We all know that there is a plethora of interventions for and specialists in low back pain (chiropractors, osteopaths, massage therapists, physiotherapists etc., etc.); and, depending whether you are an optimist or a pessimist, each of these therapies is as good or as useless as the next. Today, a widely-publicised series of articles in the Lancet confirms that none of the current options is optimal:
Almost everyone will have low back pain at some point in their lives. It can affect anyone at any age, and it is increasing—disability due to back pain has risen by more than 50% since 1990. Low back pain is becoming more prevalent in low-income and middle-income countries (LMICs) much more rapidly than in high-income countries. The cause is not always clear, apart from in people with, for example, malignant disease, spinal malformations, or spinal injury. Treatment varies widely around the world, from bed rest, mainly in LMICs, to surgery and the use of dangerous drugs such as opioids, usually in high-income countries.
The Lancet publishes three papers on low back pain, by an international group of authors led by Prof Rachelle Buchbinder, Monash University, Melbourne, Australia, which address the issues around the disorder and call for worldwide recognition of the disability associated with the disorder and the removal of harmful practices. In the first paper, Jan Hartvigsen, Mark Hancock, and colleagues draw our attention to the complexity of the condition and the contributors to it, such as psychological, social, and biophysical factors, and especially to the problems faced by LMICs. In the second paper, Nadine Foster, Christopher Maher, and their colleagues outline recommendations for treatment and the scarcity of research into prevention of low back pain. The last paper is a call for action by Rachelle Buchbinder and her colleagues. They say that persistence of disability associated with low back pain needs to be recognised and that it cannot be separated from social and economic factors and personal and cultural beliefs about back pain.
Overview of interventions endorsed for non-specific low back pain in evidence-based clinical practice guidelines (Danish, US, and UK guidelines)
In this situation, it makes sense, I think, to opt for a treatment (amongst similarly effective/ineffective therapies) that is at least safe, cheap and readily available. This automatically rules out chiropractic, osteopathy and many others. Exercise, however, does come to mind – but what type of exercise?
The aim of this meta-analysis of randomized controlled trials was to gain insight into the effectiveness of walking intervention on pain, disability, and quality of life in patients with chronic low back pain (LBP) at post intervention and follow ups.
Six electronic databases (PubMed, Science Direct, Web of Science, Scopus, PEDro and The Cochrane library) were searched from 1980 to October 2017. Randomized controlled trials (RCTs) in patients with chronic LBP were included, if they compared the effects of walking intervention to non-pharmacological interventions. Pain, disability, and quality of life were the primary health outcomes.
Nine RCTs were suitable for meta-analysis. Data was analysed according to the duration of follow-up (short-term, < 3 months; intermediate-term, between 3 and 12 months; long-term, > 12 months). Low- to moderate-quality evidence suggests that walking intervention in patients with chronic LBP was as effective as other non-pharmacological interventions on pain and disability reduction in both short- and intermediate-term follow ups.
The authors concluded that, unless supplementary high-quality studies provide different evidence, walking, which is easy to perform and highly accessible, can be recommended in the management of chronic LBP to reduce pain and disability.
I know – this will hardly please the legions of therapists who earn their daily bread with pretending their therapy is the best for LBP. But healthcare is clearly not about the welfare of the therapists, it is/should be about patients. And patients should surely welcome this evidence. I know, walking is not always easy for people with severe LBP, but it seems effective and it is safe, free and available to everyone.
My advice to patients is therefore to walk (slowly and cautiously) to the office of their preferred therapist, have a little rest there (say hello to the staff perhaps) and then walk straight back home.
“In my medical practice, writes Sheila Patel, M.D. on the website of Deepak Chopra, I always take into consideration the underlying dosha of a patient, or what their main imbalance is, when choosing treatments out of the many options available. For example, if I see someone who has the symptoms of hypertension as well as a Kapha imbalance, I may prescribe a diuretic, since excess water is more likely to be a contributing factor. I would also encourage more exercise or physical activity, since lack of movement is often a causative factor for these individuals. However, in a Vata-type person with hypertension, a diuretic may actually cause harm, as the Vata system tends to have too much dryness (air and space). I’ve observed that Vatas often have more side effects and electrolyte imbalances due to the diuretic medication. For these individuals, a beta-blocker may be a better choice, as this “slows” down the excitatory pathways in the body. In addition, I recommend meditation and calming activities to settle the excess energy as an adjunct to (or at times, instead of) the medicine. Alternatively, for someone with hypertension who is predominantly a Pitta type or who has a Pitta imbalance, I may choose a calcium-channel blocker, as this medication may be more beneficial in regulating the process of “energy exchange” in the body, which is represented by the fire element of Pitta. This is just one example of the way in which we can tailor our choice of medication to best suit the individual.
