MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

causation

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So-called alternative medicine (SCAM) is a seriously dangerous option for cancer patients who aim at curing their cancer with it. One cannot warn patients often and strongly enough, I believe. But when it comes to supportive cancer treatment (care that does not aim at changing the natural history of the disease), SCAM might have a place. I said ‘might’ because its exact role is far from clear.

The aim of this study was to investigate the effects of a complex, nurse-led, supportive care intervention using SCAM on patients’ quality of life (QoL) and associated patient-reported outcomes. In this prospective, pragmatic, bicentric, randomized controlled trial, women with breast or gynaecologic cancers undergoing a new regimen of chemotherapy (CHT) were randomly assigned to routine supportive care plus intervention (intervention group, IG) or routine care alone (control group, CG). The intervention consisted of SCAM applications and counseling for symptom management, as well as SCAM information material. The primary endpoint was global QoL measured with the EORTC-QLQ-C30 before and after SCAM.

In total, 126 patients were randomly assigned into the IG and 125 patients into the CG. The patients’ medical and socio-demographic characteristics were homogenous at baseline and at follow-up. No group effects on QoL were found upon completion of CHT, but there was a significant group difference in favour of the IG, 6 months later. IG patients did also experience significant better emotional functioning and less fatigue.

The authors concluded that the tested supportive intervention did not improve patients’ QoL outcomes directly after CHT (T3), but was associated with significant QoL improvements when considering the change from baseline to the time point T4, which could be assessed 6 months after patients’ completion of CHT. This delayed effect may have resulted due to a strengthening of patients’ self-management competencies.

A prospective, pragmatic, bicentric, randomized controlled trial! Doesn’t this sound rigorous? In fact, this term merely hides a trial that was destined to generate a positive result. As it followed the infamous A+B versus B design, it hardly had a chance to not come out positive.

The only thing I find amazing is that the short-term results failed to be statistically significant. Far too many SCAM researchers, it seems to me, view science as a tool for promoting their dubious ideas.

The use of SCAM with the aim of improving QoL might be helpful. But this assumption cannot be accepted on the basis of opinion; we need good science to find out which forms of SCAM are worth employing. Sadly, studies like the above are not in this category.

If you ask me, it is high time that this misleading nonsensical and unethical pseudo-research stops!

Spinal manipulation is an umbrella term for numerous manoeuvres chiropractors, osteopaths, physiotherapists and other clinicians apply to their patients’ vertebral columns.  Spinal manipulations are said to be effective for a wide range of conditions. But how do they work? What is their mode of action? A new article tries to address these questions. here is its abstract:

Spinal manipulation has been an effective intervention for the management of various musculoskeletal disorders. However, the mechanisms underlying the pain modulatory effects of spinal manipulation remain elusive. Although both biomechanical and neurophysiological phenomena have been thought to play a role in the observed clinical effects of spinal manipulation, a growing number of recent studies have indicated peripheral, spinal and supraspinal mechanisms of manipulation and suggested that the improved clinical outcomes are largely of neurophysiological origin. In this article, we reviewed the relevance of various neurophysiological theories with respect to the findings of mechanistic studies that demonstrated neural responses following spinal manipulation. This article also discussed whether these neural responses are associated with the possible neurophysiological mechanisms of spinal manipulation. The body of literature reviewed herein suggested some clear neurophysiological changes following spinal manipulation, which include neural plastic changes, alteration in motor neuron excitability, increase in cortical drive and many more. However, the clinical relevance of these changes in relation to the mechanisms that underlie the effectiveness of spinal manipulation is still unclear. In addition, there were some major methodological flaws in many of the reviewed studies. Future mechanistic studies should have an appropriate study design and methodology and should plan for a long-term follow-up in order to determine the clinical significance of the neural responses evoked following spinal manipulation.

I have to admit, this made me laugh. Any article that starts with the claim spinal manipulation is an effective intervention and speaks about its observed clinical effects without critically assessing the evidence for it must be ridiculous. The truth is that, so far, it is unclear whether spinal manipulations cause any therapeutic effects at all. To take them as a given, therefore discloses a bias that can only be a hindrance to any objective evaluation.

