It hardly is a secret: we have a growing problem with obesity. Worldwide it is predicted to cause millions of premature deaths – unless, of course, we come up with a safe and effective treatment that patients find acceptable.
Many herbal remedies are being promoted as the solution to this serious problem. My team looked at the evidence for such treatments in much detail. Sadly the results were less than impressive.
But now, there seems to be new hope! Two recent studies of a specific herbal mixture report amazingly good results – or are they perhaps too good to be true?
Stern JS, Peerson J, Mishra AT, Sadasiva Rao MV and Rajeswari KP from the Department of Nutrition and the Department of Internal Medicine, University of California Davis, have just published an RCT in 60 subjects with body mass index (BMI) between 30 and 40 kg/square meter. Participants received either 400 mg herbal capsules with extracts from Sphaeranthus indicus and Garcinia mangostana or 400 mg placebo capsules twice daily. During the study period, participants consumed a standard diet (2,000 kcal per day) and walked 30 min 5 days per week.
After 8 weeks of this treatment, significant reductions in body weight (3.7 kg), BMI (1.6 kg/m2), and waist circumference (5.4 cm) were observed in the herbal group compared with placebo. Additionally, a significant increase in serum adiponectin concentration was found in the herbal group versus placebo. Adverse events were mild and were equally distributed between the two groups.
The authors’ conclusion leave no doubt: Supplementation with the herbal blend resulted in a greater degree of weight loss than placebo over 8 weeks.
As our own review had suggested that extracts of Garcinia cause small short-term weight reductions, the results did not come as a complete surprise to me. What did strike me as odd, however, was the fact that almost simultaneously another article was published. It was authored by Stern JS, Peerson J, Mishra AT, Mathukumalli VS and Konda PR from the Department of Nutrition, University of California-Davis, and it reported the pooled data from the above plus another, similarly designed trial.
The two studies together enrolled 100 patients who were treated either with the same herbal formula or with placebo. All subjects received 2000 kcal/day throughout the study and walked 5 days a week for 30 min. The primary outcome was the reduction in body weight. Secondary outcomes were reductions in BMI and in waist and hip circumference. Serum glycaemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and the data from these two studies were pooled and analysed.
At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg), BMI (2.2 kg/m2), as well as waist (11.9 cm) and hip circumferences (6.3 cm) were observed in the pooled herbal groups compared with placebo. A significant increase in serum adiponectin concentration was also found in the herbal groups versus placebo at study conclusion along with reductions in fasting blood glucose (12.2%), cholesterol (13.8%), and triglyceride (41.6%) concentrations. No changes were seen across organ function panels, multiple vital signs, and no major adverse events were reported. The minor adverse events were equally distributed between the two groups.
And what should be odd about that? Authors are entitled to pool the data of two of their own trials! Yes, of course, but what confuses me is the fact that the data from the second study of 40 patients cannot be found anywhere. I would have liked to see how it is possible that the results from just 40 more patients (actually just 35 seemed to have been included in the analysis) raise the average weight loss from 3.7 kg in the first RCT to a remarkable 5.2 kg in the two RCTs together. As a rough estimate, this means that, in the second trial, patients who took the herbal mixture must have lost about one kilo per week more than those who were on placebo. If true, this outcome is pretty sensational! It could signal the end of the obesity epidemic. It would also mean that the manufacturer of this herbal wonder mixture stands to earn billions.
Considering the potential importance of these findings, I would also like to know what precisely the Californian researchers’ involvement has been in these two studies. In the second article they state that: The two clinical trials were performed at Alluri Sitarama Raju Academy of Medical Sciences (ASRAM), Eluru, Andhra Pradesh, India from November 2009 to April 2010 (clinical trial registration number: ISRCTN45078827) and from March 2010 to July 2010 (clinical trial registration number: ISRCTN52261953). I find this puzzling.
Moreover, it would be interesting to learn what happened to the following co-authors of the first study: Sadasiva, Rao MV and Rajeswari KP. As authors of the largest of the two trials, I would have thought their names would have to be included in the article reporting the pooled data of the two studies.
Call me sceptical, perhaps even cynical, but I do wonder about trials which seem to beg so many intriguing questions. In case you want to know who funded these studies and who thus stands to make the above-named billions, the answer is provided in the second paper: This work was supported by an unrestricted grant from InterHealth Nutraceuticals Inc., Benicia, CA, to J.S.S.
