MD, PhD, FMedSci, FSB, FRCP, FRCPEd

causation

Linus Carl Pauling (1901 – 1994), the American scientist, peace activist, author, and educator who won two Nobel prizes, was one of the most influential chemists in history and ranks among the most important scientists of the 20th century. Linus Pauling’s work on vitamin C, however, generated considerable controversy. Pauling wrote many papers and a popular book, Cancer and Vitamin C. Vitamin C, we know today, protects cells from oxidative DNA damage and might thereby block carcinogenesis. Pauling popularised the regular intake of vitamin C; eventually he published two studies of end-stage cancer patients; their results apparently showed that vitamin C quadrupled survival times. A re-evaluation, however, found that the vitamin C groups were less sick on entry to the study. Later clinical trials concluded that there was no benefit to high-dose vitamin C. Since then, the established opinion is that the best evidence does not support a role for high dose vitamin C in the treatment of cancer. Despite all this, high dose IV vitamin C is in unexpectedly wide use by CAM practitioners.

Yesterday, new evidence has been published in the highly respected journal ‘Nature’; does it vindicate Pauling and his followers?

Chinese oncologists conducted a meta-analysis to assess the association between vitamin C intake and the risk to acquire lung cancer. Pertinent studies were identified by a searches of several electronic databases through December of 2013. Random-effect model was used to combine the data for analysis. Publication bias was estimated using Begg’s funnel plot and Egger’s regression asymmetry test.

Eighteen articles reporting 21 studies involving 8938 lung cancer cases were included in this meta-analysis. Pooled results suggested that highest vitamin C intake level versus lowest level was significantly associated with the risk of lung cancer. The effect was largest in investigations from the United States and in prospective studies. A linear dose-response relationship was found, with the risk of lung cancer decreasing by 7% for every 100 mg/day increase in the intake of vitamin C . No publication bias was found.

The authors conclude that their analysis suggested that the higher intake of vitamin C might have a protective effect against lung cancer, especially in the United States, although this conclusion needs to be confirmed.

Does this finding vindicate Pauling’s theory? Not really.

Even though the above-quoted conclusions seem to suggest a causal link, we are, in fact, far from having established one. The meta-analysis pooled mainly epidemiological data from various studies. Such investigations are doubtlessly valuable but they are fraught with uncertainties and cannot prove causality. For instance, there could be dozens of factors that have confounded these data in such a way that they produce a misleading result. The simplest explanation of the meta-analytic results might be that people who have a very high vitamin C intake tend to have generally healthier life-styles than those who take less vitamin C. When conducting a meta-analysis, one does, of course, try to account for such factors; but in many cases the necessary information to do that is not available, and therefore uncertainty persists.

In other words, the authors were certainly correct when stating that their findings needed to be confirmed. Pauling’s theory cannot be vindicated by such reports – in fact, the authors do not even mention Pauling with one word.

Dodgy science abounds in alternative medicine; this is perhaps particularly true for homeopathy. A brand-new trial seems to confirm this view.

The aim of this study was to test the hypothesis that homeopathy (H) enhances the effects of scaling and root planing (SRP) in patients with chronic periodontitis (CP).

The researchers, dentists from Brazil, randomised 50 patients with CP to one of two treatment groups: SRP (C-G) or SRP + H (H-G). Assessments were made at baseline and after 3 and 12 months of treatment. The local and systemic responses to the treatments were evaluated after one year of follow-up. The results showed that both groups displayed significant improvements, however, the H-G group performed significantly better than C-G group.

The authors concluded that homeopathic medicines, as an adjunctive to SRP, can provide significant local and systemic improvements for CP patients.

Really? I am afraid, I disagree!

Homeopathic medicines might have nothing whatsoever to do with this result. Much more likely is the possibility that the findings are caused by other factors such as:

  • placebo-effects,
  • patients’ expectations,
  • improved compliance with other health-related measures,
  • the researchers’ expectations,
  • the extra attention given to the patients in the H-G group,
  • disappointment of the C-G patients for not receiving the additional care,
  • a mixture of all or some of the above.

I should stress that it would not have been difficult to plan the study in such a way that these factors were eliminated as sources of bias or confounding. But this study was conducted according to the A+B versus B design which we have discussed repeatedly on this blog. In such trials, A is the experimental treatment (homeopathy) and B is the standard care (scaling and root planning). Unless A is an overtly harmful therapy, it is simply not conceivable that A+B does not generate better results than B alone. The simplest way to comprehend this argument is to imagine A and B are two different amounts of money: it is impossible that A+B is not more that B!

It is unclear to me what relevant research question such a study design actually does answer (if anyone knows, please tell me). It seems obvious, however, that it cannot test the hypothesis that homeopathy (H) enhances the effects of scaling and root planing (SRP). This does not necessarily mean that the design is necessarily useless.  But at the very minimum, one would need an adequate research question (one that matches this design) and adequate conclusions based on the findings.