“In contrast with conventional medicine, which until very recently has assumed that a given disorder or disease is the same in all people, Ayurveda places great importance on recognizing the unique qualities of individual human beings. Ayurveda’s understanding of constitutional types or doshas offers us a remarkably accurate way to pinpoint what is happening inside each individual, allowing us to customize treatment and offer specific lifestyle recommendations to prevent disease and promote health and longevity. Keeping the doshas balanced is one of the most important factors in keeping the whole mind-body system in balance. When our mind-body system is in balance and we are connecting to our inner wisdom and intelligence, then we are most able to realize our full human potential and achieve our optimal state of being…”
END OF QUOTE
From such texts, some might conclude that Ayurvedic medicine is gentle and kind (personally, I am much more inclined to feel that Ayurvedic medicine is full of BS). This may be true or not, but Ayurvedic medicines are certainly anything but gentle and kind. In fact, they can be positively dangerous. I have repeatedly blogged about their risks, in particular the risk of heavy metal poisoning (see here, here, and here, for instance).
My 2002 systematic review summarised the evidence available at the time and concluded that heavy metals, particularly lead, have been a regular constituent of traditional Indian remedies. This has repeatedly caused serious harm to patients taking such remedies. The incidence of heavy metal contamination is not known, but one study shows that 64% of samples collected in India contained significant amounts of lead (64% mercury, 41% arsenic and 9% cadmium). These findings should alert us to the possibility of heavy metal content in traditional Indian remedies and motivate us to consider means of protecting consumers from such risks.
Meanwhile, new data have emerged and a new article with important information has recently been published by authors from the Department of Occupational and Environmental Health , College of Public Health, The University of Iowa and the State Hygienic Laboratory at the University of Iowa, USA. They present an analysis based on reports of toxic metals content of Ayurvedic products obtained during an investigation of lead poisoning among users of Ayurvedic medicine. Samples of Ayurvedic formulations were analysed for metals and metalloids following established US. Environmental Protection Agency methods. Lead was found in 65% of 252 Ayurvedic medicine samples with mercury and arsenic found in 38 and 32% of samples, respectively. Almost half of samples containing mercury, 36% of samples containing lead, and 39% of samples containing arsenic had concentrations of those metals per pill that exceeded, up to several thousand times, the recommended daily intake values for pharmaceutical impurities.
The authors concluded that lack of regulations regarding manufacturing and content or purity of Ayurvedic and other herbal formulations poses a significant global public health problem.
I could not have said it better myself!
The plethora of dodgy meta-analyses in alternative medicine has been the subject of a recent post – so this one is a mere update of a regular lament.
This new meta-analysis was to evaluate evidence for the effectiveness of acupuncture in the treatment of lumbar disc herniation (LDH). (Call me pedantic, but I prefer meta-analyses that evaluate the evidence FOR AND AGAINST a therapy.) Electronic databases were searched to identify RCTs of acupuncture for LDH, and 30 RCTs involving 3503 participants were included; 29 were published in Chinese and one in English, and all trialists were Chinese.
The results showed that acupuncture had a higher total effective rate than lumbar traction, ibuprofen, diclofenac sodium and meloxicam. Acupuncture was also superior to lumbar traction and diclofenac sodium in terms of pain measured with visual analogue scales (VAS). The total effective rate in 5 trials was greater for acupuncture than for mannitol plus dexamethasone and mecobalamin, ibuprofen plus fugui gutong capsule, loxoprofen, mannitol plus dexamethasone and huoxue zhitong decoction, respectively. Two trials showed a superior effect of acupuncture in VAS scores compared with ibuprofen or mannitol plus dexamethasone, respectively.
The authors from the College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, China, concluded that acupuncture showed a more favourable effect in the treatment of LDH than lumbar traction, ibuprofen, diclofenac sodium, meloxicam, mannitol plus dexamethasone and mecobalamin, fugui gutong capsule plus ibuprofen, mannitol plus dexamethasone, loxoprofen and huoxue zhitong decoction. However, further rigorously designed, large-scale RCTs are needed to confirm these findings.
Why do I call this meta-analysis ‘dodgy’? I have several reasons, 10 to be exact:
- There is no plausible mechanism by which acupuncture might cure LDH.
- The types of acupuncture used in these trials was far from uniform and included manual acupuncture (MA) in 13 studies, electro-acupuncture (EA) in 10 studies, and warm needle acupuncture (WNA) in 7 studies. Arguably, these are different interventions that cannot be lumped together.
- The trials were mostly of very poor quality, as depicted in the table above. For instance, 18 studies failed to mention the methods used for randomisation. I have previously shown that some Chinese studies use the terms ‘randomisation’ and ‘RCT’ even in the absence of a control group.
