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

supplements

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By guest blogger Loretta Marron

If scientists were fearful of a clinical trial’s producing negative results, would they even pursue it? A draft Chinese regulation issued in late May aims to criminalise individual scientists and organisations whom China claims damage the reputation of Traditional Chinese Medicine (TCM).

Beijing has a reputation for reprimanding those who decry TCM. Such criticism is blocked on Chinese Internet. Silencing doctors is becoming the norm.

In January 2018, former anaesthetist, Tan Qindong, was arrested and spent more than three months in detention after criticising a widely advertised, best-selling ‘medicinal’ TCM liquor. Claiming that it was a ‘poison’, he believed that he was protecting the elderly and vulnerable patients with high blood pressure. Police claimed that a post on social media damaged the reputation of the TCM ‘liquor’ and of the company making it. Shortly after release, he suffered post-traumatic stress and was hospitalised.

On 30 December 2019, Chinese ophthalmologist, the late Dr Li Wenliang, was one of the first to recognise the outbreak of COVD-19. He posted a private warning to a group of fellow doctors about a possible outbreak of an illness resembling severe acute respiratory syndrome (SARS). He encouraged them to protect themselves from infection. Days later, after his post when viral, he was summoned to the Public Security Bureau in Wuhan and forced to “admit to lying about the existence of a worrying new virus”. Li was accused of violating the provisions of the “People’s Republic of China Public Order Management and Punishment Law” for spreading “unlawful spreading of untruthful topics on the internet” and of disturbing the social order. He was made to sign a statement that he would “halt this unlawful behaviour”.

In April 2020, Chinese physician Yu Xiangdong, a senior medico who worked on the front line battling COVID-19, posted on Weibo, a Twitter-like site, a criticism of the use of antibiotics and TCM to treat COVID-19. He was demoted from his positions as assistant dean at the Central Hospital in the central city of Huangshi and director of quality management for the city’s Edong Healthcare Group. Well known for promoting modern medicine amongst the Chinese, Yu had almost a million followers on social media. All his postings vanished.

Beijing insists that TCM has been playing a crucial role in COVID-19 prevention, treatment and rehabilitation. Claims continue to be made for “effective TCM recipes”. However, no randomised clinical trial has been published in any reputable journal.

TCM needs proper scrutiny, but criticising it could land you years in prison. If the benefits of suggested herbal remedies are to be realised, good clinical studies must be encouraged. For TCM, this might never be permitted.

Don’t think for a moment that you are safe in Australia.

Article 8.25 of the Free Trade Agreement Between the Government of Australia and the Government of the People’s Republic of China reads:

Traditional Chinese Medicine Services (“TCM”)

  1. Within the relevant committees to be established in accordance with this Agreement, and subject to available resources, Australia and China shall cooperate on matters relating to trade in TCM services.
  2. Cooperation identified in paragraph 2 shall:

(a)    include exchanging information, where appropriate, and discussing policies, regulations and actions related to TCM services; and

(b)   encourage future collaboration between regulators, registration authorities and relevant professional bodies of the Parties to facilitate trade in TCM and complementary medicines, in a manner consistent with all relevant regulatory frameworks. Such collaboration, involving the competent authorities of both Parties – for Australia, notably the Department of Health, and for China the State Administration of Traditional Chinese Medicine – will foster concrete cooperation and exchanges relating to TCM.

The objective of this study was to identify adverse drug reactions (ADR) associated with the use of so-called alternative medicine (SCAM) in Malaysia and to define factors which are associated with the more serious reactions. For this purpose, all ADR associated with the use of SCAM products (including health supplements) submitted to the Malaysian Centre for ADR Monitoring, National Pharmaceutical Regulatory Agency over a 15-year period were reviewed and analysed. Multivariate logistic regression analysis was performed to identify predictors of serious ADR.

From a total of 74 997 reports in the database, 930 (1.2%) involved SCAM products. From a total of 930 reports, 242 (26%) were serious ADR with 36 deaths. Six people died as a result of taking the SCAM, while another 30 cases were possibly associated with the SCAM products. Among the 36 mortality cases, adulterants were detected in 30% of cases. Examples of adulterants were dexamethasone, avanafil, nortadalafil and banned drugs such as phenylbutazone and sibutramine

About a third of the reports involved used SCAM products for health maintenance. Most (78.1%) of the ADR reports implicated unregistered products with 16.7% confirmed to contain adulterants which were mainly dexamethasone. Of the 930 reports, the ADR involved skin and appendages disorders (18.4%) followed by liver and biliary system disorders (13.7%). The odds of someone experiencing serious ADR increased if the SCAM products were used for chronic illnesses (odds ratio [OR] 1.99, confidence interval [CI] 1.46-2.71), having concurrent diseases (OR 1.51, CI 1.04-2.19) and taking concurrent drugs (OR 1.44, CI 1.03-2.02).

