Turmeric is certainly a plant with fascinating properties; we have therefore discussed it before. Reseach into turmeric continues to be active, and I will continue to report about new studies.
This study was aimed at estimating the effect of turmeric supplementation on quality of life (QoL) and haematological parameters in breast cancer patients who were on Paclitaxel chemotherapy. In this case series with 60 participants, QoL was assessed using a standard questionnaire and haematological parameters were recorded from the patients’ hospital records.
Turmeric supplementation for 21 days resulted in clinically relevant and statistically significant improvement in global health status, symptom scores (fatigue, nausea, vomiting, pain, appetite loss, insomnia), and haematological parameters.
The authors concluded that turmeric supplementation improved QoL, brought about symptom palliation and increased hematological parameters in breast cancer patients.
The way the conclusions are phrased, they clearly imply that turmeric caused the observed outcomes. How certain can we be that this is true?
On a scale of 0 -10, I would say 0.
Because there are important other determinants of the outcomes:
- concommittant treatments,
- natural history,
- etc., etc.
Why does this matter?
- Because such unwarranted conclusions mislead patients, healthcare professionals and carers.
- Because such bad science gives a bad name to clinical research.
- Because this type of nonsense might deter meaningful research into a promising subject.
- Because no ‘scientific’ journal should be permitted to publish such nonsense.
- Because it is unethical of ‘scientists’ to make false claims.
But maybe the Indian authors are just a few well-meaning and naive practitioners who merely were doing their unexperienced best? Sadly not! The authors of this paper give the following affiliations:
- Clinical Pharmacology, Pfizer Healthcare Private Limited, Chennai, Tamil Nadu, India.
- Department of Radiation Oncology, Faculty of Medicine, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu, India.
- Process Development, HCL Technologies, Chennai, Tamil Nadu, India.
- Department of Pharmacognosy, Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu, India.
Yes, they really should know better!
Dr Jennifer Jacobs is a homeopaths from the US. She is a family physician and a clinical assistant professor in epidemiology at the University of Washington School of Public Health and Community Medicine. She received her MD degree from Wayne State University and a Masters in Public Health from the University of Washington.
Jennifer is foremost famous for the homeopathic childhood diarhoea studies, but does that justify her joining THE ALTERNATIVE MEDICINE HALL OF FAME with its 15 current members who managed the impossible feast of never publishing a negative conclusion about their pet SCAM:
- Jenise Pellow (homeopath, South Africa)
- Adrian White (acupuncturist, UK)
- Michael Frass (homeopath, Austria)
- Jens Behnke (research officer, Germany)
- John Weeks (editor of JCAM, US)
- Deepak Chopra (entrepreneur, Us)
- Cheryl Hawk (US chiropractor)
- David Peters (osteopathy, homeopathy, UK)
- Nicola Robinson (TCM, UK)
- Peter Fisher (homeopathy, UK)
- Simon Mills (herbal medicine, UK)
- Gustav Dobos (various, Germany)
- Claudia Witt (homeopathy, Germany and Switzerland)
- George Lewith (acupuncture, UK)
- John Licciardone (osteopathy, US)
A Medline search generated 25 papers of hers on homeopathy. Here are the key findings of the … that report original data on the effectiveness of homeopathy (clinical trials or reviews):
- If and when conventional medicine runs out of options for treating epidemic diseases, homeopathy could be seen as an attractive alternative, but only if there is viable experimental evidence of its success.
- The homeopathic syrup appeared to be effective in reducing the severity of cold symptoms in the first day after beginning treatment.
- …the medicines prescribed in individualised homeopathy may have small, specific, treatment effects.
- Homeopathic ear drops may be effective in reducing the use of antibiotics in children with AOM managed with a delayed antibiotic approach.
- This study suggests that homeopathic ear drops were moderately effective in treating otalgia in children with AOM and may be most effective in the early period after a diagnosis of AOM. Pediatricians and other primary health care providers should consider homeopathic ear drops a useful adjunct to standard therapy.
