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

supplements

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We live in truly grim times! Let me therefore try to cheer you up a little. Here is a story that might make you smile.

In 1981, I moved back from London to Munich. While still in London, I had written an article on garlic for a German medical journal. It was published just as we arrived in our new home. Here is it’s English abstract:

Garlic has had a firm place in folk medicine since ancient times. More recent results are summarized here which show that extracts of the plant have an antimicrobial action, they are capable of lowering blood cholesterol and of reducing secondary vascular changes. They raise fibrinolytic activity and inhibit thrombocyte aggregation. Therefore the plant contains highly active therapeutic principles which appear to be particularly suitable for prophylaxis of arteriosclerosis.

Yes, you are quite right, this paper is nothing to write home about. So, why do I consider it ‘most consequential‘? Here is what happened:

My wife and I had barely arrived in our new home, when a man phoned (he had gone to a lot of trouble to find my number) and said: “I know you are the leading expert on garlic; I urgently need to talk to you”. Never correct a man’s mistake, if it’s in your favour, I thought, and we made an appointment for a meeting at the Munich train station hotel.

When I met him a few days later, he ordered me a coffee (which later I had to pay for) and explained that he had worked his whole life (he was about 50, I guessed) for the pharmaceutical industry and had now decided that this was enough. He thus planned to set up his own pharmaceutical company. He already had a photocopy machine in his basement, he proudly told me, and a wife who was willing to work as hard as he was. Specifically, his plan was to launch a garlic pill, and for that he needed my advice. I told him what he wanted to know, and we parted after about two hours promising to stay in contact.

The man’s name was Kuno Lichtwer.

During the weeks that followed, he often phoned me to pick my brain. One day, he told me that he had everything in place: he had found a supplier of the materials, a manufacturer to produce the pills and even registered a name for it:

KWAI

Then he popped the question that was foremost on his mind: ‘What do you think, Dr Ernst, should I risk it and go ahead with this or not?’. I had started to like that man; he was going to lose all his savings on a crazy idea, I felt. So, I told him: ‘If I were you, I would not do it. There are already plenty of garlic pills on the market. You are risking to lose everything.’ Then there was a long pause; eventually, he thanked me for my honest advice and hung up.

Weeks later he phoned again to tell me that he had truly appreciated my brutally direct advice, thought long and hard about it, but went ahead with his plan anyway. Would I now accept the position of ‘medical advisor’ to Lichwer Pharma? I was surprised, but accepted this new post. Thereafter, I advised him the best I could. We even conducted and published the very first clinical trial with his product. It was a rather flimsy study (we had no funds at all), but did suggest a positive result.

Each time Mr Lichtwer called me, he was elated; things were not just going well, they were booming! He was evidently hugely gifted in promoting KWAI. Then he invited me several times to come to Berlin where Lichtwer Pharma was based for business meetings. Proudly, he showed me that meanwhile his firm had moved out of his basement into a proper building. The next I knew was that he had a dozen employees. Lichtwer seemed unstoppable. This went on for 2 or 3 years, if I remember correctly.

During all this time, we had never talked about money, and my work for him had always been unpaid – that is, until one day just before Christmas he phoned and explained that he had moved his firm to yet a bigger building and hired yet more staff. He also realised that I deserved some renumeration for my advice; therefore, he had put a cheque in the post. When I told my wife about it, we both celebrated in anticipation of the substantial windfall. Two days later, his letter arrived. He very kindly thanked me for years of work and included a cheque of 500 DM (about 150 DM per year of work). A few months later, his firm had grown so big that a full time medical and research director was badly needed. He informed me that he had found a highly experienced expert and invited me to meet the new man, Prof Schulz.

No, I did not feel hard done by! On the contrary, I was happy that my prediction had been grossly wrong and that my friend Kuno was doing so well. In addition, I was also relieved, because my research at the University did not give me nearly enough time to look adequately after the now substantial firm of Lichtwer Pharma.

Thereafter, Lichtwer’s garlic pill went from strength to strength. Several larger studies confirmed our initial results that garlic positively influenced blood lipids (in 2000, our systematic review concluded: The available data suggest that garlic is superior to placebo in reducing total cholesterol levels. However, the size of the effect is modest, and the robustness of the effect is debatable. The use of garlic for hypercholesterolemia is therefore of questionable value). One day, I read somewhere that KWAI had become the most consumed pill in Germany (even beating Aspirin). Then Lichtwer Pharma went international and added several further herbal products to its portfolio. In 1991, Lichtwer Pharma was estimated to be worth 100 Million DM. Several years later, the firm had almost 400 employees and a yearly turnover of 353 Million DM.

To his credit, Kuno Lichtwer never entirely forgot me. When I had moved to the UK, he even came to Exeter, was entertained by my University, and made a donation of £100 000 towards a ‘Lichtwer Research Fellowship’ for my department. I am not sure whether Kuno Lichtwer is still alive. If he is, he would probably agree that, had I offered him 10 000 DM of my savings during our 1st meeting in 1981 (he did hint at that possibility), he would have gladly made me a partner in his enterprise.

But, as they say: money is not everything.

And a good story to tell is also not bad.

