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

coronary heart disease

Dr Mathias Rath, the German born purveyor of multiple food supplements, and his organisation puzzle me a great deal. As previously reported, the ‘Dr Rath Foundation’ published an article about me. In it, the author got my name right, but not much more. Here is its opening passage [the numbers in square brackets refer to my comments below].

Professor Edzard Ernst: A Career Built On Discrediting Natural Health Science? [1]

Professor Edzard Ernst, a retired German [2] physician and academic, has recently [3] become a prominent advocate of plans that could potentially outlaw [4] the entire profession of naturopathic doctors [5] in Germany. Promoting the nonsensical idea that naturopathic medicine somehow poses a risk to public health, Ernst attacks its practitioners as supposedly having been educated in “nonsense” [6]. Tellingly, however, given that he himself has seemingly not published even so much as one completely original scientific trial of his own [7], Ernst’s apparent attempts to discredit natural healthcare approaches are largely reliant instead on his analysis or review of handpicked negative studies carried out by others [8].

  1. When I was appointed at Exeter to research alternative medicine in 1993, I had already been a full professor at Hannover, Germany and subsequently at Vienna, Austria. If anything, coming to Exeter was a big step down in terms of ‘career’, salary, number of co-workers etc. (full details in my memoir)
  2. I am German-born, became an Austrian citizen in 1990, and since 2000 I am a British national.
  3. I have been critical about the German ‘Heilpraktiker’ for more than 20 years.
  4. This refers to the recent ‘Muensteraner Memorandum’ which is the work of an entire team of multidisciplinary experts and advocates reforming this profession.
  5. ‘Heilpraktiker’ are certainly not doctors; they have no academic or medical background.
  6. This is correct, and I stand by my statement that educating people in vitalism and other long-obsolete concepts is pure nonsense.
  7. Since I am researching alternative medicine, I have conducted and published about 40 ‘scientific trials’, and before that time (1993) I have published about the same number again in various other fields.
  8. This refers to systematic reviews which, by definition, include all the studies available on a defines research question, regardless of their conclusion (their aim is to minimise random and selection biases)  .

Rath states about himself that “Dr. Rath heads a research and development institute in nutritional and Cellular Medicine. His institute is conducting basic research and clinical studies to scientifically document the health benefits of micronutrients in fighting a multitude of diseases.”

But this is equally puzzling.

Firstly, because research does not aim ‘to scientifically document the health benefits of ‘ anything; it is for testing hypotheses; Rath surely must know that. Secondly, on Medline, I find dozens of publications by Rath. These refer mostly to mechanistic in-vitro or animal studies about the mode of action of vitamins and other natural compounds.

But ‘clinical studies‘?

None!

Hold on! My Medline searches did deliver one clinical trial – just one – (Rath himself lists more, but they seem to be meaningless observational studies without a control group). It was published as an abstract on his own website. Here is the abstract:

Healing of bone fractures is a prolonged process that can be affected by nutrition. Our objective was to critically evaluate the effect of supplementation with an essential nutrient complex, containing ascorbic acid, lysine, proline, and vitamin B6 on healing time of tibial fractures.

Design:

Random double-blind placebo-controlled study

Setting:
Dr. Jamdar Hospital, Jabalpur, India

Subjects and Intervention:
113 patients with unilateral displaced closed or grade I open tibial fractures were randomized to receive either standard care with placebo or with supplementation with an essential nutrient complex containing ascorbic acid, lysine, proline, and vitamin B6. Qualifying patients, on admission to the study, were clinically examined, radiographs of the affected limbs taken, fractures reduced under anesthesia, and above knee plaster casts applied. Radiographs were taken at each follow-up visit to confirm reduced alignment of fracture and proper callus formation.

Primary Outcome Measure:
The primary outcome measure was the number of weeks required for fracture to be healed. Healing was defined as absence of abnormal mobility at fracture site clinically, absence of pain elicited by stressing the fracture or by walking, and radiographic confirmation of callus formation.

Results:
Data analysis demonstrated reduced fracture-healing time associated with experimental supplementation. For PP analysis group, fracture healing time in 75% of the supplemented group of patients (N=21) was 17 weeks or less and 19 weeks or less in 75% of the placebo group patients (N=36). The percentage of patients with fractures healing in 10 weeks or less was 33.3% for the supplemented group and 11.1% for the placebo group. However, the difference in healing time between the two groups did not reach statistical significance.

Conclusion:
Results showed encouraging trends that fracture-healing time is reduced by supplementation with an essential nutrient complex containing ascorbic acid, lysine, proline, and vitamin B6. In addition, the nutrient supplemented participants reported improved feeling of well-being with use of the supplement.

