MD, PhD, FMedSci, FSB, FRCP, FRCPEd

supplements

Herbal medicine is popular. Consumers seem to be attracted by the notion that they are natural – and if it’s natural, it must be safe!!! But do we really know what is in the product that we might be buying? A recently published analytical study aimed to investigate herbal product integrity and authenticity with the goal of protecting consumers from health risks associated with product substitution and contamination.

The researchers used DNA barcoding to conduct a blind test of the authenticity for (i) 44 herbal   products representing 12 companies and 30 different species of herbs, and (ii) 50 leaf samples collected from 42 herbal species. They also assembled the first   standard reference material (SRM) herbal barcode library from 100 herbal species of   known provenance that were used to identify the unknown herbal products and leaf samples.

DNA barcodes from 91% of the herbal products and all leaf samples could be recovered. 59% of the products tested contained DNA barcodes from plant species not listed on the labels. 48% of the products could be authenticated but one-third of these also contained contaminants and or fillers not listed on the label. Product substitution occurred in 30 of the 44 products tested and only 2 of the 12 companies sold products without any substitution, contamination or fillers. Some of the contaminants we found pose serious health risks to consumers.

Based on these findings, the authors drew the following conclusions: Most of the herbal products tested were of poor quality, including considerable product substitution, contamination and use of fillers. These activities dilute the effectiveness of otherwise useful remedies, lowering the perceived value of all related products because of a lack of consumer confidence in them. We suggest that the herbal industry should embrace DNA barcoding for authenticating herbal products through testing of raw materials used in manufacturing products. The use of an SRM DNA herbal barcode library for testing bulk materials could provide a method for ‘best practices’ in the manufacturing of herbal products. This would provide consumers with safe, high quality herbal products.

These findings are fairly alarming. I have previously blogged about the fact that herbal products are far to often adulterated or contaminated. Now it seems that we have to add to this list of dangers the substitution of the herbal ingredient with a presumably less expensive but potentially toxic herb that should not legally be there at all.

The fish oil (FO) story began when a young Danish doctor noticed that there were no heart attacks in Greenland. Large epidemiological studies were initiated, mechanistic investigations followed, and a huge amount of fascinating data emerged. Today, we know more about FO than most other dietary supplements.

Fish oil contains large amounts of omega-3 fatty acids which are thought to be beneficial in treating hypertriglyceridemia,  preventing heart disease.  In addition, FO is often recommended for a wide variety of other conditions, such as  cancer, depression, and macular degeneration. Perhaps the most compelling evidence exists in the realm of inflammatory diseases; the mechanism of action of FO is well-studied and includes powerful anti-inflammatory properties.

Australian rheumatologists just published a study of FO supplements for patients suffering from rheumatoid arthritis (RA). Specifically, they examined  the effects of high versus low dose FO in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).

Patients with chronic RA <12 months’ who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or plaacebo (low dose FO for masking). These groups were given 5.5 or 0.4 g/day, respectively, of  eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.

The results indicate that, the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti–cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.

The authors conclude that FO was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.

These findings are most encouraging, particularly as they collaborate those of systematic reviews which concluded that evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs and …there is evidence from 6 of 14 randomized controlled trials supporting a favourable effect of n-3 LCP supplementation in decreasing joint inflammation in RA. And you don’t need to buy the supplements either; regularly eating lots of fatty fish like mackerel, sardine or salmon has the same effects.

So, here we have an alternative, ‘natural’, dietary supplement or diet that is supported by reasonably sound evidence for efficacy, that has very few adverse effects (the main one being contamination of the supplement with toxins), that generates a host of potentially useful effects on other organ systems, that is affordable, that has a plausible mechanism of action…. Hold on, I hear some people interrupting me, FO is not an alternative medicine, it is mainstream! Exactly, an alternative medicine that works is called….MEDICINE.

Guest post by Louise Lubetkin

Those who recognize and appreciate a fine example of pseudoscientific baloney when they see one know that there is no richer seam, no more inexhaustible source, than the bustling, huckster-infested street carnival that is alternative medicine. There one can find intellectual swindlers in abundance, all offering outrageously implausible claims with the utmost earnestness and sincerity. But the supreme prize, the Fabergé egg found buried among the bric-a-brac, surely belongs to that most convincing of illusionists, the physician reborn as an ardent advocate of alternative medicine.