So, do I think that we have finally identified a safe and effective treatment to combat the worldwide epidemic of obesity? Well….
S.O. Hansson from the Royal Institute of Technology, Stockholm, Sweden recently published an interesting comment on the law regulating the labelling of homeopathic products. In it he points out that, in the European Union (EU), all pre-packaged food products must contain a list of ingredients and their quantities. The list should be “accurate, clear and easy to understand for the consumer.” Similar requirements apply to pharmaceutical drugs and products – with one notable exception: homeopathic preparations.
For such products, the ingredients need not be disclosed on the label, which should instead specify “the scientific name of the stock or stocks followed by the degree of dilution.” The degree of homeopathic dilutions is, in turn, given in an understandable jargon, such as “C60”, which actually describes a dilution of 1:10120.
The point Hansson is trying to make is that very few health care professionals and even fewer consumers would understand such abbreviations and jargon. This means that, manufacturers of homeopathic products are legally permitted to hide the fact from their customers that their remedies typically contain no active ingredient at all. Considering that homeopathic products are typically bought ‘over the counter’ (OTC), i.e. without interference from a health care professional, just like food products, the exemption seems most surprising.
The most OTC homeopathic remedies are in the “C30” potency; this signifies a dilution of 1: 1 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000. The likelihood that any potency higher than “C12” might contain a single molecule of active ingredient is very close to zero. In order to comprehend the degree of dilution in homeopathy more fully, a visual approach might be best: for it to have a reasonable chance to contain just one single molecule of active ingredient, a homeopathic pill in a “C30” potency would need to have a diameter roughly equal to the distance between the earth and the sun. Homeopathy is truly impossible to swallow.
If homeopathic manufacturers were obliged to provide a description that is “accurate, clear and easy to understand for the consumer”, it would need to state that any dilution beyond “C12” contains no active molecule. It seems clear that such accurate, clear and understandable information would discourage most consumers to spend their hard-earned money for such nonsense. It seems thus to be obvious that the EU exemption of homeopathic remedies from honest labelling protects the interests of the homeopathic industry.
But surely, this is deeply wrong. Regulations in health care are not supposed to protect commercial interests, they should protect the consumer. In my view, it is time to change such profoundly misguided EU-regulation – in the interest of honesty, single standards, transparency and foremost in the interest of the patient and the consumer.
Sorry, but I am fighting a spell of depression today.
Why? I came across this website which lists the 10 top blogs on alternative medicine. To be precise, here is what they say about their hit-list: this list includes the top 10 alternative medicine bloggers on Twitter, ranked by Klout score. Using Cision’s media database, we compiled the list based on Cision’s proprietary research, with results limited to bloggers who dedicate significant coverage to alternative medicine and therapies…
And here are the glorious top ten:
All of these sites are promotional and lack even the slightest hint of critical evaluation. All of them sell or advertise products and are thus out to make money. All of them are full of quackery, in my view. Some of the most popular bloggers are world-famous quacks!
What about impartial information for the public? What about critical review of the evidence? What about a degree of balance? What about guiding consumers to make responsible, evidence-based decisions? What about preventing harm? What about using scarce resources wisely?
I don’t see any of this on any of the sites.
You see, now I have depressed you too!
Quick, buy some herbal, natural, holistic and integrative anti-depressant! As it happens, I have some for sale….
Even after all these years of full-time research into alternative medicine and uncounted exchanges with enthusiasts involved in this sector, I find the logic that is often applied in this field bewildering and the unproductiveness of the dialogue disturbing.
To explain what I mean, it be might best to publish a (fictitious, perhaps slightly exaggerated) debate between a critical thinker or scientist (S) and an uncritical proponent (P) of one particular form of alternative medicine.
P: Did you see this interesting study demonstrating that treatment X is now widely accepted, even by highly critical GPs at the cutting edge of health care?
S: This was a survey, not a ‘study’, and I never found the average GP “highly critical”. Surveys of this nature are fairly useless and they “demonstrate” nothing of real value.
P: Whatever, but it showed that GPs accept treatment X. This can only mean that they realise how safe and effective it is.
S: Not necessarily, GPs might just give in to consumer demand, or the sample was cleverly selected, or the question was asked in a leading manner, etc.
P: Hardly, because there is plenty of good evidence for treatment X.
S: Really? Show me.
P: There is this study here which proves that treatment X works and is risk-free.
S: The study was far too small to demonstrate safety, and it is wide open to multiple sources of bias. Therefore it does not conclusively show efficacy either.