Hesperidin is a flavonoid found in citrus fruits, especially orange and grapefruit. It is said to have antioxidant and anti-inflammatory effects. Research into hesperidin began in the 1940s but only recently interest turned buoyant, and all sorts of benefits have been suggested. Here are just three recent clinical studies:

  1. This study investigated the effects of chronic intake of an orange extract (2S-hesperidin) or placebo on non-oxidative/glycolytic and oxidative metabolism markers and performance markers in amateur cyclists. A double-blind, randomized, placebo-controlled trial was carried out between late September and December 2018. Forty amateur cyclists were randomized into two groups: one taking 500 mg/day 2S-hesperidin and the other taking 500 mg/day placebo (microcellulose) for eight weeks. All participants completed the study. An incremental test was used to evaluate performance, and a step test was used to measure oxygen consumption, carbon dioxide, efficiency and oxidation of carbohydrates and fat by indirect calorimetry. The anaerobic power (non-oxidative) was determined using Wingate tests (30 s). After eight weeks supplementation, there was an increase in the incremental test in estimated functional threshold power (FTP) (3.2%; p ≤ 0.05) and maximum power (2.7%; p ≤ 0.05) with 2S-hesperdin compared to placebo. In the step test, there was a decrease in VO2 (L/min) (-8.3%; p ≤ 0.01) and VO2R (mL/kg/min) (-8.9%; p ≤ 0.01) at VT2 in placebo. However, there were no differences between groups. In the Wingate test, there was a significant increase (p ≤ 0.05) in peak and relative power in both groups, but without differences between groups. Supplementation with an orange extract (2S-hesperdin) 500 mg/day improves estimated FTP and maximum power performance in amateur cyclists.
  2. In this clinical trial with a parallel-group design, 49 patients with MetS received either 500-mg hesperidin or placebo, twice daily, for 12 weeks. Number of participants with treated MetS was considered as a primary end point. Anthropometric parameters, dietary intake, physical activity, lipid profile, glucose homeostasis parameter, tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP) were assessed at the beginning and at the end of the study. Compared with the placebo group, hesperidin decreased fasting glucose level (- 6.07 vs. – 13.32 mg/dL, P = 0.043), triglyceride (- 8.83 vs. – 49.09 mg/dL, P = 0.049), systolic blood pressure (- 0.58 vs. – 2.68 mmHg, P = 0.048) and TNF-α (- 1.29 vs. – 4.44 pg/mL, P = 0.009). Based on the within-group analysis, hesperidin led to significant decrease in serum levels of glucose, insulin, triglyceride, total cholesterol, low density lipoprotein cholesterol, TNF-α and hs-CRP, while in control group only glucose and insulin significantly decreased. The results indicate that hesperidin supplementation can improve metabolic abnormalities and inflammatory status in patients with MetS.
  3. In this study, 64 patients were randomly allocated to receive 500 mg/day hesperidin or placebo capsules for 6 weeks. Data on systolic blood pressure (SBP), diastolic blood pressure, serum total antioxidant capacity (TAC), tumor necrosis factor alpha, interleukin 6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) were collected at the baseline and at the end of the study. In the hesperidin group, SBP (122.7 ± 8.5 vs. 119.0 ± 7.4; p = .005), mean arterial blood pressure (94.2 ± 5.5 vs. 91.8 ± 5.5; p = .009), IL-6 (8.3 ± 2.1 vs. 7.4 ± 1.8; p = .001), and hs-CRP (1.9 ± 1.2 vs. 1.1 ± 0.9; p < .000) decreased whereas TAC increased (0.74 ± 0.1 vs. 0.82 ± 0.1; p < .000) in comparison to the baseline values. There was a significant difference in mean percent change of SBP, diastolic blood pressure, mean arterial blood pressure, serum TAC, and inflammatory markers (tumor necrosis factor alpha, IL-6, and hs-CRP) between hesperidin and control groups following intervention in adjusted models (p < .05). These results suggest that hesperidin may have antihypertensive and anti-inflammatory effects in type 2 diabetes.

The latest suggestion for Hesperidin is – how could be be otherwise? – that it helps against COVID-19: Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection. Anti-viral activity of hesperidin might constitute a treatment option for COVID-19 through improving host cellular immunity against infection and its good anti-inflammatory activity may help in controlling cytokine storm. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression. Based on that, hesperidin might be used as a meaningful prophylactic agent and a promising adjuvant treatment option against SARS-CoV-2 infection.

According to one source, Hesperidin can cause several problems:

  • abdominal pain,
  • diarrhea,
  • contact dermatitis,
  • nausea,
  • interactions with medications (including anticoagulants, blood pressure drugs, and calcium channel blockers),
  • increased risk of bleeding.

No doubt, Hesperidin is an interesting substance. Yet, I feel that much more research is needed until we can be reasonably sure that it is clinically effective for any condition, particularly COVID-19.

I often hear that my ambitions to inform the public and inspire critical thinking are hopeless: there are simply too many quacks trumpeting nonsense, and their collective influence is surely bigger than mine. This can be depressing, of course. And because I often feel that I am fighting an unwinnable battle, stories like this are so importand and up-lifting.

Denby Royal was a ‘holistic nutritionist’, then she became a critic of so-called alternative medicine (SCAM). Here is the story about her transformation:

… I had gone to holistic nutrition school. I was running my own nutrition consulting business. And suddenly I didn’t believe in any of it anymore. How did this flip flop come to pass?