- The homeopathic combination therapy tested in this study did not significantly reduce the duration or severity of acute diarrhea in Honduran children. Further study is needed to develop affordable and effective methods of using homeopathy to reduce the global burden of childhood diarrhea.
- This pilot study provides no evidence to support a therapeutic effect of individually selected homeopathic remedies in children with ADHD. A therapeutic effect of the homeopathic encounter is suggested and warrants further evaluation.
- Small sample size precludes definitive answers, but results from this preliminary trial suggest that homeopathy may be of value in the treatment of menopausal symptoms and improving quality of life, especially in those women not on tamoxifen.
- The results from these studies confirm that individualized homeopathic treatment decreases the duration of acute childhood diarrhea and suggest that larger sample sizes be used in future homeopathic research to ensure adequate statistical power. Homeopathy should be considered for use as an adjunct to oral rehydration for this illness.
- These results suggest that a positive treatment effect of homeopathy when compared with placebo in acute otitis media cannot be excluded and that a larger study is justified.
- These results are consistent with the finding from the previous study that individualized homeopathic treatment decreases the duration of diarrhea and number of stools in children with acute childhood diarrhea.
- The statistically significant decrease in the duration of diarrhea in the treatment group suggests that homeopathic treatment might be useful in acute childhood diarrhea. Further study of this treatment deserves consideration.
Next to Claudia Witt, Jennifer might be the researcher who has published the most clinical trials of homeopathy with positive conclusions (don’t be jealous Michael Frass, you might be in third place!). Attentive readers have probably noticed, she also published a negative trial with a negative conclusion (No 6) and a negative trial with a not so negative conclusion (No 7). The negative study almost cost her the place in the HALL OF FAME. But let’s be generous, and let’s consider the TRUSTWORTHINESS INDEX which, in her case, is still well and safely in the untrustworthy region. Therefore, I hope we all agree: Jenifer does deserve a place in THE ALTERNATIVE MEDICINE HALL OF FAME.
This is an analysis that I have long hesitated to conduct. The reason for my hesitation is simple: some people might think it is vindictive, revengeful or ad hominem. After reflecting about it for years, I have now decided to go ahead with it (sorry, it’s a bit lengthy). This case study is not meant to be vindictive, but offers an important insight into the power of conflicts of interest in SCAM that are not financial but ideological. I think it is crucial that people are aware of and consider such conflicts carefully, and I can’t see how else I might demonstrate my point so plainly.
Dr Adrian White was a co-worker of mine for about 10 years. He became a trusted colleague, my ‘right hand’ man and even my deputy at my Exeter department. When I discovered that my trust had been misplaced, I did not prolong his contract (I will not dwell on this episode, those who are interested find it in my memoir). Adrian then got a senior research fellowship with Prof John Campbell (not my favourite colleague at Exeter) at the department of general practice where he continued his research on acupuncture for about 10 more years largely unsupervised.
Adrian had been an acupuncturist body and soul (in fact, I had never before met anyone so utterly convinced of the value of this therapy). When he joined my team, he was scientifically naive, and we spent many month trying to teach him how to think like a scientist. Initially, he found it very difficult to think critically about acupuncture. Later, I thought the problem was under control. Yet, most of his research in my department was guided by me and tightly supervised (i.e. I made sure that out studies were testing rather than promoting SCAM, and that our reviews were critical assessments of the existing evidence).
Thus there exist two separate and well-documented periods of a pro-acupuncture researcher:
- 10 years guided by me and members of my team;
- 10 years largely unsupervised.
What could be more tempting than to compare Adrian’s output during these two periods?
To do this, I looked up all of Adrian’s 120 publications on acupuncture and selected those 52 articles that generated factual new data (mostly clinical trials or systematic reviews). As it happens, they are numerically distributed almost equally within the two periods. The endpoints for my analysis were the directions of the conclusions of his papers. I therefore extracted, dated, and rated the 52 articles as follows:
- P = positive from the point of view of an acupuncture advocate,
- N = negative from the point of view of an acupuncture advocate.
