vitamin
Numerous so-called alternative medicines (SCAMs) have been touted as the solution for COVID-19. In fact, it is hard to find a SCAM that is not claimed to be useful for corona patients. Crucially, such claims are being made in the complete absence of evidence. A recent paper offers a bibliometric analysis of global research trends at the intersection of SCAM and COVID-19.
SCOPUS, MEDLINE, EMBASE, AMED and PSYCINFO databases were searched on July 5, 2020. All publication types were included, however, articles were only deemed eligible, if they made mention of one or more SCAMs for the potential prevention, treatment, and/or management of COVID-19 or a health issue indirectly resulting from the COVID-19 pandemic. The following eligible article characteristics were extracted: title; author names, affiliations, and countries; DOI; publication language; publication type; publication year; journal (and whether it is TICAM-focused); 2019 impact factor, and TICAMs mentioned.
A total of 296 eligible articles were published by 1373 unique authors at 977 affiliations across 56 countries. The most common countries associated with author affiliation included:
- China,
- the United States,
- India,
- Italy.
Four journals had published more that 10 papers each on the subject:
- Chinese Traditional and Herbal Drugs,
- Journal of Biomolecular Structure & Dynamics,
- Zhongguo Zhongyao Zazhi (China Journal of Chinese Materia Medica),
- Pharmacological Research
The vast majority of articles were published in English, followed by Chinese. Eligible articles were published across 157 journals, of which 33 were SCAM-focused; a total of 120 journals had a 2019 impact factor, which ranged from 0.17 to 60.392. A total of 327 different SCAMs were mentioned across eligible articles, with the most common ones including:
- traditional Chinese medicine (n = 94),
- vitamin D (n = 67),
- melatonin (n = 16),
- phytochemicals (n = 12),
- general herbal medicine (n = 11).
The Canadian author concluded that this study provides researchers and clinicians with a greater knowledge of the characteristics of articles that been published globally at the intersection of COVID-19 and SCAM to date. At a time where safe and effective vaccines and medicines for the prevention and treatment of COVID-19 have yet to be discovered, this study provides a current snapshot of the quantity and characteristics of articles written at the intersection of SCAM therapies and COVID-19.
If anyone repeated the research today, I fear that the number of different SCAMs would have at least doubled. There is simply no form of SCAM that would not have joined the bandwagon of snake-oil salesmen trying to make a quick buck or satisfying their dangerous delusion of a panacea. Today (11/12/2020) my very quick Medline search on just a few SCAMs resulted in the following:
- Herbal medicine: 253
- Dietary supplement: 139
- Acupuncture: 68
- Homeopathy (not mentioned at all above): 20
- Chiropractic: 13
- Naturopathy: 6
One of the most chilling reads during my ‘rough and ready’ trawl through the literature was an article co-authored by a Viennese professor who has featured repeatedly on this blog. Here is its abstract:
Successful homeopathic prescriptions are based on careful individualization of symptoms, either for an individual patient or collectively in the case of epidemic outbreaks. The ongoing COVID-19 pandemic was initially represented as a severe acute respiratory illness, with eventual dramatic complications. However, over time it revealed to be a complex systemic disease with manifestations derived from viral-induced inflammation and hypercoagulability, thus liable to affect any body organ or system. As a result, clinical presentation is variable, in addition to variations associated with several individual and collective risk factors. Given the extreme variability of pathology and clinical manifestations, a single, or a few, universal homeopathic preventive Do not split medicine(s) do not seem feasible. Yet homeopathy may have a relevant role to play, inasmuch as the vast majority of patients only exhibit the mild form of disease and are indicated to self-care at home, without standard monitoring, follow-up, or treatment. For future pandemics, homeopathy agencies should prepare by establishing rapid-response teams and efficacious lines of communication.
The Canadian author of the above paper did not analyse how many of the papers he included would make therapeutic claims. I suspect that the majority did. In this context, one of the clearest indications of how deluded SCAM practitioners tend to be during these difficult times was provided by this paper:
Coronavirus disease 2019 (COVID-19), caused by a new coronavirus, first appeared in late 2019. What initially seemed to be a mild influenza quickly revealed itself as a serious and highly contagious disease, and the planet was soon faced with a significant morbidity and mortality associated with this pathogen. For homeopathy, shunned during its 200 years of existence by conventional medicine, this outbreak is a key opportunity to show potentially the contribution it can make in treating COVID-19 patients. This should be done through performance of impeccably controlled, prospective, randomized clinical trials, with publication of their findings in well-ranked conventional medicine journals. If the homeopathy community fails to take advantage of this rare opportunity, it might wait another century for the next major pandemic.
