pointed out above, this study is, in many ways, much more interesting than Berman’s, because the control group did not have ‘sham acupuncture’. Needles were really inserted, but they were inserted in points that have nothing to do with the mumbo jumbo of meridians. The fact that the controls were much the same as the treated group suggests that, whatever effect the needles produce, it doesn’t matter much where they are inserted. The only obvious interpretation of this is that the ‘principles’ on which acupuncture is based are so much nonsense (and, therefore, it is not a subject that can possibly be taught in a university).

This crucial point was ignored by the TV programme. A big fuss was made of a functional magnetic resonance experiment, staged for TV, that showed that the effects on brain ‘activation’ are different for superficial needling and for real needling. There is nothing in the least surprising in the observation that have a needle pushed into you affects the brain, but it really does not help at all in answering the important questions. Incidentally that experiment had already been done anyway.

In summary, the first programme, failed to give a fair assessment of current knowledge about acupuncture, and failed to consider the important questions of what sort of controls are appropriate, and whether talk of meridians means anything whatsoever. Sadly, I can’t agree with the boast that “It’s the deepest investigation into the efficacy of alternative medicine ever attempted on TV”.  Let’s hope the second programme is a bit more critical.

The second programme: healing

The second programme (31st January, 2006). I liked this programme much better than the first, even if it left the crucial questions unresolved.

The programme started with a healing meeting by the notorious Benny Hinn.  The meeting had all the mass hysteria of a Nuremburg rally, though no mention was made of the fact that this (very rich) man’s financial malpractice had been revealed by a CBC TV programme.

On the right is his receipt for £3347 for two nights at the Lanesborough hotel in London (that did not include $1700 he gave in tips).

The lovely Ghanaian lady who cleans my office and lab every morning gives gives money to this mega-rich man because “he needs it to preach the gospel”.

The National Institutes of Health provided $1.8 m of US taxpayers’ money for this project which seems not to do real research at all. After seeing a demonstration of the “Gas Discharge Visualization”, GDV, or Kirlian camera, given by a very gullible Dr Melinda Connor, Sykes comments that this ‘research’ “is not so much trying to find the evidence for ‘healing energy’,  but is rather working on the basis that there is one”

Kathy Sykes did, though show a pretty healthy degree of scepticism about the people who pretend to photograph “auras” and other imaginary “force fields”. She visited the “Center for Frontier Medicine in Biofield Science” at the University of Arizona.

In other words, the ‘research’ is a con. Once again (see above) we see money given by well-intentioned governments diverted form the purpose for which it was given.  For more first class boloney on ‘imaging’, see for example, Biofield Sciences in Exeter (UK)  and ‘electro-crystal therapy’.  The list is endless.

Kathy Sykes went on to show several interesting experiments on placebo effects. For example sham healers (played by actors) do at least as well as ‘real’ healers.  And sham knee surgery may be as effective as real surgery, though the programme failed to mention the obvious possibility that this could mean nothing more than that real knee surgery is itself pretty ineffective.  As so often in this series, the producers failed to talk to the right people.

She concludes “healing does not work beyond placebo”.

So I’m right with her, though it would have been better if there had been a more critical mention of the fact that not all placebo effects are real.  Many probably depend on the natural fluctuations in the intensity of the patient’s condition.  Anything can ‘cure a cold’, because you recover from a cold in a few days anyway,

Sykes concludes, speaking of the placebo effect, “I want to see that power properly harnessed -we’d be mad not to”.  But that, disappointingly, was the end of the programme.  That point is where the problems begin.  How do you harness the placebo effect?  How do you justify lying to the patient in order to maximize the effect?  How do you train the ‘healers’? Are they themselves to believe the same lies, or are they to be trained in the art of deception?  As pointed out in a recent review of the neurobiology of placebos (Colloca and Benedetti, 2005)

“For example, the assertion that placebos, fake therapies, fresh water and sugar pills could  positively affect the brain biochemistry in the appropriate psychosocial context might lead to a dangerous justification for deception, lying and quackery”.

These are the central dilemmas of sCAM, as listed at the top of this page. The programme did nothing to solve them, or even to draw attention to them.

