methodology
Melatonin is an indolamine hormone which is secreted from the human pineal gland during night-time acting as physiological regulator. In many countries, dietary supplements containing synthetically produced melatonin are available. Melatonin is being promoted as a treatment of a range of conditions, including virtually all types of cancer.
One website, for instance, states that the anti-cancer benefits of melatonin aren’t just indirect; this miracle molecule is also classified as a directly cytotoxic hormone and anti-cancer agent. Studies have referred to melatonin as a “full-service anti-cancer agent” due to its ability to inhibit the initiation of cell mutation and cancer growth, and to halt the progression and metastasis of cancer cell colonies.
Such statements sound far too good to be true. So, let’s have a look and find out what the evidence tells us. Test-tube experiments suggest that melatonin has anti-cancer effects.[1] Its actions include the advancement of apoptosis, the arrest of the cell cycle, inhibition of metastasis, and antioxidant activity.[2]
A review of 21 clinical trials of melatonin for cancer found positive effects for complete response, partial response, and stable disease. In trials combining melatonin with chemotherapy, adjuvant melatonin therapy decreased 1-year mortality and improved outcomes of complete response, partial response, and stable disease. In these studies, melatonin also significantly reduced asthenia, leukopenia, nausea and vomiting, hypotension, and thrombocytopenia. The authors concluded that melatonin may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy.[3]
A further systematic review of RCTs of melatonin in solid tumour cancer patients evaluated its effect on one-year survival. Ten trials were included of melatonin as either sole treatment or as adjunct treatment. Melatonin reduced the risk of death at 1 year. Effects were consistent across melatonin dose, and type of cancer. No severe adverse events were reported.[4]
A 2012 systematic review confirmed these findings by concluding that Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission, 1-year survival, and alleviation of radiochemotherapy-related side effects.[5]
Finally, a 2020 review concluded that melatonin in combination with anticancer agents may improve the efficacy of routine medicine and survival rate of patients with cancer. [6] Apart from its direct anticancer potential, melatonin also seems to reduce chemotherapy toxicity, while improving its therapeutic efficacy.[7]
So, is this evidence compelling? While all this does indeed sound encouraging, it is necessary to mention several important caveats:
- The primary studies of melatonin suffer from several methodological shortcomings.
- Their vast majority originate from one single research group.
- In recent years, there have been no further clinical studies trying to replicate the initial findings.
This means that definitive trials are still missing, and it would seem wise to interpret the existing evidence with great caution.
References
[1] Kong X, Gao R, Wang Z, Wang X, Fang Y, Gao J, Reiter RJ, Wang J. Melatonin: A Potential Therapeutic Option for Breast Cancer. Trends Endocrinol Metab. 2020 Sep 3:S1043-2760(20)30155-7. doi: 10.1016/j.tem.2020.08.001. Epub ahead of print. PMID: 32893084.
[2] Samanta S. Melatonin: an endogenous miraculous indolamine, fights against cancer progression. J Cancer Res Clin Oncol. 2020 Aug;146(8):1893-1922. doi: 10.1007/s00432-020-03292-w. Epub 2020 Jun 24. PMID: 32583237.
[3] Seely D, Wu P, Fritz H, Kennedy DA, Tsui T, Seely AJ, Mills E. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integr Cancer Ther. 2012 Dec;11(4):293-303. doi: 10.1177/1534735411425484. Epub 2011 Oct 21. PMID: 22019490.
[4] Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005 Nov;39(4):360-6. doi: 10.1111/j.1600-079X.2005.00258.x. PMID: 16207291.
[5] Wang YM, Jin BZ, Ai F, Duan CH, Lu YZ, Dong TF, Fu QL. The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials. Cancer Chemother Pharmacol. 2012 May;69(5):1213-20. doi: 10.1007/s00280-012-1828-8. Epub 2012 Jan 24. PMID: 22271210.
[6] Pourhanifeh MH, Mehrzadi S, Kamali M, Hosseinzadeh A. Melatonin and gastrointestinal cancers: Current evidence based on underlying signaling pathways. Eur J Pharmacol. 2020 Nov 5;886:173471. doi: 10.1016/j.ejphar.2020.173471. Epub 2020 Aug 30. PMID: 32877658.