… As a holistic nutritionist, I was an active participant in what I now consider alternative medicine tomfoolery, specifically pushing supplements on a clientele of the “worried well” who often mistook wellness enthusiasts like me for medical experts. I want to be clear that I wasn’t knowingly deceiving anyone—I really did believe in the solutions I was offering my clients… To holistic nutrition enthusiasts and people who believe in a certain kind of alt wellness, these “natural” and “holistic” products seem more trustworthy than what mainstream medicine offers. The truth is, they often lack sufficient, peer-reviewed, reliable scientific evidence of their supposed effectiveness.

Did I have rock-solid evidence that these products would do what their labels promised they would do? Not really. Sure, I read studies here and there that found specific health benefits for some of the products. But I rarely mentioned the fine print (if I knew it at all)—that the sample sizes of many of these studies often were so small that the results couldn’t be generalized to a larger population, that the studies’ authors sometimes noted that more research was needed to support any findings on the effects they found, or that systematic reviews later found that many studies were poorly constructed or at risk for bias, making their findings even less compelling than they seemed initially. And in some cases, study authors themselves note that their findings are merely jumping off points, and that more long-term studies are needed in order to draw more solid conclusions…

Was I relying on strong, valid evidence? Nah, not really. But at the time, I thought what I had was better than strong evidence: Faith in a lifestyle and a dogmatic belief that all things traditional and mainstream were unhealthy or harmful, and therefore, that all things unconventional and alternative were curative and would bring about “wellness.”

In an effort to expand my product knowledge I researched a lot of the different supplements available. I was using all the best bias-confirming websites where other homeopathic medicine enthusiasts evangelized their favorite remedies, their enthusiasm and insistence, and anecdotal evidence standing in for what typically shows us that a product is safe and effective—clinical trials and FDA approval.

When their arguments and reasoning started to sink in, I realized that my faith in the healing powers of supplements may have been overzealous at best, unfounded at worst. My world crumbled like a piece of raw gluten-free paleo cheesecake. It started to sink in: Where there was a morsel of convincing medical information blended with enough compelling nonsense and communicated with enough conviction, I believed it, hook, line, and sinker.

When I started to notice the holes in the fabric of holistic nutrition, the fabric looked, well, pretty threadbare. I subsequently disconnected from social media and distanced myself from the entire culture. I took a good look at how I was personally and publicly communicating my relationships with food and wellness. After spending my twenties experimenting with all kinds of specialty diets, I was left feeling exhausted, anxious, underweight, overweight, and fed-up.

And so that last domino fell when I took away the thing that was propping it up for me: social media. Instagram is a playground for wellness influencers, including, at the time, me. My Instagram account was the best way to advertise my nutrition consulting business, so maintaining a certain persona there felt completely crucial to my success, and eventually, my identity. It was a world full of beautifully curated accounts of thin yogis gathering wild herbs in nature or making raw desserts with ingredients that cost more than my entire monthly food budget. I started to feel like the alternative wellness community I was part of—myself included—was an echo chamber, where we stockpiled likes and positive comments to build a wall that would keep out ideas that challenged our status quo. In fact, the more reassurance I received from my online community, the harder I believed in our gospel.

As I was disentangling my beliefs from everything I was learning by looking at the actual evidence, I realized that my education to become a holistic nutritionist hadn’t prepared me to understand health and wellness as completely and comprehensively as I’d once thought. Sure, I’d spent a some time studying the pathology of disease, and a little longer learning about how each bodily system works to get your human suit from point A to point B, but I am only slightly closer to being a medical professional than I am to becoming a professional cricket player. First of all, in total, my entire formal education as a holistic nutritionist was 10 months long. Second of all, that education was intended to complement—not replace—traditional medical treatment. But as soon as I finished the program, I could immediately start taking on clients. And lots of potential clients out there are just like the way I used to be—wishing they looked or felt different and in search of the panacea, willing (if not eager) to defer to an expert.

There may have been many people willing to look to me as an expert, but here’s the thing: in my school, there were no residency or clinical hours required to prepare us for the real world or to take on clients—unlike dietitians here in Canada, who must obtain a bachelor’s degree in Nutritional and Food Sciences, qualify to complete a rigorous post-degree internship program and register with a provincial dietetics organization, or get a master’s degree. We received a certificate, and that was that. It was a credential that wholeheartedly fell short of resembling anything close to making me an authority on the subject of health as it relates to food and diet. But most people in the general public can’t be expected to understand the ins and outs of how experts are credentialed and licensed—many of us assume that someone calling themselves something that we associate with authority is, in fact, an authority we can trust.

The brief education that I received to become a holistic nutritionist did provide me with valuable stepping stones and a general understanding of how the body works. My program discouraged students from saying “treat,” “heal,” “prevent,” or “cure.” Generally speaking holistic nutrition programs don’t provide the training and medical education that registered dietitians receive, which enables them to give sound, ethical medical nutrition advice, nor are they required by law, the way dietitian programs are, to provide it. In fact, in 2015 graduates of the Canadian School of Natural Nutrition were barred from identifying as Registered Holistic Nutritionists, and since then must use the title “Holistic Nutritional Consultant.”