The fact that the conclusions drawn from a dodgy trial are inadequate and misleading could be seen as merely a mild irritation. The facts that, in homeopathy, such poor science and misleading conclusions emerge all too regularly, and that journals continue to publish such rubbish are not just mildly irritating; they are annoying and worrying – annoying because such pseudo-science constitutes an unethical waste of scarce resources; worrying because it almost inevitably leads to wrong decisions in health care.

Readers of this blog will know that few alternative treatments are more controversial and less plausible than homeopathy. Therefore they might be interested to read about the latest attempt of homeopathy-enthusiasts to convince the public that, despite all the clinical evidence to the contrary, homeopathy does work.

The new article was published in German by Swiss urologist and is a case-report describing a patient suffering from paralytic ileus. This condition is a typical complication of ileocystoplasty of the bladder, the operation the patient had undergone. The patient had also been suffering from a spinal cord injury which, due to a pre-existing neurogenic bowel dysfunction, increases the risk of paralytic ileus.

The paraplegic patient developed a massive paralytic ileus after ileocystoplasty and surgical revision. Conventional stimulation of bowel function was unsuccessful. But after adjunctive homeopathic treatment normalization of bowel function was achieved.

The authors conclude that adjunctive homeopathic therapy is a promising treatment option in patients with complex bowel dysfunction after abdominal surgery who do not adequately respond to conventional treatment.

YES, you did read correctly: homeopathic therapy is a promising treatment

In case anyone doubts that this is more than a trifle too optimistic, let me suggest three much more plausible reasons why the patient’s bowel function finally normalised:

  • It could have been a spontaneous recovery (in most cases, even severe ones, this is what happens).
  • It could have been all the conventional treatments aimed at stimulating bowel function.
  • It could have been a mixture of the two.

The article made me curious, and I checked whether the authors had previously published other material on homeopathy. Thus I found two further articles in a very similar vein:

Article No 2 (dated 2014):

We present the clinical course of a patient with an epididymal abscess caused by multiresistant bacteria. As the patient declined surgical intervention, a conservative approach was induced with intravenous antibiotic treatment. As the clinical findings did not ameliorate, adjunctive homeopathic treatment was used. Under combined treatment, laboratory parameters returned to normal, and the epididymal abscess was rapidly shrinking. After 1 week, merely a subcutaneous liquid structure was detected. Fine-needle aspiration revealed sterile purulent liquid, which was confirmed by microbiological testing when the subcutaneous abscess was drained. Postoperative course was uneventful.

As the risk for recurrent epididymitis is high in persons with spinal cord injury, an organ-preserving approach is justified even in severe cases. Homeopathic treatment was a valuable adjunctive treatment in the above-mentioned case. Therefore, prospective studies are needed to further elucidate the future opportunities and limitations of classical homeopathy in the treatment of urinary tract infections.

Article No 3 (dated 2012):

Recurrent urinary tract infections (UTI) in patients with spinal cord injury are a frequent clinical problem. Often, preventive measures are not successful. We present the case reports of five patients with recurrent UTI who received additional homeopathic treatment. Of these patients, three remained free of UTI, whereas UTI frequency was reduced in two patients. Our initial experience with homeopathic prevention of UTI is encouraging. For an evidence-based evaluation of this concept, prospective studies are required.

It seems clear that all of the three more plausible explanations for the patients’ recovery listed above also apply to these two cases.

One might not be far off speculating that J Pannek, the first author of all these three articles, is a fan of homeopathy (this suspicion is confirmed by a link between him and the HOMEOPATHY RESEARCH INSTITUE: Prof Jürgen Pannek on the use of homeopathy for prophylaxis of UTI’s in patients with neurogenic bladder dysfunction). If that is so, I wonder why he does not conduct a controlled trial, rather than publishing case-report after case-report of apparently successful homeopathic treatments. Does he perhaps fear that his effects might dissolve into thin air under controlled conditions?

Case-reports of this nature can, of course, be interesting and some might even deserve to be published. But it would be imperative to draw the correct conclusions. Looking at the three articles above, I get the impression that, as time goes by, the conclusions of Prof Pannek et al (no, I know nobody from this group of authors personally) are growing more and more firm on less and less safe ground.

In my view, responsible authors should have concluded much more cautiously and reasonably. In the case of the paralytic ileus, for instance, they should not have gone further than stating something like this: adjunctive homeopathic therapy might turn out to be a promising treatment option for such patients. Despite the implausibility of homeopathy, this case-report might deserve to be followed up with a controlled clinical trial. Without such evidence, firm conclusions are clearly not possible.

If you believe herbalists, the Daily Mail or similarly reliable sources, you come to the conclusion that herbal medicines are entirely safe – after all they are natural, and everything that is natural must be safe. However, there is plenty of evidence that these assumptions are not necessarily correct. In fact, herbal medicines can cause harm in diverse ways, e. g. because:

  • one or more ingredients of a plant are toxic,
  • they interact with prescribed drugs,
  • they are contaminated, for instance, with heavy metals,
  • they are adulterated with prescription drugs.