The authors concluded that the prevalence of serious ADR associated with SCAM products is high. Factors identified with serious ADR included ethnicity, SCAM users with pre-existing diseases, use of SCAM for chronic illnesses and concomitant use of SCAM products with other drugs. The findings could be useful for planning strategies to institute measures to ensure safe use of SCAM products.

The authors also point out that underreporting of ADRs remains a major ongoing issue in pharmacovigilance. Many SCAM consumers may not be vigilant or may be unaware of ADR they experience due to misconceptions on the
safety of SCAM products. Most doctors rarely ask their patients about the use of SCAM.

To this, I would add that SCAM providers do their utmost to give the impression that their products are natural and therefore safe. Furthermore the press is far too often perpetuating the myth, and the regulators tend to turn a blind eye.

I expect that some readers of this post will now point out that the rate of SCAM-related ADRs is very small compared to that of conventional drugs. They would be correct, of course. But they would also miss the point that the value of a treatment is not determined by its risk alone. It is determined by the risk/benefit balance. Where there is no effectiveness, this balance is negative, even if the risk is tiny.

So, now let me challenge the defenders of SCAM to name a few SCAMs that are demonstrably associated with a positive risk/benefit balance.

 

Spermidine is a polyamine which is a natural component of our cells. It has its name from the fact that it was first found in sperm. It can also be found in varying concentrations in different fruits, vegetables, meat and cheese. About one third of the spermidine levels in our body is produced by our own cells, the rest is absorbed through food and certain bacteria found in our digestive tract. A balanced diet can therefore help maintain high levels of spermidine.

There has been a flurry of research into spermidine, not least because epidemiologic evidence supports to the concept that nutrition rich in spermidine is linked to increased survival in humans. Unsurprisingly, many spermidine supplements are now available for sale (at around £50 for one month’s supply). In order to check whether there is any clinical evidence to suggest that they are effective, I ran a quick Medline search for placebo-controlled, double-blind RCTs. I found 4 such studies; here are their abstracts:

1st study

Introduction: Nutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine supplementation on memory performance in older adults at risk for the development of Alzheimer’s disease.

Methods: Cognitively intact participants with subjective cognitive decline (n = 30, 60-80 years of age) were included in this three-months, randomized, placebo-controlled, double-blind Phase IIa pilot trial with a spermidine-rich plant extract supplement. Effects of intervention were assessed using the behavioral mnemonic similarity task, measured at baseline and post-intervention visits. Data analysis was focused on reporting and interpreting effectiveness based on effect sizes.

Results: Memory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention [contrast mean = .17, 95% confidence interval (CI): -.01, .35, Cohen’s d = .77, 95% CI: 0, 1.53]. Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = -.11, 95% CI: -.19, -.03, Cohen’s d = .79, 95% CI: .01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = .07, 95% CI: -.13, .27, Cohen’s d = -.20, 95% CI: -.94, .54).

Discussion: In this pilot trial, nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. The beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system. A follow-up Phase IIb randomized controlled trial will help validate the therapeutic potential of spermidine supplementation and delineate possible neurophysiological mechanisms of action.

2nd study

Supplementation of spermidine, an autophagy-inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28-days repeated-dose tolerance study. Post mortem examination of the mice organs showed no increase in tumorigenic and fibrotic events. In the human cohort (participants with subjective cognitive decline, n=30, 60 to 80 years of age), a 3-month randomized, placebo-controlled, double-blind Phase II trial was conducted with supplementation of the spermidine-rich plant extract (dosage: 1.2 mg/day). No differences were observed between spermidine and placebo-treated groups in vital signs, weight, clinical chemistry and hematological parameters of safety, as well as in self-reported health status at the end of intervention. Compliance rates above 85% indicated excellent tolerability. The data demonstrate that spermidine supplementation using a spermidine-rich plant extract is safe and well-tolerated in mice and older adults. These findings allow for longer-term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.