[7] Iravani S, Eslami P, Dooghaie Moghadam A, Moazzami B, Mehrvar A, Hashemi MR, Mansour-Ghanaei F, Mansour-Ghanaei A, Majidzadeh-A K. The Role of Melatonin in Colorectal Cancer. J Gastrointest Cancer. 2020 Sep;51(3):748-753. doi: 10.1007/s12029-019-00336-4. PMID: 31792737.
Alzheimer is a devastating condition. Despite much research, we are still far from being able to effectively prevent or treat it. Some claim that relatively simple dietary interventions might work. What does the evidence tell us?
The aim of this systematic review was to evaluate the effect of dietary interventions on the cognitive performance of individuals with Alzheimer’s disease (AD). Thirty-two RCT could be included.
The findings show that a wide range of supplements have been submitted to testing in RCTs. Most of the supplements seem to be less than useful. However, some seem to show some promise:
- Omega-3 fatty acid has positive effects at different doses.
- ‘Fortasyn Connect’ (a multi-nutrient mixture) seems to be effective in the early stages of the disease.
- Probiotic, Ginseng, Inositol and specialized nutritional formulas seem to have a positive effect on cognition.
Most of the primary studies had poor methodological quality, included patients with mild AD, small samples, and did not obtain significative results for all the cognitive outcomes.
The authors concluded that the effect of most dietary interventions on cognition in AD patients remains inconclusive, however, several nutrients, isolated or not, show potential to improve cognitive function in AD, especially in its early stages.
I am relieved that the authors of this thoroughly-researched review phrased their conclusions as cautiously as they did. The thing is, most of the primary trials are truly not worth writing home about. Some are just 4 weeks long, others include merely 30 odd patients. Many look more like marketing excercises than science.
The authors also stated that better quality studies are urgently needed to confirm the therapeutic potential of the diet so that a dietary recommendation in AD that contributes to the quality of life of patients and relatives can be established. This has become almost a standard sentence for ending a scientific paper. In this instance, however, it seems very true.
Some of us got used to the idea that acupuncture might be effective for pain. But could it work for infections? Unlikely! Well, let’s not rely on gut feelings; let’s have a fair and critical look at the evidence.
This systematic review assessed the evidence for acupuncture for uncomplicated recurrent urinary tract infections (rUTI) women. Five randomised controlled trials (RCTs) evaluating the effects of acupuncture and related therapies for prophylaxis or treatment of uncomplicated rUTI in women were included. The methodological quality of the studies and the strength of the evidence were low to moderate. The chance of achieving a composite cure with acupuncture therapies was greater than that with antibiotics (three studies, 170 participants, RR 1.92, 95% CI 1.31‐2.81, I2 = 38%). The risk of UTI recurrence was lower with acupuncture than with no treatment (two studies, 135 participants, RR 0.39, 95% CI 0.26–0.58, I2 = 0%) and sham acupuncture (one study, 53 participants, RR 0.45, 95% CI 0.22–0.92).
The authors concluded that acupuncture showed promising results compared to no treatment and sham acupuncture in reducing recurrence, based on low to moderate certainty evidence. Low certainty evidence found acupuncture increased the chance of achieving a composite cure compared to antibiotics. Findings from this review should be interpreted with caution, taking into consideration the biases identified and small sample size of the included trials. Included studies suggest acupuncture has a good safety profile for women with UTI, and may be considered as a therapeutic option in the treatment and prevention of rUTI in women, particularly those who are unresponsive to, or intolerant of, antibiotics. Rigorously designed research is needed to inform clinical decisionmaking about the use of acupuncture for women with UTIs.
The authors of this review are affiliated to the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangdong Provincial Academy of Chinese Medical Sciences and The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China and the China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia. The review was funded by the China-Australia International Research Centre for Chinese Medicine (CAIRCCM) (International Cooperation Project, Grant Number 2012DFA31760), and the National Natural Science Foundation of China (NSFC) (Grant Number 81873261). In view of these facts, it is strange, I think, that the authors declared no conflicts of interest.