This is odd in several ways:

  1. Even though the conclusions hide it quite well, the trial was in fact negative, i. e. it failed to show a significant difference between the verum and the placebo in the primary outcome measure.
  2. The trial was never published as a peer-reviewed full paper. The website refers to its publication as a ‘letter to the editor’ (LTTE) in the notorious JACM (a LTTE is not normally peer-reviewed).
  3. Why was it never properly published?
  4. Could it be because there was no ethics approval [none was mentioned in the LTTE]?
  5. Could it be because there was no informed consent [none was mentioned in the LTTE]?
  6. The LTTE mentions that a larger study with 200 patients is planned. This was 16 years ago, and to date there is no trace of such a trial.

Rath’s latest contribution to the world of science is a paper implying that his supplements could play a role in the fight against the present pandemic; it is entitled ‘Effective and safe global public health strategy to fight the COVID-19 pandemic: Specific micronutrient composition inhibits Coronavirus cell-entry receptor (ACE2) expression’. Here is the abstract which clearly shows that Rath has not a jot of clinical evidence:

Optimum micronutrient intake is the only scientifically proven way to improve general immune resistance against infections, a fact documented in every leading textbook of biology.  This study provides scientific evidence that, in addition, specific micronutrient compositions are powerful tools in the fight against the COVID-19 pandemic.

Both, SARS-CoV-2 – the virus that causes the current pandemic – and other coronaviruses enter body cells via a specific receptor, the Angiotensin-Converting-Enzyme 2 (ACE2). The ACE2 receptor is expressed by many cell types, including lung epithelial cells as well as endothelial cells of the vascular system.

Based on our earlier research that demonstrated that specific micronutrients can block several mechanisms of viral infections, we tested the efficacy of these natural compounds in suppressing the expression of the ACE2 receptor on human endothelial cells and small airway epithelial cells.

Our results show that a micronutrient composition comprising vitamin C as well as certain amino acids, polyphenols, and trace elements is able to suppress this viral ‘entry door’ into the body under both normal and inflammatory conditions, which are associated with infections.

Thus, vitamin-rich nutrition and micronutrient supplementation should be implemented as effective, safe and affordable public health strategies to fight the COVID-19 pandemic and help prevent future outbreaks.  Optimizing the micronutrient status of the entire population should form the basis for any global strategy to help prevent future pandemics across the world, including the developing nations.

The Wiki-page on Rath lists 10 (!) legal cases in which he has been involved. This looks like he easily sues people who disagree with his often bizarre views and sales techniques. Considering this suspicion, I better be careful what I say here. Therefore let me conclude by meekly repeating the title of this post which comes from my friend Ben Goldacre who, together with THE GUARDIAN won a famous and expensive legal battle against Rath:

Rath is an example of the worst excesses of the alternative therapy industry.

 

 

 

PS

What I like best about the many supplements sold by Rath is the footnote in the patient leaflets:

THIS PRODUCT IS NOT INTENDED TO DIAGNOSE, TREAT, CURE OR PREVENT ANY DISEASE

Glucosamine is currently one of the most popular of all dietary supplements. It is marketed as a treatment for arthritis, and there is some evidence that it is moderately helpful for this indication. But evidence had been accumulating to suggest that glucosamine might have other effects as well. The latest analysis evaluated the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.

This population-based prospective cohort study included 495 077 women and men from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. The investigators evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. Hazard ratios (HRs) and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.

At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).

The authors concluded that regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Previous epidemiological investigations indicated that glucosamine use might play a role in prevention of cancer, cardiovascular disease and other diseases. This suggests that the finding is more than the result of a large ‘fishing expedition’ to which epidemiological studies are sadly prone. It we are indeed dealing with a true phenomenon, we should ask by what mechanism these remarkable outcomes might be achieved. It is well documented that glucosamine has powerful anti-inflammatory effects. Therefore it is conceivable that such anti-inflammatory mechanisms are the cause for the observed outcomes.

How do we prove or disprove the hypothesis that glucosamine reduces the mortality of a range of diseases? A reasonable starting point would be to consult the good old Hill criteria of causality:

(1) The strength of association is small to moderate – certainly not strong

(2) The consistency of the findings is quite remarkable; that is unless dozens of epidemiological studies that failed to yield and association were never published.

(3) The specificity of the association with diseases linked to inflammation is also impressive (with the caveat above).

(4) Temporality seems also not a problem, as far as I can see.

(5) Biological gradient needs further testing, I think.

(6) Plausibility is not a problem, since there is a possible mechanism that could explain the findings.

(7) The same applies to coherence.

(8) Experiment is needed, but it is far from easy to conduct clinical trials where mortality is an endpoint.

(9) Analogy is realised through the well-established concept of (cardiovascular) risk factors.

What does all this actually mean?