There is no shortage of evidence for any of these 4 scenarios. Here are some very recent and relevant publications:

German authors reviewed recent case reports and case series that provided evidence for herbal hepatotoxicity caused by Chinese herbal mixtures. The implicated remedies were the TCM products Ban Tu Wan, Chai Hu, Du Huo, Huang Qin, Jia Wei Xia Yao San, Jiguja, Kamishoyosan, Long Dan Xie Gan Tang, Lu Cha, Polygonum multiflorum products, Shan Chi, ‘White flood’ containing the herbal TCM Wu Zhu Yu and Qian Ceng Ta, and Xiao Chai Hu Tang. the authors concluded that stringent evaluation of the risk/benefit ratio is essential to protect traditional Chinese medicines users from health hazards including liver injury.

A recent review of Nigerian anti-diabetic herbal remedies suggested hypoglycemic effect of over 100 plants. One-third of them have been studied for their mechanism of action, while isolation of the bioactive constituent(s) has been accomplished for 23 plants. Several plants showed specific organ toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of some liver function enzymes. Twenty-eight plants have been identified as in vitro modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes, while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly glutathione, with the potential to alter the pharmacokinetics of co-administered drugs

US authors published a case of a 44-year-old female who developed subacute liver injury demonstrated on a CT scan and liver biopsy within a month of using black cohosh to resolve her hot flashes. Since the patient was not taking any other drugs, they concluded that the acute liver injury was caused by the use of black cohosh. The authors concluded: we agree with the United States Pharmacopeia recommendations that a cautionary warning about hepatotoxicity should be labeled on the drug package.

Hong Kong toxicologists recently reported five cases of poisoning occurring as a result of inappropriate use of herbs in recipes or general herbal formulae acquired from books. Aconite poisoning due to overdose or inadequate processing accounted for three cases. The other two cases involved the use of herbs containing Strychnos alkaloids and Sophora alkaloids. These cases demonstrated that inappropriate use of Chinese medicine can result in major morbidity, and herbal formulae and recipes containing herbs available in general publications are not always safe.

Finally, Australian emergency doctors just published this case-report: A woman aged 34 years presented to hospital with a history of progressive shortness of breath, palpitations, decreased exercise tolerance and generalised arthralgia over the previous month. A full blood count revealed normochromic normocytic anaemia and a haemoglobin level of 66 g/L. The blood film showed basophilic stippling, prompting measurement of lead levels. Her blood lead level (BLL) was 105 µg/dL. Mercury and arsenic levels were also detected at very low levels. On further questioning, the patient reported that in the past 6 months she had ingested multiple herbal preparations supplied by an overseas Ayurvedic practitioner for enhancement of fertility. She was taking up to 12 different tablets and various pastes and powders daily. Her case was reported to public health authorities and the herbal preparations were sent for analytical testing. Analysis confirmed high levels of lead (4% w/w), mercury (12% w/w), arsenic and chromium. The lead levels were 4000 times the maximum allowable lead level in medications sold or produced in Australia. Following cessation of the herbal preparations, the patient was commenced on oral chelation therapy, iron supplementation and contraception. A 3-week course of oral DMSA (2,3-dimercaptosuccinic acid) was well tolerated; BLL was reduced to 13 µg/dL and haemoglobin increased to 99 g/L. Her symptoms improved over the subsequent 3 months and she remains hopeful about becoming pregnant.

So, how safe are herbal medicines? Unfortunately, the question is unanswerable. Some herbal medicines are quite safe, others are not. But always remember: whenever you administer a treatment you should ask yourself one absolutely crucial question: do the documented benefits outweigh the risks? There are several thousand different herbal medicines, and for less than a dozen of them can the honest answer to this question be YES.

The above title was used for a Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

I have taken the liberty to quote its abstract in full:

Purpose—Cervical artery dissections (CDs) are among the most common causes of stroke in young and middle-aged adults. The aim of this scientific statement is to review the current state of evidence on the diagnosis and management of CDs and their statistical association with cervical manipulative therapy (CMT). In some forms of CMT, a high or low amplitude thrust is applied to the cervical spine by a healthcare professional.

Methods—Members of the writing group were appointed by the American Heart Association Stroke Council’s Scientific Statements Oversight Committee and the American Heart Association’s Manuscript Oversight Committee. Members were assigned topics relevant to their areas of expertise and reviewed appropriate literature, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge.