- None of the trials made any attempt to control for placebo effects.
- None of the trials were conducted against sham acupuncture.
- Only 10 studies 10 trials reported dropouts or withdrawals.
- Only two trials reported adverse reactions.
- None of these shortcomings were critically discussed in the paper.
- Despite their affiliation, the authors state that they have no conflicts of interest.
- All trials were conducted in China, and, on this blog, we have discussed repeatedly that acupuncture trials from China never report negative results.
And why do I find the journal ‘dodgy’?
Because any journal that publishes such a paper is likely to be sub-standard. In the case of ‘Acupuncture in Medicine’, the official journal of the British Medical Acupuncture Society, I see such appalling articles published far too frequently to believe that the present paper is just a regrettable, one-off mistake. What makes this issue particularly embarrassing is, of course, the fact that the journal belongs to the BMJ group.
… but we never really thought that science publishing was about anything other than money, did we?
What an odd title, you might think.
Systematic reviews are the most reliable evidence we presently have!
Yes, this is my often-voiced and honestly-held opinion but, like any other type of research, systematic reviews can be badly abused; and when this happens, they can seriously mislead us.
A new paper by someone who knows more about these issues than most of us, John Ioannidis from Stanford university, should make us think. It aimed at exploring the growth of published systematic reviews and meta‐analyses and at estimating how often they are redundant, misleading, or serving conflicted interests. Ioannidis demonstrated that publication of systematic reviews and meta‐analyses has increased rapidly. In the period January 1, 1986, to December 4, 2015, PubMed tags 266,782 items as “systematic reviews” and 58,611 as “meta‐analyses.” Annual publications between 1991 and 2014 increased 2,728% for systematic reviews and 2,635% for meta‐analyses versus only 153% for all PubMed‐indexed items. Ioannidis believes that probably more systematic reviews of trials than new randomized trials are published annually. Most topics addressed by meta‐analyses of randomized trials have overlapping, redundant meta‐analyses; same‐topic meta‐analyses may exceed 20 sometimes.
Some fields produce massive numbers of meta‐analyses; for example, 185 meta‐analyses of antidepressants for depression were published between 2007 and 2014. These meta‐analyses are often produced either by industry employees or by authors with industry ties and results are aligned with sponsor interests. China has rapidly become the most prolific producer of English‐language, PubMed‐indexed meta‐analyses. The most massive presence of Chinese meta‐analyses is on genetic associations (63% of global production in 2014), where almost all results are misleading since they combine fragmented information from mostly abandoned era of candidate genes. Furthermore, many contracting companies working on evidence synthesis receive industry contracts to produce meta‐analyses, many of which probably remain unpublished. Many other meta‐analyses have serious flaws. Of the remaining, most have weak or insufficient evidence to inform decision making. Few systematic reviews and meta‐analyses are both non‐misleading and useful.
The author concluded that the production of systematic reviews and meta‐analyses has reached epidemic proportions. Possibly, the large majority of produced systematic reviews and meta‐analyses are unnecessary, misleading, and/or conflicted.
Ioannidis makes the following ‘Policy Points’:
- Currently, there is massive production of unnecessary, misleading, and conflicted systematic reviews and meta‐analyses. Instead of promoting evidence‐based medicine and health care, these instruments often serve mostly as easily produced publishable units or marketing tools.
- Suboptimal systematic reviews and meta‐analyses can be harmful given the major prestige and influence these types of studies have acquired.
- The publication of systematic reviews and meta‐analyses should be realigned to remove biases and vested interests and to integrate them better with the primary production of evidence.
Obviously, Ioannidis did not have alternative medicine in mind when he researched and published this article. But he easily could have! Virtually everything he stated in his paper does apply to it. In some areas of alternative medicine, things are even worse than Ioannidis describes.
Take TCM, for instance. I have previously looked at some of the many systematic reviews of TCM that currently flood Medline, based on Chinese studies. This is what I concluded at the time:
Why does that sort of thing frustrate me so much? Because it is utterly meaningless and potentially harmful:
- I don’t know what treatments the authors are talking about.
- Even if I managed to dig deeper, I cannot get the information because practically all the primary studies are published in obscure journals in Chinese language.
- Even if I did read Chinese, I do not feel motivated to assess the primary studies because we know they are all of very poor quality – too flimsy to bother.
- Even if they were formally of good quality, I would have my doubts about their reliability; remember: 100% of these trials report positive findings!
- Most crucially, I am frustrated because conclusions of this nature are deeply misleading and potentially harmful. They give the impression that there might be ‘something in it’, and that it (whatever ‘it’ might be) could be well worth trying. This may give false hope to patients and can send the rest of us on a wild goose chase.