Why would any physician, exhaustively trained in the basic sciences that underpin every aspect of medical practice, decide to toss aside the entire canon in favor of a return to blatant mumbo jumbo?

There can be only two possible explanations, and they’re mutually exclusive.

First is the unsavory possibility that the physician who embraces alternative medicine is a cynical charlatan who knows full well that what is being offered is worthless, but sees it as a path to a more lucrative form of practice that is largely paid for out of pocket, in cash, requiring no tedious insurance company paperwork and avoiding the unpleasant possibility of Medicare audits.

And then there is the opposite explanation: the physician has actually become a true believer, in which case the wholesale rejection of his or her scientific training is essential in order to resolve the uneasy tension between what the physician knows to be fundamentally true and what he or she ardently believes and wishes were true. The two are diametrically opposed: one is a system of thinking in which each component has been painstakingly validated, assessed and reassessed over time, and revised where necessary with the emergence of new knowledge. The other is a simply a belief system founded on faith and wishful thinking.

Alternative medicine, particularly in the realm of cancer, has a long history of attracting people who are seduced by simplistic explanations of this dauntingly implacable and hugely complex constellation of diseases and become gripped by a messianic conviction that this is the true path to a cure. Never mind that such explanations have usually been around for a very long time and have been repeatedly debunked in carefully conducted studies. There is usually an element of paranoia involved: they see themselves as martyrs and explain the medical profession’s indifference to this revolutionary truth as a conspiracy designed to maintain a profitable status quo by silencing dissidents, especially when they arise from within the medical profession itself.

Which of these explanations is the correct one in any particular situation is not always easy to discern. Take the case of Nicholas James Gonzalez, M.D., a New York physician turned alternative practitioner whose practice focuses largely on the treatment of advanced cancer by nutritional means.

THE ORIGINS OF GONZALEZ’S TREATMENT

Gonzalez presents himself as a true believer who became a convert to alternative medicine after coming across the work of William Donald Kelley, D.D.S., a Texas orthodontist who had his own Damascene conversion when his doctors told him that he was dying of pancreatic cancer and that there was nothing more that they could do for him. Undeterred, Kelley claimed that he had cured himself by means of a rigorous diet combined with frequent self-administered coffee enemas. After thus miraculously dragging himself (and his enema bucket) back from the banks of the River Styx, Kelley decided to abandon straightening children’s teeth in favor of treating people with advanced cancer – perhaps not the most logical career move, to be sure, but Texas is Texas.

Probably the most famous of Kelley’s patients was the actor Steve McQueen, who, in the advanced stages of mesothelioma, turned to the erstwhile orthodontist in search of a cure. Not surprisingly, McQueen died despite Kelley’s ministrations, an unfortunate turn of events which Kelley rationalized away by claiming that he had in fact successfully cured McQueen, but that the medical establishment had subsequently had McQueen murdered in order to prevent him “blowing the lid off the cancer racket.”

But back to Gonzalez.

Like Kelley before him, Gonzalez bases his treatment on the work of James Beard, a long-dead Scottish embryologist who, more than 100 years ago, put forward the notion that all cancer was caused by wayward cells called trophoblasts. Trophoblasts are the cells which organize around the developing embryo very early in pregnancy, and which ultimately give rise to the placenta. Beard, of course, lived and died long before the advent of electron microscopy, the unraveling of the structure of DNA and a myriad other crucial discoveries that have helped to elucidate the hugely complex phenomenon that is collectively referred to as cancer. While his observations concerning the similarities between the invasiveness of cancer and the ability of the primitive placenta to tunnel its way into the uterine wall were undoubtedly astute, they are inadequate to explain what is now known about the etiology and progression of cancer.

Having observed that the placenta’s invasion of the uterine wall ceased at the very moment that the fetal pancreas became active, he took a leap of faith and postulated that it was the fetal pancreatic enzymes that were responsible for arresting the growth and invasion of the trophoblast layer. Beard went further, suggesting that quite apart from their role in digestion, pancreatic enzymes actually represent the body’s main defense against cancer, and therefore it should be possible to control cancer by administering large quantities of pancreatic enzymes.

This hundred-year-old hypothesis forms the cornerstone of the cancer treatment program devised by Gonzalez. (It should also be mentioned that Gonzalez doesn’t limit himself to the treatment of cancer, but uses the same methodology for treating a range of chronic degenerative diseases, including multiple sclerosis, presumably on the assumption that wayward trophoblasts are responsible for these, also, although it is difficult to imagine exactly how.)