The link with Open University Course K221

The blurb on this programme on the Open University/BBC site concludes

“So, could the power of the mind explain the benefits people experience from healers? And have healers tapped into this power somehow? The conclusion throws new light on all healing processes, and has a surprising and inspirational message for every practitioner and patient.”

But what is to be done about this “inspiration”? Nothing is said about that.  The TV programme was immediately followed by voice-over that advertised an Open University pamphlet, which is publicity for their course K221. That course, judging from what is posted on the web, is run by true believers who are a lot less sceptical than Sykes. She says that she did the voice-over but has not yet been shown the contents of the course.

The third programme: herbalism

Oooh dear. The third programme was, in my view, by far the worst.  Hardly a single critical voice was heard. Despite the odd word of reservation,  the programme left the impression of being an advertisement for the herbal medicine industry. Did the BBC not think of asking a pharmacologist?  In my view, this programme was a disservice to human knowledge.  Let’s look at some of the details.

The programme once again starts with dramatic testimonials from satisfied customers. No hint is given to the viewer of the total unreliability of such testimonials. References, in awed voice, are mad to “a vast body of ancient knowledge that herbalists draw on”.  No mention of the superb track record that ‘ancient knowledge’ has for turning out to being dead wrong.  It was 11 minutes into the programme before the question of evidence was even mentioned and then we had a herbalist wandering through a field. At 13 minutes, the herbalist, Simon Mills, was interviewed -he rattled on about dampness. marshy conditions. “There
are herbs for heating and drying”. Sheer gobbledygook. And still no discussion of evidence.

Sutherlandia At 18 minutes “To get another view I’m going to a country where herbs are claimed to have dramatic effects”. Off to Africa to spend a good 10 minutes on Sutherlandia, a totally unverified treatment for AIDS.  Why spend all this time (and licence-payers money) to end up with the conclusion that clinical trials have
not been done yet, and we have no real idea whether it works or not?  A search of Pubmed for Sutherlandia and AIDS produces a mere five papers.  Mills et al. Nutrition Journal 2005, 4:19 write as follows.

“Despite the popularity of their use and the support of Ministries of Health and NGOs in some  African countries, no clinical trials of efficacy exist, and low-level evidence of harm identifies the potential for drug interactions with antiretroviral drugs.”

(and one of the authors on that paper is from the Canadian College of Naturopathic Medicine: hardly likely to have a bias against herbs). The comments made in the programme about AIDS were irresponsible and potentially dangerous:  they could kill people..

It took until almost half way through the programme, before we got round to the question of whether any of these claims are true. Very impressive to learn that the Nazis pushed herbal medicine, but totally uninformative (or does it mean that herbalism appeals to nutters?). We are shown the German herbal bible, but again it is pointed out that it contains no evidence about their efficacy. So no further forward yet.  Then we are introduced to chromatography: very pretty, but still no evidence about whether herbs help people.

At 9.34 pm we are last get round to some evidence. Or do we? Not yet, just another personal testimonial about the the wonders of St John’s Wort. St John’s Wort (Hypericum) is an interesting case, because there is at least some evidence that it works, though certainly not enough for it to be described as a “superherb”, as Sykes did.  Of course depression (like knee surgery -above) makes a pretty good case for herbalists, because conventional antidepressants are so very unsatisfactory themselves.  It doesn’t take much to do better than Seroxat (Paxil, paroxetine).  At 9.38 pm we get the first actual numbers. And very selective numbers they are
too. The view presented in the programme was desperately over-optimistic about the wondrous effects of St John’s wort.  Consider the recent review by Linde et al. (2005 Brit J. Psychiatry, 186, 99-107) (read
it yourself –download pdf file).  The conclusion was as follows.

“Current evidence regarding Hypericum extracts inconsistent and confusing. In patients who meet criteria for major depression, several recent placebo-controlled trials suggest that Hypericum has minimal beneficial effects while other trials suggest that Hypericum and standard antidepressants have similar beneficial effects. ”

And another trial, again not mentioned in the programme, was published in Journal of the American Medical Association, 2002, 287, 1807 – 1814) [download the pdf file]. This paper was interesting because it compared placebo, St John’s Wort and sertraline (Zoloft), a drug of the same class as Seroxat).  All three were indistinguishable (on the two primary outcome measures).  So St John’s Wort was as good as Zoloft, but only because Zoloft was no better than placebo either.  The paper concluded thus.