I must admit, I felt vaguely sick while reading it.
I very rarely discuss animal experiments on this blog. Their applicability to clinical situations in human patients is almost invariably doubtful. Of course, this does not mean that they cannot be important; on the contrary, they may point the way towards relevant research and help formulate hypotheses.
This study might be exceptionally relevant in this way. To investigate the safety and efficacy of megadose sodium ascorbate in sepsis, sheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg).
Sepsis-induced fever (41.4 ± 0.2°C; mean ± SE), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial PO2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue PO2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01).
Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary PO2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg).
These physiologic findings were subsequently confirmed in a coronavirus patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours.
The authors concluded that IV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.
As always with animal experiments, it is difficult to extrapolate to clinical situations in human patients. However, the fact that the authors did try their approach on one COVID-19 patient is encouraging. I agree with their conclusion that careful human studies are now required.
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.
Graphic demonstrated survival without COVID-19 during follow up time between groups
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.
And meanwhile?
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.
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.
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.
Speachless?
Me too!
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.
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Yes, I know, I am an incurable optimist!
I know of one patient who turned to the Gerson Therapy having been told that she was suffering from terminal cancer and would not survive another course of chemotherapy. Happily, seven years later she is alive and well. So therefore it is vital that, rather than dismissing such experiences, we should further investigate the beneficial nature of these treatments.
HRH The Prince of Wales (2004)
I was reminded of this embarrassing (because displaying profound ignorance) quote when I looked at the website of the ‘GERSON SUPPORT GROUP UK‘ where it is prominently cited. Under the heading ‘SCIENCE & CLINICAL RATIONAL’ the site offers a long article about the Gerson therapy (GT). Allow me to show you a few quotes from it:
Dr Max Gerson’s therapy is based on the belief that insufficient nutrients within the cells and an accumulation of toxins in the tissues lead to a breakdown in healthy cellular function which, if left unchecked, can trigger cancer.
That is interesting, I find, because the statement clearly admits that the GT is not an evidence-based therapy but a belief-based treatment.
The therapy that he developed uses a restrictive, plant-based diet and specific supplements to boost healthy cellular function; and various detoxification procedures, including coffee enemas, to eliminate waste products.
The claims hidden in this sentence remain unproven. There is no evidence that cellular fuction is boosted, nor that the procedures eliminate toxins.
… we only need to look at communities across the globe which exist in a pre-industrialised state to see that, whilst they might be more likely to die from pneumonia or tuberculosis, rates of degenerative illness are a fraction of those in the ‘developed‘ world. The age-adjusted death rate from breast cancer is less than 2 per 100,000 of the population in Thailand, Sri Lanka and El Salvador and around 33 per 100,000 in the UK, US, The Netherlands and numerous other affluent, Western countries.
Correlation is not causation! Pre-industrial societies also watch less TV, eat less ice-cream, read less fashion magazines, etc., etc. Are these habits also the cause of cancer?
… migrant studies show that within two generations the cancer rates of migrants increase rapidly towards Western rates, again underlining the assertion that cancer is caused primarily by diet and lifestyle rather than ‘faulty’ genes.
In no way is this an argument for eating raw vegetable and taking your coffee via the rectum.
In the German scientific golden age of the 1920s and 30s…
Golden age for what, for fascists?
Gerson had used a restricted diet to cure himself of migraines. He then helped another patient to reverse tuberculosis, and many others to reverse a variety of degenerative illnesses, all by similar means. He later developed his therapy to the point where he was able to help individuals reverse cancer.
In this case, Max Gerson was ignorant of the fact that experience and evidence are two fundamentally different things.
Max Gerson developed his therapy in an iterative way, starting with a restrictive plant-based diet, adding vitamins, minerals and enzymes to encourage the oxygenation of the cells and then introducing the coffee enemas to aid detoxification of waste products. What is fascinating is that science has subsequently explained the mechanism of action behind some of his theories. (See Biochemical Basis to the Therapy).
Science has not explained the mechanism of action, not least because the action has never been verified. There are no robust clinical trials of Gerson’s therapy. Evidently, 100 years were not enough to conduct any – or perhaps the proponents know only too well that they would not generate the results they hoped?