It means, I think, that glucosamine could well have clinical effects that go far beyond easing the pain of arthritis. However, we cannot be sure. Once again, it boils down to the need of robust clinical trial data. The subject certainly seems important enough to consider this option.

 

It is hard to deny that many practitioners of so-called alternative medicine (SCAM) advise their patients to avoid ‘dangerous chemicals’. By this they usually mean prescription drugs. If you doubt how strong this sentiment often is, you have not followed the recent posts and the comments that regularly followed. Frequently, SCAM practitioners will suggest to their patients to not take this or that drug and predict that patients would then see for themselves how much better they feel (usually, they also administer their SCAM at this point).

Lo and behold, many patients do indeed feel better after discontinuing their ‘chemical’ medicines. Of course, this experience is subsequently interpreted as a proof that the drugs were dangerous: “I told you so, you are much better off not taking synthetic medicines; best to use the natural treatments I am offering.”

But is this always interpretation correct?

I seriously doubt it.

Let’s look at a common scenario: a middle-aged man on several medications for reducing his cardiovascular risk (no, it’s not me). He has been diagnosed to have multiple cardiovascular risk factors. Initially, his GP told him to change his life-style, nutrition and physical activity – to which he was only moderately compliant. Despite the patient feeling perfectly healthy, his blood pressure and lipids remained elevated. His doctor now strongly recommends drug treatment and our chap soon finds himself on statins, beta-blockers plus ACE-inhibitors.

Our previously healthy man has thus been turned into a patient with all sorts of symptoms. His persistent cough prompts his GP to change the ACE-inhibitor to a Ca-channel blocker. Now the patients cough is gone, but he notices ankle oedema and does not feel in top form. His GP said that this is nothing to worry about and asks him to grin and bear it. But the fact is that a previously healthy man has been turned into a patient with reduced quality of life (QoL).

This fact takes our man to a homeopath in the hope to restore his QoL (you see, it certainly isn’t me). The homeopath proceeds as outlined above: he explains that drugs are dangerous chemicals and should therefore best be dropped. The homeopath also prescribes homeopathics and is confident that they will control the blood pressure adequately. Our man complies. After just a few days, he feels miles better, his QoL is back, and even his sex-life improves. The homeopath is triumphant: “I told you so, homeopathy works and those drugs were really nasty stuff.”

When I was a junior doctor working in a homeopathic hospital, my boss explained to me that much of the often considerable success of our treatments was to get rid of most, if not all prescription drugs that our patients were taking (the full story can be found here). At the time, and for many years to come, this made a profound impression on me and my clinical practice. As a scientist, however, I have to critically evaluate this strategy and ask: is it the correct one?

The answer is YES and NO.

YES, many (bad) doctors over-prescribe. And there is not a shadow of a doubt that unnecessary drugs must be scrapped. But what is unnecessary? Is it every drug that makes a patient less well than he was before?

NO, treatments that are needed should not be scrapped, even if this would make the patient feel better. Where possible, they might be altered such that side-effects disappear or become minimal. Patients’ QoL is important, but it is not the only factor of importance. I am sure this must sound ridiculous to lay people who, at this stage of the discussion, would often quote the ethical imperative of FIRST DO NO HARM.

So, let me use an extreme example to explain this a bit better. Imagine a cancer patient on chemo. She is quite ill with it and QoL is a thing of the past. Her homeopath tells her to scrap the chemo and promises she will almost instantly feel fine again. With some side-effect-free homeopathy see will beat the cancer just as well (please, don’t tell me they don’t do that, because they do!). She follows the advice, feels much improved for several months. Alas, her condition then deteriorates, and a year later she is dead.

I know, this is an extreme example; therefore, let’s return to our cardiovascular patient from above. He too followed the advice of his homeopath and is happy like a lark for several years … until, 5 years after discontinuing the ‘nasty chemicals’, he drops dead with a massive myocardial infarction at the age of 62.

I hope I made my message clear: those SCAM providers who advise discontinuing prescribed drugs are often impressively successful in improving QoL and their patients love them for it. But many of these practitioners haven’t got a clue about real medicine, and are merely playing dirty tricks on their patients. The advise to stop a prescribed drug can be a very wise move. But frequently, it improves the quality, while reducing the quantity of life!

The lesson is simple: find a rational doctor who knows the difference between over-prescribing and evidence-based medicine. And make sure you start running when a SCAM provider tries to meddle with necessary prescribed drugs.

Some people seem to think that all so-called alternative medicine (SCAM) is ineffective, harmful or both. And some believe that I am hell-bent to make sure that this message gets out there. I recommend that these guys read my latest book or this 2008 article (sadly now out-dated) and find those (admittedly few) SCAMs that demonstrably generate more good than harm.

