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

antioxidants

In the UK, a new post-Brexit regulatory framework is being proposed for food supplements by the government. The nutraceutical sector is estimated to be worth £275bn globally and £4bn in the UK.  A new report claims that “science is starting to point the way to a new sector of nutritional products with increasingly explicable and/or verifiable medicinal benefits, which needs to be reflected in our regulatory framework.” Tory MP George Freeman, one of the authors of the report, was quoted saying:

“We are living through an extraordinary period of technological change – not just in life science but in host of sectors: from AI to robotics to agri-tech, nutraceuticals, nanotechnology, synthetic biology, biofuels, satellites and fusion energy. The UK is indeed a ‘science superpower’. But we have traditionally been woeful at commercialising here in the UK. There are many reasons. But, in recent years, the EU’s increasingly slow, bureaucratic and ‘precautionary’ approach – copied in Whitehall – has made the EU and the UK an increasingly poor place to commercialise new technology.”

If a product like a food or a herbal remedy makes ‘medicinal’ claims, it is currently regulated by the MHRA. If a product only makes general ‘health’ claims, it is regulated by the Department of Health and Social Care in England, by the FSA in Wales and Northern Ireland, and by Food Standards Scotland in Scotland. This ‘patchwork of regulators’ is bound to change as it is deemed to create additional costs and uncertainty for businesses who would like to see the relevant functions brought together in a central regulatory body and a clearer UK landscape.

In response to the task force’s report, PM Boris Johnson stated that bold and ambitious ideas such as these are needed to encourage growth and innovation:

“The Government, through our Better Regulation Committee, is already hard at work on reform of the UK’s regulatory framework. Your bold proposals provide a valuable template for this, illustrating the sheer level of ambitious thinking needed to usher in a new golden age of growth and innovation right across the UK. So we will give your report the detailed consideration it deserves, consult widely across industry and civil society, and publish a response as soon as is practicable.”

Am I the only one who feels more than a little uneasy about all this? I honestly do not see much new science that, according to the report, points to ‘verifiable medicinal benefits’ of food supplements or nutraceuticals. What the report does however point to, I fear, is that the UK government is about to deregulate quackery with a view to making some entrepreneurs wealthy snake oil salesmen at the cost of public health and wealth.

I hope I am mistaken.

Due to polypharmacy and the rising popularity of so-called alternative medicines (SCAM), oncology patients are particularly at risk of drug-drug interactions (DDI) or herb-drug interactions (HDI). The aims of this study were to assess DDI and HDI in outpatients taking oral anticancer drugs.

All prescribed and non-prescribed medications, including SCAMs, were prospectively collected by hospital pharmacists during a structured interview with the patient. DDI and HDI were analyzed using four interaction software programs: Thériaque®, Drugs.com®, Hédrine, and Memorial Sloan Kettering Cancer Center (MSKCC) database. All detected interactions were characterized by severity, risk, and action mechanism. The need for pharmaceutical intervention to modify drug use was determined on a case-by-case basis.

A total of 294 patients were included, with a mean age of 67 years [55-79]. The median number of chronic drugs per patient was 8 [1-29] and 55% of patients used at least one SCAM. At least 1 interaction was found for 267 patients (90.8%): 263 (89.4%) with DDI, 68 (23.1%) with HDI, and 64 (21.7%) with both DDI and HDI. Only 13% of the DDI were found in Thériaque® and Drugs.com® databases, and 125 (2.5%) were reported with a similar level of risk on both databases. 104 HDI were identified with only 9.5% of the interactions found in both databases. 103 pharmaceutical interventions were performed, involving 61 patients (20.7%).

The authors concluded that potentially clinically relevant drug interactions were frequently identified in this study, showing that several databases and structured screening are required to detect more interactions and optimize medication safety.

These data imply that DDIs are more frequent than HDIs. This does, however, not tell us which are more important. One crucial difference between DDIs and HDIs is that the former are usually known to the oncology team who should thus be able to prevent them or deal with them appropriately; in contrast, HDIs are often not known to the oncology team because many patients fail to disclose the fact that they take herbal remedies. Some forget, some do not think of herbals as medicine, others may be worried about their physician’s reaction.