Equally interesting is that in 2012 Dr Thomas Seyfried published the results of many years research in Cancer as a Metabolic Disease.
Really? On Medline, I find only two cancer-related papers for Seyfried T. 2012:
Dietary restriction promotes vessel maturation in a mouse astrocytoma.
Thus, nearly a century after their original proposition that the fundamental cause of cancer was faulty cellular metabolism, it seems that doctors Otto Warburg and Max Gerson might be vindicated.
No, to ‘vindicate’ a therapeutic suggestion one needs several rigorous clinical trials. And for the GT, they remain absent.
_______________________________
So, what does the GT amount to?
- proponents had ~100 years to produce evidence;
- they failed to do so;
- thus the therapy is at best unproven;
- it is also biologically implausible;
- moreover, it is expensive;
- crucially it is not free of serious adverse effects;
- it is promoted only by those who seem to make money from it.
The only controlled clinical trial of a Gerson-like therapy that I know of is this one (rarely cited by Gerson fans):
Conventional medicine has had little to offer patients with inoperable pancreatic adenocarcinoma; thus, many patients seek alternative treatments. The National Cancer Institute, in 1998, sponsored a randomized, phase III, controlled trial of proteolytic enzyme therapy versus chemotherapy. Because most eligible patients refused random assignment, the trial was changed in 2001 to a controlled, observational study.
METHODS
All patients were seen by one of the investigators at Columbia University, and patients who received enzyme therapy were seen by the participating alternative practitioner. Of 55 patients who had inoperable pancreatic cancer, 23 elected gemcitabine-based chemotherapy, and 32 elected enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. Primary and secondary outcomes were overall survival and quality of life, respectively.
RESULTS
At enrollment, the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values. Kaplan-Meier analysis found a 9.7-month difference in median survival between the chemotherapy group (median survival, 14 months) and enzyme treatment groups (median survival, 4.3 months) and found an adjusted-mortality hazard ratio of the enzyme group compared with the chemotherapy group of 6.96 (P < .001). At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P < .01).
CONCLUSION
Among patients who have pancreatic cancer, those who chose gemcitabine-based chemotherapy survived more than three times as long (14.0 v 4.3 months) and had better quality of life than those who chose proteolytic enzyme treatment.
Considering all this, I believe, it would be hard to name a cancer quackery that is less credible than the GT.
The spread of misinformation has accompanied the coronavirus pandemic, including topics such as immune boosting to prevent COVID-19. This study explores how immune boosting is portrayed on the internet during the COVID-19 pandemic. The researchers compiled a dataset of 227 webpages from Google searches in Canada and the USA using the phrase ‘boost immunity’ AND ‘coronavirus’ on 1 April 2020. They coded webpages for typology and portrayal of immune boosting and supplements. They recorded mentions of microbiome, whether the webpage was selling or advertising an immune boosting product or service, and suggested strategies for boosting immunity.
No significant differences were found between webpages that appeared in the searches in Canada and the USA. The most common types of webpages were from:
- news (40.5%),
- commercial (24.7%) websites.
The concept of immune boosting was portrayed as beneficial for avoiding COVID-19 in 85.5% of webpages and supplements were portrayed as beneficial in 40% of the webpages, but commercial sites were more likely to have these portrayals. The top immune boosting strategies were:
- vitamin C (34.8%),
- diet (34.4%),
- sleep (34.4%),
- exercise (30.8%),
- zinc (26.9%).
Less than 10% of the webpages provide any critique of the concept of immune boosting.
The authors concluded that pairing evidence-based advice for maintaining one’s health (eg, healthy diet, exercise, sleep) with the phrase immune boosting and strategies lacking in evidence may inadvertently help to legitimise the concept, making it a powerful marketing tool. Results demonstrate how the spread of misinformation is complex and often more subtle than blatant fraudulent claims.
The authors did not search for evidence to check whether any of the named interventions have any influence on the immune system. As reported previously, this review did just that. Its authors aimed to evaluate evidence from clinical trials that studied nutrition-based interventions for viral diseases (with special emphasis on respiratory infections). Studies were considered eligible if they were controlled trials in humans, measuring immunological parameters, on viral and respiratory infections. Clinical trials on vitamins, minerals, nutraceuticals and probiotics were included.