The truth, as far as this blog is concerned, is that I am constantly on the lookout to review research that shows or suggests that a therapy is effective or a diagnostic technique is valid (if you see such a paper that is sound and new, please let me know). And yesterday, I have been lucky:

This paper has just been presented at the ESC Congress in Paris.

Its authors are: A Pandey (1), N Huq (1), M Chapman (1), A Fongang (1), P Poirier (2)

(1) Cambridge Cardiac Care Centre – Cambridge – Canada

(2) Université Laval, Faculté de Pharmacie – Laval – Canada

Here is the abstract in full:

Introduction: Regular physical activity may modulate the inflammatory process and be cardio-protective. Yoga is a form of exercise that may have cardiovascular benefits. The effects of yoga on global cardiovascular risk have not been adequately described. The purpose of this study is to determine whether the addition of yoga to a regular exercise regimen reduces global cardiovascular risk.
Methods: Sixty consecutive individuals with essential hypertension were recruited in a lifestyle intervention program. All individuals with known hypertensive end organ damage, known cardiovascular diseases, as well as those taking medications/supplements that affected blood pressure, blood sugar, cholesterol or vascular inflammation were excluded. Participants were randomized to either a yoga group or similar duration stretching control group. Participants, over the 3-month intervention regimen, performed 15 minutes of either yoga or stretching in addition to 30 minutes of aerobic exercises thrice weekly. Blood pressure, cholesterol levels and hs-CRP were measured, and Reynold’s Global Cardiovascular Risk Score was calculated at baseline and at the end of the 3-month intervention program.
Results: At screening, there were no statistically significant differences between the groups in any measured parameters or the 10-year risk of a cardiovascular event as measured by the Reynolds Risk Score. (8.2 vs. 9.0%; yoga vs. control group) After the 3-month intervention period, there was a statistically significantly greater decrease in the Reynold’s Risk Score in the yoga vs. the control group. (7.0 vs. 8.4%, p=0.003, relative reduction 13.2 vs. 6.5%, p<0.0001)
Conclusions: In patients with essential hypertension on no medications and with no known end organ damage, the practice of yoga incorporated into a 3-month exercise intervention program was associated with significant greater improvement in the Reynold’s Risk of a 10-year cardiovascular event, when compared to the control stretching group. If these results are validated in more diverse populations over a longer duration of follow up, yoga may represent an important addition to traditional cardiovascular disease prevention programs.

Yes, this study was small, too small to draw far-reaching conclusions. And no, we don’t know what precisely ‘yoga’ entailed (we need to wait for the full publication to get this information plus all the other details needed to evaluate the study properly). Yet, this is surely promising: yoga has few adverse effects, is liked by many consumers, and could potentially help millions to reduce their cardiovascular risk. What is more, there is at least some encouraging previous evidence.

But what I like most about this abstract is the fact that the authors are sufficiently cautious in their conclusions and even state ‘if these results are validated…’

SCAM-researchers, please take note!

Acupuncture is effective in alleviating angina when combined with traditional antianginal treatment, according to a study published today in JAMA Internal Medicine. Researchers conducted a 20-week randomized clinical trial at 5 clinical centres in China. Patients with chronic, stable angina (a serious symptom caused by coronary heart disease) were randomly assigned to 4 groups:

  1. acupuncture on acupoints in the disease-affected meridian,
  2. acupuncture on a non-affected meridian,
  3. sham acupuncture,
  4. waitlist group that did not receive acupuncture.

All participants also received recommended antianginal medications. Acupuncture was given three times each week for 4 weeks. Patients were asked to keep a diary to record angina attacks. 398 patients were included in the intention-to-treat analysis. Greater reductions in angina attacks occurred in those who received acupuncture at acupoints in the disease-affected meridian compared with those in the nonaffected meridian group, the sham acupuncture group and the wait list group.

“Acupuncture was safely administered in patients with mild to moderate angina”, Zhao et al wrote. “Compared with the [control] groups, adjunctive acupuncture showed superior benefits … Acupuncture should be considered as one option for adjunctive treatment in alleviating angina.”

This study is well-written and looks good – almost too good to be true!

Let me explain: during the last 25 years, I must have studied several thousand clinical trials of SCAM, and I think that, in the course of this work, I have developed a fine sense for detecting trials that are odd or suspect. While reading the above RCT, my alarm-bells were ringing loud and clear.