“This study fails to support the efficacy the efficacy of H. perforatum [St John’s Wort] in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the  complete absence of trends suggestive of efficacy for H. perforatum is noteworthy.”

Why were we not told about trials like these?

At 9.43 pm, almost three quarters of the way through the programme, we are eventually told that ginseng, echinacea and evening primrose oil do not work. What took so long?

9.46 pm. Off to South Africa to look at research in Johannesburg on Sutherlandia by Carl Albrecht (more of him below).  Some impressive stuff about flavonoids but no results.   Flavonoids can’t be absorbed, but, aha, it contains saponins too. Perhaps they allow the flavonoids into cells. Well perhaps.
But this is not information, it is idle speculation.

At 9.51, we get back to brain imaging, this time at Imperial College. Professor Sykes seems to be excessively impressed by brain imaging. We are then treated to more idle speculation about how ginko might help in Alzheimer’s disease. Dr Warner is running a clinical trial to find out whether ginko really helps. But there were no results yet. In that case why not wait until there is a result, before telling us all about it?

We are told that herbs now “have to go through rigorous quality standards”.  It was NOT made clear that the standards don’t include anything about the herb actually doing anything useful.  The standards may give some protection against your being poisoned.  They do nothing at all to guarantee you’ll be helped.

The conclusions

“What’s really impressed me is the way that different ingredients from particular herb can combine together and have really powerful effects on us humans. So I believe that herbs are going to play a key role in medicines of the future”

“What started as an ancient wisdom may just might provide new medicines that will help us all live longer, fuller lives”

These statements are quite outrageous!   The first statement has no basis whatsoever.  It is sheer idle speculation.  It could be true, but there is no reason to believe it is.

The second statement is content-free.  Yes, it “may just” do that. On the other hand it may not.

The web site for the third programme. (7th February, 2006, 2100-2200) concludes thus.

“So, what’s their secret? Working with fellow scientists, Kathy discovers that plants contain much  more than a single – or even two or three – active ingredients. They are enormously complex

Chemical cocktails that have medicinal properties modern pharmaceuticals simply can’t reproduce.”

Just one snag (apart from the misleading implication the Sykes was doing pharmacological experiments), There is not the slightest reason, thus far, to think there is any advantage in using an “enormously complex chemical cocktail”.

Stop press: on Saw palmetto (one of the “superherbs” of the TV series)

The New England Journal of Medicine, for February 9th 2006 (354, 557 – 566), reports a clinical trial of “Saw Palmetto for Benign Prostatic Hyperplasia”. This is what they say.

“Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration.”

“In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo.”

“Conclusions. In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia.”

I hope that the BBC, the Open University and Prof Sykes now appreciate the folly of judging treatments before the results are in.

Postscript. Some reviews of the TV programmes

  • There has been some lively discussion of the BBC2 series on a forum of the James Randi Educational Foundation, on the BBC2/Open University site, on Ben Goldacres’s Badscience site, and at ebm-first.com.

  • The Times TV critic was unenthusiastic.

    “So having started out as a sceptic, Sykes ended the programme chirruping, like a born-again Christian, about how herbs contain complex combinations of chemicals that scientists cannot yet reproduce&”;

  • Simon Singh writes in the Daily Telegraph (14 Feb., 2006): "Did we really witness the ‘amazing power’ of acupuncture?

    “A BBC series on unorthodox therapies was devoid of scepticism and rigour, says Simon Singh.”

    “Although the second programme was indeed a rational look at the placebo effect, the other two episodes were little more than rose-tinted adverts for the alternative medicine industry.”