3rd study

Recently, it was demonstrated that spermidine-induced autophagy reduces the risk of cardiovascular disease in mice. Intestinal bacteria are a major source of polyamines, including spermidine. We previously reported that the intake of both Bifidobacterium animalis subsp. lactis (Bifal) and arginine (Arg) increases the production of putrescine, a spermidine precursor, in the gut. Here, we investigated the effects of Bifal and Arg consumption on endothelial function in healthy subjects. Healthy individuals with body mass index (BMI) near the maximum value in the “healthy” range (BMI: 25) (n = 44) were provided normal yogurt containing Bifal and Arg (Bifal + Arg YG) or placebo (normal yogurt) for 12 weeks in this randomized, double-blinded, placebo-controlled, parallel-group comparative study. The reactive hyperemia index (RHI), the primary outcome, was measured using endo-peripheral arterial tone (EndoPAT). The change in RHI from week 0 to 12 in the Bifal + Arg YG group was significantly higher than that in the placebo group, indicating that Bifal + Arg YG intake improved endothelial function. At week 12, the concentrations of fecal putrescine and serum putrescine and spermidine in the Bifal + Arg YG group were significantly higher than those in the placebo group. This study suggests that consuming Bifal + Arg YG prevents or reduces the risk of atherosclerosis.

4th study

Background: Spermidine has been shown both in vitro and in mice models to have an anagen-prolonging effect on hair follicles (HFs).

Objectives: To evaluate the effects of a spermidine-based nutritional supplement on the anagen phase of HFs in healthy human subjects in a randomized, double-blind, placebo-controlled trial.

Methods: One hundred healthy males and females were randomized to receive a tablet containing a spermidine-based nutritional supplement or a placebo once daily for 90 days. At the beginning and the end of the treatment period, 100 HFs were plucked and subjected to microscopic evaluation to determine the number of anagen V-VI HFs, and immunohistochemical examination was performed to quantify the Ki-67 and c-Kit levels in the hair bulbs. Pull test was performed after three and six months.

Results: The spermidine-based nutritional supplement increased the number of anagen V-VI HFs after three months of treatment, accompanied by increased Ki-67, a marker for cellular proliferation, and decreased c-Kit, a marker for apoptosis, levels. All results were also significantly better when compared to the placebo group. The pull test remained negative after six months in all patients receiving the spermidine supplement, while 68% of the subjects in the placebo group had a positive pull test.

Conclusions: This preliminary study shows that a spermidine-based nutritional supplement can prolong the anagen phase in humans, and therefore might be beneficial for hair loss conditions. Further studies are needed to evaluate its effects in specific different clinical settings.

_____________________

Convinced?

I could certainly do with a few more hair on my head.

And living longer with less cognitive decline would also be not a bad prospect.

Do I therefore rush to the next health food shop to buy a spermidine supplement?

No.

Yes, the evidence – particularly the pre-clinical one – is fascinating. But it seems to me that a normal diet will provide all the spermidine I need (and for £50 I can buy a lot of good food).

There are many proponents of so-called alternative medicine (SCAM) who advocate the use of high-dose vitamin D for the prevention or treatment of corona-virus infections. Considering that ethnic minorities are disproportionately affected with Covid-19 further research seems justified, especially as there is clear evidence that vitamin D deficiency is particularly common in these ethnic groups.

However, an international team of experts strongly caution against doses higher than the upper limit (4000 IU/day; 100 µg/day); and certainly of very high doses of vitamin D (in some reports, 10 000 IU/day (250 µg/day) of vitamin D are being promoted) unless under personal medical advice/clinical advice by a qualified health professional. Instead, they advocate the following lifestyle strategies for avoiding vitamin D deficiency and ensuring a healthy, balanced diet.