Beard rightly surmised that pancreatic enzymes could not be successfully administered by mouth because the acid environment of the stomach would inactivate them immediately. Furthermore, being proteins themselves, any orally administered pancreatic enzymes would be quickly broken down by the gastric enzyme pepsin. Beard therefore advocated administering the enzymes by hypodermic injection.

In this, and in other ways, Beard seems to have been considerably more circumspect about his theory and its therapeutic implications than his modern day acolytes. It is interesting to note that he conspicuously refrained from making any claim that his method was a cure for cancer. A contemporary account of the public debate over Beard’s theory of cancer origins and treatment, which appeared in 1907 in the New York Times, is available here.

Much has happened since Beard’s day, it’s true, but gastric physiology and the essentials of protein digestion have not changed an iota. Pepsin is still pepsin, and the stomach is still awash in acid. Nevertheless, Gonzalez insists that the oral route is perfectly adequate. This odd departure from otherwise strict historical orthodoxy may have more to do with regulatory issues than pharmacokinetics: the type of enzymes he uses are viewed as dietary supplements by the Food and Drug Administration (FDA) rather than as prescription drugs, and are therefore unregulated.

GONZALEZ’S TREATMENT

In addition to pancreatic enzymes taken by mouth, Gonzalez prescribes a restrictive diet (which, even for those whom be pronounces to be obligate vegetarians, includes raw liver), and a staggering number of nutritional supplements which patients must take at regular intervals throughout the day and night.

The dietary guidelines he issues to his patients contain an amazing array of obviously unsound statements which bespeak not only a total abandonment of logical thinking on the part of their author, but also a casual disregard for objective fact, as though the solid benchmarks of physiology and biochemistry, such as pH, were just another narrative.

And then of course there’s the obligatory detoxification, without which no alternative treatment regimen could possibly be considered complete. But beyond its role as a doctrinal tenet, the notion that the body is inadequate to the task of handling its own waste holds a special utility for the practitioner of alternative cancer treatment. By insisting on regular and vigorous detoxification, the practitioner can reinforce the idea that the treatment regime – in this case, the pancreatic enzyme barrage – is working so well that the patient’s liver and bloodstream are in danger of being overrun by waste products from tumor breakdown. This must be a great boost to a patient in the advanced stages of cancer who is grimly contemplating his umpteenth coffee enema of the week and struggling to swallow another round of 30 supplement pills. However, most self-respecting physicians and patients would surely like to have that comforting assertion about massive tumor destruction confirmed with some kind of objective test such as imaging. And if the liver is really so hobbled by its task that it has to be supported by regular retrograde sluicing with tepid coffee, perhaps a few blood tests of liver function might be in order? It appears that such considerations are purely for pedants and infidels: real believers have no need for such niceties.

And then there are the supplements, in staggering quantities and bewildering combinations:

Five times during your waking hours take:

  • 16 pancreas glandular tissue
  • 1 magnesium citrate 60mg

With two doses of pancreas glandular take

  • 2 chicken collagen type II

During breakfast and dinner (twice daily) take:

  • 1 amino acids
  • 1 Calsym (vitamin D3 and calcium carbonate)
  • 1 thyroid (sic)
  • 1 vitamin E 100 IU

During each meal (3 times daily) take:

  • 1 adrenal glandular
  • 2 vitamin C
  • 1 Atlantic kelp
  • 2 Formula #1 (sic)
  • 1 liver
  • 1 lung
  • 2 magnesium citrate 60mg
  • 1 digest aid
  • 1 multivitamin
  • 1 multimineral
  • 3 pancreas glandular tissue
  • 3 thymus glandular tissue
  • 1 vitamin 400 IU

During lunch only take:

  • 1 beta carotene 25,000
  • 1 copper gluconate
  • 1 potassium citrate
  • 1 vitamin A 10,000 (which incidentally is twice the recommended daily allowance)

At bedtime take:

  • 2 iron
  • 2 magnesium citrate 60mg
  • 4 RNA/DNA (sic)

At 3:30am take:

  • 16 pancreas glandular tissue

The patient following such a program would take 187 supplement pills daily. Regardless of the dosage of active ingredients involved, the sheer volume and weight of excipients that are ingested during any one 24 hour period is surely something to take into account, especially in a patient debilitated by the ravages of advanced cancer. In a regimen that puts such emphasis on detoxification this is a curious departure indeed.