… With what I do have from my classroom education, I can analyze a lifestyle that needs some fine-tuning and provide guidance on how to structure a solid meal plan. That’s about it. After years of self-diagnosis and hashtagging all my fad-diet escapades (for this, I greatly apologize to all those I have alienated with my profuse self-righteousness), I can at least say I have a deep appreciation for those who are actually on the front lines in the fight against unproven medical remedies and the potential damage it may do to those who use it to the exclusion of traditional medicine.

The influence of these remedies is not harmless, and I have seen firsthand in many different examples and situations how it can lure people away from real, evidence-based help in their times of need. I am fortunate enough that within my practice I had enough foresight to turn away individuals who required more guidance than I was capable of giving. But along the way I made many embarrassing and conjectural recommendations. Like I said, I was far from knowingly deceiving anyone. I firmly held the belief that alternative medicine, no matter the cost, was an investment in a healthful future. My own medicine cabinet, an arsenal full of supplements, tincture, and powders, was a personal testament to how deeply I was devoted to holistic nutrition.

This essay is a firm farewell from a world I disconnected from long ago. The person that over years I let myself become through naiveté, not doing my own research, and a misguided desire to be different. So here I am now, officially having left the church of woo, bidding the world of alternative health adieu.

_________________________________

Reading Denby’s account, I was reminded of many themes we have previously discussed on this blog. One issue that perhaps needs more focus is this notion:

I was far from knowingly deceiving anyone.”

I have not yet met a SCAM practitioner who says:

“I am in the business of  deceiving my patients.”

The reasons for this are simple:

  1. if they knowingly deceive, they would not tell us,
  2. and if they don’t know that they are deciving their patients, they cannot possibly admit to it.

The way Denby repeatedly assures us that she was far from knowingly deceiving anyone sounds charmingly naive and is, in my experience, very typical for SCAM practitioners. It depicts them as honorable people. Yet, in actual fact, it is neither charming nor honorable. It merely demonstrates the fact that they were perhaps not ruthlessly dishonest but all the more dangerous.

Let me explain this with a deliberately extreme example:

  • A man with a chronic condition – say type 2 diabetes – consults a SCAM practitioner who is knowingly deceiving him claiming that her SCAM effectively treats his condition. The patient follows the advice but, since he is not totally convinced (deception is rarely perfect), consults his doctor who puts him straight. This patient will therefore survive.
  • The same chap consults a SCAM practitioner who is deeply convinced of the effectiveness of her SCAM and thus not knowingly deceiving her patient when she claims that it is effective for his diabetes. Her conviction is so strong that the patient blindly believes her. Thus he stops his conventional medication and hopes for the best. This patient could easily die.

In a nutshell:

‘Honest’ conviction might render a quack more socially acceptable but also more dangerous to her patients.

 

It has been reported that Karnataka’s Deputy Chief Minister, Dr CN Ashwathnarayan, has launched eight products, several of which fall in the category of so-called alternative medicine (SCAM), aimed at mitigating COVID-19, developed by various start-ups at Bangalore Bioinnovation Centre (BBC). Dr CN Ashwathnarayan said the launch of the products shows that Karnataka has emerged as a leading state in developing solutions to fight the COVID 19 pandemic.

Here are short descriptions of the innovations:

  • Padma Vitals +: Developed by Innovator start-up Dr. Madan Gopal of Cardiac Design labs,Padma Vitals + is a  centralized monitoring system for ECG, respiration, Spo2 and body temperature, which can measure the vitals continuously and the analysis sent through telemetry, with an alerting system embedded in it. The device is much needed for contactless monitoring of patients during COVID 19 Pandemic. The product has been validated at Narayana Hrudayalaya.
  • Malli’s Cordytea: Developed by Dr. Moushmi Mondal from Mallipatra Neutraceuticals, this product is an Immunity booster tea prepared from medicinal mushroom – Cordyceps. The mushroom variety grown under laboratory conditions is developed by the Innovator. Cordicepin, an active ingredient is known to have anti-viral properties too. In the COVID 19 times, it will be helpful in boosting the immunity levels. The product has been patented and is approved by FSSAI.
  • CD4 Shield : Developed by Dr. Vijay Lanka and his team from Stabicon, this product is a chewable tablet containing curcumin and Vitamin B12. Both the ingredients fight inflammation and infection. The product ensures activation of innate immunity by activating CD4+, CD8+ and IFN 1 to virus specific effect and has immunomodulatory properties. It also reduces cytokine storm in response to viral infection. The product is approved by FSSAI.
  • BeamRoti : Developed by Dr. Srinivas from Aspartika, the product is an immunity booster chapati having mixture of herbs recommended by AYUSH ministry. The ingredients have been prepared using supercritical fluid extraction technology to ensure optimum concentration of herbal extract reaches the body. The chapatis are easy to store with good shelf life and Patent application has been filed. The product is approved by FSSAI.
  • Immune booster daily drops: Developed by Dr. Srinivas from Aspartika, the product is an immunity booster drop having mixture of herbs recommended by AYUSH ministry. The ingredients have been prepared using supercritical fluid extraction technology to ensure optimum concentration of herbal extract reaches the body by mixing just one drop of the product in a glass of hot water. The product is approved by FSSAI.
  • VegPhal – Fruit and Vegetable Sanitizer: Developed by Deepak Bhajantri from Krimmi Biotech, this fruit and vegetable sanitizer is prepared using edible ingredients effective against microbes and removal of pesticides. It is chorine and alcohol free.
  • Water Sanitizer – Kitchen Tap: The product is developed by Ravi Kumar from Biofi and is a miniaturized version of UV purifier that can be attached to a water tap and kill 99% of microbes including viruses such as phages.
  • nti-Micobial HVAC module: The product is developed by Ravi Kumar from Biofi and is a module that can be fitted to HVAC system to ensure circulating air is sanitized. This is especially useful during COVID 19 times as many enclosed spaces in which AC circulated air may be contaminated. Based on UV-silver titanium dioxide technology, the product is patented and has been validated.