It follows that firstly, conventional healthcare practitioners should always ask about the usage of herbal remedies, and secondly, they need to be informed about which herbal remedy might interact with which drug. The first can easily be implemented into routine history-taking; the second is more problematic, not least because our knowledge about HDIs is still woefully incomplete. In view of this, it might often be wise to tell patients to stop taking herbal remedies while they are on prescription drugs.

A low intake of selenium has been associated with increased cardiovascular mortality in some epidemiological studies. This could be reduced by supplementation with selenium and coenzyme Q10. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease.

The objective of this trial was to examine the impact of selenium and coenzyme Q10 on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years.

All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance, and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer.

In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups.

The authors concluded that supplementation with selenium and coenzyme Q10 in a group of elderly low in selenium and coenzyme Q10 prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.

These results are interesting and potentially important. The authors agree that their study is not fully conclusive: “Even if the size of the study population is small, we regard the results as being interesting from a scientific point of view, and for hypothesis-generating. The included participants represented a relatively narrow age stratum, so it is not possible to extrapolate the results to other age groups without uncertainty. Finally, as the evaluated population consisted of Caucasians who were low in selenium and coenzyme Q10, it is not necessarily true that the obtained results could be extrapolated to another population.” It might furthermore be of interest to note that part of the analysis cost was supported by grants from Pharma Nord Aps, Denmark, the County Council of Östergötland, Linköping University.

What is needed next, I think, are independent replications. Also of interest would be to determine whether the effects are due to the selenium, or the Q10, or both. And finally, one must caution consumers to not overdose on selenium which could have a host of negative effects on health.

“Today, scientists note that the glycyrrhizic acid contained in this plant prevents the development of a new coronavirus, which the whole world is fighting against. Moreover, even a small concentration of an aqueous extract of licorice root has a neutralizing effect.”

These are the words of President Gurbanguly Berdymukhamedov of Turkmenistan. The plant he referred to is licorice. With is the promotion of a herbal solution for the pandemic, he is in good company:

  • Thailand’s health ministry approved the use of Andrographis Paniculata, commonly known as green chiretta, to treat patients who are in the early stages of a Covid-19 infection.
  • The health authorities of Tamil Nadu distributed herbal medicine to the general public as a preventive measure against Coronavirus disease.
  • Madagascar claims to have a cure for Covid-19, the herbal tea named Covid-Organics has the plant artemisia as an ingredient.
  • China has been using TCM alongside conventional treatment methods to treat Covid-19 patients. Some of the herbal formulations used in the treatment are:
    • Jinhua Qinggan Granule
    • Sheganmahuang decoction
    • Lianhuaqingwen capsule
    • Maxingshigan decoction
    • Xuebijing Injection
  • Indonesia is testing two herbal medicines: Cordyceps militaris, a fungus common in the Himalayas, and a herbal formulation comprising Ginger, gripeweed, Ngai camphor, and Andrographis paniculata.

And what about some evidence? In 2020, Medline listed 302 articles on herbal medicine for COVID-19. Here I selected just 10 of them to give you a flavor:

1st article

COVID-19 is the most recently discovered coronavirus infectious disease and leads to pandemic all over the world. The clinical continuum of COVID-19 varies from mild illness with non-specific signs and symptoms of acute respiratory disease to extreme respiratory pneumonia and septic shock. It can transmit from animal to human in the form of touch, through the air, water, utensils, fomite and feco-oral route blood. The pathogenesis and clinical features of COVID-19 be the same as the clinical manifestation associated epidemic Fever. In Unani medicine, various herbal drugs are described under the caption of epidemic disease. Great Unani scholar also Avicenna (980-1037 AD) recommended that during epidemic condition movement should be restricted, self-isolation, fumigation around the habitant with perfumed herbs (Ood, Kafoor, Sumbuluttib, Saad Kofi, Loban, etc.), and use of appropriate antidotes (Tiryaqe Wabai) and vinegar (Sirka) as prophylaxis. Herbal approach is based on single (Unnab-Ziziphus jujuba, Sapistan-Cordia myxa, Bahidana-Cydonia oblonga, Khatmi-Althea officinalis, Khubazi-Malva sylvestris, Zafran-Crocus sativus, Sibr-Aloe barbedensis, Murmuki-Commiphora myrrha, Darchini-Cinnamomum zeylanicum, Qaranfal-Syzygium aromaticum, Rihan-Oscimum sanctum, Habtus Sauda-Nigella sativa, Aslus Sus-Glycyrrhiza glabra, Maghze Amaltas-Cassia fistula and Adusa-Adhatoda vasica) and compound drugs (Habbe Bukhar, Sharbat Khaksi, Sharbat Zanjabeel, Naqu Nazla, Majoon Chobchini, Jawrish Jalinus and Khamira Marvareed) most of them are claimed for anti-viral, anti-pyretic, blood purifier, cardioprotective and expectorant activities. Traditionally most of the herbal practitioners are using it.

2nd article

According to the World Health Organization (WHO), viral diseases continue to rise, and pose a significant public health problem. Novel coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. The pathogenesis and clinical manifestations of COVID-19 is close to Amraz-e-Wabai (epidemic diseases) which was described by Hippocrates, Galen, Aristotle, Razes, Haly Abbas, Avicenna, Jurjani etc. Presently, there is no specific or challenging treatment available for COVID-19. Renowned Unani Scholars recommended during epidemic situation to stay at home, and fumigate the shelters with aromatics herbs like Ood kham (Aquilaria agallocha Roxb.), Kundur (Boswellia serrata Roxb), Kafoor (Cinnamomum camphora L.), Sandal (Santalum album L), Hing (Ferula foetida L.) etc. Use of specific Unani formulations are claimed effective for the management of such epidemic or pandemic situation like antidotes (Tiryaqe Wabai, Tiryaqe Arba, Tiryaqe Azam, Gile Armani), Herbal Decoction (Joshandah), along with Sharbate Khaksi, Habbe Bukhar, Sharbate Zanjabeel, Khamira Marwareed, Jawarish Jalinus, and Sirka (vinegar). Such drugs are claimed for use as antioxidant, immunomodulatory, cardiotonic, and general tonic actions. The study enumerates the literature regarding management of epidemics in Unani medicine and attempts to look the same in the perspective of COVID-19 prevention and management.

3rd article

Unani system of medicine is based on the humoral theory postulated by Hippocrates, according to him the state of body health and disease are regulated by qualitative and quantitative equilibrium of four humours. Amraz-e-Waba is an umbrella term which is used in Unani medicine for all types of epidemics (smallpox, measles, plague, Hameer Saifi, influenza, Nipaha, Ebola, Zika, and 2019 novel coronavirus, etc.) mostly fatal in nature. The coronavirus disease 2019 (COVID-19) is a severe acute respiratory infection, and the pathogenesis and clinical features resemble with those of Nazla-e-Wabaiya (influenza) and Zatul Riya (pneumonia) which were well described many years ago in Unani text such as high-grade fever, headache, nausea and vomiting, running nose, dry cough, respiratory distress, alternate and small pulse, asthenia, foul smell from breath, insomnia, frothy stool, syncope, coldness in both upper and lower extremities, etc. The World Health Organization declared COVID-19 as a global emergency pandemic. Unani scholars like Hippocrates (370-460 BC), Galen (130-200 AD), Rhazes (865-925 AD), and Avicenna (980-1037 AD) had described four etiological factors for Amraz-e-Waba viz., change in quality of air, water, Earth, and celestial bodies, accordingly mentioned various preventive measures to be adopted during epidemics such as restriction of movement, isolation or “quarantena”, and fumigation with loban (Styrax benzoin W. G. Craib ex Hartwich.), sandalwood (Santalum album L.), Zafran (Crocus sativus L.), myrtle (Myrtus communis L.), and roses (Rosa damascena Mill.) and use of vinegar (sirka) and antidotes (Tiryaq) as prophylaxis, and avoiding consumption of milk, oil, sweet, meat, and alcohol. This review focuses and elaborates on the concept, prevention, and probable management of COVID-19 in the light of Amraz-e-Waba.