But onward.

THE EVIDENCE

In 1999, Gonzalez published a paper in the journal Nutrition and Cancer (abstract here) claiming that he had achieved significantly increased survival in 11 patients with inoperable pancreatic cancer by treating them with what he described as “an aggressive nutritional therapy with large doses of pancreatic enzymes.”

Now bear in mind that pancreatic cancer is one of the most aggressive and deadly of all malignancies. The majority of people with pancreatic adenocarcinoma, which is by far the commonest form of pancreatic cancer, die within a few months of their diagnosis; only one in five patients survive the first year, and just four percent of patients live five years beyond diagnosis.

So when Gonzalez published his paper asserting that 9 of the 11 patients (81%) whom he had treated with this regimen survived one year, while 5 (45%) survived two years, and the remaining 4 patients were still alive and holding their own at the 3 year mark, people sat up and took notice.

Despite the fact that this was a very small study, and rife with biases (not least, an obvious selection bias: a further 12 patients who were unable to comply fully with the treatment were excluded from the analysis), it was sufficiently positive a report in an otherwise unrelievedly gloomy prognostic landscape that it prompted further investigation. Ultimately a full-fledged phase III clinical trial comparing Gonzalez’ nutritional protocol to the standard chemotherapy regimen in pancreatic cancer patients was sponsored by the National Institutes of Health and was carried out at Columbia University.

Perhaps not surprisingly, the trial turned out to be hugely contentious and very unorthodox. As a means of eliminating experimental bias, clinical trials are typically “blinded” and randomized – i.e., they are carefully designed so that patients are randomly assigned to one group or the other, and neither the patients nor the physicians know which treatment they are receiving. But in this case there was no way that the trial could be randomized or blinded. Patients could choose whether to undergo chemotherapy or to be assigned to the Gonzalez protocol group, so both they and the investigating physicians knew what treatment they were getting from the beginning.

When it became apparent, as it quickly did, that the results were not going to reflect well on his treatment protocol. Gonzalez began clamoring loudly for an investigation, claiming that the clinical trial had been deliberately rigged to discredit him. (Those interested in the background to the clinical trial, including a very thorough discussion of its ethical and scientific implications, can read about it in several installments, titled “The Ethics of CAM Trials” (parts I-V), here.)

The results of the clinical trial were reported in a paper published in October, 2009, in the Journal of Clinical Oncology (article here). To summarize the results, the 32 patients who underwent traditional chemotherapy lived more than three times as long (14 months vs 4.3 months), and had a measurably better quality of life, including less pain than those treated by the Gonzalez protocol – and since pancreatic cancer is notoriously painful, this is a hugely important consideration in any treatment, regardless of whether or not it extends survival.

But perhaps the most extraordinary and disturbing aspect of the paper was this paragraph, in the Methods section, describing the Gonzalez protocol:

“The enzyme treatment included orally ingested proteolytic enzymes, nutritional supplements, detoxification, and an organic diet (unaltered from the pilot study). Patients received three pancreatic enzyme and two magnesium citrate capsules with each meal. The patients also took specified numbers of capsules with magnesium citrate and Papaya Plus every 4 hours on an empty stomach. The dose for patients with stage II disease was 69 enzyme capsules, and the dose for patients with stages III or IV was 81 capsules per day. After day 16, patients had a 5-day rest period and then resumed treatment on day 22. Treatment could be adjusted by the physician and could be increased for cancer progression. A diet that required at least 70% of the food to be raw or minimally cooked was required. All food was organic. Prescribed detoxification procedures included coffee enemas twice each day; skin brushing and cleansing; salt and soda baths; and a liver flush, clean sweep, and purging.”

Excuse me? A liver flush? What is that, exactly? And could someone please explain what is meant by “a clean sweep”? And purging? If it’s not an indelicate question, might we be told exactly what that consists of?

How this extraordinary paragraph found its way into print, unchallenged, in the venerable Journal of Clinical Oncology is unfathomable. Why didn’t the editors, or the authors, for that matter, feel that it might be useful – in fact, essential – to (a) append an explanation of exactly what was meant by these terms, and (b) to include some kind of rationale for their use?

And then, of course, there’s the larger question of how the institutional review board at Columbia managed to sidestep the ethical issues inherent in approving a trial that was set up to compare the apples of standard treatment with the oranges of liver flushes and clean sweeps. If there was genuine clinical equipoise here we’re in deep, deep trouble.

