A second look at old research suggested that the recommended dose for vitamin C is far too low. Here is the abstract of the recently published paper:
A double-blind controlled trial initiated in 1944 has led to the common narrative that a 10-mg daily vitamin C intake is adequate to prevent and treat impaired wound healing, and by inference, other collagen-related diseases such as heart disease or stroke. The WHO relies on this narrative to set the recommended nutrient intake for vitamin C. This narrative, however, is based on what is known as the eyeball method of data assessment. The 1944 trial published individual participant data on scar strength providing an opportunity to statistically probe the validity of the 10-mg narrative, something which has not yet been done. The findings show that a vitamin C intake that averages to 10 mg/d over a mean follow-up of 11.5 mo was associated with a 42% weakened scar strength when compared with 80 mg vitamin C intake/d (P < 0.001). The observed dose-response curve between scar strength and vitamin C intake suggests that the daily vitamin C intake needed to prevent collagen-related pathologies is in the range recommended by the National Academy of Medicine and the European Food Safety Authority (75 to 110 mg/d), not the WHO recommendation (45 mg/d). The findings also show that a vitamin C intake that averages to 65 mg/d over a mean follow-up of 6.5 mo failed to restore the normal wound-healing capacity of vitamin C-depleted tissues; such tissues had a 49% weaker scar strength when compared with nondepleted tissues (P < 0.05). Thus, average daily vitamin C intakes ∼50% higher than the WHO recommends may fail to treat existing collagen-related pathologies. It is concluded that the prior lack of statistical analyses of a landmark trial may have led to a misleading narrative on the vitamin C needs for the prevention and treatment of collagen-related pathologies.
The lead author of the recent re-analysis, Professor Philippe Hujoel from the Department of Epidemiology, School of Public Health, University of Washington, Seattle, said: “The vitamin C experiment is a shocking study. They depleted people’s vitamin C levels long-term and created life-threatening emergencies. It would never fly now. The findings of the re-analyses of the Sorby data suggest that the WHO’s recommendation is too low to prevent weak scar strength. Robust parametric analyses of the trial data reveal that an average daily vitamin C intake of 95mg is required to prevent weak scar strength for 97.5 percent of the population. Such a vitamin C intake is more than double the daily 45mg vitamin C intake recommended by the WHO but is consistent with the writing panels for the National Academy of Medicine and (other) countries.”
The original research of 1944 was headed by the British-German biologist and Nobel-prize winner Sir Hans Adolf Krebs. At the time, researchers conducted an experiment that controlled and monitored vitamin C consumption of just 20 volunteers. They were each given varying amounts of vitamin C, which helps the body to produce collagen – and given wounds to observe how quickly their scar tissue healed. The research aimed to ascertain how much vitamin C navy members living off rations is required in order to prevent them from developing scurvy, rather than how much is needed to boost health overall.
Prof Hujoel concluded that: “The failure to reevaluate the data of a landmark trial with novel statistical methods as they became available may have led to a misleading narrative on the vitamin C needs for the prevention and treatment of collagen-related pathologies.”
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.
I often hear that my ambitions to inform the public and inspire critical thinking are hopeless: there are simply too many quacks trumpeting nonsense, and their collective influence is surely bigger than mine. This can be depressing, of course. And because I often feel that I am fighting an unwinnable battle, stories like this are so importand and up-lifting.
… I had gone to holistic nutrition school. I was running my own nutrition consulting business. And suddenly I didn’t believe in any of it anymore. How did this flip flop come to pass?
… As a holistic nutritionist, I was an active participant in what I now consider alternative medicine tomfoolery, specifically pushing supplements on a clientele of the “worried well” who often mistook wellness enthusiasts like me for medical experts. I want to be clear that I wasn’t knowingly deceiving anyone—I really did believe in the solutions I was offering my clients… To holistic nutrition enthusiasts and people who believe in a certain kind of alt wellness, these “natural” and “holistic” products seem more trustworthy than what mainstream medicine offers. The truth is, they often lack sufficient, peer-reviewed, reliable scientific evidence of their supposed effectiveness.
Did I have rock-solid evidence that these products would do what their labels promised they would do? Not really. Sure, I read studies here and there that found specific health benefits for some of the products. But I rarely mentioned the fine print (if I knew it at all)—that the sample sizes of many of these studies often were so small that the results couldn’t be generalized to a larger population, that the studies’ authors sometimes noted that more research was needed to support any findings on the effects they found, or that systematic reviews later found that many studies were poorly constructed or at risk for bias, making their findings even less compelling than they seemed initially. And in some cases, study authors themselves note that their findings are merely jumping off points, and that more long-term studies are needed in order to draw more solid conclusions…
Was I relying on strong, valid evidence? Nah, not really. But at the time, I thought what I had was better than strong evidence: Faith in a lifestyle and a dogmatic belief that all things traditional and mainstream were unhealthy or harmful, and therefore, that all things unconventional and alternative were curative and would bring about “wellness.”