4th article

Background: Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines.

Aims: To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment.

Method: The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positivepromisingnegative, and unknown.

Results: A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativumAndrographis paniculataEchinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalisMikania glomerataPelargonium sidoidesPimpinella anisumSalix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine.

Conclusions: Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches.

5th article

Recently, the novel life-threatening coronavirus infection (COVID-19) was reported at the end of 2019 in Wuhan, China, and spread throughout the world in little time. The effective antiviral activities of natural products have been proved in different studies. In this review, regarding the effective herbal treatments on other coronavirus infections, promising natural products for COVID-19 treatment are suggested. An extensive search in Google Scholar, Science Direct, PubMed, ISI, and Scopus was done with search words include coronavirus, COVID-19, SARS, MERS, natural product, herb, plant, and extract. The consumption of herbal medicine such as Allium sativum, Camellia sinensis, Zingiber officinale, Nigella sativa, Echinacea spp. Hypericum perforatum, and Glycyrrhiza glabra, Scutellaria baicalensis can improve the immune response. It seems that different types of terpenoids have promising effects in viral replication inhibition and could be introduced for future studies. Additionally, some alkaloid structures such as homoharringtonine, lycorine, and emetine have strong anti-coronavirus effects. Natural products can inhibit different coronavirus targets such as S protein (emodin, baicalin) and viral enzymes replication such as 3CLpro (Iguesterin), PLpro (Cryptotanshinone), helicase (Silvestrol), and RdRp (Sotetsuflavone). Based on previous studies, natural products can be introduced as preventive and therapeutic agents in the fight against coronavirus.

6th article

Background: The aim of the present review is to provide basic knowledge about the treatment of Coronavirus via medicinal plants. Coronavirus (COVID-19, SARS-CoV, and MERS-CoV) as a viral pneumonia causative agent, infects thousands of people in China and worldwide. There is currently no specific medicine or vaccine available and it is considered a threat to develop effective novel drug or anti-coronavirus vaccine treatment. However, natural compounds to treat coronaviruses are the most alternative and complementary therapies due to their diverse range of biological and therapeutic properties.

Methods: We performed an open-ended, English restricted search of Scopus database, Web of Science, and Pubmed for all available literature from Jan-March, 2020, using terms related to phytochemical compounds, medicinal plants and coronavirus.

Results: The view on anti-coronavirus (anti-CoV) activity in the plant derived phytochemicals and medicinal plants give the strong base to develop a novel treatment of corona virus activity. Various phytochemicals and medicinal plant extracts have been revised and considered to be the potential anti-CoV agents for effective control and future drug development. We discuss some important plants (Scutellaria baicalensis, Psorothamnus arborescens, Glycyrrhiza radix, Glycyrrhiza uralensis , Lycoris radiate, Phyllanthus emblica, Camellia sinensis, Hyptis atrorubens Poit, Fraxinus sieboldiana, Erigeron breviscapus, Citri Reticulatae Pericarpium, Amaranthus tricolor, Phaseolus vulgaris, Rheum palmatum, Curcuma longa and Myrica cerifera) emerged to have broad spectrum antiviral activity.

Conclusion: Nigella sativa has potent anti-SARS-CoV activity and it might be useful souce for developing novel antiviral therapies for coronaviruses.