Yet, perhaps unwittingly, the paper raises an important question: do we need to search for a mode of action of treatments that are unproven? It is a question, of course, that is relevant to all or at least much of SCAM.

Do we need to research the mode of action of acupuncture?

Do we need to research the mode of action of energy healing?

Do we need to research the mode of action of reflexology?

Do we need to research the mode of action of homeopathy?

Do we need to research the mode of action of Bach flower remedies?

Do we need to research the mode of action of cupping?

Do we need to research the mode of action of qigong?

In the absence of compelling evidence that a mode of action (other than the placebo response) exists, I would say: no, we don’t. Such research might turn out to be wasteful and carries the risk of attributing credibility to treatments that do not deserve it.

What do you think?

 

Many cancer patients use so-called alternative medicine (SCAM) such as Traditional Chinese Medicine (TCM). On this blog, we have repeatedly discussed whether this does more good than harm. This study sheds new light on the question. Specifically, it aims to explore the benefits of TCM therapy in the long-term survival of patients with hepatocellular carcinoma in China.

In total, 3483 patients with HCC admitted to the Beijing Ditan Hospital of Capital Medical University were enrolled. The researchers used 1:1 frequency matching by sex, age, diagnosis time, Barcelona Clinic Liver Cancer staging, and type of treatments to compare the TCM users (n = 526) and non-TCM users (n = 526). A Cox multivariate regression model was employed to evaluate the effects of TCM therapy on the HR value and Kaplan-Meier survival curve for mortality risk in HCC patients. A log-rank test was performed to analyse the effect of TCM therapy on the survival time of HCC patients.

The Cox multivariate analysis indicated that TCM therapy was an independent protective factor for 5-year survival in patients with HCC. The Kaplan-Meier curve also showed that after PS matching, TCM users had a higher overall survival rate and a higher progression-free survival rate than non-TCM users. TCM users, regardless of the classification of etiology, tumor stage, liver function level, or type of treatment, all benefited significantly from TCM therapy. The most commonly used Chinese patent medications used were Fufang Banmao Capsule, Huaier Granule, and Jinlong Capsule.

The authors concluded that using traditional Chinese medications as adjuvant therapy can probably prolong median survival time and improve the overall survival among patients with HCC. Further scientific studies and clinical trials are needed to examine the efficiency and safety.

I was unable to access the full article and therefore am unable to provide a detailed critique of it. From reading the abstract, I should point out, however, that this was not an RCT. To minimise bias, the researchers used a matching technique to generate two comparable groups. Such methods can be successful in matching for the named parameters, but they cannot match for the plethora of variables that might be relevant but were not measured. Therefore, the survival difference between the two groups might be due not to the therapies they received, but to the fact that the groups were not comparable in terms of factors that impact on survival.

Another important point about this paper is the obvious fact that it originates from China. We know from several independent investigations that such studies almost never report negative findings. We also know that TCM is a hugely important export item for China. Adding two and two together should therefore make us sceptical. I for one take the present findings with more than a pinch of salt.

Indian doctors have just published the case of a 38-year old man with cirrhosis of the liver due to compensated non-alcoholic fatty-liver-disease. He presented with acute worsening of his chronic liver disease. The acute event was not discernible even after extensive work up. Eventually, a transjugular liver biopsy revealed features suggestive of severe alcoholic hepatitis.

The patient and the family denied occult alcohol use when questioned over multiple times. According to the authors, the culprit ‘alcohol’ was found to be the homoeopathy medicines: the patient had been consuming a homeopathic remedy over a month for treatment of Gilbert’s syndrome. The researchers retrieved and tested the homoeopathy drug for alcohol content and found it contained 18% of ethanol. This, they felt, confirmed their diagnosis of alcoholic liver disease caused by the regular consumption of a homeopathic remedy.