So, to ease the task of future authors of such papers, I decided give them a text for a proper EVIDENCE-BASED conclusion which they can adapt to fit every review. This will save them time and, more importantly perhaps, it will save everyone who might be tempted to read such futile articles the effort to study them in detail. Here is my suggestion for a conclusion soundly based on the evidence, not matter what TCM subject the review is about:
OUR SYSTEMATIC REVIEW HAS SHOWN THAT THERAPY ‘X’ AS A TREATMENT OF CONDITION ‘Y’ IS CURRENTLY NOT SUPPORTED BY SOUND EVIDENCE.
On another occasion, I stated that I am getting very tired of conclusions stating ‘…XY MAY BE EFFECTIVE/HELPFUL/USEFUL/WORTH A TRY…’ It is obvious that the therapy in question MAY be effective, otherwise one would surely not conduct a systematic review. If a review fails to produce good evidence, it is the authors’ ethical, moral and scientific obligation to state this clearly. If they don’t, they simply misuse science for promotion and mislead the public. Strictly speaking, this amounts to scientific misconduct.
In yet another post on the subject of systematic reviews, I wrote that if you have rubbish trials, you can produce a rubbish review and publish it in a rubbish journal (perhaps I should have added ‘rubbish researchers).
And finally this post about a systematic review of acupuncture: it is almost needless to mention that the findings (presented in a host of hardly understandable tables) suggest that acupuncture is of proven or possible effectiveness/efficacy for a very wide array of conditions. It also goes without saying that there is no critical discussion, for instance, of the fact that most of the included evidence originated from China, and that it has been shown over and over again that Chinese acupuncture research never seems to produce negative results.
The main point surely is that the problem of shoddy systematic reviews applies to a depressingly large degree to all areas of alternative medicine, and this is misleading us all.
So, what can be done about it?
My preferred (but sadly unrealistic) solution would be this:
STOP ENTHUSIASTIC AMATEURS FROM PRETENDING TO BE RESEARCHERS!
Research is not fundamentally different from other professional activities; to do it well, one needs adequate training; and doing it badly can cause untold damage.
Newsweek recently reported that a herbalist has been charged with the death of a 13-year-old diabetic boy. Allegedly, the therapist replaced the boy’s insulin with herbal remedies. Tim Morrow, 83, was charged with
- child abuse causing death
- and with practicing medicine without a license.
Morrow stated that god had guided him to use herbs rather than conventional medicine and that he successfully treated treat his own prostate cancer in this way. Marrow can be seen on multiple YouTube videos from his ‘University of Common Sense’ promoting his bizarre ideas of health and disease.
Perhaps god also guided Marrow to make lots of money? He runs regular seminars and a thriving herbal on-line business, the ‘Common Sense Herbal Products‘. There are few ailments, for which ‘Common Sense Herbal Products’ do not seem to offer a herbal cure.
One of the remedies, ‘Pancreas Reg‘, for instance, claims to “act as natural insulin”. The 270 Tablets tub of this product costs US $74.22. It is easy to see, I find, how bold claims attract gullible customers depriving them not just of their money but also of their health.
Morrow started treating the boy suffering from Type 1 diabetes after he met his mother at one of his seminars. When the boy subsequently became semi-comatose, Morrow told his parents to treat their son with his herbal remedies rather than insulin which had been prescribed by qualified medical doctors. The boy, Edgar L., died only hours later. There is little doubt that he would have survived, if he had undergone conventional treatment, the medical examiner concluded.
“The allegations in this case underscore the serious health and safety risks of taking medical advice from someone who lacks a license and the proper training that goes with it,” the medical examiner said in a statement. “No family should have to suffer the tragedy of losing a child because of irresponsible, un-credentialed medical advice.”
On this blog, during lectures etc., I often stress that by far the biggest danger of seemingly harmless alternative therapies is that they are used to replace effective treatments for serious conditions. Diabetes is such a condition, and there are numerous instances where the advice of incompetent practitioners has endangered the lives of diabetics.
Three examples will have to suffice as examples of the plethora of such unethical neglect:
- “In homeopathy, diabetes is seen as a reflection of the body’s inability to function optimally. There is an imbalance that results in the body’s incapacity to effectively utilize the insulin that it produces, or to produce sufficient insulin for its needs. While symptoms often disappear after conventional treatment, the vital force does not. Homoeopathy can be used effectively in the treatment of diabetes. Here we mainly concentrate on functioning of the pancreas in efficient insulin production. The metabolic condition of a patient suffering from diabetes requires both therapeutic and nutritional measures to correct the illness. Homeopathy can regulate sugar metabolism while helping to resolve the metabolic disturbances that lead to diabetes. Furthermore, homeopathy helps stimulate the body’s self-healing powers in order to prevent complications such as open leg sores and other dysfunctions of the blood vessel, loss of vision, kidney failure. Homeopathic treatment does not target one illness, an organ, a body part or a symptom. Remedies are prescribed based on an assembly of presenting symptoms, their stresses in life.”