In an effort to expand my product knowledge I researched a lot of the different supplements available. I was using all the best bias-confirming websites where other homeopathic medicine enthusiasts evangelized their favorite remedies, their enthusiasm and insistence, and anecdotal evidence standing in for what typically shows us that a product is safe and effective—clinical trials and FDA approval.
When their arguments and reasoning started to sink in, I realized that my faith in the healing powers of supplements may have been overzealous at best, unfounded at worst. My world crumbled like a piece of raw gluten-free paleo cheesecake. It started to sink in: Where there was a morsel of convincing medical information blended with enough compelling nonsense and communicated with enough conviction, I believed it, hook, line, and sinker.
When I started to notice the holes in the fabric of holistic nutrition, the fabric looked, well, pretty threadbare. I subsequently disconnected from social media and distanced myself from the entire culture. I took a good look at how I was personally and publicly communicating my relationships with food and wellness. After spending my twenties experimenting with all kinds of specialty diets, I was left feeling exhausted, anxious, underweight, overweight, and fed-up.
And so that last domino fell when I took away the thing that was propping it up for me: social media. Instagram is a playground for wellness influencers, including, at the time, me. My Instagram account was the best way to advertise my nutrition consulting business, so maintaining a certain persona there felt completely crucial to my success, and eventually, my identity. It was a world full of beautifully curated accounts of thin yogis gathering wild herbs in nature or making raw desserts with ingredients that cost more than my entire monthly food budget. I started to feel like the alternative wellness community I was part of—myself included—was an echo chamber, where we stockpiled likes and positive comments to build a wall that would keep out ideas that challenged our status quo. In fact, the more reassurance I received from my online community, the harder I believed in our gospel.
As I was disentangling my beliefs from everything I was learning by looking at the actual evidence, I realized that my education to become a holistic nutritionist hadn’t prepared me to understand health and wellness as completely and comprehensively as I’d once thought. Sure, I’d spent a some time studying the pathology of disease, and a little longer learning about how each bodily system works to get your human suit from point A to point B, but I am only slightly closer to being a medical professional than I am to becoming a professional cricket player. First of all, in total, my entire formal education as a holistic nutritionist was 10 months long. Second of all, that education was intended to complement—not replace—traditional medical treatment. But as soon as I finished the program, I could immediately start taking on clients. And lots of potential clients out there are just like the way I used to be—wishing they looked or felt different and in search of the panacea, willing (if not eager) to defer to an expert.
There may have been many people willing to look to me as an expert, but here’s the thing: in my school, there were no residency or clinical hours required to prepare us for the real world or to take on clients—unlike dietitians here in Canada, who must obtain a bachelor’s degree in Nutritional and Food Sciences, qualify to complete a rigorous post-degree internship program and register with a provincial dietetics organization, or get a master’s degree. We received a certificate, and that was that. It was a credential that wholeheartedly fell short of resembling anything close to making me an authority on the subject of health as it relates to food and diet. But most people in the general public can’t be expected to understand the ins and outs of how experts are credentialed and licensed—many of us assume that someone calling themselves something that we associate with authority is, in fact, an authority we can trust.
The brief education that I received to become a holistic nutritionist did provide me with valuable stepping stones and a general understanding of how the body works. My program discouraged students from saying “treat,” “heal,” “prevent,” or “cure.” Generally speaking holistic nutrition programs don’t provide the training and medical education that registered dietitians receive, which enables them to give sound, ethical medical nutrition advice, nor are they required by law, the way dietitian programs are, to provide it. In fact, in 2015 graduates of the Canadian School of Natural Nutrition were barred from identifying as Registered Holistic Nutritionists, and since then must use the title “Holistic Nutritional Consultant.”
… With what I do have from my classroom education, I can analyze a lifestyle that needs some fine-tuning and provide guidance on how to structure a solid meal plan. That’s about it. After years of self-diagnosis and hashtagging all my fad-diet escapades (for this, I greatly apologize to all those I have alienated with my profuse self-righteousness), I can at least say I have a deep appreciation for those who are actually on the front lines in the fight against unproven medical remedies and the potential damage it may do to those who use it to the exclusion of traditional medicine.