The authors claim they have no conflicts of interest. This may well be true as far as financial conflicts of interest are concerned, but I have long argued that, in SCAM, ideological conflicts are much more powerful than financial ones. If we look at some of the authors’ affiliations, we get a glimpse of this possibility:

  • Acupuncture and Tuina School, Chengdu University o fTraditional Chinese Medicine, Chengdu, Sichuan, China
  • Department of Acupuncture, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
  • Acupuncture and Tuina School, Hunan University of  Traditional Chinese Medicine, Changsha, Hunan, China
  • Acupuncture and Tuina School, Guiyang University of Traditional Chinese Medicine, Guiyang, Guizhou, China
  • Acupuncture and Tuina School, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
  • Acupuncture and Tuina School, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, Yunnan, China

I have reported repeatedly that several independent analyses have shown that as good as no TCM studies from China ever report negative results. I have also reported that data falsification is said to be rife in China.

I am aware, of course, that these arguments are hardly evidence-based and therefore amount to mere suspicions. So, let me also mention a few factual points about the new trial:

  • The study was concluded 4 years ago; why is it published only now?
  • The primary outcome measure was entirely subjective; an objective endpoint would have been valuable.
  • Patient blinding was not checked but would have been important.
  • The discussion is devoid of any critical input; this is perhaps best seen when looking at the reference list. The authors cite none of the many critical analyses of acupuncture.
  • The authors did actually not use normal acupuncture but electroacupuncture. One would have liked to see a discussion of effects of the electrical current versus those of acupuncture.
  • The therapists were not blinded (when using electroacupuncture, this would have been achievable). Therefore, one explanation for the outcome is lies in the verbal/non-verbal communication between therapists and patients.
  • Acupuncture was used as an add-on therapy, and it is conceivable that patients in the acupuncture group were more motivated to take their prescribed medications.
  • The costs for 12 sessions of acupuncture would have been much higher (in the UK) than those for an additional medication.
  • The practicality of consulting an acupuncturist three times a week need to be addressed.
  • The long-term effects of acupuncture on angina pectoris (which is a long-term condition) are unknown.

Coming back to my initial point about the reliability of the data, I feel that it is important to not translate these findings into clinical routine without independent replications by researchers from outside China who are not promoters of acupuncture. Until such data are available, I believe that acupuncture should NOT be considered as one option for adjunctive treatment in alleviating angina.

Glucosamine supplements are often advocated for the treatment of osteoarthritis. But there is evidence that they might convey other benefits as well. This prospective observational study assessed the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events. The UK Biobank data of 466 039 participants without CVD at baseline was used. They completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016. The main outcome measures were incident CVD events, including CVD death, coronary heart disease, and stroke.

During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00).

The authors concluded that habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events.

This is an impressive study! It incorporates both a huge sample size and a long observation period. Moreover, the authors analysed the data expertly and interpreted their results with the necessary caution.

The association between glucosamine intake and CVD risk were independent of CVD risk factors, such as gender, age, income, body mass index, physical activity, healthy diet, alcohol intake, smoking status, diabetes, hypertension, high cholesterol, arthritis, drug use, and other supplement use. Moreover, the findings are in line with several previous studies that show inverse associations of glucosamine use with CVD risk and mortality. And finally, the authors discuss several biologically plausible mechanisms that could explain the observed findings.

Yet, it is conceivable that the association is not of a causal nature. There might be a host of confounders responsible for the finding. Therefore, before we now all rush to the next health-food store to buy glucosamine supplements – they are not all that cheap! – we should perhaps wait for further independent replications and research.

The objective of this ‘real world’ study was to evaluate the effectiveness of integrative medicine (IM) on patients with coronary artery disease (CAD) and investigate the prognostic factors of CAD in a real-world setting.

A total of 1,087 hospitalized patients with CAD from 4 hospitals in Beijing, China were consecutively selected between August 2011 and February 2012. The patients were assigned to two groups:

  1. Chinese medicine (CM) plus conventional treatment, i.e., IM therapy (IM group). IM therapy meant that the patients accepted the conventional treatment of Western medicine and the treatment of Chinese herbal medicine including herbal-based injection and Chinese patent medicine as well as decoction for at least 7 days in the hospital or 3 months out of the hospital.
  2. Conventional treatment alone (CT group).

The endpoint was a major cardiac event [MCE; including cardiac death, myocardial infarction (MI), and the need for revascularization].

A total of 1,040 patients finished the 2-year follow-up. Of them, 49.4% received IM therapy. During the 2-year follow-up, the total incidence of MCE was 11.3%. Most of the events involved revascularization (9.3%). Cardiac death/MI occurred in 3.0% of cases. For revascularization, logistic stepwise regression analysis revealed that age ⩾ 65 years [odds ratio (OR), 2.224], MI (OR, 2.561), diabetes mellitus (OR, 1.650), multi-vessel lesions (OR, 2.554), baseline high sensitivity C-reactive protein level ⩾ 3 mg/L (OR, 1.678), and moderate or severe anxiety/depression (OR, 1.849) were negative predictors (P<0.05); while anti-platelet agents (OR, 0.422), β-blockers (OR, 0.626), statins (OR, 0.318), and IM therapy (OR, 0.583) were protective predictors (P<0.05). For cardiac death/MI, age ⩾ 65 years (OR, 6.389) and heart failure (OR, 7.969) were negative predictors (P<0.05), while statin use (OR, 0.323) was a protective predictor (P<0.05) and IM therapy showed a beneficial tendency (OR, 0.587), although the difference was not statistically significant (P=0.218).