  1. Supplementation with vitamin D according to Government guidelines (eg, 400 IU/day (10 µg/day) for the UK;7 600 IU/day (15 µg/day) for the USA (800 IU/day (20 µg/day) for >70 years) and Europe. These recommendations were established to ensure that 25OHD concentrations in the majority of the population are above 25 nmol/L (UK) in order to protect musculoskeletal health or above 30 nmol/L (USA) to minimise the risk of vitamin D deficiency (the USA recommendation was also established to optimise musculoskeletal health in the population using a 25OHD concentration of 50 nmol/L). Supplementation with vitamin D is particularly important during times of self-isolation associated with limited sunlight exposure. This is in line with the UK Scientific Advisory Committee on Nutrition (SACN) recommendations for vitamin D, and the US Institute of Medicine (IOM) recommendations for vitamin D, both of which were established under the assumption of minimal exposure to sunlight. Thus, re-emphasis of advice on safe sun exposure (below) and reinforcing government advice on supplements especially when sunlight exposure is low would further boost vitamin D status. The UK SACN, US IOM and EU European Food Safety Agency recommend that vitamin D intake (total from both foods and dietary supplements) should be limited to 4000 IU/day (100 µg/day) for adults, and there is broad international consensus that the general public should avoid higher dose supplements that risk total intake from all sources exceeding this level.
  2. Consumption of a nutritionally balanced diet, for example, according to the UK Eatwell Guide and US Food Pyramid including vitamin D rich foods, that is, oily fish, red meat, egg yolk and fortified foods, such as breakfast cereals in the UK, as well as fortified milk in the USA and Canada.
  3. Safe sunlight exposure to boost vitamin D status. Safe sunlight exposure will enable vitamin D production in skin from March through September in the UK, and at most northern latitudes. Dermal synthesis of vitamin D is most efficient with short, regular (daily) exposures when the sun is at its strongest (in the middle of the day). The efficiency of vitamin D synthesis declines well before the threshold for sunburn is reached but the desirable dose is skin-type dependent and so exposure times required differ for different skin types. For the UK about 10 min of exposure at around lunchtime, in-season appropriate clothing, can meet vitamin D needs for white-skinned people; this increases to about 25 min for those of skin type V (ie, South Asian, brown skin tones). What is key is to try to achieve the sunlight exposure without leaving home (eg, in the garden/balcony); and if that is not possible ensure that social distancing is maintained at all times. Increasing the unprotected skin area (skin not protected by clothing or sunscreen) will increase the vitamin D supply from skin while keeping exposure times short and sub-erythemal. Exposing as much skin as temperature and social comfort allow will maximise vitamin D supply through this route. For those of skin type V and VI (brown or black skin) the exposure requirements in UK sunlight are more challenging to achieve than for white-skinned people and oral vitamin D intake is especially important.
  4. Appropriate diet and lifestyle measures, as emphasised by the WHO at this time, including adequate nutrition to protect the immune system.
  5. Targeted nutritional advice, for example, for UK Military personnel as advised by the Defence Nutrition Advisory Service, with specific reference to COVID-19.
  6. Vitamin D—advice for bone health. The Royal Osteoporosis Society provides specific guidelines on the management of vitamin D deficiency in adults with, or at risk of developing, bone disease.

In conclusion, the experts recommend appropriate RCTs to evaluate the effects of vitamin D supplementation on COVID-19 infections. Until there is more robust scientific evidence for vitamin D,  they strongly caution against the use of high vitamin D supplementation (greater than the upper limit of 4000 IU/day (100 µg/day)). Rather, they strongly endorse avoidance of vitamin D deficiency in the population (as per the six points above) and complete adherence to government’s advice worldwide on the prevention of the spread of COVID-19.

I am sure that this will not stop self-appointed SCAM-experts to continue recommending mega-doses of vitamin D. Therefore it is perhaps worth reminding consumers that an excess of vitamin D will lead to a condition called hypervitaminosis D. It is characterised by the following symptoms:

  • Anorexia
  • Dehydration
  • Fatigue
  • Frequent urination
  • Irritability
  • Tinnitus
  • Dizziness
  • Disorientation
  • Confusion
  • Weight loss
  • Muscle weakness
  • Vomiting
  • Excessive thirst
  • High blood pressure
  • Arrhythmias
  • Passing large amounts of urine

It can lead to serious complication, including permanent kidney damage.

This study by Australian pharmacists, assessed the quality and relevance of community pharmacists’ information gathering (questioning), counselling and product selection when interacting with customers requesting a s0-called alternative medicine (SCAM) product for stress and consequently determine whether Australian pharmacy practice indicates the need for guidelines similar to those provided for ‘pharmacy only’ (S2) and ‘pharmacist only’ (S3) medicines.

A covert simulated patient (SP) was used to investigate the response of pharmacists to a request for a natural product for stress. The SP documented the details of the pharmacist-simulated patient interaction immediately on leaving the pharmacy and then re-entered the pharmacy to debrief the pharmacist. The quality of the interaction was scored as a Total CARE (check, assess, respond, explain) Score, based on anticipated questions and counselling advice. The appropriateness of the product was scored as a Product Efficacy Score, based on evidence-based literature.