The 5 primary studies included in this review are the following:
-
- Alraek T, Soedal LI, Fagerheim SU, Digranes A, Baerheim A. Acupuncture treatment in the
prevention of uncomplicated recurrent lower urinary tract infections in adult women. American journal of
public health. 2002;92(10):1609-11. - Aune A, Alraek T, LiHua H, Baerheim A. Acupuncture in the prophylaxis of recurrent lower urinary
tract infection in adult women. Scandinavian journal of primary health care. 1998;16(1):37-9. - Hong JY, Li F, Liang XQ, Hou Z. [Efficacy observation on female chronic pyelonephritis treated with
abdominal cluster-needling therapy]. Zhongguo zhen jiu = Chinese acupuncture & moxibustion.
2013;33(4):303-5. - Yu SM, Guo DD. Moxibustion combined with antibiotics was used to treat 30 cases of chronic
urinary tract infection in adult women. Shandong Journal of Traditional Chinese Medicine.
2010;29(09):621-2. - Liu JL, Luo Q, Liu XH, Lin L. Observation on the clinical effect of external treatment of strong renal
moxibustion on recurrent urinary tract infection. China Modern Doctor. 2018;56(29):116-8.
- Alraek T, Soedal LI, Fagerheim SU, Digranes A, Baerheim A. Acupuncture treatment in the
As always, it is worth checking these studies for reliability.
In the trial by Alraek et al patients were randomised patients to receive either acupuncture or no treatment. Is anyone surprised that the former group fared better than the latter? (I am not!)
The trial by Aune et al is the only study that attempted to control for placebo effects by using a sham control group. This is what they used as a sham treatment: Sham acupuncture was given using six needles superficially inserted in the calves, thighs or abdomen outside known acupuncture points or meridians. Needles were not manipulated in the sham group. Sham controls have the purpose of rendering patients unaware whether they receive the real or the sham treatment. The method used here cannot achieve this aim; patients were easily able to determine that they were in the control group.
The last three trials are all not Medline-listed studies authored by Chinese investigators published in inaccessible journals in Chinese. We know that such studies invariably report positive outcomes which are often fabricated and thus have a reliability close to zero. But even if we ignore these facts for a moment, from what I see in the results table of the review, these studies are invalid. All three are equivalence trials of acupuncture versus antibiotics; with a sample size of merely around 30, they must be woefully underpowered and thus unable to generate a reliable result.
The authors of this review claim that the risk of bias of trials was generally high or unclear. This is an understatement to put it mildly. In fact, the quality of the studies was mostly dismal.
In view of all this, I take the liberty to re-formulate the conclusions drawn by the review authors as follows:
Due to the lack of reliable RCTs, the effectiveness of acupuncture as a treatment or prevention of rUTIs remains unproven. Due to the implausibility of the therapy, its effectiveness seems highly unlikely.
PS
The BJOG should never have published such a deeply misleading paper.
Reflexology (originally called ‘zone therapy’ by its inventor) is a manual technique where pressure is applied to the sole of the patient’s foot. Reflexology is said to have its roots in ancient cultures. Its current popularity goes back to the US doctor William Fitzgerald (1872-1942) who did some research in the early 1900s and thought to have discovered that the human body is divided into 10 zones each of which is represented on the sole of the foot. Reflexologists thus drew maps of the sole of the foot where all the body’s organs are depicted. Numerous such maps have been published and, embarrassingly, they do not all agree with each other as to the location of our organs on the sole of our feet. By massaging specific zones which are assumed to be connected to specific organs, reflexologists believe to positively influence the function of these organs.
So, does reflexology do more good than harm?
The aim of this review was to conduct a systematic review, meta-analysis, and metaregression to determine the current best available evidence of the efficacy and safety of foot reflexology for adult depression, anxiety, and sleep quality.
Twenty-six studies could be included. The meta-analyses showed that foot reflexology intervention significantly improved adult depression, anxiety, and sleep quality. Metaregression revealed that an increase in total foot reflexology time and duration can significantly improve sleep quality.
The authors concluded that foot reflexology may provide additional nonpharmacotherapy intervention for adults suffering from depression, anxiety, or sleep disturbance. However, high quality and rigorous design RCTs in specific population, along with an increase in participants, and a long-term follow-up are recommended in the future.
Sounds good!
Finally a so-called alternative medicine (SCAM) that is backed by soild evidence!
Or perhaps not?
Here are a few concerns that lead me to doubt these conclusions:
- Most of the primary studies were of poor methodological quality.