The authors concluded that in a real-world setting, for patients with CAD, IM therapy was associated with a decreased incidence of revascularization and showed a potential benefit in reducing the incidence of cardiac death or MI.

What the authors call ‘real world setting’ seems to be a synonym of ‘lousy science’, I fear. I am not aware of good evidence to show that herbal injections and concoctions are effective treatments for CAD, and this study can unfortunately not change this. In the methods section of the paper, we read that the treatment decisions were made by the responsible physicians without restriction. That means the two groups were far from comparable. In their discussion section, the authors state; we found that IM therapy was efficacious in clinical practice. I think that this statement is incorrect. All they have shown is that two groups of patients with similar diagnoses can differ in numerous ways, including clinical outcomes.

The lessons here are simple:

  1. In clinical trials, lack of randomisation (the only method to create reliably comparable groups) often leads to false results.
  2. Flawed research is currently being used by many proponents of  SCAM (so-called alternative medicine) to mislead us about the value of SCAM.
  3. The integration of dubious treatments into routine care does not lead to better outcomes.
  4. Integrative medicine, as currently advocated by SCAM-proponents, is a nonsense.

Personally, I like sauna bathing. It makes me feel fine. But is it healthy? More specifically, is it good for the cardiovascular system?

Finnish researchers had already shown in a large cohort study with 20 years of follow-up that increased frequency of sauna bathing is associated with a reduced risk of sudden cardiac death (SCD), fatal coronary heart disease (CHD), fatal cardiovascular disease (CVD), and all-cause mortality. Now the same group of researchers report more encouraging news for sauna-fans.

The aim of their new study was to investigate the relationship between sauna habits and CVD mortality in men and women, and whether adding information on sauna habits to conventional cardiovascular risk factors is associated with improvement in prediction of CVD mortality risk.

Sauna bathing habits were assessed at baseline in a sample of 1688 participants (mean age 63; range 53-74 years), of whom 51.4% were women. Multivariable-adjusted hazard ratios (HRs) were calculated to investigate the relationships of frequency and duration of sauna use with CVD mortality.

A total of 181 fatal CVD events occurred during a median follow-up of 15.0 years (interquartile range, 14.1-15.9). The risk of CVD mortality decreased linearly with increasing sauna sessions per week with no threshold effect. In age- and sex-adjusted analysis, compared with participants who had one sauna bathing session per week, HRs (95% CIs) for CVD mortality were 0.71 (0.52 to 0.98) and 0.30 (0.14 to 0.64) for participants with two to three and four to seven sauna sessions per week, respectively. After adjustment for established CVD risk factors, potential confounders including physical activity, socioeconomic status, and incident coronary heart disease, the corresponding HRs (95% CIs) were 0.75 (0.52 to 1.08) and 0.23 (0.08 to 0.65), respectively. The duration of sauna use (minutes per week) was inversely associated with CVD mortality in a continuous manner. Addition of information on sauna bathing frequency to a CVD mortality risk prediction model containing established risk factors was associated with a C-index change (0.0091; P = 0.010), difference in - 2 log likelihood (P = 0.019), and categorical net reclassification improvement (4.14%; P = 0.004).

(Hazard ratios for cardiovascular mortality by quartiles of the duration of sauna bathing. a Adjusted for age and gender. b Adjusted for age, gender, body mass index, smoking, systolic blood pressure, serum low-density lipoprotein cholesterol, alcohol consumption, previous myocardial infarction, and type 2 diabetes. CI, confidence interval.)

The authors concluded that higher frequency and duration of sauna bathing are each strongly, inversely, and independently associated with fatal CVD events in middle-aged to elderly males and females. The frequency of sauna bathing improves the prediction of the long-term risk for CVD mortality.