Data from 100 pharmacies was provided. Information gathering illustrated by the questioning components Check and Assess (C and A) of the total CARE score by pharmacists was poor. The number of questions asked ranged from zero (13 pharmacists) to 7 (four pharmacists), the average being 3.1 (SD 1.9). Provision of advice was generally better (a description of the suggested product was offered by 87 pharmacists) but was lacking in other areas (duration of use and side effects were explained by only 41 and 16 pharmacists respectively). The most common product suggested was B-group vitamins (57 pharmacists) followed by a proprietary flower essence product (19 pharmacists). A two-step cluster analysis revealed two sub-groups of pharmacists: one cluster (74 pharmacists) with a high Total CARE score provided an appropriate product. The other cluster (20 pharmacists) had a low total CARE score and provided an inappropriate product.

The authors concluded that the pharmacy visits revealed major shortcomings in questioning, counselling and product recommendation. There is a need to develop guidelines for pharmacists to make evidence-based decisions in recommending SCAMs.

This paper offers a host of interesting information. For instance, it reveals that almost all pharmacists recommended at least one product for sale, about half of them recommended more than one. Considering that the evidence for most of the products in question is weak (to say the least), this seems concerning.

The second most recommended product, the ‘Bach Rescue Remedy‘, is perhaps a good case in point. There is no evidence that it has any effect on stress or any other condition. As the product contains no active ingredient, it is also implausible to assume it might work beyond placebo. Yet, many pharmacists are happy not only to sell it to the unsuspecting public, but even to recommend it to a customer who seeks out their advice.

I find this quite intolerable.

The paper thus confirms the point I have made repeatedly on this blog and elsewhere: community pharmacists seem to behave like commercially motivated shopkeepers, yet they are healthcare professionals who have to abide by an ethical code. When confronted with this overt conflict of interest, their vast majority seem to opt for violating their professional ethics in favour of profit.

I fail to understand why, despite these facts being well-known for so long, the professional organisations of pharmacists are doing do very little to rectify this appalling situation.

Many experts are wondering whether it is possible to stimulate our immune system such that we are better protected against getting infected with the coronavirus. Several options have been considered.

An innovative approach, for instance, seems to be this one:

Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut. Immunotherapy with IVIg could be employed to neutralize COVID-19. However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus. These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients. Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 °C heat-treatment, and nanofiltration. Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available.

Another suggestion involves monoclonal antibodies:

The therapeutic potential of monoclonal antibodies has been well recognized in the treatment of many diseases. Here, we summarize the potential monoclonal antibody based therapeutic intervention for COVID-19 by considering the existing knowledge on the neutralizing monoclonal antibodies against similar coronaviruses SARS-CoV and MERS-CoV. Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen.

These and several further options have in common that they are not backed by robust clinical evidence. Such a lack of data rarely bothers charlatans who use the corona-panic for promoting their bizarre concepts. Numerous promoters of so-called alternative medicine (SCAM) are trying their very best to mislead the public into thinking that their particular SCAM will do the trick.

In comes the PYROMANIAC IN A FIELD OF (INTEGRATIVE) STRAW-MEN, Dr Michael Dixon who recently proclaimed that ‘boosting immunity against coronavirus: ‘Now’s the time to turn to antioxidants and polyphenols’. Specifically, he recommended:

‘Eat dark greens, broccoli, spinach or any coloured root vegetable such as beetroot or carrots and any fruit ending in the word berry; black, blue… The alliums, such as leeks and garlic and onions, are very strong in the same sort of chemicals and also even things like dark chocolate and certain teas, particularly green tea. Those who want a glass of red wine, well that’s something that’s very much permitted too.’

Inspired by such positive thinking, I ventured to find some evidence for Dixon’s infinite wisdom. It could be that I am not very gifted at locating evidence – or perhaps there isn’t any?

Well, not quite; there is some on garlic that Dixon praises for its immune-boosting activity. Here is the abstract of a Cochrane review:

Background

Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four.

Objectives

To determine whether garlic (Allium sativum) is effective for the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments.

Search methods

We searched CENTRAL (2014, Issue 7),OLDMEDLINE (1950 to 1965),MEDLINE (January 1966 to July week 5, 2014), EMBASE(1974 to August 2014) and AMED (1985 to August 2014).

Selection criteria

Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment.

Data collection and analysis

Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data.

Main results

In this updated review, we identified eight trials as potentially relevant from our searches. Again, only one trial met the inclusion criteria. This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily)for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour.

Authors’ conclusions

There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor-quality evidence.

Of course, this is not about corona but about the common cold. As for green tea, a recent review found a lack of reliable clinical data demonstrating its immune-boosting activities, a deficit also noted for chocolate.