- “Management of Blood sugar. The commonly used remedies are Uranium Nitricum, Phosphoric Acid, Syzygium Jambolanum, Cephalandra Indica etc. These are classical Homeopathic remedies. These are used in physiologically active doses such as Mother tincture, 3x etc. depending up on the level of the blood sugar and the requirement of the patient. Several pharmaceutical companies have also brought in propriety medicines with a combination of the few Homeopathic medicines. Biochemic remedies which is a part of Homeopathy advocates Biocombination No 7 as a specific for Diabetes. Another Biochemic medicine Natrum Phos 3x is widely used with a reasonable success in controlling the blood sugar. Scientific studies on the impact of homeopathic medicines in bringing down blood sugar are limited, but many of the above remedies have some positive effects either as a stand-alone remedy or as an adjunct along with other medications.”
- “Modern medicine has no permanent cure for diabetes but alternative medicines like yoga ,mudra,ayurveda is very useful to control and even cure diabetes.Ayurveda is an alternative medicine to cure diabetes.”
But these are very rare instances!!!
That’s what apologists usually respond.
Yet, the truth is that NOBODY knows how often such harm occurs.
There is no monitoring system anywhere that would provide such information.
The ‘European Scientific Cooperative on Anthroposophic Medicinal Products‘ claim that there is a need for a regulatory framework for anthroposophic medicinal products (AMPs) in Europe. The existing regulatory requirements for conventional medicinal products are not appropriate for AMPs. Special registration procedures exist in some countries for homeopathic products and in the European Union for herbal products. However, these procedures only apply to a proportion of AMPs and the particular properties of AMPs are only in part accounted for. Suitable registration procedures especially for AMPs exist only in Germany and Switzerland.
The European Commission has acknowledged the existence of therapy systems, whose products have no adequate regulation, and it has proposed that the suitability of a separate legal framework for products of certain traditions such as Anthroposophic Medicine should be assessed. This statement should be seen in the context of developments in international trade, whereby representatives of therapy systems such as Traditional Chinese Medicine and Ayurveda wish to market their products in Europe.
It seems obvious that the safety of AMPs must be demonstrated, if regulators are to comply with the wishes of the AMP-industry. In other words, they require evidence. As luck has it, a recent paper provides just what they need.
The main objective of this analysis was to determine the frequency of adverse drug reactions (ADRs) to AMPs, relative to the number of AMP prescriptions.
The researchers conducted a prospective pharmacovigilance study with the patients of physicians in outpatient care in Germany. Diagnoses and prescriptions were extracted from the electronic medical records. A total of 38 German physicians trained in AM were asked to link all AMP prescriptions to the respective indications (diagnoses), and to document all serious ADRs as well as all ADRs of intensity III–IV. In addition, a subgroup of 7 ‘prescriber physicians’ agreed to also document all non-serious ADRs of any intensity. The study was conducted under routine care conditions with ADRs identified at ordinary follow-up consultations, without any additional scheduled follow-up visits. Physicians were remunerated with 15 Euro for each ADR report but not for their regular participation; patients received no remuneration. Patients were eligible for this analysis, if they had one or more AMP prescription in the years 2001–2010, followed by one or more physician visit.
A total of 44,662 patients with 311,731 AMP prescriptions, comprising 1722 different AMPs, were included. One hundred ADRs to AMPs occurred, caused by 83 different AMPs. ADR intensity was mild, moderate, and severe in 50% (n = 50/100), 43%, and 7% of cases, respectively; one ADR was serious. ADRs of any intensity occurred in 0.071% (n = 67/94,734) of AMP prescriptions and in 0.502% (n = 65/12,956) of patients prescribed AMPs. The highest ADR frequency was 0.290% of prescriptions for one specific AMP. Among all patients, serious ADRs occurred in 0.0003% (n = 1/311,731) of prescriptions and 0.0022% (n = 1/44,662) of patients.
The authors concluded that in this analysis from a large sample, ADRs to AMP therapy in outpatient care were rare; ADRs of high intensity as well as serious ADRs were very rare.
Most AMPs are highly diluted, and therefore, one would not expect frequent or serious ADRs. Yet, I still find these incidence figures mysterious. The reason is simple: even the ARDs of pure placebos (such as most AMPs) are known to be much more frequent. In other words, the nocebo-effects of drugs are much more common than these results seem to reflect.
This, I think, leads to one of two possible conclusions:
- AMPs are somehow miraculously exempt from the known facts of ADRs.