P: You just say this because you don’t like its result! You have a closed mind!
In any case, it was merely an example! There are plenty more positive studies; do your research properly before you talk such nonsense.
S: I did do some research and I found a recent, high quality systematic review that arrived at a negative conclusion about the value of treatment X.
P: That review was done by sceptics who clearly have an axe to grind. It is based on studies which do not account for the intrinsic subtleties of treatment X. Therefore they are unfair tests of treatment X. These trials don’t really count at all. Every insider knows that! The fact that you cite it merely confirms that you do not understand what you are talking about.
S: It seems to me, that you like scientific evidence only when it confirms your belief. This, I am afraid, is what quacks tend to do!
P: I strongly object to being insulted in this way.
S: I did not insult you, I merely made a statement of fact.
P: If you like facts, you have to see that one needs to have sufficient expertise in treatment X in order to apply it properly and effectively. This important fact is neglected in all of those trials that report negative results; and that’s why they are negative. Simple! I really don’t understand why you are too stupid to understand this. Such studies do not show that treatment X is ineffective, but they demonstrate that the investigators were incompetent or hired with the remit to discredit treatment X.
S: I would have thought they are negative because they minimised bias and the danger of generating a false positive result.
P: No, by minimising bias, as you put it, these trials eliminated the factors that are important elements of treatment X.
S: Such as the placebo-effect?
P: That’s what you call it because you irrationally believe in reductionist science.
S: Science requires no belief, I think you are the believer here.
P: The fact is that scientists of your ilk negate all factors related to human interactions. Patients are no machines, you know, they need compassion; we clinicians know that because we work at the coal face of health care. Scientists in their ivory towers have no idea about patient care and just want science for science sake. This is not how you help patients. Show some compassion man!
S: I do know about the importance of compassion and care, but here we are discussing an entirely different topic, namely tests the efficacy or effectiveness of treatments, not patient-care. Let’s focus on one issue at a time.
P: You cannot separate things in this way. We have to take a holistic view. Patients are whole individuals, and you cannot do them justice by running artificial experiments. Every patient is different; clinical trials fail to account for this fact and are therefore fairly irrelevant to us and to our patients. Real life is very different from your imagined little experiments, you know.
S: These are platitudes that are nonsensical in this context and do not contribute anything meaningful to the present discussion. You do not seem to understand the methodology or purpose of a clinical trial.
P: That is typical! Whenever you run out of arguments, you try to change the subject or throw a few insults at me.
S: Not at all, I thought we were talking about clinical trials evaluating the effectiveness of treatment X.
P: That’s right; and they do show that it is effective, provided you consider those which are truly well-done by experts who know about treatment X and believe in it.
S: Not true. Only if you cherry-pick the data will you be able to produce an overall positive result for treatment X.
P: In any case, the real world results of clinical practice show very clearly that it works. It would not have survived for so long, if it didn’t. Nobody can deny that, and nobody should claim that silly little trials done in artificial circumstances are more meaningful than a wealth of experience.
S: Experience has little to do with reliable evidence.
P: To deny the value of experience is just stupid and clearly puts you in the wrong. I have shown you plenty of reliable evidence but you just ignore everything I say that does not go along with your narrow-minded notions about science; science is not the only way of knowing or comprehending things! Stop being obsessed with science.
S: No, you show me rubbish data and have little understanding of science, I am afraid.
P: Here we go again! I have had about enough of that and your blinkered arguments. We are going in circles because you are ignorant and arrogant. I have tried my best to show you the light, but your mind is closed. I offer true insight and you pay me back with insults. You and your cronies are in the pocket of BIG PHARMA. You are cynical, heartless and not interested in the wellbeing of patients. Next you will tell me to vaccinate my kids!
S: I think this is a waste of time.
P: Precisely! Everyone who has followed this debate will see very clearly that you are obsessed with reductionist science and incapable of considering the suffering of whole individuals. You want to deny patients a treatment that really helps them simply because you do not understand how treatment X works. Shame on you!!!
One of the best-selling supplements in the UK as well as several other countries is evening primrose oil (EPO). It is available via all sorts of outlets (even respectable pharmacies – or is that supposedly respectable?), and is being promoted for a wide range of conditions, including eczema. The NIH website is optimistic about its efficacy: “Evening primrose oil may have modest benefits for eczema.” Our brand-new Cochrane review was aimed at critically assessing the effects of oral EPO or borage oil (BO) on the symptoms of atopic eczema, and it casts considerable doubt on this somewhat uncritical view.