- Most studies failed to mention adverse effects.
- Very few studies controlled for placebo effects.
- There was evidence of publication bias (negative studies tended to remain unpublished).
- Studies published in languages other than English were not considered.
- The authors fail to point out that a foot massage is, of course, agreeable (and thus may relieve a range of symptoms), but reflexology with all its weird assumptions is less than plausible.
- Many of the studies located by the authors were excluded for reasons that are less than clear.
The last point seems particularly puzzling. Our own trial, for instance, was excluded because, according to the review authors, it did not include relevant outcomes. However, our method secion makes it clear that the primary focus for this study was the subscores for anxiety and depression, which comprise four and seven items, respectively. As it happens, our study was negative.
Also cuirous is the fact that the authors did not mention our own 2011 systematic review of reflexology:
Reflexology is a popular form of complementary and alternative medicine (CAM). The aim of this update is to critically evaluate the evidence for or against the effectiveness of reflexology in patients with any type of medical condition. Six electronic databases were searched to identify all relevant randomised clinical trials (RCTs). Their methodological quality was assessed independently by the two reviewers using the Jadad score. Overall, 23 studies met all inclusion criteria. They related to a wide range of medical conditions. The methodological quality of the RCTs was often poor. Nine high quality RCTs generated negative findings; and five generated positive findings. Eight RCTs suggested that reflexology is effective for the following conditions: diabetes, premenstrual syndrome, cancer patients, multiple sclerosis, symptomatic idiopathic detrusor over-activity and dementia yet important caveats remain. It is concluded that the best clinical evidence does not demonstrate convincingly reflexology to be an effective treatment for any medical condition.
I wonder why!
Low-level laser therapy has been used clinically to treat musculoskeletal pain; however, there is limited evidence available to support its use. The current Cochrance review fails to be positive: there are insufficient data to draw firm conclusions on the clinical effect of LLLT for low‐back pain. So, perhaps studies on animals generate clearer answers?
The objective of this study was to evaluate the clinical effectiveness of low-level laser therapy and chiropractic care in treating thoracolumbar pain in competitive western performance horses. The subjects included 61 Quarter Horses actively involved in national western performance competitions judged to have back pain. A randomized, clinical trial was conducted by assigning affected horses to either:
- laser therapy,
- chiropractic,
- or combined laser and chiropractic treatment groups.
Low-level laser therapy was applied topically to local sites of back pain. The laser probe contained four 810-nm laser diodes spaced 15-mm apart in a square array that produced a total optical output power of 3 watts. Chiropractic treatment was applied to areas of pain and stiffness within the thoracolumbar and sacral regions. A single application of a high velocity, low-amplitude (HVLA) manual thrust was applied to affected vertebral segments using a reinforced hypothenar contact and a body-centered, body-drop technique. The HVLA thrusts were directed dorsolateral to ventromedial (at a 45° angle to the horizontal plane) with a segmental contact near the spinous process with the goal of increasing extension and lateral bending within the adjacent vertebral segments. If horses did not tolerate the applied chiropractic treatment, then truncal stretching, spinal mobilization, and the use of a springloaded, mechanical-force instrument were used as more conservative forms of manual therapy in these acute back pain patients.
Outcome parameters included a visual analog scale (VAS) of perceived back pain and dysfunction and detailed spinal examinations evaluating pain, muscle tone, and stiffness. Mechanical nociceptive thresholds were measured along the dorsal trunk and values were compared before and after treatment. Repeated measures with post-hoc analysis were used to assess treatment group differences.
Low-level laser therapy, as applied in this study, produced significant reductions in back pain, epaxial muscle hypertonicity, and trunk stiffness. Combined laser therapy and chiropractic care produced similar reductions, with additional significant decreases in the severity of epaxial muscle hypertonicity and trunk stiffness. Chiropractic treatment by itself did not produce any significant changes in back pain, muscle hypertonicity, or trunk stiffness; however, there were improvements in trunk and pelvic flexion reflexes.
The authors concluded that the combination of laser therapy and chiropractic care seemed to provide additive effects in treating back pain and trunk stiffness that were not present with chiropractic treatment alone. The results of this study support the concept that a multimodal approach of laser therapy and chiropractic care is beneficial in treating back pain in horses involved in active competition.