- There is something fundamentally wrong with this study.
I let you decide which is the case.
Oh, I almost forgot. At the end of this paper there is a not unimportant note:
The EvaMed study was funded by the Software AG-Stiftung. This analysis and publication was commissioned by the European Scientific Cooperative on Anthroposophic Medicinal Products (http://www.escamp.org) with financial support from foundations (Christophorus-Stiftung, Damus-Donata-Stiftung, Ekhagastiftelsen, Mahle-Stiftung, Software AG-Stiftung) and manufacturers (Wala, Weleda). The sponsors had no influence on the planning or conduct of the EvaMed study; the collection, preparation, analysis or interpretation of data for this paper; nor on the preparation, review or approval of the manuscript.
Rapidly rising in popularity, kratom is hailed by some as a readily available pain remedy that is safer than traditional opioids, an effective addiction withdrawal aid and a pleasurable recreational tonic. But kratom also is assailed as a dangerous and unregulated drug that can be purchased on the Internet, a habit-forming substance that authorities say can result in opioid-like abuse and death.
Last week, the Food and Drug Administration announced that the herbal supplement kratom possesses the properties of an opioid, thus escalating the government’s effort to slow usage of this alternative pain reliever. The FDA states that the number of deaths associated with kratom use has increased to a total of 44, up from a total of 36 since the FDA’s November 2017 report. In the majority of deaths that FDA attributes to kratom, subjects ingested multiple substances with known risks, including alcohol. The presence of multiple drugs makes it difficult to determine the role any one of them played.
So, what is kratom, and why might it be dangerous?
A recent review explains that the leaves of Mitragyna speciosa (commonly known as kratom), a tree endogenous to parts of Southeast Asia, have been used traditionally for their stimulant, mood-elevating, and analgesic effects. The plant’s active constituents, mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as partial agonists at mu-opioid receptors and competitive antagonists at kappa- and delta-opioid receptors. Both alkaloids are G protein-biased agonists of the mu-opioid receptor and therefore, may induce less respiratory depression than classical opioid agonists. The Mitragyna alkaloids also appear to exert diverse activities at other brain receptors (including adrenergic, serotonergic, and dopaminergic receptors), which may explain the complex pharmacological profile of raw kratom extracts. Kratom exposure alone has not been causally associated with human fatalities to date. However, further research is needed to clarify the complex mechanism of action of the Mitragyna alkaloids and unlock their full therapeutic potential.
Another review adds that, by the early 2000s, kratom was increasingly used in the US as a natural remedy to improve mood and quality of life and as substitutes for prescription and illicit opioids for managing pain and opioid withdrawal by people seeking abstinence from opioids. There has been no documented threat to public health that would appear to warrant emergency scheduling of the products and placement in Schedule I of the CSA carries risks of creating serious public health problems. Banning kratom, risks creating public health problems that do not presently exist.
A third review explains that there are no published human pharmacologic, pharmacokinetic, or drug interaction studies on kratom or mitragynine, making it virtually impossible to fully understand kratom‘s therapeutic potential and risks and the populations most likely to benefit or experience harm from its use. Kratom has been used to ameliorate opioid withdrawal symptoms but also induces withdrawal. Human pharmacologic, pharmacokinetic and clinical data are of low quality precluding any firm conclusions regarding safety and efficacy. Kratom does cause a host of adverse effects without clear guidance for how they should be treated. There are numerous assessments where people have been unable to stop using kratom therapy and withdrawal signs and symptoms are problematic. Kratom does not appear in normal drug screens and, when taken with other substances of abuse, may not be recognized.
A systematic review evaluated all studies on kratom use and mental health published between January 1960 and July 2017. Its findings indicate kratom‘s potential as a harm reduction tool, most notably as a substitute for opioids among people who are addicted. Kratom also enhances mood and relieves anxiety among many users. For many, kratom‘s negative mental health effects – primarily withdrawal symptoms – appear to be mild relative to those of opioids. For some users, however, withdrawal is highly uncomfortable and maintaining abstinence becomes difficult.
In Europe, as of 2011, kratom has become a controlled drug in Denmark, Latvia, Lithuania, Poland, Romania and Sweden. In the UK, since 2016, the sale, import, and export of kratom are prohibited.
On balance, my conclusion is that we urgently need more data and meanwhile should avoid this ‘herbal drug’.
Many hard-nosed sceptics might claim that there is no herbal treatment for upper respiratory infections that makes the slightest difference difference. But is this assumption really correct?