You might think that this study, with its damning result, would be the end of it. But you’d be wrong. Gonzalez has written a book, a paranoid, self-exculpatory monologue, a martyr’s manifesto detailing what he perceives as his deliberate persecution at vast public expense by a pernicious cancer industry mafia whose goal is to silence him forever. (Presumably the hit man who got Steve McQueen was no longer available?)

So what are we to make of Gonzalez? Is he a cynical fraud or does he genuinely believe that coffee enemas, skin brushing and massive doses of supplements are capable of holding back the tsunami of cancer?

At the end of the day it hardly matters: either way, he’s a dangerous man.

Antioxidant vitamins include vitamin E, beta-carotene, and vitamin C. They are often recommended and widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamins on cardiovascular events remains unclear. There is plenty of evidence but the trouble is that it is not always of high quality and confusingly contradictory. Consequently, it is possible to cherry-pick the studies you prefer in order to come up with the answer you like. That this approach is counter-productive should be obvious to every reader of this blog. Only a rigorous systematic review can provide an answer that is as reliable as possible with the data available to date. Chinese researchers have just published such an assessment.

They searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant investigations. To be eligible, studies had to be randomized, placebo-controlled trials reporting on the effects of antioxidant vitamins on cardiovascular outcomes. The primary outcome measures were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any adverse events.

The searches identified 293 articles of which 15 RCTs reporting data on 188209 participants met the inclusion criteria. In total, these studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation, as compared to placebo, had no effect on major cardiovascular events (RR, 1.00; 95% CI, 0.96-1.03), myocardial infarction (RR, 0.98; 95% CI, 0.92-1.04), stroke (RR, 0.99; 95% CI, 0.93-1.05), total death (RR, 1.03; 95% CI, 0.98-1.07), cardiac death (RR, 1.02; 95% CI, 0.97-1.07), revascularization (RR, 1.00; 95% CI, 0.95-1.05), total CHD (RR, 0.96; 95% CI, 0.87-1.05), angina (RR, 0.98; 95% CI, 0.90-1.07), and congestive heart failure (RR, 1.07; 95% CI, 0.96 to 1.19).

The authors’ conclusion from these data could not be clearer: Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.

Few subjects in the realm of nutrition have attracted as much research during recent years as did antioxidants, and it is hard to think of a disease for which they are not recommended by this expert or another. Cardiovascular disease used to be the flag ship in this fleet of conditions; not so long ago, even the conventional medical wisdom sympathized with the notion that the regular supplementation of our diet with antioxidant vitamins might reduce the risk of cardiovascular disease and mortality.

Today, the pendulum has swung back, and it now seems to be mostly the alternative scene that still swears by antioxidants for that purpose. Nobody doubts that antioxidants have important biological functions, but this excellent meta-analysis quite clearly and fairly convincingly shows that buying antioxidant supplements is a waste of money. It does not promote cardiovascular health, it merely generates very expensive urine.

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?

I think I must have mentioned this once or twice before: I am constantly on the look-out for new evidence which shows or suggests that some form of alternative medicine works. Today, it seems, I have been lucky.

In this randomised, double-blind, placebo-controlled clinical trial, 200 patients suffering from chronic obstructive pulmonary disease (COPD) were randomly allocated to receive oral therapy with 3 × 30 drops/day of an extract of Pelargonium sidoides (EPs 7630) or placebo. Both treatments were administered in addition to standardised COPD- therapies, and the treatment period lasted 24 weeks. The primary endpoint of this study was the time to the next exacerbation of COPD. Secondary endpoints were the number of such exacerbations, consumption of antibiotics, quality of life, patient satisfaction, inability to work, and the tolerability of the treatment.

The results show that the median time to exacerbation was significantly prolonged with the herbal treatment compared to placebo (57 versus 43 days). The superiority of EPs 7630 over placebo was also confirmed in secondary endpoints, e.g., fewer exacerbations, less patients with antibiotic use, improved quality of life, higher patient satisfaction, and less days of inability to work. The incidence of minor gastrointestinal adverse events was higher in the EPs 7630 group.

The authors of the study conclude that “the results demonstrate a statistically significant and clinically relevant superiority of add-on therapy with EPs 7630 over placebo and a good long-term tolerability in the treatment of moderate to severe COPD. EPs 7630 prolonged time to exacerbations and reduced exacerbation frequency and antibiotic use.”