Karnataka is of course a state in the south western region of India. The region has so far about one million COVID-19 cases, while almost 12 000 people have died. One would therefore very much hope that the newly launched innovations can make a difference.

But will they?

As far as the SCAM-related products (e.g. ‘immune boosters’) are concerned, I see no convincing evidence to assume that they are effective. If anyone has information to the contrary, please let me know.

But why not? They can’t do any harm!

Sadly, I am am not so sure. I see the potential for considerable harm from all the useless SCAMs that are being promoted left right and centre for protecting the public against COVID-19. Firstly, there is the financial harm of paying for products that are useless. Secondly, ineffective effords might distract from finding and adhering to efforts that are effective. Thirdly, believing in a SCAM that does not work will create a sense of false security which, in turn, renders consumers more vulnerable to catch the virus.

As always in healthcare, even harmless interventions that do not work can become dangerous, as they lead to neglecting effective measures. I shudder to think of how many deaths have been caused by the many SCAM merchants who see the current pandemic as an opportunity.

Numerous so-called alternative medicines (SCAMs) have been touted as the solution for COVID-19. In fact, it is hard to find a SCAM that is not claimed to be useful for corona patients. Crucially, such claims are being made in the complete absence of evidence. A recent paper offers a bibliometric analysis of global research trends at the intersection of SCAM and COVID-19.

SCOPUS, MEDLINE, EMBASE, AMED and PSYCINFO databases were searched on July 5, 2020. All publication types were included, however, articles were only deemed eligible, if they made mention of one or more SCAMs for the potential prevention, treatment, and/or management of COVID-19 or a health issue indirectly resulting from the COVID-19 pandemic. The following eligible article characteristics were extracted: title; author names, affiliations, and countries; DOI; publication language; publication type; publication year; journal (and whether it is TICAM-focused); 2019 impact factor, and TICAMs mentioned.

A total of 296 eligible articles were published by 1373 unique authors at 977 affiliations across 56 countries. The most common countries associated with author affiliation included:

  • China,
  • the United States,
  • India,
  • Italy.

Four journals had published more that 10 papers each on the subject:

  • Chinese Traditional and Herbal Drugs,
  • Journal of Biomolecular Structure & Dynamics,
  • Zhongguo Zhongyao Zazhi (China Journal of Chinese Materia Medica),
  • Pharmacological Research

The vast majority of articles were published in English, followed by Chinese. Eligible articles were published across 157 journals, of which 33 were SCAM-focused; a total of 120 journals had a 2019 impact factor, which ranged from 0.17 to 60.392. A total of 327 different SCAMs were mentioned across eligible articles, with the most common ones including:

  • traditional Chinese medicine (n = 94),
  • vitamin D (n = 67),
  • melatonin (n = 16),
  • phytochemicals (n = 12),
  • general herbal medicine (n = 11).

The Canadian author concluded that this study provides researchers and clinicians with a greater knowledge of the characteristics of articles that been published globally at the intersection of COVID-19 and SCAM to date. At a time where safe and effective vaccines and medicines for the prevention and treatment of COVID-19 have yet to be discovered, this study provides a current snapshot of the quantity and characteristics of articles written at the intersection of SCAM therapies and COVID-19.

If anyone repeated the research today, I fear that the number of different SCAMs would have at least doubled. There is simply no form of SCAM that would not have joined the bandwagon of snake-oil salesmen trying to make a quick buck or satisfying their dangerous delusion of a panacea. Today (11/12/2020) my very quick Medline search on just a few SCAMs resulted in the following:

  • Herbal medicine: 253
  • Dietary supplement: 139
  • Acupuncture: 68
  • Homeopathy (not mentioned at all above): 20
  • Chiropractic: 13
  • Naturopathy: 6

One of the most chilling reads during my ‘rough and ready’ trawl through the literature was an article co-authored by a Viennese professor who has featured repeatedly on this blog. Here is its abstract:

Successful homeopathic prescriptions are based on careful individualization of symptoms, either for an individual patient or collectively in the case of epidemic outbreaks. The ongoing COVID-19 pandemic was initially represented as a severe acute respiratory illness, with eventual dramatic complications. However, over time it revealed to be a complex systemic disease with manifestations derived from viral-induced inflammation and hypercoagulability, thus liable to affect any body organ or system. As a result, clinical presentation is variable, in addition to variations associated with several individual and collective risk factors. Given the extreme variability of pathology and clinical manifestations, a single, or a few, universal homeopathic preventive Do not split medicine(s) do not seem feasible. Yet homeopathy may have a relevant role to play, inasmuch as the vast majority of patients only exhibit the mild form of disease and are indicated to self-care at home, without standard monitoring, follow-up, or treatment. For future pandemics, homeopathy agencies should prepare by establishing rapid-response teams and efficacious lines of communication.