    “For example, the scene showing a patient punctured with needles and undergoing open heart surgery left viewers with the strong impression that acupuncture was providing immense pain relief. In fact, in addition to acupuncture, the patient had a combination of three very powerful sedatives (midazolam, droperidol, fentanyl) and large volumes of local anaesthetic injected into the tissues on the front of the chest.
    With such a cocktail of chemicals, the acupuncture needles were apparently cosmetic. In short, this memorable bit of telly was emotionally powerful, but scientifically meaningless in building a case for acupuncture. ”

    “This TV series pretended to be scientific and had the chance to set the record straight, but instead it chickened out of confronting the widespread failure of alternative medicine. ”

  • Advertisers cash in. Sadly, but predictably, the programme on herbalism has
    already been exploited by vendors of unproven treatments. While it is true that the programme did not actually assert that this herb cured AIDS, it certainly left the impression that it was good stuff.  Here is an example: “As seen on BBC2”

    “In South Africa, BBC 2 TV presenter, Professor Kathy Sykes learnt of the herb Sutherlandia, which is being touted as a new weapon in the fight against HIV and ”

    “It is with thanks to programmes such as Alternative Medicine shown on BBC 2 on Tuesday 7th February, and the work carried out by Professor Kathy Sykes that medicinal herbs can receive the acknowledgement they truly deserve, and this knowledge be passed on to the general public.”

    “Bioharmony Sutherlandia is available from Revital Ltd in 60 x 300mg tablets for £19.99rrp. ”

  • A groundbreaking experiment … or a sensationalised TV stunt?

    Simon Singh, in The Guardian (25 March 2006) followed through with some more details on the BBC2 series. It’s not only pharmacologists who were unhappy about it. So were several of the people who advised the BBC and/or appeared on the programme.

    “But this week scientists involved in the series have complained that elements of the programmes were misleading, the production team was uninformed, and scientists were used as “marionettes” ”

    At the end of the first programme a “hugely ambitious” imaging experiment was shown with an enormous flourish. The outcome was, roughly speaking, that pushing needles into yourself produces a signal in the brain. Good heavens! Who’d have thought it? Even George Lewith, normally an apologist for CAM, was critical.

    “The interpretation of the science in this particular programme was not good and was inappropriately sensationalised by the production team. I think all of us on the experiment felt like that.”

    “The experiment was not groundbreaking, its results were sensationalised and there was insufficient time to analyse the data properly and so draw any sound conclusions. It was oversold and over-interpreted. We were encouraged to over-interpret, and proper scientific qualifications that might suggest alternative interpretations of the data appear to have been edited out of the programme.”

    Edzard Ernst, professor of complementary medicine at Exeter University, and the main consultant for the series says:

    “The BBC decided to do disturbingly simple storylines with disturbingly happy endings. But none of these stories is as simple as they presented, nor do they have such happy endings. Even when the evidence was outright negative, they somehow bent over backwards to create another happy ending.
    “I feel that they abused me in a way. It was as if they had instructions from higher up that this had to be a happy story about complementary medicine without any complexity, and they used me to give a veneer of respectability.”

    The BBC, thus far, remain unapologetic

    “We take these allegations very seriously and we strongly refute them.We used two scientific consultants for the series, Prof Ernst and Dr Jack Tinker, dean emeritus of the Royal Society of Medicine, both of whom signed off the programme scripts.”

    This is the same Jack Tinker who, as Chairman of the Ethics Committee of the Dr Foster organisation, also approved their “COMPLEMENTARY therapists Guide 2004”, and the utterly uncritical complementary practioner directory. The ‘Dr Foster’ organisation is a commercial business that supplies "management information", "market research services", "marketing services" and "information for the public". Let’s hope their services in conventional health care are a bit more critical than their evaluation of CAM. Their “Guide to [CAM] therapies” repeats all the usual pseudo-scientific gobbledygook in a totally uncritical way.

    Singh’s article ended with some quotations from this site, concerning Sutherlandia and AIDS, with the remark made above, highlighted: "Comments about Aids were irresponsible and potentially dangerous".

  • Science accuses BBC of medical quackery

    Lois Rogers, in the Sunday Times for 26th March, reports on the same topic.

    “Ernst yesterday released the contents of a letter that he has written to Martin Wilson, the series producer, criticising him for promoting “US-style anti-science”.

    He said he felt “abused” by the programme makers: “It was as if they had instructions from higher up that this had to be a happy story about complementary medicine without any complexity, and they used me to give a veneer of respectability.”  “

    “This is no longer a fringe game played by new age people,” said Colquhoun. “It is beginning to erode intellectual standards at real universities.”