Why did the patient help from a homeopath? Gilbert’s syndrome doesn’t usually require any treatment at all. Two weeks into his new treatment, the patient claimed he was feeling drowsy and slurring his speech, as if intoxicated. The liquid homeopathic formulation was therefore reduced at this stage. A further two weeks passed when his eyes yellowed, his urine darkened, and his legs began to swell. A liver tests confirmed a spike in his bilirubin 10 times above normal, with liver enzymes also elevated. All signs were thus pointing to an acute form of hepatitis commonly associated with alcohol binges. With the patient adamant he hadn’t touched alcohol, the doctors looked for other causes of hepatitis. None were found. When the patient admitted using homeopathy, his doctors thought to have found an explanation for the problem.

Despite starting the patient on a range of treatments and referring him to a liver transplant centre for further management, the damage to the patient’s liver proved to be irreversible. One month and 12 days later, the patient developed multiple organ failure and passed away. The authors of this case report point out “at risk patients and the general population need to be educated regarding the fact that complementary and alternative medications are not without side-effects.”

I do agree with their comment, but I very much doubt that their diagnosis of homeopathy-induced liver disease was correct. If the alcohol in the homeopathic remedy truly had been the cause, the patient would have needed to consume well in excess of one litre of it per day. The authors do not tell us about the volume of consumption, but I doubt that a patient would be able to afford such an orgy in homeopathy.

Highly diluted homeopathic remedies contain nothing, it is often said. This is not entirely true. In the case of solid preparations (globuli), they do contain sugar, and in the case of liquid remedies, they contain alcohol. Yet, as a source of either ingredient, they are neither practical nor economical. I fear therefore that the medical team of the diseased man are mistaken when accusing homeopathy of being the cause of their patient’s death.

Kampo, the traditional Japanese herbal medicine, developed out of traditional Chinese herbal medicine after it was introduced into Japan in the 7th century. In the early 20th century, Kampo was further influenced by modern Western medicine and science. The Kampo system is a pragmatic and simplified version of Chinese herbal medicine. Kampo medicines are standardised and not normally individualised as in Chinese herbal medicine. They are based on the symptoms of the patient, interpreted in the tradition of Kampo. Kampo diagnostic criteria consider hypofunction and hyperfunction, heat and cold, superficies and interior, and yin and yang.

Today, Kampō is fully integrated into the Japanese national health care system, and numerous Kampo preparations are registered in Japan and reimbursable from public funds. In Japan, Kampo is thus not a so-called alternative medicine (SCAM), but outside this country it clearly is.

Standardised Kampo formulas contain mixtures of herbal ingredients. They are manufactured under proper quality control. The most commonly used plants include liquorice, ginger and Chinese peony root. Most Japanese doctors routinely prescribe Kampo medicines, and most patients combine Kampo with Western medicine. Since 2002, the teaching of Kampo has been included in Japanese curricula of medical and pharmacy education. The efficacy of Kampo medicines is often less solidly documented than one would hope or expect. There is a remarkable shortage of high-quality clinical trials.

As Kampo medicines contain pharmacologically active ingredients, they can also cause adverse effects and might interact with synthetic drugs. Yet, the risks of Kampo are currently woefully under-investigated. And this is why an analysis of adverse events associated with Kampo formulations that was just published is particularly important.

The researchers obtained reports of adverse events associated with ethical Kampo formulations from the domestic adverse-event data from July 30, 2003, to March 31, 2018. Adverse events were then categorized, and the relationships between categories of adverse events and crude drugs were analysed.

There were 4,232 reported adverse events associated with Kampo. They related to liver injury, 1,193; lung injury, 1,177; pseudoaldosteronism, 889; mesenteric phlebosclerosis, 223; drug eruption, 185; and others, 565. Among events related to both liver injury and lung injury, approximately 70% were suspected to be induced by Kampo formulations containing Scutellariae Radix.

The pseudoaldosteronism-related events, which are induced by Glycyrrhizae Radix, included several events related to muscle injury, heart failure, and arrhythmia. Events related to mesenteric phlebosclerosis, believed to be induced by long-term use of Kampo formulas containing Gardeniae Fructus, increased remarkably during the study period. Among the events related to drug eruption, approximately 35% were suspected to be induced by Kampo formulations containing Ephedrae Herba.