Results—Patients with CD may present with unilateral headaches, posterior cervical pain, or cerebral or retinal ischemia (transient ischemic or strokes) attributable mainly to artery–artery embolism, CD cranial nerve palsies, oculosympathetic palsy, or pulsatile tinnitus. Diagnosis of CD depends on a thorough history, physical examination, and targeted ancillary investigations. Although the role of trivial trauma is debatable, mechanical forces can lead to intimal injuries of the vertebral arteries and internal carotid arteries and result in CD. Disability levels vary among CD patients with many having good outcomes, but serious neurological sequelae can occur. No evidence-based guidelines are currently available to endorse best management strategies for CDs. Antiplatelet and anticoagulant treatments are both used for prevention of local thrombus and secondary embolism. Case-control and other articles have suggested an epidemiologic association between CD, particularly vertebral artery dissection, and CMT. It is unclear whether this is due to lack of recognition of preexisting CD in these patients or due to trauma caused by CMT. Ultrasonography, computed tomographic angiography, and magnetic resonance imaging with magnetic resonance angiography are useful in the diagnosis of CD. Follow-up neuroimaging is preferentially done with noninvasive modalities, but we suggest that no single test should be seen as the gold standard.

Conclusions—CD is an important cause of ischemic stroke in young and middle-aged patients. CD is most prevalent in the upper cervical spine and can involve the internal carotid artery or vertebral artery. Although current biomechanical evidence is insufficient to establish the claim that CMT causes CD, clinical reports suggest that mechanical forces play a role in a considerable number of CDs and most population controlled studies have found an association between CMT and VAD stroke in young patients. Although the incidence of CMT-associated CD in patients who have previously received CMT is not well established, and probably low, practitioners should strongly consider the possibility of CD as a presenting symptom, and patients should be informed of the statistical association between CD and CMT prior to undergoing manipulation of the cervical spine.

In my view, this is an important statement to which I have little to add – however, I hope that the readers of this post will have comments, criticisms, observations, opinions, etc.

Reiki is a Japanese technique which, according to a proponent, … is administered by “laying on hands” and is based on the idea that an unseen “life force energy” flows through us and is what causes us to be alive. If one’s “life force energy” is low, then we are more likely to get sick or feel stress, and if it is high, we are more capable of being happy and healthy…

A treatment feels like a wonderful glowing radiance that flows through and around you. Reiki treats the whole person including body, emotions, mind and spirit creating many beneficial effects that include relaxation and feelings of peace, security and wellbeing. Many have reported miraculous results.

Reiki is a simple, natural and safe method of spiritual healing and self-improvement that everyone can use. It has been effective in helping virtually every known illness and malady and always creates a beneficial effect. It also works in conjunction with all other medical or therapeutic techniques to relieve side effects and promote recovery [my emphasis].

Many websites give much more specific information about the health effects of Reiki:

Some Of The Reiki Healing Health Benefits 

  • Creates deep relaxation and aids the body to release stress and tension,
  • It accelerates the body’s self-healing abilities,
  • Aids better sleep,
  • Reduces blood pressure
  • Can help with acute (injuries) and chronic problems (asthma, eczema, headaches, etc.) and aides the breaking of addictions,
  • Helps relieve pain,
  • Removes energy blockages, adjusts the energy flow of the endocrine system bringing the body into balance and harmony,
  • Assists the body in cleaning itself from toxins,
  • Reduces some of the side effects of drugs and helps the body to recover from drug therapy after surgery and chemotherapy,
  • Supports the immune system,
  • Increases vitality and postpones the aging process,
  • Raises the vibrational frequency of the body,
  • Helps spiritual growth and emotional clearing.

With such remarkable claims being made, I had to look into this extraordinary treatment.

In 2008, I had a co-worker in my team who was (still is, I think) a Reiki healer. He also happened to be a decent scientist, and we thus decided to conduct a systematic review summarising the evidence for the effectiveness of Reiki. We searched the literature using 23 databases from their respective inceptions through to November 2007 (search again 23 January 2008) without language restrictions. Methodological quality was assessed using the Jadad score. The searches identified 205 potentially relevant studies. Nine randomised clinical trials (RCTs) met our inclusion criteria. Two RCTs suggested beneficial effects of Reiki compared with sham control on depression, while one RCT did not report intergroup differences. For pain and anxiety, one RCT showed intergroup differences compared with sham control. For stress and hopelessness, a further RCT reported effects of Reiki and distant Reiki compared with distant sham control. For functional recovery after ischaemic stroke there were no intergroup differences compared with sham. There was also no difference for anxiety between groups of pregnant women undergoing amniocentesis. For diabetic neuropathy there were no effects of reiki on pain. A further RCT failed to show the effects of Reiki for anxiety and depression in women undergoing breast biopsy compared with conventional care.

Overall, the trial data for any one condition were scarce and independent replications were not available for any condition. Most trials suffered from methodological flaws such as small sample size, inadequate study design and poor reporting. We therefore concluded that the evidence is insufficient to suggest that Reiki is an effective treatment for any condition. Therefore the value of Reiki remains unproven.