7th article

COVID-19 has been declared a pandemic by WHO on March 11, 2020. No specific treatment and vaccine with documented safety and efficacy for the disease have been established. Hence it is of utmost importance to identify more therapeutics such as Chinese medicine formulae to meet the urgent need. Qing Fei Pai Du Tang (QFPDT), a Chinese medicine formula consisting of 21 herbs from five classical formulae has been reported to be efficacious on COVID-19 in 10 provinces in mainland China. QFPDT could prevent the progression from mild cases and shorten the average duration of symptoms and hospital stay. It has been recommended in the 6th and 7th versions of Clinical Practice Guideline on COVID-19 in China. The basic scientific studies, supported by network pharmacology, on the possible therapeutic targets of QFPDT and its constituent herbs including Ephedra sinicaBupleurum chinensePogostemon cablinCinnamomum cassiaScutellaria baicalensis were reviewed. The anti-oxidation, immuno-modulation and antiviral mechanisms through different pathways were collated. Two clusters of actions identified were cytokine storm prevention and angiotensin converting enzyme 2 (ACE2) receptor binding regulation. The multi-target mechanisms of QFPDT for treating viral infection in general and COVID-19 in particular were validated. While large scale clinical studies on QFPDT are being conducted in China, one should use real world data for exploration of integrative treatment with inclusion of pharmacokinetic, pharmacodynamic and herb-drug interaction studies.

8th article

In December 2019, a novel coronavirus SARS-CoV-2, causing the disease COVID-19, spread from Wuhan throughout China and has infected people over 200 countries. Thus far, more than 3,400,000 cases and 240,000 deaths have occurred worldwide, and the coronavirus pandemic continues to grip the globe. While numbers of cases in China have been steadying, the number of infections outside China is increasing at a worrying pace. We face an urgent need to control the spread of the COVID-19 epidemic, which is currently expanding to a global pandemic. Efforts have focused on testing antiviral drugs and vaccines, but there is currently no treatment specifically approved. Traditional Chinese medicine (TCM) is grounded in empirical observations and the Chinese people use TCM to overcome these sorts of plagues many times in thousands of years of history. Currently, the Chinese National Health Commission recommended a TCM prescription of Qing-Fei-Pai-Du-Tang (QFPDT) in the latest version of the “Diagnosis and Treatment guidelines of COVID-19” which has been reported to provide reliable effects for COVID-19. While doubts about TCM still exist today, this review paper will describe the rationalities that QFPDT is likely to bring a safe and effective treatment of COVID-19.

9th article

The fight against the novel coronavirus pneumonia (namely COVID-19) that seriously harms human health is a common task for all mankind. Currently, development of drugs against the novel coronavirus (namely SARS-CoV-2) is quite urgent. Chinese medical workers and scientific researchers have found some drugs to play potential therapeutic effects on COVID-19 at the cellular level or in preliminary clinical trials. However, more fundamental studies and large sample clinical trials need to be done to ensure the efficacy and safety of these drugs. The adoption of these drugs without further testing must be careful. The relevant articles, news, and government reports published on the official and Preprint websites, PubMed and China National Knowledge Infrastructure (CNKI) databases from December 2019 to April 2020 were searched and manually filtered. The general pharmacological characteristics, indications, adverse reactions, general usage, and especially current status of the treatment of COVID-19 of those potentially effective drugs, including chemical drugs, traditional Chinese medicines (TCMs), and biological products in China were summarized in this review to guide reasonable medication and the development of specific drugs for the treatment of COVID-19.

10th article

Objective: To analysis the medication characteristics of the prescriptions issued via open channel by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine in treating coronavirus disease 2019 (COVID-19).

Methods: We collected the data of traditional Chinese medicine related to treatment plans published by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine from the start of COVID-19 outbreak to February 19, 2020. The frequency analysis, cluster analysis and association analysis were performed.

Results: The study collected 4 national and 34 regional prevention and treatment plans, 578 items, 84 traditional Chinese formulations, 60 Chinese patent medicines, and 230 Chinese herbs. The high frequently used herbs were Liquorice, Scutellariabaicalensis, Semen armeniacaeamarae, and Gypsum. The commonly used traditional formulations included Maxing Shigan decoction, Yin Qiao powder, and Xuanbai Chengqi decoction. The Chinese patent drugs included Angong Niuhuang pill, Xuebijing injection, and Lianhua Qingwen capsule. The most common paired medications were Ephedra and Semen armeniacaeamarae, Fructusforsythiae and Liquorice. Two core combinations and one novel formula were discovered in the study.