The authors concluded that Kampo medicines may cause various adverse events. The present results provide valuable information regarding adverse events associated with Kampo medicines from the viewpoint of patient safety.

While this paper presents invaluable data, its authors offer little by way of critical discussion. There is hardly any good evidence to show that any of the Kampo formulas are effective. Thus a discussion needs to be had about the question whether they generate more good than harm. The authors are completely silent on this important issue, and I suspect the reason might be that Kampo is a bit of a ‘holy cow’ in Japan that must not be questioned.

The numbers of adverse events are impressively high, but we do not know how they compare to adverse events in other areas of healthcare. For instance, it would be valuable to have comparative data indicating how many adverse events occurred with Kampo compared to synthetic drugs per 1 000 patients using them.

Thus we are left with the conclusion that, once proper post-marketing methods are employed to monitor SCAM, we are likely to realise that adverse events do occur more frequently than SCAM enthusiasts might have predicted. In my view, it is high time that we have effective adverse event monitoring in all areas of SCAM.

Spinal manipulation has been associated with a wide range of serious complications. Usually, they occur after neck manipulations. Neurologists from Morocco just published a case-report of a patient suffering a subdural haematoma after lumbar spinal manipulation.

A previously healthy 23 years-old man was receiving spinal manipulation for chronic back pain by a physiotherapist when he experienced a knife-like low back pain and lower limbs radiculalgia. The manipulation consisted on high velocity pression in the lumbar region while the patient was in prone position. He woke up the next morning with a weakness of both lower limbs and sensation of bladder fullness.

On presentation to the emergency department, 24 hours after the manipulation, the neurological examination found a cauda equina syndrome with motor strength between 2/5 and 3/5 in the left lower limb, 4/5 in the right lower limb, an abolition of the patellar and Achilles reflexes, a saddle hypoesthesia and a tender bladder. The general examination was normal. Magnetic resonance imaging (MRI) of the lumbar spine was performed promptly and showed intradural collection extending from L2 to L3 level with signal intensity consistent with blood. There were no adjacent fractures, disc or ligament injuries. Routine blood investigations were normal.

The patient underwent an emergency operation via L2-L3 laminectomy. The epidural space had no obvious abnormalities but the dura mater was tense and bluish. After opening the dura, a compressive blood clot was removed completely. The origin of the bleeding could not be determined. At the end of the intervention, nerve roots appeared free with normal courses. Subsequently, the patient’s the motor function of lower limbs gradually returned. He was discharged without neurological deficits 6 days postoperatively. At 6-months’ follow-up, the neurological examination was totally normal.

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Subdural haematoma is a rare occurrence. As a complication after spinal manipulation, it seems to be ever rarer. Our case-series of serious adverse effects after chiropractic manipulation did include such a case, albeit not at the lumbar level (as far as I remember):

To obtain preliminary data on neurological complications of spinal manipulation in the UK all members of the Association of British Neurologists were asked to report cases referred to them of neurological complications occurring within 24 hours of cervical spine manipulation over a 12-month period. The response rate was 74%. 24 respondents reported at least one case each, contributing to a total of about 35 cases. These included 7 cases of stroke in brainstem territory (4 with confirmation of vertebral artery dissection), 2 cases of stroke in carotid territory and 1 case of acute subdural haematoma. There were 3 cases of myelopathy and 3 of cervical radiculopathy. Concern about neurological complications following cervical spine manipulation appears to be justified. A large long-term prospective study is required to determine the scale of the hazard.

The big problem with adverse events of this nature is that their true incidence is essentially unknown. The  two cases of subdural haematoma mentioned above seem to be the only two reported in the medical literature. But, as there is no monitoring system, the true figure is anybody’s guess.

Fibromyalgia (FM) is one of the most frequent generalized pain disorders. It accounts for a sizable proportion of healthcare costs. Despite extensive research, the etiology (the ‘root cause’) of FM remains unknown – except, of course, to SCAM practitioners!