A total 43 studies met the inclusion criteria:
- vitamins: 13;
- minerals: 8;
- nutraceuticals: 18
- probiotics: 4
Among vitamins, A and D showed a potential benefit, especially in deficient populations. Among trace elements, selenium and zinc have also shown favourable immune-modulatory effects in viral respiratory infections. Several nutraceuticals and probiotics may also have some role in enhancing immune functions. Micronutrients may be beneficial in nutritionally depleted elderly population.
There were 15 studies with a high score for methodological quality. Here is what their results showed:
- No significant difference in incidence of winter-time upper respiratory tract infection in children with high versus low dose vitamin D.
- Significantly less acute respiratory infections in elderly individuals with vitamin D versus placebo.
- Higher TGFbeta plasma level in response to influenza vaccination but no improved antibody response in elderly, vitamin D-deficient individuals with vitamin D versus placebo.
- No effect on lower respiratory tract infections; however, a protective effect was noted on upper respiratory tract infections in elderly individuals with vitamin E versus placebo.
- Neither daily multivitamin + mineral supplementation at physiological dose nor 200 mg of vitamin E showed a favourable effect on incidence and severity of acute respiratory tract infections in well-nourished, non- institutionalized elderly individuals.
- Better improvement in the clinical status, respiratory rate and oxygen saturation in children suffering from pneumonia with zinc sulphate versus placebo.
- Selenium-yeast increased Tctx-antibody-dependent cellular cytotoxicity cell counts in blood before flu vaccination + dose-dependent increase in T cell proliferation, IL-8 and IL-10 secretion after in vivo flu challenge in healthy volunteers.
- Frequency and duration of acute respiratory infections during the first two months was unaffected in healthy elderly with ginseng versus placebo.
- Broccoli sprout homogenate favourably affected immunological variables in healthy volunteers.
- The incidence of illness was not reduced, however significantly fewer symptoms were reported and the proliferation index of gd-T cells in culture was almost five times higher after 10 weeks of cranberry polyphenol supplements versus placebo.
- Higher antibody titres against all 3 strains contained in the seasonal influenza virus vaccine than the placebo in healthy elderly individuals with a sea-weed extract versus placebo.
- Non-inferiority was demonstrated for Echinacea compared to oseltamivir in early treatment of clinically diagnosed and virologically confirmed influenza virus infections.
- Significant reduction of cold duration and severity in air travellers with elderberry supplement versus placebo.
- Increased NK cell activity with probiotics versus placebo in tube-fed elderly patients.
- Titres against the influenza B strain increased significantly more with probiotics compared to placebo in healthy elderly individuals.
I want to thank our friend ‘OLD BOB’ for alerting me to Patrick Holford’s comment on a recent trial of vitamin C for COVID-19. Here are three short quotes from Holford:
… Overall, 5 out 26 people (19%) died in the vitamin C group while 10 out of 28 (36%) receiving the placebo died. That means that vitamin C almost halved the number of deaths. Those on vitamin C were 60% more likely to survive.
… Of those most critically ill, 4 people (18%) in the vitamin C group died, compared to 10 (50%) in the placebo group. That’s two-thirds less deaths. Statistically this meant that of those most critically ill who were given vitamin C, they were 80% less likely to die…
… now there is another proven treatment – vitamin C…
And here is the abstract of the actual trial Holford refers to:
Background: No specific medication has been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19.
Methods: This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 hours for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way. The primary outcome was invasive mechanical ventilation-free days in 28 days(IMVFD28). Secondary outcomes were 28-day mortality, organ failure, and inflammation progression.
Results: Only fifty-six critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups. During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P=0.01). Patients with SOFA scores ≥3 in the HDIVC group exhibited a trend of reduction in 28-day mortality (P=0.06) in univariate survival analysis. IL-6 in the HDIVC) group was lower than that in the placebo group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P=0.04) on day 7.
Conclusion: This pilot trial showed that HDIVC might show a potential signal of benefit for critically ill patients with COVID-19, improving oxygenation even though it failed to improve IMVFD28.
The following points are, I think, worth mentioning:
- This was, according to its authors, a PILOT study.
- It was far too small (n=56) to provide reliable results on mortality.
- The trial authors know that and interpret their findings with sufficient caution.
- The primary endpoint, the IMVFD28, showed NO significant difference between the groups.
- The secondary endpoint: HDIVC infusion exhibited a non-significant trend of reduction in 28-day mortality (P=0.06).
- In more severe patients (SOFA score ≥3), univariate survival analysis and Cox regression showed a similar results (P=0.07, HR, 0.32 [95% CI 0.10-1.06]).