But where IS the evidence that any of the above claims are true?

Could it be that there is no sound evidence to support Dixon’s recommendations?

Impossible!!!

That would mean that Dixon, advisor to Prince Charles, is stating nonsense in the name of his COLLEGE OF MEDICINE AND INTEGRATED HEALTH. This organisation has many very respectable people as members and officers. They would never allow that sort of thing to happen!

Or would they?

When John Ioannidis publishes a paper, it is well worth, in my view, to pay attention. In the context of this blog, his latest article seems particularly relevant.

The researchers identified the top 100 best-selling books and assessed for both the claims they make in their summaries and the credentials of the authors. Weight loss was a common theme in the summaries of nutritional best-selling books. In addition to weight loss, 31 of the books promised to cure or prevent a host of diseases, including diabetes, heart disease, cancer, and dementia.

The nutritional advice given to achieve these outcomes varied widely in terms of which types of foods should be consumed or avoided and this information was often contradictory between books. Recommendations regarding the consumption of carbohydrates, dairy, proteins, and fat in particular differed greatly between books.

To determine the qualifications of each author in making nutritional claims, the highest earned degree and listed occupations of each author was researched and analyzed. Out of 83 unique authors, 33 had an M.D. or Ph.D degree. Twenty-eight of the authors were physicians, three were dietitians, and other authors held a wide range of jobs, including personal trainers, bloggers, and actors. Of 20 authors who had or claimed university affiliations, seven had a current university appointment that could be verified online in university directories.

The authors concluded that this study illuminates the range of the incongruous information being dispersed to the public and emphasizes the need for future efforts to improve the dissemination of sound nutritional advice.

The authors also provide a ‘sample of claims that appear disputable and/or unsubstantiated according to our expertize and opinion’:

1. “Carbs are destroying your brain”—Grain Brain

2. “Have high blood pressure? Hibiscus tea can work better than a leading hypertensive drug-and without the side effects. Fighting off liver disease? Drinking coffee can reduce liver inflammation. Battling breast cancer? Consuming soy is associated with prolonged survival.”—How Not to Die

3. “Zero Belly diet attacks fat on a genetic level, placing a bull’s-eye on the fat cells that matter most: visceral fat, the type of fat ensconced in your belly.”—Zero Belly Diet

4. “SKIP THE CRUNCHES: They just build muscle under the fat…LESS (EXERCISE) IS MORE”—This Is Why You’re Fat (And How to Get Thin Forever)

5. “Eating pasta, bread, potato, and pizza will actually make you happier, healthier, and thinner—for good”—The Carb Lovers Diet

6. “Skip breakfast, stop counting calories, eat high levels of healthy saturated fat, work out and sleep less, and add smart supplements”—The Bulletproof Diet

7. “Modern “improvements” to our food supply—including refrigeration, sanitation, and modified grains—have damaged our intestinal health. Dr. Axe offers simple ways to get these needed microbes, from incorporating local honey and bee pollen into your diet to forgoing hand sanitizers and even ingesting a little probiotic-rich soil”—Eat Dirt

8. “Overeating doesn’t make you fat; the process of getting fat makes you overeat.”—Always Hungry?

9. “Do you have an overall sense of not feeling your best, but it has been going on so long it’s actually normal to you? You may have an autoimmune disease, and this book is the “medicine” you need.”—The Immune System Recovery Plan

10. “Shows you how to grow new receptors for your seven metabolic hormones, making you lose weight and feel great fast!”—The Hormone Reset Diet

11. “The world’s foremost expert on the therapeutic use of culinary spices, takes an in-depth look at 50 different spices and their curative qualities, and offers spice “prescriptions”–categorized by health condition–to match the right spice to a specific ailment.”—Healing Spices

12. “The idea that people simply eat too much is no longer supported by science”—The Adrenal Reset Diet

13. “Most of us think God is not concerned with what we eat, but the Bible actually offers great insight and instruction about the effects of food on our bodies”—Let Food Be Your Medicine

14. “Dieters can actually lose weight by eating foods, nutrients, teas, and spices that change the chemical balance of the brain for permanent weight loss—a major factor contributing to how quickly the body ages. In fact, everyone can take years off their age by changing their brain chemistry.”—Younger (Thinner) You Diet

15. “Weight gain is not about the food, but about the body’s environment. Excess weight is a result of the body being in a toxic, inflammatory state. If your body is not prepared or ‘primed’ for weight loss, you will fight an uphill biochemical battle”—The Prime

16. “Throwing ice cubes in your water to make it more “structured”. Skipping breakfast, as it could be making you fat. Eating up to 75 percent of your calories each day in fat for optimal health, reduction of heart disease, and cancer prevention”—Effortless Healing

To call these statements ‘disputable’ must be the understatement of the year!