The influence of these remedies is not harmless, and I have seen firsthand in many different examples and situations how it can lure people away from real, evidence-based help in their times of need. I am fortunate enough that within my practice I had enough foresight to turn away individuals who required more guidance than I was capable of giving. But along the way I made many embarrassing and conjectural recommendations. Like I said, I was far from knowingly deceiving anyone. I firmly held the belief that alternative medicine, no matter the cost, was an investment in a healthful future. My own medicine cabinet, an arsenal full of supplements, tincture, and powders, was a personal testament to how deeply I was devoted to holistic nutrition.
This essay is a firm farewell from a world I disconnected from long ago. The person that over years I let myself become through naiveté, not doing my own research, and a misguided desire to be different. So here I am now, officially having left the church of woo, bidding the world of alternative health adieu.
Reading Denby’s account, I was reminded of many themes we have previously discussed on this blog. One issue that perhaps needs more focus is this notion:
“I was far from knowingly deceiving anyone.”
I have not yet met a SCAM practitioner who says:
“I am in the business of deceiving my patients.”
The reasons for this are simple:
- if they knowingly deceive, they would not tell us,
- and if they don’t know that they are deciving their patients, they cannot possibly admit to it.
The way Denby repeatedly assures us that she was far from knowingly deceiving anyone sounds charmingly naive and is, in my experience, very typical for SCAM practitioners. It depicts them as honorable people. Yet, in actual fact, it is neither charming nor honorable. It merely demonstrates the fact that they were perhaps not ruthlessly dishonest but all the more dangerous.
Let me explain this with a deliberately extreme example:
- A man with a chronic condition – say type 2 diabetes – consults a SCAM practitioner who is knowingly deceiving him claiming that her SCAM effectively treats his condition. The patient follows the advice but, since he is not totally convinced (deception is rarely perfect), consults his doctor who puts him straight. This patient will therefore survive.
- The same chap consults a SCAM practitioner who is deeply convinced of the effectiveness of her SCAM and thus not knowingly deceiving her patient when she claims that it is effective for his diabetes. Her conviction is so strong that the patient blindly believes her. Thus he stops his conventional medication and hopes for the best. This patient could easily die.
In a nutshell:
‘Honest’ conviction might render a quack more socially acceptable but also more dangerous to her patients.
Numerous so-called alternative medicines (SCAMs) have been touted as the solution for COVID-19. In fact, it is hard to find a SCAM that is not claimed to be useful for corona patients. Crucially, such claims are being made in the complete absence of evidence. A recent paper offers a bibliometric analysis of global research trends at the intersection of SCAM and COVID-19.
SCOPUS, MEDLINE, EMBASE, AMED and PSYCINFO databases were searched on July 5, 2020. All publication types were included, however, articles were only deemed eligible, if they made mention of one or more SCAMs for the potential prevention, treatment, and/or management of COVID-19 or a health issue indirectly resulting from the COVID-19 pandemic. The following eligible article characteristics were extracted: title; author names, affiliations, and countries; DOI; publication language; publication type; publication year; journal (and whether it is TICAM-focused); 2019 impact factor, and TICAMs mentioned.
A total of 296 eligible articles were published by 1373 unique authors at 977 affiliations across 56 countries. The most common countries associated with author affiliation included:
- the United States,
Four journals had published more that 10 papers each on the subject:
- Chinese Traditional and Herbal Drugs,
- Journal of Biomolecular Structure & Dynamics,
- Zhongguo Zhongyao Zazhi (China Journal of Chinese Materia Medica),
- Pharmacological Research
The vast majority of articles were published in English, followed by Chinese. Eligible articles were published across 157 journals, of which 33 were SCAM-focused; a total of 120 journals had a 2019 impact factor, which ranged from 0.17 to 60.392. A total of 327 different SCAMs were mentioned across eligible articles, with the most common ones including:
- traditional Chinese medicine (n = 94),
- vitamin D (n = 67),
- melatonin (n = 16),
- phytochemicals (n = 12),
- general herbal medicine (n = 11).
The Canadian author concluded that this study provides researchers and clinicians with a greater knowledge of the characteristics of articles that been published globally at the intersection of COVID-19 and SCAM to date. At a time where safe and effective vaccines and medicines for the prevention and treatment of COVID-19 have yet to be discovered, this study provides a current snapshot of the quantity and characteristics of articles written at the intersection of SCAM therapies and COVID-19.