Chronic obstructive pulmonary disease, is a progressive and serious condition linked to smoking which makes breathing increasingly difficult. The symptoms of COPD typically include a productive cough, wheezing, shortness of breath and chest tightness. Long-term exposure to other lung irritants—such as air pollution, chemical fumes, or dust may contribute to COPD. The condition is a major cause of disability, and currently it is the third leading cause of death, which means that millions of people suffer from COPD.

There is no cure for COPD; the damage to the airways and lungs is not reversible. Various symptomatic treatments exist, for instance, antibiotics, bronchio-dilators, steroids and physiotherapy. Lifestyle changes can further improve the situation,  help patients to stay more active, and slow the progress of the disease.

It is clear that COPD is a very serious condition, that the burden of suffering for individual patients can be immense, that therapeutic options are limited and often associated with adverse-effects. In this situation, any new effective and safe therapy would be more than welcome. Pelargonium has previously shown promise in the treatment of asthma, acute bronchitis as well as other respiratory infections. It seems generally safe but is not totally devoid of adverse-effects.

This new study gives hope to COPD-sufferers as it suggests that Pelargonium sidoides might alleviate their symptoms. The trial seems rigorous but the benefit is not huge and the treatment is not a cure of COPD. Moreover, I should point out that any new finding of this nature requires independent confirmations. I do think that the trial is an important step in the right direction, yet I feel that it is too early for issuing general recommendations.

The developed world is in the middle of a major obesity epidemic. It is predicted to cause millions of premature deaths and billions of dollars, money that would be badly needed elsewhere. The well-known method of eating less and moving more is most efficacious but sadly not very effective, that is to say people do not easily adopt and adhere to it. This is why many experts are searching for a treatment that works and is acceptable to all or at least most patients.

Entrepreneurs of alternative medicine have long jumped on this band waggon. They have learnt that the regulations are lax or non-existent, that consumers are keen to believe anything they tell them and that the opportunities to make a fast buck are thus enormous. Today, they are offering an endless array of treatments which are cleverly marketed, for instance via the Internet.

Since many years, my research team are involved in a programme of assessing the alternative slimming aids mostly through systematic reviews and occasionally also through conducting our own clinical trials. Our published analyses include the following treatments:

Phaseolus vulgaris

Supplements containing conjugated linoleic acid

Green tea

Garcinia extracts

Calcium supplements

Chromium picolinate

Guar gum

Chitosan

Acupuncture

There are, of course, many more but, for most, no evidence exist at all. The treatments listed above have all been submitted to clinical trials. The results show invariably that the outcomes were not convincingly positive: either there were too few data, or there were too many flaws in the studies, or the weight reduction achieved was too small to be clinically relevant.

Our latest systematic review is a good example; its aim was to evaluate the evidence from randomized controlled trials (RCTs) involving the use of the African Bush Mango, Irvingia gabonensis, for body weight reduction in obese and overweight individuals. Three RCTs were identified, and all had major methodological flaws. All RCTs reported statistically significant reductions in body weight and waist circumference favoring I. gabonensis over placebo. They also suggested positive effects of I. gabonensis on blood lipids. Adverse events included headache and insomnia. Despite these apparently positive findings, our conclusions had to be cautious: “Due to the paucity and poor reporting quality of the RCTs, the effect of I. gabonensis on body weight and related parameters are unproven. Therefore, I. gabonensis cannot be recommended as a weight loss aid. Future research in this area should be more rigorous and better reported.”

People who want to loose weight are often extremely desperate and ready to try anything. They are thus easy victims of the irresponsible promises that are being made on the Internet and elsewhere. Despite the overwhelmingly evidence to the contrary, consumers are led to believe that alternative slimming aids are effective. What is more, they are also misled to assume they are risks-free. This latter assumption is false too: apart from the harm done to the patient’s bank account, many alternative slimming aids are associated with side-effects which, in some cases, are  serious and can even include death.

The conclusion from all this is short and simple: alternative slimming aids are bogus.

In my very first post on this blog, I proudly pronounced that this would not become one of those places where quack-busters have field-day. However, I am aware that, so far, I have not posted many complimentary things about alternative medicine. My ‘excuse’ might be that there are virtually millions of sites where this area is uncritically promoted and very few where an insider dares to express a critical view. In the interest of balance, I thus focus of critical assessments.