And what does all of this mean? It means that, in this pilot study, vitamin C failed to produce a significant result. Only in a subgroup analysis related to a secondary endpoint was there a slight advantage of vitamin C. This effect is, of course, interesting and needs further investigation (I am sure that is happening as we speak). It could have some clinical significance but, just as likely, it could just be due to chance. There is not way of knowing which is which.
In other words, to hype the findings and to even make statements such as ‘now there is another proven treatment, vitamin C’ is not just exaggerated, it is irresponsible.
This begs the question: why does Mr Holford do it? In case you don’t already know about this man, go on the Internet, and you will quickly find possible answers. Here is an excerpt from his Wiki page which might give you a clue:
Patrick Holford is a British author and entrepreneur who endorses a range of controversial vitamin tablets. As an advocate of alternative nutrition and diet methods, he appears regularly on television and radio in the UK and abroad. He has 36 books in print in 29 languages. His business career promotes a wide variety of alternative medical approaches such as orthomolecular medicine, many of which are considered pseudoscientific by mainstream science and medicine.
Holford’s claims about HIV and autism are not in line with modern medical thought, and have been criticised for putting people in danger and damaging public health.
In 2006 Holford was discovered to be using his PR advisor to delete critical content from his Wikipedia page…
Holford has been the subject of criticism for his promotion of medically dubious techniques and products including hair analysis, his support of the now struck off doctor Andrew Wakefield, and advocating the use of “non-drug alternatives for mental health” for which he has been given an award by the Church of Scientology-backed Citizens Commission on Human Rights.
SAY NO MORE!
This study assessed the patterns of dietary supplement usage among cancer survivors in the United States in a population-based setting. National Health and Nutrition Examination Survey (NHANES) datasets (1999-2016) were accessed, and adult respondents (≥ 20 years old) with a known status of cancer diagnosis and a known status of dietary supplements intake were included. Multivariable logistic regression analysis was then used to assess factors associated with dietary supplements intake. Moreover, and to evaluate the impact of dietary supplements on overall survival among respondents with cancer, multivariable Cox regression analysis was conducted.
A total of 49,387 respondents were included in the current analysis, including a total of 4,575 respondents with cancer. Among respondents with cancer, 3,024 (66.1%) respondents reported the use of dietary supplements; while 1,551 (33.9%) did not report the use of dietary supplements. Using multivariable logistic regression analysis, factors associated with the use of dietary supplements included:
- older age (OR: 1.028; 95% CI: 1.027-1.030);
- white race (OR for black race vs. white race: 0.67; 95% CI: 0.63-0.72);
- female gender (OR for males vs. females: 0.56; 95% CI: 0.53-0.59),
- higher income (OR: 1.13; 95% CI: 1.11-1.14),
- higher educational level (0.59; 95% CI: 0.56-0.63),
- better self-reported health (OR: 1.36; 95% CI: 1.17-1.58),
- health insurance (OR: 1.35; 95% CI: 1.27-1.44),
- history of cancer (OR: 1.20; 95% CI: 1.10-1.31).
Using multivariable Cox regression analysis and within the subgroup of respondents with a history of cancer, the use of dietary supplements was not found to be associated with a difference in overall survival (HR: 1.13; 95% CI: 0.98-1.30).
The authors concluded that dietary supplement use has increased in the past two decades among individuals with cancer in the United States, and this increase seems to be driven mainly by an increase in the use of vitamins. The use of dietary supplements was not associated with any improvement in overall survival for respondents with cancer in the current study cohort.
Many cancer patients, when they first get diagnosed, are tested for vitamin D levels and found to be low or borderline. Consequently, they get a prescription for supplements. Other than this, there is rarely an indication to take any vitamins or other dietary supplements. Yet, cancer patients take them because they think these ‘natural’ preparations can do no harm (and because the industry can be persuasive [there is big money at stake] and the odd breed of ‘integrated’ oncologists might even recommend them). Sadly, this assumption is not correct. The biggest danger, in my view, is the possibility of supplements to interact with one of the many drugs that cancer patients need to take. So, in a way, it is reassuring that, on average, there is no detrimental effect on overall survival.
The paper will probably also reignite the perennial discussion about the effects of vitamin C on the natural history of cancer. My understanding is that there is none (and this verdict seems to be supported by the findings reported here). But I am, of course, aware that this is a ‘hot potato’ and that some readers will think differently. To them I say: please show me the evidence.