If anyone repeated the research today, I fear that the number of different SCAMs would have at least doubled. There is simply no form of SCAM that would not have joined the bandwagon of snake-oil salesmen trying to make a quick buck or satisfying their dangerous delusion of a panacea. Today (11/12/2020) my very quick Medline search on just a few SCAMs resulted in the following:
- Herbal medicine: 253
- Dietary supplement: 139
- Acupuncture: 68
- Homeopathy (not mentioned at all above): 20
- Chiropractic: 13
- Naturopathy: 6
One of the most chilling reads during my ‘rough and ready’ trawl through the literature was an article co-authored by a Viennese professor who has featured repeatedly on this blog. Here is its abstract:
Successful homeopathic prescriptions are based on careful individualization of symptoms, either for an individual patient or collectively in the case of epidemic outbreaks. The ongoing COVID-19 pandemic was initially represented as a severe acute respiratory illness, with eventual dramatic complications. However, over time it revealed to be a complex systemic disease with manifestations derived from viral-induced inflammation and hypercoagulability, thus liable to affect any body organ or system. As a result, clinical presentation is variable, in addition to variations associated with several individual and collective risk factors. Given the extreme variability of pathology and clinical manifestations, a single, or a few, universal homeopathic preventive Do not split medicine(s) do not seem feasible. Yet homeopathy may have a relevant role to play, inasmuch as the vast majority of patients only exhibit the mild form of disease and are indicated to self-care at home, without standard monitoring, follow-up, or treatment. For future pandemics, homeopathy agencies should prepare by establishing rapid-response teams and efficacious lines of communication.
The Canadian author of the above paper did not analyse how many of the papers he included would make therapeutic claims. I suspect that the majority did. In this context, one of the clearest indications of how deluded SCAM practitioners tend to be during these difficult times was provided by this paper:
Coronavirus disease 2019 (COVID-19), caused by a new coronavirus, first appeared in late 2019. What initially seemed to be a mild influenza quickly revealed itself as a serious and highly contagious disease, and the planet was soon faced with a significant morbidity and mortality associated with this pathogen. For homeopathy, shunned during its 200 years of existence by conventional medicine, this outbreak is a key opportunity to show potentially the contribution it can make in treating COVID-19 patients. This should be done through performance of impeccably controlled, prospective, randomized clinical trials, with publication of their findings in well-ranked conventional medicine journals. If the homeopathy community fails to take advantage of this rare opportunity, it might wait another century for the next major pandemic.
I must admit, I felt vaguely sick while reading it.
I very rarely discuss animal experiments on this blog. Their applicability to clinical situations in human patients is almost invariably doubtful. Of course, this does not mean that they cannot be important; on the contrary, they may point the way towards relevant research and help formulate hypotheses.
This study might be exceptionally relevant in this way. To investigate the safety and efficacy of megadose sodium ascorbate in sepsis, sheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg).
Sepsis-induced fever (41.4 ± 0.2°C; mean ± SE), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial PO2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue PO2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01).
Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary PO2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg).
These physiologic findings were subsequently confirmed in a coronavirus patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours.
The authors concluded that IV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.
As always with animal experiments, it is difficult to extrapolate to clinical situations in human patients. However, the fact that the authors did try their approach on one COVID-19 patient is encouraging. I agree with their conclusion that careful human studies are now required.
The amount of different so-called alternative medicines (SCAMs) that are being tried or promoted against COVID-19 is legion. Anything really from vitamins to herbal remedies, homeopathics to chiropractic. In fact, it is hard these days to find a SCAM that is not touted for COVID-19.
This study aimed to evaluate if a dietary supplement of quercetin (a polyphenol contained in many fruit and vegetables), vitamin C and bromelain (a proteolytic enzyme contained in pineapple) could be protective against coronavirus infections.
In the verum group, a supplement containing
- 500mg of quercetin,
- 500mg of vitamin C,
- 50mg of bromelain (QCB)
was administered daily in 2 divided doses for 71 healthcare workers working in areas with high risk of COVID-19, whereas 42 were the control group who received no supplements. The maximum period of follow-up was 120 days. Termination of QCB use prematurely or having a coronavirus infection was the end of a volunteer’s study participation. A rapid diagnostic test was used to detect immunoglobulin positivity.
A total of 113 persons were included. No significant difference were detected between groups at baseline. Mean age of QCB group was 39.0 ± 8.8 years and control group was 32.9 ± 8.7. Average follow-up period for the QCB group was 113 days, and for the control group, 118 days. During the follow-up period, 1 healthcare worker in the QCB group and 9 out in 42 in control group contracted COVID-19. One case was asymptomatic, while others were not. Transmission risk hazard ratio of participants who did not receive QCB was 12.04 (95% Confidence interval= 1.26-115.06, P = 0.031). No significant effect of gender, smoking, antihypertensive medication exposure and having chronic disease on rate of transmission. The authors concluded that this study revealed that QCB was protective for healthcare workers.