Most types of SCAM are said to be effective for FM (while the evidence for such claims is less than solid).

And almost every one of them claims to treat the ‘root cause’ of the condition. Which must mean that they are able to tackle its etiology, usually some disturbance of the ‘vital force’ or ‘energy’ flow. To patients, this sadly sounds impressive.

But what, if the etiology of FM is something entirely different?

New research shows that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated haemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analysing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively).

A subgroup of FM patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain. This was shown comparing pre and post-treatment numerical pain rating scale (NPRS). Response to metformin plus standard treatment (ST) was followed by complete resolution of the pain (report of 0 of 10 in the NPRS) in 8 of 16 patients who had been treated with metformin (50%), a degree of improvement never observed before in such a large proportion of FM patients subjected to any available treatment. In contrast, patients treated with ST alone improved, but complete resolution of pain was generally not observed. Interestingly, some patients responded only to metformin and not to ST with NSRIs or membrane stabilizing agents. Importantly, there was a long-term retention of the analgesic effect of metformin.

The authors concluded that these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder.

From my perspective, these findings also suggest that all the many SCAMs allegedly claiming to tackle the ‘root cause’ of FM have been barking up the wrong tree. In fact, all these claims of SCAM practitioners about treating the ‘root causes’ can easily be disclosed as a simple (and sadly effective) marketing gimmick. Six years ago, I even challenged the world of SCAM to name a single treatment that treats the ‘root cause’ of any disease. As yet, nobody has come forward with a convincing suggestion.

Chiropractic spinal manipulative therapy (CSMT) for migraine?

Why?

There is no good evidence that it works!

On the contrary, there is good evidence that it does NOT work!

A recent and rigorous study (conducted by chiropractors!) tested the efficacy of chiropractic CSMT for migraine. It was designed as a three-armed, single-blinded, placebo -controlled RCT of 17 months duration including 104 migraineurs with at least one migraine attack per month. Active treatment consisted of CSMT (group 1) and the placebo was a sham push manoeuvre of the lateral edge of the scapula and/or the gluteal region (group 2). The control group continued their usual pharmacological management (group 3). The results show that migraine days were significantly reduced within all three groups from baseline to post-treatment. The effect continued in the CSMT and placebo groups at all follow-up time points (groups 1 and 2), whereas the control group (group 3) returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT than in group 3 towards the end of follow-up. Adverse events were few, mild and transient. Blinding was sustained throughout the RCT. The authors concluded that the effect of CSMT observed in our study is probably due to a placebo response.

One can understand that, for chiropractors, this finding is upsetting. After all, they earn a good part of their living by treating migraineurs. They don’t want to lose patients and, at the same time, they need to claim to practise evidence-based medicine.

What is the way out of this dilemma?

Simple!

They only need to publish a review in which they dilute the irritatingly negative result of the above trial by including all previous low-quality trials with false-positive results and thus generate a new overall finding that alleges CSMT to be evidence-based.

This new systematic review of randomized clinical trials (RCTs) evaluated the evidence regarding spinal manipulation as an alternative or integrative therapy in reducing migraine pain and disability.

The searches identified 6 RCTs eligible for meta-analysis. Intervention duration ranged from 2 to 6 months; outcomes included measures of migraine days (primary outcome), migraine pain/intensity, and migraine disability. Methodological quality varied across the studies. The results showed that spinal manipulation reduced migraine days with an overall small effect size as well as migraine pain/intensity.

The authors concluded that spinal manipulation may be an effective therapeutic technique to reduce migraine days and pain/intensity. However, given the limitations to studies included in this meta-analysis, we consider these results to be preliminary. Methodologically rigorous, large-scale RCTs are warranted to better inform the evidence base for spinal manipulation as a treatment for migraine.

Bob’s your uncle!

Perhaps not perfect, but at least the chiropractic profession can now continue to claim they practice something akin to evidence-based medicine, while happily cashing in on selling their unproven treatments to migraineurs!