I have long been concerned about the dangerous rubbish published in so-called ‘self-help books’. In 1998, we assessed for the first time the quality of books on so-called alternative medicine (SCAM) [Int J Risk Safety Med 1998, 11: 209-215. [for some reason, this article is not Medline-listed]. We chose a random sample of 6 such books all published in 1997, and we assessed their contents according to pre-defined criteria. The findings were sobering: the advice given in these volumes was frequently misleading, not based on good evidence and often inaccurate. If followed, it would have caused significant harm to patients.

In 2006, we conducted a similar investigation the results of which we reported in the first and second editions of our book THE DESKTOP GUIDE TO COMPLEMENTARY AND ALTERNATIVE MEDICINE. This time, we selected 7 best-sellers in SCAM and scrutinised them in much the same way. We found that almost every treatment seemed to be recommended for almost every condition. There was no agreement between the different books which therapy might be effective for which condition. Some treatments were even named as indications for a certain condition, while, in other books, they were listed as contra-indications for the same problem. A bewildering plethora of treatments was recommended for most conditions, for instance:

  • addictions: 120 different treatments
  • arthritis: 131 different treatments
  • asthma: 119 different treatments
  • cancer: 133 different treatments

This experience, which we published as a chapter in the above-mentioned book entitled AN EPITAPH TO OPINION-BASED MEDICINE, confirmed our suspicion that books on SCAM are a major contributor to the  misinformation in this area.

The new paper by Ioannidis et al adds substantially to all this. It shows that the problem is wide-spread and has not gone away. Since such books have a huge readership, they are a danger to public health. Now that the problem has been identified and confirmed, it is high time, I think, that we do something about it … but I wish I knew what.

ANY SUGGESTIONS?

Wouldn’t it be wonderful, if we had a treatment that reduces the risk of getting infected with the corona-virus? Well, this paper claims that there is one. Here is its abstract:

Since December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies.

Methods

Historical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases.

Results

The use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi’s Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24–0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao).

Conclusions

Based on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM.

So, what should we make of this conclusion?

To provide an evidence-based answer, I tried to look up the original studies cited in the article. The links provided by the authors seem to be all dead except one which leads to a paper published in the infamous JCAM. Here is its abstract:

Objectives: To investigate the efficacy of an herbal formula in the prevention of severe acute respiratory syndrome (SARS) transmission among health care workers. The secondary objectives are to investigate quality of life (QOL) and symptomology changes among supplement users, and to evaluate the safety of this formula.

Design: Controlled clinical trial.

Settings: Hong Kong during epidemic of SARS.

Subjects: Two cohorts of health care workers from 11 hospitals in Hong Kong, 1 using an herbal supplement for a 2-week period (n = 1063) and a control cohort comprising all other health care workers who did not receive the supplement (n = 36,111) were compared prospectively.

Interventions: Taking an herbal supplement for a 2-week period.

Outcome measures: SARS attack rates and changes in quality of life and influenza-like symptoms were also examined at three timepoints among herbal supplement users.

Results: None of the health care workers who used the supplement subsequently contracted SARS compared to 0.4% of the health care workers who did not use the supplement (p = 0.014). Improvements in influenza-like symptoms and quality of life measurements were also observed among herbal supplement users. Less than 2% reported minor adverse events.

Conclusion: The results of this pilot study suggest that there is a good potential of using Traditional Chinese Medicine (TCM) supplements to prevent the spread of SARS.

How can I be polite and still say what I think about this article? Perhaps by stating this: THIS STUDY WAS INCAPABLE OF INVESTIGATING THE ‘EFFICACY’ OF ANYTHING AND ITS RESULTS ARE NOT CONVINCING.

So, are the Chinese authors correct when concluding that Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population?

No, I don’t think so! And I even feel that it is irresponsible in the current situation to misguide consumers, patients, scientists and decision-makers into believing that TCM offers an answer to the pandemic.

 

Resveratrol is one of the most popular dietary supplements. It is an antioxidant found in red grape skin, Japanese knotweed, blueberries and other berries. Resveratrol is available as dietary supplements from red wine extracts, grape seed extracts, Japanese knotweed extracts and other plants. The amount and purity of resveratrol in supplements varies significantly; absorption in the gut is low.