The Canadian author of the above paper did not analyse how many of the papers he included would make therapeutic claims. I suspect that the majority did. In this context, one of the clearest indications of how deluded SCAM practitioners tend to be during these difficult times was provided by this paper:

Coronavirus disease 2019 (COVID-19), caused by a new coronavirus, first appeared in late 2019. What initially seemed to be a mild influenza quickly revealed itself as a serious and highly contagious disease, and the planet was soon faced with a significant morbidity and mortality associated with this pathogen. For homeopathy, shunned during its 200 years of existence by conventional medicine, this outbreak is a key opportunity to show potentially the contribution it can make in treating COVID-19 patients. This should be done through performance of impeccably controlled, prospective, randomized clinical trials, with publication of their findings in well-ranked conventional medicine journals. If the homeopathy community fails to take advantage of this rare opportunity, it might wait another century for the next major pandemic.

I must admit, I felt vaguely sick while reading it.

I very rarely discuss animal experiments on this blog. Their applicability to clinical situations in human patients is almost invariably doubtful. Of course, this does not mean that they cannot be important; on the contrary, they may point the way towards relevant research and help formulate hypotheses.

This study might be exceptionally relevant in this way. To investigate the safety and efficacy of megadose sodium ascorbate in sepsis, sheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg).

Sepsis-induced fever (41.4 ± 0.2°C; mean ± SE), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial PO2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue PO2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01).

Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary PO2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg).

These physiologic findings were subsequently confirmed in a coronavirus patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours.

The authors concluded that IV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.

As always with animal experiments, it is difficult to extrapolate to clinical situations in human patients. However, the fact that the authors did try their approach on one COVID-19 patient is encouraging. I agree with their conclusion that careful human studies are now required.

In these pre-Xmas days, many homes will smell of cinnamon. It’s certainly a wonderful spice for creating an atmosphere. But ther are also other uses for ciannamon.

Current treatments for overactive bladder (OAB) have limited efficacy, low persistence and a high rate of adverse events commonly leading to treatment cessation in clinical practice. Clinicians in Asia commonly use traditional Chinese medicine as an alternative for OAB treatment despite it having uncertain efficacy and safety. To evaluate the efficacy and safety of cinnamon patch (CP) treatment for alleviating symptoms of OAB, this double-blind randomized, placebo-controlled trial was conducted.

The 6-week study was conducted in an outpatient setting; 66 subjects diagnosed as having OAB were enrolled and treated with a placebo (n=33) or CP (n=33). The OAB symptom score (OABSS) was selected as the primary end point, and a patient perception of bladder condition (PPBC), an urgency severity scale (USS), and post-voiding residual urine (PVR) volume were selected as secondary end points.

In total, 66 participants (40 women and 26 men), 60 years of age, were included in the intention-to-treat analyses. Baseline characteristics were comparable between the CP and placebo groups. Treatment with a CP showed statistically significant differences in reductions in OABSS scores, PPBC scores, and USS scores.

The authors concluded that compared to a placebo, treatment with CP might be considered an effective and safe complementary therapy for OAB. Further studies employing a positive control, different dosage forms, larger sample sizes, and longer treatment periods are warranted.

Cinnamon (Cinnamomum zeylanicum and Cinnamon cassia)belongs to the Lauraceae family. It contains manganese, iron, dietary fiber, and calcium as well as cinnamaldehyde, cinnamic acid, cinnamate, and  numerous other components such as polyphenols and antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer effects. Several reports have dealt with the numerous properties of cinnamon in the forms of bark, essential oils, bark powder, and phenolic compounds, and each of these properties can play a key role in human health.

The new study is interesting and prompts me to ponder:

So, for the time being, I think, I prefere cinnamon, the spice, to cinnamon, the medicine.

In so-called alternative medicine (SCAM), we have numerous diets that are either promoted for specific conditions or that are popular in a more general sense. Meat-free forms of nutrition can perhaps not be characterised as SCAM, but they are certainly popular with consumers as well as practitioners of SCAM. It is often said that meat-free diets are healthy, but few entusiasts like to consider that it might be associated with health risks.

This study tested whether vegetarianism and veganism are risk factors for bone factures in a prospective cohort with a large proportion of non-meat eaters.

In EPIC-Oxford, dietary information was collected at baseline (1993–2001) and at follow-up (≈ 2010). Participants were categorised into four diet groups at both time points (with 29,380 meat eaters, 8037 fish eaters, 15,499 vegetarians, and 1982 vegans at baseline in analyses of total fractures). Outcomes were identified through linkage to hospital records or death certificates until mid-2016. The risks were calculated of total (n = 3941) and site-specific fractures (arm, n = 566; wrist, n = 889; hip, n = 945; leg, n = 366; ankle, n = 520; other main sites, i.e. clavicle, rib, and vertebra, n = 467) by diet group over an average of 17.6 years of follow-up.