Later a letter appeared in defence of the programmes. Investigation showed that this letter had actually been written by the BBC and not all of the ‘signatories’ had seen it.This is dealt with in a separate post, Alternative Medicine series: dirty tricks at the BBC?

This is a slightly modified version of some thoughts from the old improbable science page, where they formed part of the review of a BBC2 series on alternative medicine. It has been moved to the new blog because of the comments posted here.

Evolution of plants

Plants didn’t evolve for our benefit. Natural selection ensures that plants, like every other living thing, evolve in a way that maximises their own chance of survival. To ensure that, plants should be as toxic as possible to anything that might eat them. The more harm a plant does to humans, the better its chance of survival. It is sheer luck that some of the toxic principles evolved by plants occasionally turn out to be useful.

Memo to: The members of the Kansas Board of Education
From: God

Re: Your decision to eliminate the teaching of evolution as science

Thank you for your support. Much obliged. Now, go forth and multiply. Beget many children. And yea, your children shall beget children. And their children shall beget children, and their children’s children after them. And in time the genes that made you such pinheads will be eliminated through natural selection. Because that is how it works.’ . . . ;

By Gene Weingarten, Washington Post Staff Writer.

Saturday, August 14, 1999; Page C01


Here are some products of nature. That doesn’t mean they are good for you.

Lead, uranium, radon, arsenic, thallium, strychnine, cyanide (in Sorghum and Prunus species), Stinging nettles, poison ivy, yew, deadly nightshade, castor beans (ricin), tobacco, curare, foxglove, fly agaric, (muscarine), death cap (amanita phalloides), . . ..

Foxgloves, heart failure and biological standardisation

Here is a bit of relevant pharmacological history.

The 24th edition of Martindale’s Extra Pharmacopoeia (1958) describes Digitalis Leaf (B.P., I.P.), also known as Digit. Fol.; Digitalis; Foxglove Leaf; Feuille de Digitale; Fingerhutblatt; Hoja de digital.

It was defined as “the dried leaves of Digitalis purpurea (Scrophulariaceae).”At that time it was sometimes prescribed as Prepared Digitalis (BP),
which is “Digitalis leaf reduced to powder, no part being rejected, and biologically assayed the strength being stated in units per g. For therapeutic purposes it must be adjusted to contain 10 units in 1 g.”Sometimes foxglove leaf was prescribed as Tincture of Digitalis (B.P., I.P.).
“It may be made from unstandardised leaf, the tincture being subsequently biologically assayed, or it may be made from prepared digitalis, using a quantity containing 1000 units per litre, by percolation or maceration, with alcohol (70 %). It contains 1 unit per ml. I.P. allows also 1 unit per g. Dose: 0.3 to 1 ml. (5 to 15 minims). ”

Although these preparations are now totally defunct, they were still better than the sort of thing that is now advocated by herbalists. Why? They were better because they were standardised.

Foxglove leaves contain several chemical compunds that are useful in certain forms of hear failure. But the margin of safety is quite low. Take a bit too much and it kills you not cures you. One batch of foxglove leaves will contain different amounts of active compounds from the last batch, and that endangered patients.

From the 1930s onwards, pharmacologists developed methods of biological assay that overcame this problem. An international
standard digitalis leaf sample was established. Every new batch had to be assayed against this standard, and diluted to a fixed level of biological activity. This ensured that each batch of digitalis powder had the same biological potency as the last batch. It was a great pharmacological advance in its time. But of course it did involve the use of animals for the biological assay.

All this was solved when the active principles were purified from the foxglove leaves. There was no longer any need to uses animals for biological assays. The right amount of pure digoxin or digitoxin could be weighed out.

Fortunately herbalists are not allowed to prescribe anything as potentially dangerous as digitalis. But in general herbalists are happy to use pre-1930, unstandardised plant extracts.

I can think of no case in which there is the slightest reason to think that the mixture of chemicals in the plant is any better than the purified active principles. Of course there could be such cases of synergy. But that is just idle speculation.

No surprise there then, because idle speculation is the stuff of alternative medicine. It’s a great deal easier than making the effort to find out what works, and probably more lucrative too.