While, for many supplements, there is no or very little research, this one has a huge amount. So, has reseveratrol any proven health effects demonstrated in clinical trials?

The answer is encouraging.

This abstract provides a useful summary:

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer’s disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5′-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH-associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.

This is a comprehensive review but it fails to critically assess the quality of the clinical trials. Once we do that, we are likely to get disappointed. Many studies are just not up to the mark.

And if we consult a Cochrane review, our enthusiasm for resveratrol disappears completely: Currently, research is insufficient for review authors to evaluate the safety and efficacy of resveratrol supplementation for treatment of adults with T2DM [type 2 diabetes mellitus]. The limited available research does not provide sufficient evidence to support any effect, beneficial or adverse, of four to five weeks of 10 mg to 1000 mg of resveratrol in adults with T2DM. Adequately powered RCTs reporting patient-relevant outcomes with long-term follow-up periods are needed to further evaluate the efficacy and safety of resveratrol supplementation in the treatment of T2DM.

So, for the time being, I might just continue to obtain my resveratrol in very small but regular doses from red wine, I think.

 

 

Many hundreds of plants worldwide have a place in folk medicine as treatments for microbial infections and antimicrobial activity of extracts in vitro may be readily assessed in microbiology laboratories. Many so tested are reported to show inhibitory effects against a range of organisms. For less than responsible entrepreneurs, this is often enough reason to promote them as therapeutic options.

But laboratory testing can at best be only a very crude, though relatively inexpensive and rapid screen, while in vivo testing is very costly and time consuming. On this background, we conducted a review in 2003 to examine the range of plants or herbs that have been tested for antiviral properties in laboratories, animals and humans. Here is its abstract:

Background and aims: Many antiviral compounds presently in clinical use have a narrow spectrum of activity, limited therapeutic usefulness and variable toxicity. There is also an emerging problem of resistant viral strains. This study was undertaken to examine the published literature on herbs and plants with antiviral activity, their laboratory evaluation in vitro and in vivo, and evidence of human clinical efficacy.

Methods: Independent literature searches were performed on MEDLINE, EMBASE, CISCOM, AMED and Cochrane Library for information on plants and herbs with antiviral activity. There was no restriction on the language of publication. Data from clinical trials of single herb preparations used to treat uncomplicated viral infections were extracted in a standardized, predefined manner.

Results: Many hundreds of herbal preparations with antiviral activity were identified and the results of one search presented as an example. Yet extracts from only 11 species met the inclusion criteria of this review and have been tested in clinical trials. They have been used in a total of 33 randomised, and a further eight non-randomised, clinical trials. Fourteen of these trials described the use of Phyllanthus spp. for treatment of hepatitis B, seven reporting positive and seven reporting negative results. The other 10 herbal medicines had each been tested in between one and nine clinical trials. Only four of these 26 trials reported no benefit from the herbal product.

Conclusions: Though most of the clinical trials located reported some benefits from use of antiviral herbal medicines, negative trials may not be published at all. There remains a need for larger, stringently designed, randomised clinical trials to provide conclusive evidence of their efficacy.

One of the herbal remedies that seemed to show some promise specifically for upper respiratory infections was Andrographis paniculata. This evidence prompted us in 2004 to conduct a systematic review focused on this herb specifically. Here is its abstract:

Acute respiratory infections represent a significant cause of over-prescription of antibiotics and are one of the major reasons for absence from work. The leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used as a medicinal herb in the treatment of infectious diseases. Systematic literature searches were conducted in six computerised databases and the reference lists of all papers located were checked for further relevant publications. Information was also requested from manufacturers, the spontaneous reporting schemes of the World Health Organisation and national drug safety bodies. No language restrictions were imposed. Seven double-blind, controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy. All trials scored at least three, out of a maximum of five, for methodological quality on the Jadad scale. Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. Adverse events reported following administration of A. paniculata were generally mild and infrequent. There were few spontaneous reports of adverse events. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted.

Before you now rush to buy a dietary supplement of A. paniculata, let me stress this in no uncertain terms: the collective evidence is at best suggestive, but it is not compelling. Importantly, there is, to the best of my knowledge, no sound evidence that any herbal remedy is effective in preventing or treating Covid-19 infections.

I truly wished to be able to report more encouraging news, but the truth is the truth, even (I would argue, particularly) in desperate times.

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