Compared with meat eaters and after adjustment for socio-economic factors, lifestyle confounders, and body mass index (BMI), the risks of hip fracture were higher in

  • fish eaters (hazard ratio 1.26; 95% CI 1.02–1.54),
  • vegetarians (1.25; 1.04–1.50),
  • vegans (2.31; 1.66–3.22).

This was equivalent to rate differences of 2.9 (0.6–5.7), 2.9 (0.9–5.2), and 14.9 (7.9–24.5) more cases for every 1000 people over 10 years, respectively. The vegans also had higher risks of total (1.43; 1.20–1.70), leg (2.05; 1.23–3.41), and other main site fractures (1.59; 1.02–2.50) than meat eaters. Overall, the significant associations appeared to be stronger without adjustment for BMI and were slightly attenuated but remained significant with additional adjustment for dietary calcium and/or total protein. No significant differences were observed in risks of wrist or ankle fractures by diet group with or without BMI adjustment, nor for arm fractures after BMI adjustment.

The authors concluded that non-meat eaters, especially vegans, had higher risks of either total or some site-specific fractures, particularly hip fractures. This is the first prospective study of diet group with both total and multiple specific fracture sites in vegetarians and vegans, and the findings suggest that bone health in vegans requires further research.

The effect is by no means large, and I doubt that it will persuade many non-meat eaters to change their diet. However, perhaps the study can serve as a reminder that people who avoid meat might some lack essential nutrients and that they should therefore consider making sure that no deficiencies can develop.

Despite reported widespread use of dietary supplements by cancer patients, few empirical data with regard to their safety or efficacy exist. Because of concerns that antioxidants could reduce the cytotoxicity of chemotherapy, a prospective study was carried out to evaluate associations between supplement use and breast cancer outcomes.

Patients with breast cancer randomly assigned to an intergroup metronomic trial of cyclophosphamide, doxorubicin, and paclitaxel were queried on their use of supplements at registration and during treatment (n =1,134). Cancer recurrence and survival were indexed at 6 months after enrollment.

There were indications that use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment was associated with an increased hazard of recurrence and, to a lesser extent, death. Relationships with individual antioxidants were weaker perhaps because of small numbers. For non-antioxidants, vitamin B12 use both before and during chemotherapy was significantly associated with poorer disease-free survival and overall survival. Use of iron during chemotherapy was significantly associated with recurrence as was use both before and during treatment. Results were similar for overall survival. Multivitamin use was not associated with survival outcomes.

The authors concluded that associations between survival outcomes and use of antioxidant and other dietary supplements both before and during chemotherapy are consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.

These data are interesting but, for a range of reasons, not compelling. There might have been several important confounding factors distorting the findings. Even though clinical and life-style variables were statistically adjusted for in this study, it might still be possible that supplement users and non-users were not comparable in impotant prognostic variables. Simply put, sicker patients might be more likely to use supplements and would then have worse outcomes not because of the supplements but their disease severity.

Moreover, it seems important to note that other research showed the opposite effects. For instance, a study prospectively examined the associations between antioxidant use after breast cancer (BC) diagnosis and BC outcomes in 2264 women. The cohort included women who were diagnosed with early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years postdiagnosis. Baseline data were collected on antioxidant supplement use since diagnosis and other factors. BC recurrence and mortality were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated.

Antioxidant supplement use after diagnosis was reported by 81% of women. Among antioxidant users, frequent use of vitamin C and vitamin E was associated with a decreased risk of BC recurrence. Vitamin E use was associated with a decreased risk of all-cause mortality. Conversely, frequent use of combination carotenoids was associated with increased risk of death from BC and all-cause mortality.

The authors concluded that frequent use of vitamin C and vitamin E in the period after BC diagnosis was associated with a decreased likelihood of recurrence, whereas frequent use of combination carotenoids was associated with increased mortality. The effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant.

Yet another study provided limited support for the hypothesis that antioxidant supplements may reduce the risk of breast cancer recurrence or breast cancer-related mortality.

Confused?

Me too!

What is needed, it seems, is a systematic review of all these contradicting studies. A 2009 review is available of the associations between antioxidant supplement use during breast cancer treatment and patient outcomes.

Inclusion criteria were: two or more subjects; clinical trial or observational study design; use of antioxidant supplements (vitamin C, vitamin E, antioxidant combinations, multivitamins, glutamine, glutathione, melatonin, or soy isoflavones) during chemotherapy, radiation therapy, and/or hormonal therapy for breast cancer as exposures; treatment toxicities, tumor response, recurrence, or survival as outcomes.

A total of 22 articles met the criteria. Their findings did not support any conclusions regarding the effects of individual antioxidant supplements during conventional breast cancer treatment on toxicities, tumor response, recurrence, or survival. A few studies suggested that antioxidant supplements might decrease side effects associated with treatment, including vitamin E for hot flashes due to hormonal therapy and glutamine for oral mucositis during chemotherapy. Underpowered trials suggest that melatonin may enhance tumor response during treatment.