Let me play the devil’s advocate and offer a different conclusion:
These results show that horses are not that different from humans when it comes to responding to treatments. One placebo has a small effect; two placebos generate a little more effects.
The aim of this RCT was to examine symptom responses resulting from a home-based reflexology intervention delivered by a friend/family caregiver to women with advanced breast cancer undergoing chemotherapy, targeted, and/or hormonal therapy.
Patient-caregiver dyads (N = 256) were randomized to 4 weekly reflexology sessions or attention control. Caregivers in the intervention group were trained by a reflexology practitioner in a 30-min protocol. During the 4 weeks, both groups completed telephone symptom assessments using the M. D. Anderson Symptom Inventory. Those who completed at least one weekly call were included in this secondary analysis (N = 209). Each symptom was categorized as mild, moderate, or severe using established interference-based cut-points. Symptom response meant an improvement by at least one category or remaining mild. Symptom responses were treated as multiple events within patients and analysed using generalized estimating equations technique.
Reflexology was more successful than attention control in producing responses for pain with no significant differences for other symptoms. In the reflexology group, greater probability of response across all symptoms was associated with lower number of comorbid condition and lower depressive symptomatology at baseline. Compared to odds of responses on pain (chosen as a referent symptom), greater odds of symptom response were found for disturbed sleep and difficulty remembering with older aged participants.
Adjusted odds ratios (ORs) of symptom responses for reflexology arm versus control (adjusted for age, number of comorbid conditions, depressive symptoms at baseline, and treatment type: chemotherapy with or without hormonal therapy versus hormonal therapy alone)
Symptom OR (95% CI) p value
Fatigue 1.76 (0.99, 3.12) 0.06
Pain 1.84 (1.05, 3.23) 0.03
Disturbed sleep 1.45 (0.76, 2.77) 0.26
Shortness of breath 0.58 (0.26, 1.30) 0.19
Remembering 0.96 (0.51, 1.78) 0.89
Lack of appetite 1.05 (0.45, 2.49) 0.91
Dry mouth 1.84 (0.86, 3.94) 0.12
Numbness and tingling 1.40 (0.75, 2.64) 0.29
Depression 1.38 (0.78, 2.43) 0.27
The authors concluded that home-based caregiver-delivered reflexology was helpful in decreasing patient-reported pain. Age, comorbid conditions, and depression are potentially important tailoring factors for future research and can be used to identify patients who may benefit from reflexology.
This is certainly one of the more rigorous studies of reflexology. It is well designed and reported. How valid are its findings? To a large degree, this seems to depend on the somewhat unusual statistical approach the investigators employed:
Baseline characteristics were summarized by study group for outcome values and potential covariates. The unit of analysis was patient symptom; multiple symptoms were treated as nested within the patient being analyzed, using methodology described by Given et al. [24] and Sikorskii et al. [17]. Patient symptom responses were treated as multiple events, and associations among responses to multiple symptoms within patients were accounted for by specifying the exchangeable correlation structure in the generalized estimating equations (GEE) model. The GEE model was fitted using the GENMOD procedure in SAS 9.4 [25]. A dummy symptom variable with 9 levels was included in the interaction with the trial arm to differentiate potentially different effects of reflexology on different symptoms. Patient-level covariates included age, number of comorbid conditions, type of treatment (chemotherapy or targeted therapy with or without
hormonal therapy versus hormonal therapy only), and the CES-D score at baseline. Odds ratios (ORs) and their 95% confidence intervals (CIs) were obtained for the essential parameter of study group for each symptom.
Another concern is the fact that the study crucially depended on the reliability of the 256 carers. It is conceivable, even likely, I think, that many carers from both groups were less than strict in adhering to the prescribed protocol. This might have distorted the results in either direction.
Finally, the study was unable to control for the possibly substantial placebo response that a reflexology massage unquestionably provokes. Therefore, we are not able to tell whether the observed effect is due to the agreeable, non-specific effects of touch and foot massages, or to the postulated specific effects of reflexology.
The objective of this RCT was to compare the effects of
- spinal thrust-manipulation + electrical dry needling + various medications (TMEDN-group)
- to non-thrust peripheral joint/soft-tissue mobilization + exercise + interferential current + various medications(NTMEX-group)
on pain and disability in patients with subacromial pain syndrome (SAPS).