The Daily Telegraph recently published two reports about acupuncture. One said it worked. The other said it didn’t work. Needle cure effect ‘is not all in the mind’ By Catriona Davies, starts

Acupuncture has a genuine ability to relieve pain, scientists have found.

The other report was

Doubt cast on needle therapy for migraine By Nic Fleming, Health Correspondent, starts

Acupuncture is no better at reducing migraines than fake treatment, researchers say today.

A study involving more than 300 patients found the healing method did reduce headaches, but only by the same amount as placing needles at non-acupuncture points.

Unfortunately the Daily Telegraph‘s reporters did nothing to help the confused reader. No comment was made on the apparent contradiction. In this particular case, there is an obvious explanation.

The first (favourable) article was said to be published in Nature, though in fact it was published in Neuroimage (Pariente J., White P., Frackowiak , Richard S. J. & Lewith G. Neuroimage, 25. 1161 – 1167, 2005). Presumably the reporter had picked it up from a rather uncritical synopsis on the news site, nature.com. It was conducted on 14 patients with painful osteoarthritis. Contrary to the first line of the Telegraph‘s report (“Acupuncture has a genuine ability to relieve pain”), the work did not measure pain at all. In fact the summary of the paper says

“The three interventions, all of which were sub-optimal acupuncture treatment, did not modify the patient’s pain.”

What the paper actually did was to use positron emission tomography (PET) to measure ‘activation’ of certain parts of the brain when needles were inserted. Some parts were activated more by having acupuncture needles piercing ths body than by ‘stage-dagger’ needles which retracted and did not pierce the body. I have no criticism of these findings: my purpose here is to explore the apparent contradiction between this trial and another.

The second, unfavourable, report was of a much bigger study, 302 patients with migraine headaches. It was published by Linde et al. (Journal of the American Medical Association. 2005 293(17):2118-25). This study concluded

“Acupuncture was no more effective than sham acupuncture in reducing migraine headaches although both interventions were more effective than a waiting list control. ”

These two studies were on quite different conditions, used different methods, and very different numbers of patients. But suppose we take them at face value, are they not contradictory? No, not necessarily, because they used quite different sorts of control group.

The study that was reported as showing that acupuncture worked compared patients that had real acupuncture with patients who had treatment with “stage dagger” needles that appeared to pierce the skin but did not.

The study that was reported as showing that acupuncture did not work (Linde et al.) used a different sort of control group, acupuncture needles that pierced the skin but were inserted in the wrong places (as defined by the ‘principles’ of acupuncturists). No difference was found between ‘real acupuncture’ and control.

There is nothing incompatible about these two studies if one adopts the view that piercing the skin with a needle can produce a physiological response that makes the patient feel that other sorts of pain are less painful, but that it does not matter where the skin is pierced. The latter hypothesis means, of course, that all talk about “meridians”` and “energy flow” that acupuncturists use, is no more than mumbo jumbo.

Dr Lewith is quoted as saying, of the negative study, “This is a badly conceived study that just adds more confusion to the debate because it uses non-site specific acupuncture as a control.” Quite on the contrary, the Linde study seems more interesting to me, because it unveils the mumbo jumbo of meridians (at least for the particular points used in this study). Dr Lewith may find this conclusion unpalatable, but it is the obvious implication of this pair of studies.

Another study confirms that the principles of acupuncture are nonsense

A trial by Melchart and colleagues on 270 patients shows conclusively that acupuncture can indeed produce amelioration of tension-type headache when compared with no treatment, BUT the relief is produced whether or not needles are inserted at ‘acupuncture points’. Very similar results were found with ‘superficial needling at non-acupuncture points’. British Medical Journal, 15 August 2005. Yet again it is shown that the mumbo-jumbo of meridians and magic points is nonsense. Yet again, that is a good reason why universities cannot be expected to train acupuncturists. Our business is to minimise mumbo-jumbo, not to propagate it.

This post was one of the earliest on my old improbable science page (late 2002). It has been reproduced here because of the interest attached to Stephen Senn’s analysis of what appears to be a rather dubious trial, and because the subject purports to be regular medicine rather than alternative quackery. It is unlikely that all of the links will still be valid.