Yet I intend, of course, report positive news when I think it is relevant and sound. So, today I shall discuss a new trial which is impressively sound and generates some positive results:

French rheumatologists conducted a prospective, randomised, double blind, parallel group, placebo controlled  trial of avocado-soybean-unsaponifiables (ASU). This dietary supplement has complex pharmacological activities and has been used since years for osteoarthritis (OA) and other conditions. The clinical evidence has, so far, been encouraging, albeit not entirely convincing. My own review arrived at the conclusion that “the majority of rigorous trial data available to date suggest that ASU is effective for the symptomatic treatment of OA and more research seems warranted. However, the only real long-term trial yielded a largely negative result”.

For the new trial, patients with symptomatic hip OA and a minimum joint space width (JSW) of the target hip between 1 and 4 mm were randomly assigned to  three years of 300 mg/day ASU-E or placebo. The primary outcome was JSW change at year 3, measured radiographically at the narrowest point.

A total of 399 patients were randomised. Their mean baseline JSW was 2.8 mm. There was no significant difference on mean JSW loss, but there was 20% less progressors in the ASU than in the placebo group (40% vs 50%, respectively). No difference was observed in terms of clinical outcomes. Safety was excellent.

The authors concluded that 3 year treatment with ASU reduces the speed of JSW narrowing, indicating a potential structure modifying effect in hip OA. They cautioned that their results require independent confirmation and that the clinical relevance of their findings require further assessment.

I like this study, and here are just a few reasons why:

It reports a massive research effort; I think anyone who has ever attempted a 3-year RCT might agree with this view.

It is rigorous; all the major sources of bias are excluded as far as humanly possible.

It is well-reported; all the essential details are there and anyone who has the skills and funds would be able to attempt an independent replication.

The authors are cautious in their interpretation of the results.

The trial tackles an important clinical problem; OA is common and any treatment that helps without causing significant harm would be more than welcome.

It yielded findings which are positive or at least promising; contrary to what some people seem to believe, I do like good news as much as anyone else.

I WISH THERE WERE MORE ALT MED STUDIES/RESEARCHERS OF THIS CALIBER!

I don’t suppose that many readers of this blog believe all things natural to be entirely safe, but the general public seems to be hard-wired victims of this myth: Mother Nature is benign, and herbal remedies must be harmless!

There are, of course, several reasons why supposedly “natural” herbal treatments can be unsafe. Plants extracts can be toxic, they might interact with prescribed drugs or they can be contaminated or adulterated.

The latter two terms describe similar but not identical phenomena: contamination means the accidental addition of substances which should not be present in an herbal remedy; and adulteration signifies the deliberate addition of ingredients. If the substances in question are not pharmacologically inert, their presence in herbal remedies can cause adverse effects.

Both contamination and adulteration break laws and regulations; both are therefore illegal. Sadly, this does not mean that such things do not happen.

We have recently published an overview of the existing knowledge in this area. For this purpose, we summarised the evidence from 26 previously published reviews. Our findings were interesting but far from reassuring: the most commonly found contaminants were dust, pollen, insects, rodents, parasites, microbes, fungi, mould, pesticides, and heavy metals. The adulterants invariably were prescription drugs such as steroids, anti-diabetic medications etc.

These substances were implicated in a wide range of serious adverse effects in the unfortunate patients who took the remedies in question: agranulocytosis, meningitis, multi-organ failure, stroke, arsenic poisoning, mercury poisoning, lead poisoning, caner, encephalopathy, hepato-renal syndrome, kidney damage, rhabdomyolosis, metabolic acidosis, renal failure, liver failure, cerebral oedema, coma, and intra-cerebral bleeding. Several patients did not survive.

To avoid such disasters, consumers need to know which types of herbal remedies are most frequently implicated; our review showed that these were foremost Chinese and Indian remedies. While herbal medicines from the US or Europe ought to comply with certain rules and regulations regarding their quality and safety, Chinese and Indian herbal mixtures frequently enter our countries illegally or are bought from dubious sources, for instance, over the Internet. It is this type of herbal remedy that we should be concerned about.

We have to ask whether the risks outweigh the proven benefits of Chinese or Indian herbal mixtures. The short answer to this question is NO. There is very little compelling evidence to suggest that these treatments are efficacious. In the absence of proven benefit, even small or rare risks weigh heavily.

If the risk-benefit profile for any medical intervention fails to be positive, there can only be one reasonable conclusion regarding the use of this therapy – and that is: DON’T DO IT!

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