Patients with SAPS were randomized into the TMEDN group (n=73) or the NTMEX group (n=72). Primary outcomes included the shoulder pain and disability index (SPADI) and the numeric pain rating scale (NPRS). Secondary outcomes included Global Rating of Change (GROC) and medication intake. The treatment period was 6 weeks; with follow-up at 2 weeks, 4 weeks, and 3 months.
At 3 months, the TMEDN group experienced significantly greater reductions in shoulder pain and disability compared to the NTMEX group. Effect sizes were large in favour of the TMEDN group. At 3 months, a greater proportion of patients within the TMEDN group achieved a successful outcome (GROC≥+5) and stopped taking medication.
The authors concluded that cervicothoracic and upper rib thrust-manipulation combined with electrical dry needling resulted in greater reductions in pain, disability and medication intake than non-thrust peripheral joint/soft-tissue mobilization, exercise and interferential current in patients with SAPS. These effects were maintained at 3 months.
The authors of this trial have impressive looking affiliations:
- American Academy of Manipulative Therapy Fellowship in Orthopaedic Manual Physical Therapy, Montgomery, AL.
- Montgomery Osteopractic Physiotherapy & Acupuncture Clinic, Montgomery, AL.
- Research Physical Therapy Specialists, Columbia, SC.
- Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Alcorcón, Spain.
- Cátedra de Clínica, Investigación y Docencia en Fisioterapia: Terapia Manual, Punción Seca y Ejercicio, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.
- Copper Queen Community Hospital, Bisbee, AZ.
- BenchMark Physical Therapy, Atlanta, GA.
- Eastside Medical Care Center, El Paso, TX.
- Department of Physical Therapy, Georgia State University, Atlanta, GA.
- Tybee Wellness & Osteopractic, Tybee Island, Georgia, GA.
If one expected a well-designed study from all this collective expertise, one would have been disappointed.
Any such clinical trial should be answering a simple question: is therapy XX effective? It is about pinning an observed effect on to a treatment. It is about establishing cause and effect. It is about finding an answer to a clinically relevant question.
The above study does none of that. Even if we accepted its result as valid, it could be interpreted as meaning one of many different things, for instance:
- Acupuncture was effective.
- Dry needling was effective.
- The electrical current was effective.
- Mobilisation made things worse.
- Exercise made things worse.
- one or multiple positive or negative interactions between the therapies.
- The drugs in the experimental group were more effective than those taken by controls.
- The experimental group adhered to their drug prescriptions better than controls.
- Any mixture of the above.
So, the reader of this paper can chose which of the interpretations he or she prefers. I suggest that:
- Any researcher who designs a foreseeably nonsensical trial should go back to school.
- Any ethics committee that passes such a study needs to retire.
- Any funder who gives money for it wastes scarce resources.
- Any reviewer who recommends publication needs to learn about trial design.
- Any editor who publishes such a trial needs to go.
The point I am trying to make is that conducting a clinical trial comes with responsibilities. Poorly designed studies are not just a waste of resources, they are a disservice to patients, they undermine the public’s trust in science and they are unethical.
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!
Research by a reputable independent research company done for Securivita a German insurance company shows that those receiving homeopathic care were much better off. Over 15,700 patients were involved in the study which also used a comparison group.
The study showed that in a wide range of patients with various pathological problems that if they had homeopathic care they faired dramatically better than those just getting conventional medicine.
Children having homeopathy treatment from birth, were particularly healthier and with less problems. Over the three year study period, the number of children needing antibiotics decreased by 16.7 per cent in the homeopathy group, whereby it increased by 73.9 per cent in the conventional medical comparison group!
The number of hospitalizations in the comparison group increased by 32.6 per cent whereby in the homeopathy treatment group it decreased by 9.8 per cent!
Adults and children treated homoeopathically had dramatic improvements in allergies, dermatitis, asthma, just to name a few.
These are just a few examples of the remarkable benefits of homeopathic treatment outlined in the study by by the Leipzig Health Forum , an independent analytical institute specializing in health services conducted for Securvita Krankenkasse Insurer.
“We don’t need fewer, but more homeopathic doctors who will continue on this successful path,” says Götz Hachtmann , director of the health insurance company Securvita.