Conclusions: Yin Qiao powder and Huopo Xialing decoction are the basic formulations for Weifen syndrome of COVID-19. In addition, Maxing Shigan decoction, Liang Ge powder, Qingwen Baidu decoction and Da Yuan decoction are the basic formulations for Qifen syndrome of COVID-19. The main medication characteristics are clearing heat, entilating lung, removing toxicity and removing turbidity. It shows that removing toxicity and eliminating evil are the prescription thought in treating epidemic disease of traditional Chinese medicine.

Confused?

Me too!

What seems to emerge is this:

  • ‘Herbalists and Co’ did not wait long to jump on the corona bandwagon.
  • They managed to confuse not just you and me, but even politicians, presidents, and their advisers.
  • They produced a plethora of articles implying that an endless array of herbs might be effective.
  • In doing so, no clear consensus emerged as to which herbs are the most promising.
  • Sound evidence seems to be not available.
  • Clinical trials are slow to start or not even planned.
  • Everything is based on more or less wild extrapolation.
  • Much of what is being published is borderline irresponsible.
  • YET, IT MUST BE GOOD FOR BUSINESS!

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.

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.

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

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

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

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

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

But this is equally puzzling.

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

But ‘clinical studies‘?

None!

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

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

Design:

Random double-blind placebo-controlled study

Setting:
Dr. Jamdar Hospital, Jabalpur, India

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

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

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

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

This is odd in several ways:

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

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

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

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

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

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

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

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

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

 

 

 

PS

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

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

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?

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.

 

 

So far, our ‘Corona-Virus Quackery Club’ (CVQC) boasts the following membership:

It is time now, I think, to admit some supplement peddlers.

How come?

Many dietary supplement merchants seem to feel that the current pandemic is an excellent opportunity to flog their useless wares to the anxious public.

“COVID-19

In order to support increasing worldwide demand for the LYMA supplement, we would like to inform new and existing customers that we have sufficient stock in place to ensure uninterrupted supply.”

This was the text of an email I received recently. It linked to a website that informed me of the following:

We continue to work with our scientific network and global supply chain to bring you the latest scientific developments as they arise.

Dr. Paul Clayton, PhD – Director of Science, LYMA

“Covid-19 is causing an enormous amount of illness and disruption. This is due to its high transmission rates, long incubation period, and the substantial numbers of people – 15 to 20% of those infected – who become ill enough to require hospitalisation. This last aspect is concerning as no health care system in the world has sufficient resources to cope with such an influx of seriously ill patients.

At the time of writing there are no specific treatments available. The only advice given is to avoid crowds, wash the hands frequently, and not touch the face. Some authorities recommend face masks and gloves; and we are increasingly being recommended to shelter in place.

But there may be more we can do to protect ourselves. Dysnutrition is common, due to our over-consumption of ultra-processed foods with little nutritional value. Supplements have a role to play in improving general nutritional status and general immunity. But we can take that further.

LYMA. The ultimate supplement.

Chronic stress reduces immuno-competence and makes us more vulnerable to infection. Adaptogens such as KSM-66 Ashwagandha in LYMA have the ability to alleviate the damaging effects of stress and have been shown to improve immunity. So have the Wellmune 1-3, 1-6 beta glucans in LYMA, with many hundreds of studies showing that these natural compounds increase resistance to infection.

These are just two elements that may improve our chances in the difficult times ahead.”
Dr. Paul Clayton, PhD – Director of Science, LYMA

In case the name ‘LYMA’ rings a bell: yes, we have previously discussed the ‘the world’s first super supplement’ and the many claims made for it. We even had the pleasure of an interesting exchange with the above-pictured Dr Paul Clayton in the comments section of that post. Given the above, I am more than happy to welcome him, his LYMA team, and all other supplement peddlers who try to make a fast buck in the present crisis to the CVQC.

WELCOME GUYS!

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