The authors concluded that the evidence is currently insufficient to inform clinician and patient guidelines on the use of antioxidant supplements during breast cancer treatment. Thus, well designed clinical trials and observational studies are needed to determine the short- and long-term effects of such agents.

Still confused?

Me too!

Antioxidants seem to have evolved as parts of elaborate networks in which each substance plays slightly different roles. This means that each antioxidant has a different spectrum of actions. And this means that it is probably not very constructive to lump them all together and excect to see uniform effects. What we would need to create more clarity is a series of RCTs on single antioxidants. But who is going to fund them? We might be waiting a long time for more clarity. Meanwhile, consuming a healthy and well-balanced diet might be the best advice for cancer patients and everyone else.

Melatonin is an indolamine hormone which is secreted from the human pineal gland during night-time acting as physiological regulator. In many countries, dietary supplements containing synthetically produced melatonin are available. Melatonin is being promoted as a treatment of a range of conditions, including virtually all types of cancer.

One website, for instance, states that the anti-cancer benefits of melatonin aren’t just indirect; this miracle molecule is also classified as a directly cytotoxic hormone and anti-cancer agent. Studies have referred to melatonin as a “full-service anti-cancer agent” due to its ability to inhibit the initiation of cell mutation and cancer growth, and to halt the progression and metastasis of cancer cell colonies.

Such statements sound far too good to be true. So, let’s have a look and find out what the evidence tells us. Test-tube experiments suggest that melatonin has anti-cancer effects.[1] Its actions include the advancement of apoptosis, the arrest of the cell cycle, inhibition of metastasis, and antioxidant activity.[2]

A review of 21 clinical trials of melatonin for cancer found positive effects for complete response, partial response, and stable disease. In trials combining melatonin with chemotherapy, adjuvant melatonin therapy decreased 1-year mortality and improved outcomes of complete response, partial response, and stable disease. In these studies, melatonin also significantly reduced asthenia, leukopenia, nausea and vomiting, hypotension, and thrombocytopenia. The authors concluded that melatonin may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy.[3]

A further systematic review of RCTs of melatonin in solid tumour cancer patients evaluated its effect on one-year survival. Ten trials were included of melatonin as either sole treatment or as adjunct treatment. Melatonin reduced the risk of death at 1 year. Effects were consistent across melatonin dose, and type of cancer. No severe adverse events were reported.[4]

A 2012 systematic review confirmed these findings by concluding that Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission, 1-year survival, and alleviation of radiochemotherapy-related side effects.[5]

Finally, a 2020 review concluded that melatonin in combination with anticancer agents may improve the efficacy of routine medicine and survival rate of patients with cancer. [6] Apart from its direct anticancer potential, melatonin also seems to reduce chemotherapy toxicity, while improving its therapeutic efficacy.[7]

So, is this evidence compelling? While all this does indeed sound encouraging, it is necessary to mention several important caveats:

  • The primary studies of melatonin suffer from several methodological shortcomings.
  • Their vast majority originate from one single research group.
  • In recent years, there have been no further clinical studies trying to replicate the initial findings.

This means that definitive trials are still missing, and it would seem wise to interpret the existing evidence with great caution.

References

[1] Kong X, Gao R, Wang Z, Wang X, Fang Y, Gao J, Reiter RJ, Wang J. Melatonin: A Potential Therapeutic Option for Breast Cancer. Trends Endocrinol Metab. 2020 Sep 3:S1043-2760(20)30155-7. doi: 10.1016/j.tem.2020.08.001. Epub ahead of print. PMID: 32893084.

[2] Samanta S. Melatonin: an endogenous miraculous indolamine, fights against cancer progression. J Cancer Res Clin Oncol. 2020 Aug;146(8):1893-1922. doi: 10.1007/s00432-020-03292-w. Epub 2020 Jun 24. PMID: 32583237.

[3] Seely D, Wu P, Fritz H, Kennedy DA, Tsui T, Seely AJ, Mills E. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integr Cancer Ther. 2012 Dec;11(4):293-303. doi: 10.1177/1534735411425484. Epub 2011 Oct 21. PMID: 22019490.

[4] Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005 Nov;39(4):360-6. doi: 10.1111/j.1600-079X.2005.00258.x. PMID: 16207291.

[5] Wang YM, Jin BZ, Ai F, Duan CH, Lu YZ, Dong TF, Fu QL. The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials. Cancer Chemother Pharmacol. 2012 May;69(5):1213-20. doi: 10.1007/s00280-012-1828-8. Epub 2012 Jan 24. PMID: 22271210.

[6] Pourhanifeh MH, Mehrzadi S, Kamali M, Hosseinzadeh A. Melatonin and gastrointestinal cancers: Current evidence based on underlying signaling pathways. Eur J Pharmacol. 2020 Nov 5;886:173471. doi: 10.1016/j.ejphar.2020.173471. Epub 2020 Aug 30. PMID: 32877658.

[7] Iravani S, Eslami P, Dooghaie Moghadam A, Moazzami B, Mehrvar A, Hashemi MR, Mansour-Ghanaei F, Mansour-Ghanaei A, Majidzadeh-A K. The Role of Melatonin in Colorectal Cancer. J Gastrointest Cancer. 2020 Sep;51(3):748-753. doi: 10.1007/s12029-019-00336-4. PMID: 31792737.

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