According to my own research of 2004, it is not. Here is the abstract of our systematic review:
Acute respiratory infections represent a significant cause of over-prescription of antibiotics and are one of the major reasons for absence from work. The leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used as a medicinal herb in the treatment of infectious diseases. Systematic literature searches were conducted in six computerised databases and the reference lists of all papers located were checked for further relevant publications. Information was also requested from manufacturers, the spontaneous reporting schemes of the World Health Organisation and national drug safety bodies. No language restrictions were imposed. Seven double-blind, controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy. All trials scored at least three, out of a maximum of five, for methodological quality on the Jadad scale. Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. Adverse events reported following administration of A. paniculata were generally mild and infrequent. There were few spontaneous reports of adverse events. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted.
A. Paniculata (Burm.f.) Wall ex Nees (Acanthaceae family), also known as nemone chinensi, Chuān Xīn Lián, has traditionally been used in Indian and Chinese herbal medicine mostly as an antipyretic for relieving and reducing the severity and duration of symptoms of common colds and alleviating fever, cough and sore throats, or as a tonic to aid convalescence after uncomplicated respiratory tract infections. The active constituents of A. paniculata include the diterpene, lactones commonly known as the andrographolides which have shown anti-inflammatory, antiviral, anti-allergic, and immune-stimulatory activities. A. Paniculata has also been shown, in vitro, to be effective against avian influenza A (H9N2 and H5N1) and human influenza A H1N1 viruses, possibly through blocking the binding of viral hemagglutinin to cells, or by inhibiting H1N1 virus-induced cell death.
But our systematic review was published 14 years ago!
We need more up-to-date information!
And I am pleased to report that a recent paper provided exactly that.
This systematic review included published and unpublished RCTs. Quasi-RCTs, crossover trials, controlled before and after studies, interrupted time series (ITS) studies, and non-experimental studies were not included due to their potential high risk of bias.
Thirty-three trials involving 7175 patients with ARTIs were included. Their methodological quality was restricted as randomisation was not well documented; 73% of the trials included were not blinded; where ITT analysis were performed, loss to follow-up data were counted as no effect; and most trials were published without a protocol available.
Findings suggested limited but consistent evidence that A. Paniculata improved cough and sore throat when compared with placebo. A. Paniculata (alone or plus usual care) had a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. A. Paniculata in pillule tended to be more effective in improving overall symptoms over A. Paniculata in tablet. Evidence also suggested that A. Paniculata (alone or plus usual care) shortens the duration of cough, sore throat and sick leave/time to resolution when compared versus usual care. Reduction in antibiotic usage was seldom evaluated in the included trials.
The authors concluded that A. Paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity. Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. Paniculata are warranted.
In case you wonder about conflicts of interest: there were none with my 2004 paper, and the authors of the new review state that this paper presents independent research funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR). The views expressed are those of the author(s) and not necessarily those of the NIHR, the NHS or the Department of Health.
Yes, the RCTs are not all of top quality.
And yes, the effect size is not huge.
But maybe – just maybe – we do have here an alternative therapy that does help against a condition for which conventional drugs are fairly useless!?!
Traditional Chinese Medicine (TCM) is popular, not least because it is heavily marketed and thus often perceived as natural and safe. But is this assumption true?
This study analysed liver tests before and following treatment with herbal Traditional Chinese Medicine (TCM) in order to evaluate the risk of liver injury. Patients with normal values of alanine aminotransferase (ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To evaluate causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method (RUCAM) was used.
The report presents data of 21470 patients. ALT ranged from 1 × to < 5 × upper limit normal (ULN) in 844 patients (3.93%) and suggested mild or moderate liver adaptive abnormalities. A total of 26 patients (0.12%) experienced higher ALT values of ≥ 5 × ULN (300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was estimated to be probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases.
Compared with the large TCM study cohort, patients in the liver injury study cohort were older and contained a higher percentage of women, whereas the duration of the hospital stay was similar in both cohorts. The TCM herbs were rarely applied mostly as mixtures consisting of several herbs adding up to 35 different drugs during the patients’ four-week stay. The daily dosage was 95 ± 30 g and thus slightly higher than in the TCM study cohort. Among the many herbal TCM used by the 26 patients in the liver injury cohort, Bupleuri radix and Scuterllariae radix were the two TCM herbs most frequently implicated in liver injury, with variable RUCAM-based causality gradings. Most of the patients received one to six TCM drugs that were associated with potential liver injury as evidenced from the scientific literature, e.g., one patient (case 8) received six potentially hepatotoxic herbal TCM drugs during their hospital stay.
The authors concluded that in 26 (0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.
In the discussion section of the paper, the authors comment that the use of TCM is widely considered less risky as compared with synthetic drugs, although data on direct comparisons are not available in support of this view. Populations using herbal TCM, drugs, either alone, or combined experience more drug-induced liver injury (DILI) than herb-induced liver injury (HILI), possibly due to a higher use of drugs. Valid data of incidence and prevalence of HILI caused by TCM herbs are lacking, and respective data cannot be derived from the present study.