These results are impressive. What could be the underlying mechanisms? The authors offer plenty of explanations: Dry and hot sauna baths have been shown to increase the demands of cardiovascular function. Sauna bathing causes an increase in heart rate which is a reaction to the body heat load. Heart rate may be elevated up to 120–150 beats per minute during sauna bathing, corresponding to low- to moderate-intensity physical exercise training for the circulatory system without active muscle work. Acute sauna exposure has been shown to produce blood pressure lowering effects, decrease peripheral vascular resistance and arterial stiffness, and improve arterial compliance. Short-term sauna exposure also activates the sympathetic nervous and the renin-angiotensin-aldosterone systems and the hypothalamus-pituitary-adrenal hormonal axis, and short-term increases in levels of their associated hormones have been reported. Repeated sauna exposure improves endothelial function, suggesting a beneficial role of thermal therapy on vascular function. Long-term sauna bathing habit may be beneficial in the reduction of high systemic blood pressure, which is in line with previous evidence showing that blood pressure may be lower among those who are living in warm conditions with higher ambient temperature. Regular sauna bathing is associated with a lowered risk of future hypertension. Typical hot and dry Finnish sauna increases body temperature which causes more efficient skin blood flow, leading to a higher cardiac output, whereas blood flow to internal organs decreases. Sweat is typically secreted at a rate which corresponds to an average total secretion of 0.5 kg during a sauna bathing session. Increased sweating is accompanied by a reduction in blood pressure and higher heart rate, while cardiac stroke volume is largely maintained, although a part of blood volume is diverted from the internal organs to body peripheral parts with decreasing venous return which is not facilitated by active skeletal muscle work. However, it has been proposed that muscle blood flow may increase to at least some extent in response to heat stress, although sauna therapy-induced myocardial metabolic adaptations are largely unexplored. There is also evidence that regular long-term sauna bathing (average of two sessions per week) increases left ventricular ejection fraction. Heat therapy may improve left ventricular function with decreased cardiac pre- and afterload, thereby maintaining appropriate stroke volume despite large reductions in ventricular filling pressures. Additionally, previous studies have demonstrated a positive alteration of the autonomic nervous system and reduced levels of natriuretic peptides, oxidative stress, inflammation, and norepinephrine due to regular sauna therapy.

It is possible that the results are influenced by confounding factors that the researchers were unable to account for. It is also possible that people who are already ill avoid sauna bathing and that this contributed to the findings. However, the authors did their best to explore such phenomena in sub-group analysis and found that a causal relationship between sauna and CVD risk is still very likely. As a sauna-fan, I am inclined to believe them and the sceptic in me tends to agree.

Ginkgo biloba is a well-researched herbal medicine which has shown promise for a number of indications. But does this include coronary heart disease?

The aim of this systematic review was to provide information about the effectiveness and safety of Ginkgo Leaf Extract and Dipyridamole Injection (GD) as one adjuvant therapy for treating angina pectoris (AP) and to evaluate the relevant randomized controlled trials (RCTs) with meta-analysis. (Ginkgo Leaf Extract and Dipyridamole Injection is a Chinese compound preparation, which consists of ginkgo flavone glycosides (24%), terpene lactones (ginkgolide about 13%, ginkgolide about 2.9%) and dipyridamole.)

RCTs concerning AP treated by GD were searched and the Cochrane Risk Assessment Tool was adopted to assess the methodological quality of the RCTs. A total of 41 RCTs involving 4,462 patients were included in the meta-analysis. The results indicated that the combined use of GD and Western medicine (WM) against AP was associated with a higher total effective rate [risk ratio (RR)=1.25, 95% confidence interval (CI): 1.21–1.29, P<0.01], total effective rate of electrocardiogram (RR=1.29, 95% CI: 1.21–1.36, P<0.01). Additional, GD combined with WM could decrease the level of plasma viscosity [mean difference (MD)=–0.56, 95% CI:–0,81 to–0.30, P<0.01], fibrinogen [MD=–1.02, 95% CI:–1.50 to–0.54, P<0.01], whole blood low shear viscosity [MD=–2.27, 95% CI:–3.04 to–1.49, P<0.01], and whole blood high shear viscosity (MD=–0.90, 95% CI: 1.37 to–0.44, P<0.01).

The authors concluded that comparing with receiving WM only, the combine use of GD and WM was associated with a better curative effect for patients with AP. Nevertheless, limited by the methodological quality of included RCTs more large-sample, multi-center RCTs were needed to confirm our findings and provide further evidence for the clinical utility of GD.

If one reads this conclusion, one might be tempted to use GD to cure AP. I would, however, strongly warn everyone from doing so. There are many reasons for my caution:

  • All the 41 RCTs originate from China, and we have repeatedly discussed that Chinese TCM trials are highly unreliable.
  • The methodological quality of the primary RCTs was, according to the review authors ‘moderate’. This is not true; it was, in fact, lousy.
  • Dipyridamole is not indicated in angina pectoris.
  • To the best of my knowledge, there is no good evidence from outside China to suggest that Ginkgo biloba is effective for angina pectoris.
  • Angina pectoris is caused by coronary artery disease (a narrowing of one or more coronary arteries due to atherosclerosis), and it seems implausible that this condition can be ‘cured’ with any medication.