The study is in German and can be found here.
____________________________
Blessed are those who don’t read German (at least in this instance)!
As I am not amongst the blessed, I ought to tell you a bit about the ‘massive’ study. The OHR, the ‘OFFICIAL HOMEOPATHIC RESOURCE’ (btw what makes the OHR ‘official’?) claims that the study can be found here. The OHR is evidently not well enough resourced for translating the German text into English; if they were, they would know that the link goes not to a ‘study’ but to some kind of a glossy marketing brochure about the ‘study’ (there is no actual published scientific paper on the ‘study’). It provides hardly any relevant information; all we learn is that 15 700 individuals who regularly consulted homeopathic physicians were compared over a three year period to an equally sized control group who did not consult homeopathic doctors… And that’s essentially it! No further relevant details are offered.
By contrast, quite a bit of information is offered about the findings, for instance:
- In the homeopathy group, the hospitalisation rate of depressive patients dropped by 10%, while it increased in controls by 33%.
- The days off work dropped by 17% vs an increase in controls of 17%.
- The use of antibiotics decreased by 17% vs an increase of 74%.
And how do they explain these differences?
Yes, you guessed it:
they are due to homeopathy!
One does not need to have a perfumer’s nose to smell a few badly decomposing rats here, for example:
- We do not learn how many variables were tested in this ‘study’. Therefore, it is likely that the ‘results’ provided are the positive ones, while the not so positive potential effects of homeopathy remained unmentioned. Perhaps the death rate was higher in the homeopathy group? Perhaps they suffered more heart attacks? Perhaps they had a lower quality of life? Perhaps they caused more costs? Perhaps they committed more suicides? etc. etc.
- Even more obvious is the stench of selection bias. The individuals in the homeopathy group were clearly different from the controls to start with. They might have been more health conscious. They clearly were more cautious about antibiotics. They might have been of better general health. They might have been younger. They could have contained more women. They might have been more afraid of going into a hospital. They might have been keener to attend work. In fact, the only variable in which the two groups were comparable is sample size.
Even if we eventually we see this ‘study’ published in a peer-reviewed journal with full methodological details etc., it will not allow even the smartest spin-doctor to establish cause and effect. Its findings would not be more conclusive than those of previously discussed attempts to produce positive evidence for homeopathy. The ‘positive’ findings could have been the result of hundreds of causes, none of which are related to homeopathy.
In a nutshell: this new German ‘study’ is a textbook example for arguing in favour of conducting proper research rather that rampant pseudo-research.
But I must not always be so negative!!!
So, let me try to point out the positive sides of this ‘study’:
The ‘massive independent study’ is a true masterpiece of advertising and marketing for both Securivita and homeopathy.
Well done guys!
I am proud of you!
- That’s exactly the stuff needed for successfully misleading the public.
- That’s precisely the info required to increase your cash flow.
- That’s helpful ‘research’ for convincing politicians.
- That’s definitely the type of baloney to impresses the Ullmanns of this world.
- That’s even the sort of ‘science’ which the ‘OFFICIAL HOMEOPATHIC RESOURCE’ cannot recognise for what it truly is:
invalid junk.
This recent review claimed to evaluate the evidence on the use of human and veterinary homeopathy, evidence level 1a studies were considered. Focusing on the external evidence on the use of homeopathy in infections, some evidence level 1a, 1b, 2c studies, and a case report, are described in more detail.
In conclusion, evidence for the effectiveness of human and veterinary homeopathy in general, and in particular, of homeopathic treatment for infections, is available. Especially, individualized homeopathy demonstrates effects at all quality levels according to Cochrane criteria, even in the methodologically high-quality studies. As in most areas of veterinary medicine and medicine, further good/excellent studies are necessary. In compliance with the principles of homeopathy, further methodologically high-quality trials focusing on the homeopathic treatment of infections are the next logical step. The selection of the simile (individually fitting homeopathic medicinal product) by appropriately trained homeopathic doctors/veterinarians is essential for the effectiveness of homeopathy. Implementation of studies at university facilities is a prerequisite for quality assurance. Consequently, further integration of homeopathy at universities is a necessary requirement for the patients’ best interests.
Who wrote this bizarre paper?
The authors who state to have no conflicts of interest are