This study is most valuable, in my view. Its strength is clearly the huge sample size. Top marks for the authors for publishing it!
Having said that, we need to take the incidence figures with a pinch of salt, I think. In reality they could be much higher because:
- other settings will not be as tightly supervised as the unusual hospital setting;
- in most other situations the quality of the Chinese herbs might be less controlled;
- there could be adulteration;
- there could be contamination.
The ‘elephant in the room’ obviously is the inevitable question about benefit. Like any other treatment, TCM cannot be judged on the basis of its risk but must be evaluated according to its risk/benefit balance. I realise that this was not the subject of the present study, but it is nevertheless crucial: do the benefits of TCM outweigh its risks?
I am not aware that this is the case (but more than willing to consider any sound evidence readers might supply). More importantly, I am not aware of good evidence to show that, for any condition, TCM would be superior in terms of risk/benefit balance than conventional options. This is not a trivial issue: clinicians have the ethical obligation to apply the best (the one with the most positive risk/benefit balance) treatment to their patients.
If I am right, then TCM should not be used in therapeutic routine in or outside hospitals.
If I am right, the ‘First German Hospital of TCM‘ should close asap; it would be violating fundamental ethical principles.
If I am right, the debate about the risks of TCM is almost irrelevant because we simply should not use it.
Or did I misunderstand something here?
What do you think?
Herb/drug interactions are important, much-neglected and potentially dangerous. We have covered this issue several times, e. g. here. Recently, a valuable new paper has been published on the subject in a respected journal. Here is the abstract:
The aim of this review was to assess the severity of adverse drug reactions (ADRs) due to herb-drug interactions in patients taking herbs and prescribed medications based on published evidence.
Electronic databases of PubMed, the Cochrane Library, Medline and Scopus were searched for randomized or non-randomized clinical studies, case-control and case reports of herb-drug interactions (HDI). The data was extracted and the causal relationship of ADRs as consequences of HDI assessed using Horn’s drug interaction probability scale (DIPS) or Roussel Uclaf Causality Assessment Method (RUCAM) scoring systems. The mechanism of interaction was ascertained using Stockley’s herbal medicine interaction companion.
Forty-nine case reports and two observational studies with 15 cases of ADRs were recorded. The majority of the patients were diagnosed with cardiovascular diseases (30.60%), cancer (22.45%) and renal transplants (16.32%) receiving mostly warfarin, alkylating agents and cyclosporine, respectively.
HDI occurred in patients resulting in clinical ADRs with different severity. Patients may poorly respond to therapeutic agents or develop toxicity due to severe HDI which in either scenario may increase the cost of treatment and /or lead to or prolong patient hospitalisation. It is warranted to increase patient awareness of the potential interaction between herbs and prescribed medicines and their consequences to curb HDI as a potential health problem.
The journal must have published a press-release, because the findings were reported in several newspapers. THE DAILY TELEGRAPH picked up the story and reported it fairly well – at least this is what I thought when I started reading it. My opinion changed when, at the end of the article, I found this:
Emeritus Professor Edzard Ernst, Britain’s first professor of complementary medicine at Exeter University said that doctors should make it clear to patients that they could not be taking herbal remedies alongside drugs.
Prof Ernst said there was no good evidence that they work and that doctors were ‘contributing to disinformation’ by turning a blind eye to the practice.
I was taken aback!
I had not spoken to anyone at THE DAILY TELEGRAPH about this new publication.
What’s the harm?, you might ask.
Call me pedantic, but I think it is wrong to cite someone without interviewing him (or her).
Yet, I agree that the whole thing might be seen as a triviality, if the quote had been picked up correctly elsewhere. Sadly, that is not the case in this particular instance: the words that were put in my mouth are factually incorrect and I have never said or written anything remotely like them.
It is wrong to claim that there is no good evidence that they [herbal medicines] work (as discussed repeatedly on this blog and elsewhere, there are several herbal medicines that have been shown to work for defined conditions; St John’s Wort/depression is probably the best example). And consequently, it is nonsense to state that doctors were ‘contributing to disinformation’ by turning a blind eye to the practice.
When I first saw this article three days ago, I posted a comment asking the journalist to explain the situation. This would have been the opportunity to set things straight and correct the error to everybody’s satisfaction. Unfortunately, no reaction followed.
You might still think that this is a triviality. And perhaps you are right. But I nevertheless feel it is worrying that we seem to have gotten used to even ‘respected’ newspapers misrepresenting experts and facts. If this happens in the realm of medicine, who tells us that it is not also happening in politics etc?