But this was in 2008! In the meantime, the evidence might have changed. Here are two recent publications which, I think, are worth having a look at:

The first article is a case-report of a nine-year-old female patient with a history of perinatal stroke, seizures, and type-I diabetes was treated for six weeks with Reiki. At the end of this treatment period, there was a decrease in stress in both the child and the mother, as measured by a modified Perceived Stress Scale and a Perceived Stress Scale, respectively. No change was noted in the child’s overall sense of well-being, as measured by a global questionnaire. However, there was a positive change in sleep patterns on 33.3% of the nights as reported on a sleep log kept by the mother. The child and the Reiki Master (a Reiki practitioner who has completed all three levels of Reiki certification training, trains and certifies individuals in the practice of Reiki, and provides Reiki to individuals) experienced warmth and tingling sensations on the same area of the child during the Reiki 7 minutes of each session. There were no reports of seizures during the study period.

The author concluded that Reiki is a useful adjunct for children with increased stress levels and sleep disturbances secondary to their medical condition. Further research is warranted to evaluate the use of Reiki in children, particularly with a large sample size, and to evaluate the long-term use of Reiki and its effects on adequate sleep.

In my view, this article is relevant because it typifies the type of research that is being done in this area and the conclusions that are being drawn from it. It should be clear to anyone who has the slightest ability of critical thinking that a case report of this nature tells us as good as nothing about the effectiveness of a therapy. Considering that Reiki is just about the least plausible intervention anyone can think of, the child’s condition in all likelihood improved not because of the Reiki healing but because of a myriad of unrelated factors; just think of placebo-effects, regression towards the mean, natural history of the condition, concomitant treatments, etc.

The plausibility of energy/biofield/spiritual healing such as Reiki is also the focus of the second remarkable article that was just published. It reports a systematic review of studies designed to examine whether bio-field therapists undergo physiological changes as they enter the healing state (remember: the Reiki healer in the above study experienced ‘warmth and tingling sensations’ during therapies). If reproducible changes could be identified, the authors argue, they might serve as markers to reveal events that correlate with the healing process.

Databases were searched for controlled or non-controlled studies of bio-field therapies in which physiological measurements were made on practitioners in a healing state. Design and reporting criteria, developed in part to reflect the pilot nature of the included studies, were applied using a yes (1.0), partial (0.5), or no (0) scoring system.

Of 67 identified studies, the inclusion criteria were met by 22, 10 of which involved human patients. Overall, the studies were of moderate to poor quality and many omitted information about the training and experience of the healer. The most frequently measured biomarkers were electroencephalography (EEG) and heart rate variability (HRV). EEG changes were inconsistent and not specific to bio-field therapies. HRV results suggest an aroused physiology for Reconnective Healing, Bruyere healing, and Hawaiian healing, but no changes were detected for Reiki or Therapeutic Touch.

The authors of this paper concluded that despite a decades-long research interest in identifying healing-related biomarkers in bio-field healers, little robust evidence of unique physiological changes has emerged to define the healers׳ state.

Now, let me guess why this is so. One does not need to be a rocket scientist to come up with the suggestion that no robust evidence for Reiki and all the other nonsensical forms of healing can be found for one disarmingly simple reason: NO SUCH EFFECTS EXIST.

Have you noticed?

Homeopaths, acupuncturists, herbalists, reflexologists, aroma therapists, colonic irrigationists, naturopaths, TCM-practitioners, etc. – they always smile!

But why?

I think I might know the answer. Here is my theory:

Alternative practitioners have in common with conventional clinicians that they treat patients - lots of patients, day in day out. This wears them down, of course. And sometimes, conventional clinicians find it hard to smile. Come to think of it, alternative practitioners seem to have it much better. Let me explain.

Whenever a practitioner (of any type) treats a patient, one of three outcomes is bound to happen:

  1. the patient gets better,
  2. the patients roughly remains how she was and experiences no improvement,
  3. the patient gets worse.

In scenario one, everybody is happy. Both alternative and conventional practitioners will claim with a big smile that their treatment was the cause of the improvement. There is a difference though: the conventional practitioner who adheres to the principles of evidence-based medicine will know that the assumption is likely to be true, while the alternative practitioner is probably just guessing. In any case, as long as the patient gets better, all is well.

In scenario two, most conventional clinicians will get somewhat concerned and find little reason to smile. Not so the alternative practitioner! He will have one of several explanations why his therapy has not produced the expected result all of which allow him to carry on smiling smugly. He might, for instance, explain to his patient:

  • You have to give it more time; another 10-20 treatment sessions and you will be as right as rain (unfortunately, further sessions will come at a price).
  • This must be because of all those nasty chemical drugs that you took for so long – they block up your system, you know; we will have to do some serious detox to get rid of all this poison (of course, at a cost).
  • You must realize that, had we not started my treatment when we did, you would be much worse by now, perhaps even dead.

In scenario three, any conventional clinician would have stopped smiling and begun to ask serious, self-critical questions about his diagnosis and treatment. Not so the alternative practitioner. He will point out with a big smile that the deterioration of the symptoms only appears to be a bad sign. In reality it is a very encouraging signal indicating that the optimal treatment for the patient’s condition has finally been found and is beginning to work. The acute worsening of the complaints is merely an ‘aggravation’ or’ healing crisis’. Such a course of events had to be expected when true healing of the root cause of the condition is to be achieved. The thing to do now is to continue with several more treatments (at a cost, of course) until deep healing from within sets in.