But that’s not very fair; research is not for promotion, research is for finding the truth; this white-wash is not in the best interest of patients! I hear you say.

Who cares about fairness, truth or conflicts of interest?

Christine Goertz, one of the review-authors, has received funding from the NCMIC Foundation and served as the Director of the Inter‐Institutional Network for Chiropractic Research (IINCR). Peter M. Wayne, another author, has received funding from the NCMIC Foundation and served as the co‐Director of the Inter‐Institutional Network for Chiropractic Research (IINCR)

And who the Dickens are the  NCMIC and the IINCR?

At NCMIC, they believe that supporting the chiropractic profession, including chiropractic research programs and projects, is an important part of our heritage. They also offer business training and malpractice risk management seminars and resources to D.C.s as a complement to the education provided by the chiropractic colleges.

The IINCR is a collaborative effort between PCCR, Yale Center for Medical Informatics and the Osher Center for Integrative Medicine at Brigham and Women’s Hospital and Harvard Medical School. They aim at creating a chiropractic research portfolio that’s truly translational. Vice Chancellor for Research and Health Policy at Palmer College of Chiropractic Christine Goertz, DC, PhD (PCCR) is the network director. Peter Wayne, PhD (Osher Center for Integrative Medicine at Brigham and Women’s Hospital and Harvard Medical School) will join Anthony J. Lisi, DC (Yale Center for Medical Informatics and VA Connecticut Healthcare System) as a co-director. These investigators will form a robust foundation to advance chiropractic science, practice and policy. “Our collective efforts provide an unprecedented opportunity to conduct clinical and basic research that advances chiropractic research and evidence-based clinical practice, ultimately benefiting the patients we serve,” said Christine Goertz.

Really: benefiting the patients? 

You could have fooled me!

Spinal manipulative therapy (SMT), especially hyperextension and rotation. have often been associated with cervical artery dissection (CAD), a tear in the internal carotid or the vertebral artery resulting in an intramural haematoma and/or an aneurysmal dilatation. But is the association causal? This question is often the subject of fierce discussions between chiropractors and the real doctors.

The lack of established causality relates to the chicken and egg discussion, i.e., whether the CAD symptoms lead the patient to seek cervical SMT or whether the cervical SMT provokes CAD along with the non-CAD presenting headache and/or neck complaint.

The aim of a new review was to provide an updated step-by-step risk-benefit assessment strategy regarding manual therapy and to provide tools for clinicians to exclude cervical artery dissection.

In light of the evidence provided, the reality, according to the review-authors, is:

  • a) that there is no firm scientific basis for direct causality between cervical SMT and CAD;
  • b) that the internal carotid artery (ICA) moves freely within the cervical pathway, while 74% of cervical SMTs are conducted in the lower cervical spine where the vertebral artery (VA) also moves freely;
  • c) that active daily life consists of multiple cervical movements including rotations that do not trigger CAD, as is true for a range of physical activities;
  • d) that a cervical manipulation and/or grade C cervical mobilization goes beyond the physiological limit but remains within the anatomical range, which theoretically means that the artery should not exceed failure strain.

These factors underscore the fact that no serious adverse event (AE) was reported in a large prospective national survey conducted in the UK that assessed all AEs in 28,807 chiropractic treatment consultations, which included 50,276 cervical spine manipulations.

The figure outlines a risk-benefit assessment strategy that should provide additional knowledge and improve the vigilance of all clinicians to enable them to exclude CAD, refer patients with suspected CAD to appropriate care, and consequently prevent CAD from progressing.

It has been argued that most patients present with at least two physical symptoms. The clinical characteristics and recommendations in the figure follow this assumption. This figure is intended to function as a knowledge base that should be implemented in preliminary screening and be part of good clinical practice. This knowledge base will likely contribute to sharpening the attention of the clinicians and alert them as to whether the presenting complaint, combined with a collection of warning signs listed in the figure, deviates from what he or she considers to be a usual musculoskeletal presentation.