During research for a talk on quack medicines. I came across several web sites that were selling the common co-enzyme, NADH, for a whole variety of ailments. One of these sites, Wizards Gate, no longer sells NADH (“because the profit is too small”). but continues to carry the following advertisement for it.

A recent Georgetown University Medical Center clinical pilot study among CFS patients reports that participants taking ENADA® were four times more likely than those taking a placebo to experience a reduction in symptoms.

Please click on the links below for more information.

pilot study graph.jpg

What this does NOT mention is that the huge column on the left represents eight people out of 26, and the tiny one on the right represents two people (out of 26)!

The reader is then referred to ImmuneSupport.com, who describe NADH as follows (with my comments in italics).

  • Improves cellular energy [This, as it stands, is meaningless]

  • Elevates mental clarity [There is no evidence that this is true]

  • Promotes mental alertness and concentration [Again, there is no evidence that this is true]

The ImmuneSupport site goes on to say

“NADH is proven to trigger energy production through ATP generation [true].
A naturally occurring coenzyme found in all living cells, NADH helps supply cells with energy.[true].
Thus, as NADH levels rise in the body, the cells become more energized, helping the body feel stronger and more vitalized. [This sentence confuses energy in the technical sense that is used in physics, with the everyday use of the term to describe a mental and physical state, In fact there is no reason to think that NADH “helps the body feel stronger” to any greater extent than a placebo].

Other sites that promote NADH heavily are Enada.com, and the Menuco Corporation, of which more below

The clinical trial referred to in all of these advertisements is Forsyth, L. M., Preuss, H. G., MacDowell, A. L., Chiazze, L., Jr., Birkmayer, G. D., & Bellanti, J. A. (1999). Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann.Allergy Asthma Immunol. 82, 185-191.

It is very clear from the letter below that this trial is flawed, but it is impossible to see exactly how flawed it is because the authors, in breach of all guidelines on such matters, have refused, for over a year, to make available the raw data that would allow a correct analysis to be done.

Annals of Allergy, Asthma, & Immunology ©2000;84:639-640

To the Editor:

We should like to comment on the paper by Forsyth et al. 1 This paper claims, on the basis of a randomized double-blind clinical trial, that NADH is effective in the treatment of chronic fatigue syndrome. It seems that there are several problems with the work described in this paper.

  • On page 187, the ‘raw symptom score’ is defined as a score from a questionnaire normalized to lie between 0 and 1 (the questionnaire had 50 questions, each scored 1, 2, 3 or 4, so raw scores are in the range 50 to 200). This was normalized to lie between 0 and 1 by first subtracting 50 and then dividing by 150. However, patients with chronic fatigue syndrome are said to have scores ranging from 10.9 to 55.8, so the normalized score has presumably been expressed as a percentage, whereas in the case of normal patients the values of 0.01 to 0.13 suggest that proportions have been used. Furthermore, even using percentages rather than proportions, we cannot reproduce the ranges given for patients. For example, a raw score of 66 yields a normalized score of 10.7 whereas the next possible value 67 translates to 11.3.  How in that case could Forsyth et al get 10.9? Similarly 133 yields a score of 55.3 but 134 yields 56.  So what raw score can have produced 55.8?
  • It is stated that, “an individual was considered improved if s/he demonstrated at least a 10% improvement,” but then it is also stated that, “the degree of improvement for the results to show a positive effect was an improvement by one point in 10 questions or by 2 points in 5 questions” (p 187). This corresponds to a decrease in the raw score of 10 points, not a “10% improvement.” Table 5 gives the scores (presumably normalized score x 100) for each of the 26 patients on each of the tests. It is stated that 8/26 improve on NADH and 2/26 improve on placebo. This appears to be a change in normalized score (x 100) by 10, not to a change in raw score of 10.
  • The method of analysis given on page 187 is a test of difference between two independent estimates of a binomial proportion. This is entirely inappropriate for the analysis of a crossover trial. 2
  • Most importantly, nothing whatsoever is said about which of the 26 patients in Table 5 received which treatment. Without knowing which treatment was given in which period it is impossible for the reader to repeat the analysis using methods more appropriate for crossover trials. The simple addition of one column here, giving the sequence to which the patient was allocated, would have permitted others to have performed the necessary calculations.