Many of us want the cake and eat it – but alternative practitioners, it seems to me, have actually achieved this goal. No wonder they smile!

There is some (albeit not compelling) evidence to suggest that chiropractic spinal manipulation might be effective for treating non-specific back pain. But what about specific back pain, such as the one caused by a herniated disc? Some experts believe that, in patients suffering from such a condition, manipulations are contra-indicated (because the latter can cause the former), while others think that manipulation might be an effective treatment option (although the evidence is far from compelling). Who is correct? The issue can only be resolved with data from well-designed clinical investigations. A new trial might therefore enlighten us.

The stated purposes of this study were:

  1. to evaluate patients with low-back pain (LBP) and leg pain due to magnetic resonance imaging-confirmed disc herniation treated with high-velocity, low-amplitude spinal manipulation in terms of their short-, medium-, and long-term outcomes of self-reported global impression of change and pain levels
  2. to determine if outcomes differ between acute and chronic patients using.

The researchers conducted a ‘prospective cohort outcomes study‘ with 148 patients with LBP, leg pain, and physical examination abnormalities with concordant lumbar disc herniations. Baseline numerical rating scale (NRS) data for LBP, leg pain, and the Oswestry questionnaire were obtained. The specific lumbar spinal manipulation was dependent upon whether the disc herniation was intraforaminal or paramedian as seen on the magnetic resonance images and was performed by a chiropractor. Outcomes included the patient’s global impression of change scale for overall improvement, the NRS for LBP, leg pain, and the Oswestry questionnaire at 2 weeks, 1, 3, and 6 months, and 1 year. The proportion of patients reporting “improvement” on the patient’s global impression of change scale was calculated for all patients and for acute vs chronic patients. Pre-treatment and post-treatment NRS scores were compared using the paired t test. Baseline and follow-up Oswestry scores were compared using the Wilcoxon test. Numerical rating scale and Oswestry scores for acute vs chronic patients were compared using the unpaired t test for NRS scores and the Mann-Whitney U test for Oswestry scores.

Significant improvements for all outcomes at all time points were reported. At 3 months, 91% of patients were “improved”, and 88% were “improved” after 1 year. Acute patients improved faster by 3 months than did chronic patients. 81.8% of chronic patients 89.2% felt “improved” at 1 year. No adverse events were reported.

The researchers concluded that a large percentage of acute and importantly chronic lumbar disc herniation patients treated with chiropractic spinal manipulation reported clinically relevant improvement.

Does this new study meaningfully contribute to our knowledge about the effectiveness of chiropractic manipulation for back pain caused by herniated discs? The short answer to this question is NO.

A longer answer might be that the report does tell us something relevant about the quality of this research project. We know from countless studies that ~50% of patients experience adverse effects after spinal manipulations by a chiropractor. This means that any report claiming that NO ADVERSE EFFECTS WERE REPORTED is puzzling to a degree that we have to seriously question its quality or even honesty. In this context, it is relevant to mention that a recent review of the evidence concluded that a cause-effect relationship exists between the manipulative treatment and the development of disc herniation.

The positive outcomes reported in this new study could, of course, be due to a range of factors which are unrelated to the manipulations administered by the chiropractors:

  1. placebo-effects
  2. natural history of disc herniation
  3. regression towards the mean
  4. other treatments employed by the patients
  5. social desirability

To be able to say with any degree of certainty that the manipulations had anything to do with the observed positive outcomes would require an entirely different study-design. Should we assume that this is not known in the world of chiropractic? Or should we consider that chiropractors shy away from rigorous research because they fear its results?

The term prospective cohort outcomes study, seems to be a chiropractic invention (cohort studies are by definition prospective, and observational studies are usually prospective). It seems that, behind this long and impressive word, one can easily hide the fact that this study design fails to make the slightest attempt of controlling for non-specific effects; the term sounds scientific – but when we analyse what it means, we discover that this methodology is little more than a self-serving consumer survey. Most scientists would call such an investigation quite simply an OBSERVATIONAL STUDY.

I think it is time that chiropractors start doing proper research which actually does answer some of the many open questions regarding spinal manipulation.

A remarkable article about homeopathy and immunisation entitled THE IMMUNISATION DILEMMA came to my attention recently. Its abstract promised: “evidence quantifying the effectiveness of vaccination and HP (homeoprophylaxis) will be examined. New international research describing and analysing HP interventions will be reported. An evidence-based conclusion will be reached.”

Sounds interesting? Let’s see what the article really offers. Here is the relevant text:

…evidence does exist to support claims regarding the effectiveness of homeopathic immunisation is undeniable.