Even though this is a seemingly thoughtful analysis, I think it omits at least two important points:

  1. The large prospective UK survey which included 50,276 cervical spine manipulations might be less convincing that it seems. It recorded about one order of magnitude less minor adverse effects of spinal manipulation than a multitude of previously published prospective surveys. The self-selected, relatively small group of participating chiropractors (32% of the total sample) were both experienced (67% been in practice for 5 or more years) and may not always have adhered to the protocol of the survey. Thus they may have employed their experience to intuitively select low-risk patients rather than including all consecutive cases, as the protocol prescribed. This hypothesis would firstly account for the unusually low rate of minor adverse effects, and secondly, it would explain why no serious complications occurred at all. Given that about 700 such complications are on record, the low incidence of serious adverse events could well be a gross underestimate.
  2. The effect of chiropractic spinal manipulative therapy is probably due to a placebo response. This means that it should probably not be done in the first place.

Fructus Psoraleae is the seed of Psoralea corylifolia Linn. It is the main ingredient of the herbal mixtures such as Qubaibabuqi, popular in China, India and other countries. It has been used for medicinal purposes for millennia. Thus many proponents would claim that it must be risk-free.

A recent case-report  suggests that it might not be as safe as often assumed.

A 53-year-old woman was diagnosed with vitiligo in September 2017 and was treated with oral Qubaibabuqi tablets (15 tablets three times daily; Xinjiang Yinduolan Uyghur Pharmaceutical Company Limited, Urumqi, China), 10 mg of prednisone acetate tablets (Xinhua Pharmaceutical Company Limited, Zibo, China) once daily, and narrowband-ultraviolet B (NB-UVB) phototherapy (Sigma household narrowband-ultraviolet phototherapy instrument [SS-01B] pocket portable; Shanghai Sigma High Technology Co., Ltd. Shanghai, China) every other day. The prednisone acetate tablets were self-discontinued 3 months later; however, she continued to take Qubaibabuqi tablets orally and NB-UVB phototherapy was undertaken at home.

After approximately 7 months of treatment, the patient developed a severe, diffuse yellow staining of the skin and sclera in March 2018. On admission, she was diagnosed with acute cholestatic hepatitis associated with Fructus Psoraleae. Despite receiving active treatment, her condition rapidly deteriorated and she died 5 days later due to acute liver failure and multiple organ dysfunction. There are 6 further reported cases of liver injury associated with Fructus Psoraleae described in the English language literature. Cases of acute liver failure associated with the use of Fructus Psoraleae have not been previously described.

The authors of the case-report concluded that as a main ingredient in the Qubaibabuqi tablet formula, Fructus Psoraleae has potential hepatotoxicity. This potentially fatal adverse effect should be considered when physicians prescribe Qubaibabuqi tablets.

Psoralea corylifolia Linn (also known as Bu-gu-zh, Bu Ku Zi, Bol-gol-zhee, Boh-Gol-Zhee, Babchi, and Bakuchi) is a plant grown in China, India, Sri Lanka, Burma, and other countries, which is considered an important herbal medicine. It is used in TCM to tonify the kidneys, particularly kidney yang and essence. It is used for helping the healing of bone fractures, for lower back and knee pain, impotence, bed wetting, hair loss, and vitiligo. A recent review named it as one of the main herbs causing liver problems (other herbs included Polygonum multiflorum, Corydalis yanhusuo, and Rheum officinale).

Another review found that Psoralea corylifolia has cardiotonic, vasodilator, pigmentor, antitumor, antibacterial, cytotoxic, and anti-helminthic properties. About one hundred bioactive compounds have been isolated from seeds and fruits; the most important ones belong to coumarins, flavonoids, and meroterpenes groups. Psoralea corylifolia is part of many Ayurvedic and Chinese herbal mixtures.

Despite of the popularity of Psoralea corylifolia in the treatment of a very wide range of conditions, and despite the pharmacological studies into its potential therapeutic uses, there is an almost complete void as to clinical trials testing its clinical effectiveness.

The case-report is a poignant and tragic reminder of the often-neglected fact that neither a long history of usage nor popularity of a (herbal) treatment are reliable indicators for safety.

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