So, what we have here is yet another nonsensical paper, published in a dubious journal, employing evidently irresponsible reviewers, run by evidently irresponsible editors, hosted by a seemingly reputable publisher (Springer). This is reminiscent of my previous post (and many posts before). Alarmingly, it is also what I encounter on a daily basis when scanning the new publications in my field.

The effects of this incessant stream of nonsense can only have one of two effects:

  1. People take this ‘evidence’ seriously. In this case, many patients might pay with their lives for this collective incompetence.
  2. People conclude that alt med research cannot be taken seriously. In this case, we are unlikely to ever see anything useful emerging from it.

Either way, the result will be profoundly negative!

It is high time to stop this idiocy; but how?

I wish, I knew the answer.

Do musculoskeletal conditions contribute to chronic non-musculoskeletal conditions? The authors of a new paper – inspired by chiropractic thinking, it seems – think so. Their meta-analysis was aimed to investigate whether the most common musculoskeletal conditions, namely neck or back pain or osteoarthritis of the knee or hip, contribute to the development of chronic disease.

The authors searched several electronic databases for cohort studies reporting adjusted estimates of the association between baseline neck or back pain or osteoarthritis of the knee or hip and subsequent diagnosis of a chronic disease (cardiovascular disease , cancer, diabetes, chronic respiratory disease or obesity).

There were 13 cohort studies following 3,086,612 people. In the primary meta-analysis of adjusted estimates, osteoarthritis (n= 8 studies) and back pain (n= 2) were the exposures and cardiovascular disease (n=8), cancer (n= 1) and diabetes (n= 1) were the outcomes. Pooled adjusted estimates from these 10 studies showed that people with a musculoskeletal condition have a 17% increase in the rate of developing a chronic disease compared to people without a musculoskeletal condition.

The authors concluded that musculoskeletal conditions may increase the risk of chronic disease. In particular, osteoarthritis appears to increase the risk of developing cardiovascular disease. Prevention and early

treatment of musculoskeletal conditions and targeting associated chronic disease risk factors in people with long

standing musculoskeletal conditions may play a role in preventing other chronic diseases. However, a greater

understanding about why musculoskeletal conditions may increase the risk of chronic disease is needed.

For the most part, this paper reads as if the authors are trying to establish a causal relationship between musculoskeletal problems and systemic diseases at all costs. Even their aim (to investigate whether the most common musculoskeletal conditions, namely neck or back pain or osteoarthritis of the knee or hip, contribute to the development of chronic disease) clearly points in that direction. And certainly, their conclusion that musculoskeletal conditions may increase the risk of chronic disease confirms this suspicion.

In their discussion, they do concede that causality is not proven: While our review question ultimately sought to assess a causal connection between common musculoskeletal conditions and chronic disease, we cannot draw strong conclusions  due  to  poor  adjustment,  the  analysis methods employed by the included studies, and a lack of studies investigating conditions other than OA and cardiovascular disease…We did not find studies that satisfied all of Bradford Hill’s suggested criteria for casual inference (e.g. none estimated dose–response effects) nor did we find studies that used contemporary causal inference methods for observational data (e.g. a structured identification approach for selection of confounding variables or assessment of the effects of unmeasured or residual confounders. As such, we are unable to infer a strong causal connection between musculoskeletal conditions and chronic diseases.

In all honesty, I would see this a little differently: If their review question ultimately sought to assess a causal connection between common musculoskeletal conditions and chronic disease, it was quite simply daft and unscientific. All they could ever hope is to establish associations. Whether these are causal or not is an entirely different issue which is not answerable on the basis of the data they searched for.

An example might make this clearer: people who have yellow stains on their 2nd and 3rd finger often get lung cancer. The yellow fingers are associated with cancer, yet the link is not causal. The association is due to the fact that smoking stains the fingers and causes cancer. What the authors of this new article seem to suggest is that, if we cut off the stained fingers of smokers, we might reduce the cancer risk. This is clearly silly to the extreme.

So, how might the association between musculoskeletal problems and systemic diseases come about? Of course, the authors might be correct and it might be causal. This would delight chiropractors because DD Palmer, their founding father, said that 95% of all diseases are caused by subluxation of the spine, the rest by subluxations of other joints. But there are several other and more likely explanations for this association. For instance,  many people with a systemic disease might have had subclinical problems for years. These problems would prevent them from pursuing a healthy life-style which, in turn, resulted is musculoskeletal problems. If this is so, musculoskeletal conditions would not increase the risk of chronic disease, but chronic diseases would lead to musculoskeletal problems.

Don’t get me wrong, I am not claiming that this reverse causality is the truth; I am simply saying that it is one of several possibilities that need to be considered. The fact that the authors failed to do so, is remarkable and suggests that they were bent on demonstrating what they put in their conclusion. And that, to me, is an unfailing sign of poor science.

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