I was first invited to visit Cuba in December 2008 to present at an international conference hosted by the Finlay Institute, which is a W. H. O.-accredited vaccine manufacturer. The Cubans described their use of HP to control an outbreak of leptospirosis (Weilʼs syndrome – a potentially fatal, water-born bacterial disease) in 2007 among the residents of the three eastern provinces which were most severely damaged by a severe hurricane – over 2.2 million people [7]. 2008 was an even worse year involving three hurricanes, and the countryʼs food production was only just recovering at the time of the conference. The HP program had been repeated in 2008, but data was not available at the conference regarding that intervention.

I revisited Cuba in 2010 and 2012, each time to work with the leader of the HP interventions, Dr. Bracho, to analyse the data available. Dr. Bracho is not a homeopath; he is a published and internationally recognised expert in the manufacture of vaccine adjuvants. He worked in Australia at Flinders University during 2004 with a team trying to develop an antimalarial vaccine.

In 2012 we accessed the raw leptospirosis surveillance data, comprising weekly reports from 15 provinces over 9 years (2000 to 2008) reporting 21 variables. This yielded a matrix with 147 420 possible entries. This included data concerning possible confounders, such as vaccination and chemoprophylaxis, which allowed a careful examination of possible distorting effects. With the permission of the Cubans, I brought this data back to Australia and it is being examined by mathematicians at an Australian university to see what other information can be extracted. Clearly, there is objective data supporting claims regarding the effectiveness of HP.

The 2008 result was remarkable, and could only be explained by the effectiveness of the HP intervention. Whilst the three hurricanes caused immense damage throughout the country it was again worse in the east, yet the three homeopathically immunised provinces experienced a negligible increase in cases whilst the rest of the country showed significant increases until the dry season in January 2009 [8].

This is but one example – there are many more. It is cited to show that there is significant data available, and that orthodox scientists and doctors have driven the HP interventions, in the Cuban case. Many people internationally now know this, so once again claims by orthodox authorities that there is no evidence merely serves to show that either the authorities are making uninformed/unscientific statements, or that they are aware but are intentionally withholding information. Either way, confidence is destroyed and leads to groups of people questioning what they are told…

Final Conclusions

The attacks against homeopathy in general and HP in particular will almost certainly continue. If we can achieve a significant level of agreement then we would be able to answer challenges to HP with a single, cohesive, evidence-based, and generally united response. This would be a significant improvement to the existing situation.

 

Reference 7 is the following article: Bracho G, Varela E, Fernández R et al. Large-scale application of highly-diluted bacteria for Leptospirosis epidemic control. Homeopathy 2010; 99: 156-166. The crucial bit if this paper are as follows:

A homeoprophylactic formulation was prepared from dilutions of four circulating strains of Leptospirosis. This formulation was administered orally to 2.3 million persons at high risk in an epidemic in a region affected by natural disasters. The data from surveillance were used to measure the impact of the intervention by comparing with historical trends and non-intervention regions.

After the homeoprophylactic intervention a significant decrease of the disease incidence was observed in the intervention regions. No such modifications were observed in non-intervention regions. In the intervention region the incidence of Leptospirosis fell below the historic median. This observation was independent of rainfall.

The homeoprophylactic approach was associated with a large reduction of disease incidence and control of the epidemic. The results suggest the use of HP as a feasible tool for epidemic control, further research is warranted.

The paper thus describes little more than an observational study. It shows that one region was less affected than another. I think it is quite clear that this could have many reasons which are unrelated to the homeopathic immunisation. Even the authors are cautious and speak in their conclusions not of a causal effect but of an “association”.

The 2012 data cited in the text remains unpublished; until it is available for public scrutiny, it is impossible to confirm that it is sound and meaningful.

Reference 8 refers to this article: Golden I, Bracho G. Adaptability of homœoprophylaxis in endemic, epidemic and stable background conditions. Homœopathic Links 2009; 22: 211-213. I have no access to this paper (if someone does, please fill us in) but, judging from both its title and the way it is described in the text, it does not seem to show reliable data about the efficacy of homeopathic immunisation.

So, is it true that “evidence does exist to support claims regarding the effectiveness of homeopathic immunisation”?

I do not think so!

Immunisation is by no means a trivial matter; wrong decisions in this area have the potential to cost the lives of millions. Therefore proofs of efficacy need to be published in peer-reviewed journals of high standing. These findings need then be criticised, replicated and re-criticised and re-replicated. Only when there is a wide consensus about the efficacy/safety or lack of efficacy/safety of a new form of immunisation, can it be generally accepted and implemented into clinical practice.

The current consensus about homeopathic immunisation is that it is nothing less than dangerous phantasy. Those who promote this quackery should be publicly exposed as charlatans of the worst kind.

Some practitioners of alternative medicine (doctors, naturopaths, chiropractors and others) earn a lot of money with the claim that chelation therapy (an effective mainstream treatment for acute heavy metal poisoning) is an effective means to  treat cardiovascular disease. However, the notion is controversial and implausible. Several systematic reviews of the best evidence concluded less than optimistically:

…more controlled studies are required to determine the efficacy of chelation therapy in cardiovascular disease before it can be used broadly in the clinical setting.