Here is what we did: We searched six databases as well as online trials registers and checked the bibliographies of included studies for further references to relevant trials. We corresponded with trial investigators and pharmaceutical companies to identify unpublished and ongoing trials. We also performed a separate search for adverse effects. All RCTs investigating oral intake of EPO or BO for eczema were included.
Two experts independently applied eligibility criteria, assessed risk of bias, and extracted data. We pooled dichotomous outcomes using risk ratios (RR), and continuous outcomes using the mean difference (MD). Where possible, we pooled study results using random-effects meta-analysis and tested statistical heterogeneity.
And here is what we found: 27 studies with a total of 1596 participants met our inclusion criteria: 19 studies tested EPO, and 8 studies assessed BO. A meta-analysis of results from 7 studies showed that EPO failed to improve global eczema symptoms as reported by participants and doctors. Treatment with BO also failed to improve global eczema symptoms. 67% of the studies had a low risk of bias for random sequence generation; 44%, for allocation concealment; 59%, for blinding; and 37%, for other biases.
Our conclusions were clear: Oral borage oil and evening primrose oil lack effect on eczema; improvement was similar to respective placebos used in trials. Oral BO and EPO are not effective treatments for eczema.
The very wide-spread notion that EPO is effective for eczema and a range of other conditions was originally promoted by the researcher turned entrepreneur, D F Horrobin, who claimed that several human diseases, including eczema, were due to a lack of fatty acid precursors and could thus be effectively treated with EPO. In the 1980s, Horrobin began to sell EPO supplements without having conclusively demonstrated their safety and efficacy; this led to confiscations and felony indictments in the US. As chief executive of Scotia Pharmaceuticals, Horrobin obtained licences for several EPO-preparations which later were withdrawn for lack of efficacy. Charges of mismanagement and fraud led to Horrobin being ousted as CEO by the board of the company. Later, Horrobin published a positive meta-analysis of EPO for eczema where he excluded the negative results of the largest published trial, but included results of 7 of his own unpublished studies. When scientists asked to examine the data, Horrobin’s legal team convinced the journal to refuse the request.
The evidence for EPO is negative not just for eczema. To the best of my knowledge, there is not a single disease or symptom for which it demonstrably works. Our own review of the data concluded ” EPO has not been established as an effective treatment for any condition”
Our new Cochrane review might help to put this long saga to rest. In my view, it is a fascinating tale of a scientist being blinded by creed and ambition. The results of such errors can be dramatic. Horrobin misled all of us: patients, health care professionals, scientists, regulators, decision makers, businessmen. This caused unnecessary expense and set back research efforts in a multitude of areas. I find the tale also fascinating from other perspectives; for instance, it begs the question why so many ‘respectable’ manufacturers and retailers are still allowed to make money on EPO. Is it not time to debunk the EPO-myth and say it as clearly as possible: EPO helps only those who financially profit from misleading the public?
This post has an odd title and addresses an odd subject. I am sure some people reading it will ask themselves “has he finally gone potty; is he a bit xenophobic, chauvinistic, or what?” I can assure you none of the above is the case.
Since many years, I have been asked to peer-review Chinese systematic reviews and meta-analyses of TCM-trials submitted to various journals and to the Cochrane Collaboration for publication, and I estimate that around 300 such articles are available today. Initially, I thought they were a valuable contribution to our knowledge, particularly for the many of us who cannot read Chinese languages. I hoped they might provide reliable information about this huge and potentially important section of the TCM-evidence. After doing this type of work for some time, I became more and more frustrated; now I have decided not to accept this task any longer – not because it is too much trouble, but because I have come to the conclusion that these articles are far less helpful than I had once assumed; in fact, I now fear that they are counter-productive.
In order to better understand what I mean, it might be best to use an example; this recent systematic review seems as good for that purpose as any.
Its Chinese authors “hypothesized that the eligible trials would provide evidence of the effect of Chinese herbs on bone mineral density (BMD) and the therapeutic benefits of Chinese medicine treatment in patients with bone loss“. Randomized controlled trials (RCTs) were thus retrieved for a systematic review from Medline and 8 Chinese databases. The authors identified 12 RCTs involving a total of 1816 patients. The studies compared Chinese herbs with placebo or standard anti-osteoporotic therapy. The pooled data from these RCTs showed that the change of BMD in the spine was more pronounced with Chinese herbs compared to the effects noted with placebo. Also, in the femoral neck, Chinese herbs generated significantly higher increments of BMD compared to placebo. Compared to conventional anti-osteoporotic drugs, Chinese herbs generated greater BMD changes.