Drs Forsythe and Bellanti were asked in June 1999 to provide the raw data, in particular the crucial information on sequences that would allow re-analysis of their results. Despite several further requests we have not had any response. This is made all the more disturbing in view of fact that their paper is being used to justify vigorous marketing 3 of NADH as a treatment that “Enhances energy naturally, elevates mental clarity, improves alertness, and concentration,” which treatment is also being claimed by some to be useful for everything from improving athletic performance to Alzheimer’s disease. In view of this it seems that the least that it is owed the readers of your journal is for the authors to produce the original data so that their claims can be verified.

David Colquhoun

Stephen Senn

Professor of Pharmacology, University College London, Hon, Director Wellcome Laboratory for Molecular Pharmacology, Dept of Pharmacology, University College London, London, United Kingdom and ,

Professor of Pharmaceutical and Health Statistics, Department of Epidemiology & Public Health,
and Department of Statistics, University College London, London, United Kingdom



1. Forsythe LM, Preuss HG, MacDowell AL, et al. Ann Allergy Asthma Immunol

2. Senn SJ. Cross-over trials in clinical research. Wiley, Chichester,

3. See, for example, http://www.enada.com/,http://www.wizardsgate.com/
and many others.

Professor Bellanti’s response:

We have reviewed the two “Letters to the Editor” from Professors Colquhoun and Senn and from Professor Lorden and wish to respond to both. Recognizing that there are various methods and points of view concerning statistical analyses, since this was a preliminary study and not a definitive one, we chose to analyze the data in the manner described. This was done to determine whether there was a basis for the therapeutic efficacy of NADH in chronic fatigue syndrome and, if so, then to proceed to a larger, more definitive study. We feel that we have accomplished this goal in obtaining sufficient evidence to proceed further. We are grateful for the constructive elements of the readers’ comments and we shall take these into consideration as we plan the definitive studies.

Joseph A Bellanti, MD

Professor of Pediatrics and Microbiology-Immunology

Georgetown University School of Medicine

Washington, DC

This reply from Professor Bellanti stands in contrast to his own statement in a recent report presented to Annual Meeting of American College of Allergy, Asthma and Immunology in which he says “We have recently demonstrated the clinical effectiveness of reduced nicotinamide adenine dinucleotide (NADH) in a group of 26 patients with CFS in a double-blinded, placebo-controlled, crossover study”.

There is no mention here (or in any of the advertisements) of the study being “preliminary” or “not definitive”. (The measurement of 5-HIAA urinary concentration as a possible predictive marker of disease activity and therapeutic efficay of NADH in the chronic fatigue syndrome. Joseph A Bellanti MD; Linda M Forsyth MD; Ana Luiza MacDowell-Carneiro MD; Dawn B. Wallerstedt, MSN, FNP; Harry G Preuss MD and Georg D Birkmayer MD. PhD ).

This reply gives no reason at all for refusing to disclose the raw data, to allow others to check the conclusions. It does say that “there are various methods and points of view concerning statistical analyses”, but does not (unsurprisingly) refer to anyone who thinks that a test of difference between two independent estimates of a binomial proportion is an appropriate way to analyse a cross over trial.

Financial interests

The editor of Annals of Allergy, Asthma, & Immunology, Dr Edward O’Connell, tells me that the journal requires authors to disclose any financial interest in the work, and that no such interests were declared in the case of Forsyth et al. This seems very odd, since the address of one of the authors, Dr G.D Birkmayer is given as Birkmayer Pharmaceuticals (Vienna), who market the ENADA brand of NADH, on which Dr Birkmayer holds patents. Birkmayer Pharmacuticals supported the work by a grant, and analysed the data

Latest news The case of the Bellanti paper was referred to the Georgetown University’s Research Integrity Committee for review, in February 2001. That committee has reported that “no violation within the purview of the Code has been committed”. In the light of the facts concerning (a) improperly analysed data, (b) non-disclosure of financial interest and (c) the refusal to allow independent analysis of the data, it seems the the University has a novel view of what constitutes research integrity!


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