The best available evidence does not support the therapeutic use of EDTA chelation therapy in the treatment of cardiovascular disease.

Given the potential of chelation therapy to cause severe adverse effects, this treatment should now be considered obsolete.

The available data do not support the use of chelation in cardiovascular diseases.

More recently, important new evidence has emerged. The largest study of chelation therapy (TACT) ever conducted cost ~ $ 30 million and concluded that among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.

At the time, the TACT trial was heavily and rightly criticised for a whole host of reasons. For instance, because of the result of the FDA inspection of the highest accruing TACT site:

  • The investigators didn’t conduct the investigation in accordance with the signed statement and investigational plan. Several examples were given of shoddy procedures, prefilled forms, and failure to train personnel.
  • Failure to report promptly to the IRB all unanticipated problems involving risk to human subjects or others. Examples are given, including failure to report the deaths of patients on the study in a timely fashion (in one case the death wasn’t reported to the IRB until four months later; in another case it was never reported at all). In other cases, adverse event reports were not submitted to the IRB.
  • Failure to prepare or maintain adequate case histories with respect to observations and data pertinent to the investigation.
  • Investigational drug disposition records are not adequate with respect to dates, quantity, and use by subjects.

Despite these problems, the study was published in JAMA, albeit with a very critical editorial:

Differential dropout in TACT suggests unmasking, but the problem of intentional unblinding is more concerning. The sponsors of the trial, the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Complementary and Alternative Medicine (NCCAM), were unblinded throughout the trial. The National Institutes of Health policy unwisely allows the sponsor access to unblinded trial data, and both organizations sent observers to the closed sessions of the data monitoring committee. This gave them access to confidential data during each of the 11 interim analyses. The unblinding of the study sponsor represents a serious deviation from acceptable standards of conduct for supervision of clinical trials. If a pharmaceutical company sponsoring a trial were allowed access to actual outcome data during the study, there would be major objections. Like any sponsor, the NHLBI and NCCAM cannot be considered unbiased observers. These agencies made major financial commitments to the trial and may intentionally or inadvertently influence study conduct if inappropriately unblinded during the study…

Given the numerous concerns with this expensive, federally funded clinical trial, including missing data, potential investigator or patient unmasking, use of subjective end points, and intentional unblinding of the sponsor, the results cannot be accepted as reliable and do not demonstrate a benefit of chelation therapy. The findings of TACT should not be used as a justification for increased use of this controversial therapy.

Orac, makes several further critical points about the published trial:

First, the primary endpoint (i.e., the aggregated serious cardiovascular events) did indeed show a modest difference, namely 30% of placebo subjects versus 26.5% of the EDTA chelation subjects (hazard ratio 0.82 for chelation). However, one notes that the result is just barely statistically significant, p = 0.035, with the 99% confidence interval for the hazard ratio ranging from 0.69 to 0.99. (The predetermined level for statistical significance for purposes of this study was 0.036; so this is statistically significant by the barest margin.) More importantly, if you look at the individual endpoints that make up that aggregate, there was no statistically significant difference in death, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. Subgroup analysis (always a questionable analysis that requires replication, even when preplanned, as in TACT) purported to show a much greater benefit for diabetics, with a hazard ratio of 0.61 (p=0.002), while patients without diabetes showed no statistically significant difference in any of the outcome measures, including the aggregated total bad outcomes.

Now a paper that has just emerged describes the intent-to-treat comparison of this trial in patients with diabetes.

This was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post-myocardial infarction (MI) patients ≥50 years of age and with creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral mixture or placebo. The primary end point was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina.

Median age was 65 years, 18% were female, 94% were Caucasian, 37% were diabetic, 83% had prior coronary revascularization, and 73% were on statins. Five-year Kaplan-Meier estimates for the primary end point was 31.9% in the chelation + high-dose vitamin group, 33.7% in the chelation + placebo vitamin group, 36.6% in the placebo infusion + active vitamin group, and 40.2% in the placebo infusions + placebo vitamin group. The reduction in primary end point by double active treatment compared with double placebo was significant (hazard ratio 0.74, 95% CI 0.57-0.95, P = .016). In patients with diabetes, the primary end point reduction of double active compared with double placebo was more pronounced (hazard ratio 0.49, 95% CI 0.33-0.75, P < .001).

The authors conclude that in stable post-MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance.

I fear that these conclusions are erroneous and misleading: the marginally positive finding might have nothing to do with chelation per se; most likely they are due to the fact that the ‘vitamin’ mixture administered along with chelation contained ingredients like heparin and procaine which are potentially beneficial for cardiovascular conditions. Moreover, the placebo contained a considerable amount of glucose which could easily explain the better outcome of the diabetic subgroup receiving the verum – in other words, the verum generated better results not because it was effective but because the ‘placebo’ had detrimental effects.

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