In their abstract, the part on the paper that most readers access, the authors reached the following conclusions: “Our results demonstrated that Chinese herb significantly increased lumbar spine BMD as compared to the placebo or other standard anti-osteoporotic drugs.” In the article itself, we find this more detailed conclusion: “We conclude that Chinese herbs substantially increased BMD of the lumbar spine compared to placebo or anti-osteoporotic drugs as indicated in the current clinical reports on osteoporosis treatment. Long term of Chinese herbs over 12 months of treatment duration may increase BMD in the hip more effectively. However, further studies are needed to corroborate the positive effect of increasing the duration of Chinese herbs on outcome as the results in this analysis are based on indirect comparisons. To date there are no studies available that compare Chinese herbs, Chinese herbs plus anti-osteoporotic drugs, and anti-osteoporotic drug versus placebo in a factorial design. Consequently, we are unable to draw any conclusions on the possible superiority of Chinese herbs plus anti-osteoporotic drug versus anti-osteoporotic drug or Chinese herb alone in the context of BMD.“
Most readers will feel that this evidence is quite impressive and amazingly solid; they might therefore advocate routinely using Chinese herbs for the common and difficult to treat problem of osteoporosis. The integration of TCM might avoid lots of human suffering, prolong the life of many elderly patients, and save us all a lot of money. Why then am I not at all convinced?
The first thing to notice is the fact that we do not really know which of the ~7000 different Chinese herbs should be used. The article tells us surprisingly little about this crucial point. And even, if we manage to study this question in more depth, we are bound to get thoroughly confused; there are simply too many herbal mixtures and patent medicines to easily identify the most promising candidates.
The second and more important hurdle to making sense of these data is the fact that most of the primary studies originate from inaccessible Chinese journals and were published in Chinese languages which, of course, few people in the West can understand. This is entirely our fault, some might argue, but it does mean that we have to believe the authors, take their words at face value, and cannot check the original data. You may think this is fine, after all, the paper has gone through a rigorous peer-review process where it has been thoroughly checked by several top experts in the field. This, however, is a fallacy; like you and me, the peer-reviewers might not read Chinese either! (I don’t, and I reviewed quite a few of these papers; in some instances, I even asked for translations of the originals to do the job properly but this request was understandably turned down) In all likelihood, the above paper and most similar articles have not been properly peer-reviewed at all.
The third and perhaps most crucial point can only be fully appreciated, if we were able to access and understand the primary studies; it relates to the quality of the original RCTs summarised in such systematic reviews. The abstract of the present paper tells us nothing at all about this issue. In the paper, however, we do find a formal assessment of the studies’ risk of bias which shows that the quality of the included RCTs was poor to very poor. We also find a short but revealing sentence: “The reports of all trials mentioned randomization, but only seven described the method of randomization.” This remark is much more significant than it may seem: we have shown that such studies use such terminology in a rather adventurous way; reviewing about 2000 of these allegedly randomised trials, we found that many Chinese authors call a trial “randomised” even in the absence of a control group (one cannot randomise patients and have no control group)! They seem to like the term because it is fashionable and makes publication of their work easier. We thus have good reason to fear that some/many/most of the studies were not RCTs at all.
The fourth issue that needs mentioning is the fact that very close to 100% of all Chinese TCM-trials report positive findings. This means that either TCM is effective for every indication it is tested for (most unlikely, not least because there are many negative non-Chinese trials of TCM), or there is something very fundamentally wrong with Chinese research into TCM. Over the years, I have had several Chinese co-workers in my team and was invariably impressed by their ability to work hard and efficiently; we often discussed the possible reasons for the extraordinary phenomenon of 0% negative Chinese trials. The most plausible answer they offered was this: it would be most impolite for a Chinese researcher to produce findings which contradict the opinion of his/her peers.
In view of these concerns, can we trust the conclusions of such systematic reviews? I don’t think so – and this is why I have problems with research of this nature. If there are good reasons to doubt their conclusions, these reviews might misinform us systematically, they might not further but hinder progress, and they might send us up the garden path. This could well be in the commercial interest of the Chinese multi-billion dollar TCM-industry, but it would certainly not be in the interest of patients and good health care.