The sudy is so poorly written and reported that I had trouble making sense of it. In fact, I first thought it was a fake. Then I saw this note:
Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed.
If the results are for real (because of the small sample size, the lack of a placebo-control, dozens of potential confounders, etc., the findings could easily false-positive), they would merit urgent replication in a larger, more rigorous trial.
Meanwhile I would be very sceptical about the validity of the results. The paper (it really is just a submission for publication in the Lancet; I am not even sure that it will be officially published and I don’t quite see why it is being made available to the public in this way) is too flimsy for words. Despite these warnings, it is likely that many consumers will fall for the claim that QCB was protective for healthcare workers.
There is some encouraging evidence regarding the positive influence of vitamin D on COVID-19. But is it convincing? Is it causal? As always, it is worth looking at the totality of the reliable evidence.
In this systematic review and meta-analysis, the researchers analyze the association between vitamin D deficiency and COVID-19 severity. They conducted an analysis of the prevalence of vitamin D deficiency and insufficiency in people with the disease. Five online databases—Embase, PubMed, Scopus, Web of Science, ScienceDirect and pre-print Medrevix were searched. The inclusion criteria were observational studies measuring serum vitamin D in adult and elderly subjects with COVID-19. The main outcome was the prevalence of vitamin D deficiency in severe cases of COVID-19.
The researchers identified 1542 articles and 27 met their inclusion criteria. The results show that
- vitamin D deficiency was not associated with a higher chance of infection by COVID-19,
- severe cases of COVID-19 present 64% more vitamin D deficiency compared with mild cases,
- vitamin D concentration insufficiency increased hospitalization and mortality rates,
- There was a positive association between vitamin D deficiency and the severity of the disease.
The authors concluded that the results of the meta-analysis confirm the high prevalence of vitamin D deficiency in people with COVID-19, especially the elderly. We should add that vitamin D deficiency was not associated with COVID-19 infection. However, we observed a positive association between vitamin D deficiency and the severity of the disease. From this perspective, evaluating blood vitamin D levels could be considered in the clinical practice of health professionals. Moreover, vitamin D supplementation could be considered in patients with vitamin D deficiency and insufficiency, if they have COVID-19. However, there is no support for supplementation among groups with normal blood vitamin D values with the aim of prevention, prophylaxis or reducing the severity of the disease.
These are interesting findings, no doubt. They relate to associations, as the authors repeatedly stress in the text of the paper. They do not, however, signify cause and effect relationships. The principal outcome of this research should be a hypothesis that subsequently needs testing in clinical trials.
So, why on earth did the authors chose that seriously misleading title of their paper? It clearly implies a causal effect; and this can only be verified by conducting clinical trials. One such study has been published (as discussed here) and it concluded that administration of calcifediol may improve the clinical outcome of subjects requiring hospitalization for COVID-19.
My conclusion: it seems well worth conducting more and more rigorous clinical trials.
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.
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.
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.
Vitamin D and Omega-3 supplements help the elderly avoid Covid-19 infection by boosting their immune systems, study claims. Yes, that was the headline in the DAILY MAIL on 11/11/2020. Naturally, I found this interesting. So, I looked up the original paper. Here is its abstract:
Importance: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear.
Objective: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults.
Design, setting, and participants: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017.
Interventions: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270).
Main outcomes and measures: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance.
Results: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups.
Conclusions and relevance: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes.
The study has noting to do with COVID-19 and very little with infections. The bit about infections shows almost the opposite of what the MAIL claims. So, where does the notion stipulated in the headline come from?
The MAIL article gives the answer: Professor Heike Bischoff-Ferrari from Zurich University in Switzerland, who led the latest study, said: ‘Our findings suggest supplementation of vitamin D and omega-3s in adults aged 70 or older who lead an active lifestyle and have no pre-existing conditions does not provide any benefits when it comes to bone health, memory and muscle function. ‘However, we believe there is an effect on infections – such as Covid-19.’
I would not be surprised, if the last sentence in the quote was taken out of context.
I would not be surprised, if this is the worst health related article in the DAIL MAIL this year.
And, by Jove, there are plenty to choose from.
And why do I report all this?
As I have pointed out before, I believe that journalists have a lot to answer for when it comes to misleading the public about so-called alternative medicine (SCAM):
- “Scientists have shown how homeopathy works” – journalists’ obsession with ‘balance’
- ACUPUNCTURE: journalists, be aware of your responsibility not to mislead the public
- Drowning in a sea of misinformation. Part 10: Journalists
My hope is that, by reminding them of their ‘errors’ every now and then, I might contribute to some progress.
Yes, I know, I am an incurable optimist!