- P/N = not clearly pointing in either direction.
To render this exercise transparent (occasionally, I was not entirely sure about my ratings), I copied all the 52 conclusions and provided links to the original papers so that anyone inferested is able to check easily.
Here are my findings. Articles 1 – 27 were published AFTER Adrian had left my department; articles 28 – 52 are his papers from the time while he worked with me.
- A definitive three-arm trial is feasible. Further follow-up reminders, minimum data collection and incentives should be considered to improve participant retention in the follow-up processes in the standardised advice and exercise booklet arm. (2016) P/N
- The available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches. Contrary to the previous findings, the updated evidence also suggests that there is an effect over sham, but this effect is small. The available trials also suggest that acupuncture may be at least similarly effective as treatment with prophylactic drugs. Acupuncture can be considered a treatment option for patients willing to undergo this treatment. As for other migraine treatments, long-term studies, more than one year in duration, are lacking. (2016) P
- The available results suggest that acupuncture is effective for treating frequent episodic or chronic tension-type headaches, but further trials – particularly comparing acupuncture with other treatment options – are needed. (2016) P
- Acupuncture during pregnancy appears to be associated with few AEs when correctly applied. (2014) P
- Although pooled estimates suggest possible short-term effects there is no consistent, bias-free evidence that acupuncture, acupressure, or laser therapy have a sustained benefit on smoking cessation for six months or more. However, lack of evidence and methodological problems mean that no firm conclusions can be drawn. Electrostimulation is not effective for smoking cessation. Well-designed research into acupuncture, acupressure and laser stimulation is justified since these are popular interventions and safe when correctly applied, though these interventions alone are likely to be less effective than evidence-based interventions. (2014) P
- The current evidence suggests that acupuncture may have some effects on drug dependence that have been missed because of choice of outcome in many previous studies, and future studies should use outcomes suggested by clinical experience. Body points and electroacupuncture, used in the original clinical observation, justify further research. (2013) P
- Acceptability is very high and may be maximised by taking a number of factors into account: full information should be provided before treatment begins; flexibility should be maintained in the appointment system and different levels of contact between fellow patients should be fostered; sufficient space and staffing should be provided and single-sex groups used wherever possible. (2012) P
- This is the first evaluation of nurse-led group (multibed) acupuncture clinics for patients with knee osteoarthritis to include a 2 year follow-up. It shows the practicability of offering a low-cost acupuncture service as an alternative to knee surgery and the service’s success in providing long-term symptom relief in about a third of patients. Using realistic assumptions, the cost consequences for the local commissioning group are an estimated saving of £100 000 a year. Sensitivity analyses are presented using different assumptions. (2012) P
- There is no consistent, bias-free evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation, but lack of evidence and methodological problems mean that no firm conclusions can be drawn. Further, well designed research into acupuncture, acupressure and laser stimulation is justified since these are popular interventions and safe when correctly applied, though these interventions alone are likely to be less effective than evidence-based interventions. (2011) P/N
- Eight (8) of 10 international acupuncture experts were able to reach consensus on the syndromes, symptoms, and treatment of postmenopausal women with hot flashes. The syndromes were similar to those used by practitioners in the ACUFLASH clinical trial, but there were considerable differences between the acupuncture points. This difference is likely to be the result of differences in approach of training schools, and whether it is relevant for clinical outcomes is not well understood. (2011) P
- 70% of those patients eligible to participate volunteered to do so; all participants had clinically identified MTrPs; a 100% completion rate was achieved for recorded self-assessment data; no serious adverse events were reported as a result of either intervention; and the end of treatment attrition rate was 17%. A phase III study is both feasible and clinically relevant. This study is currently being planned. (2010) P
- In conclusion, the results from all studies are in agreement with the hypothesis that acupuncture needling relieves hot flushes. There are few data however supporting the hypothesis that the effect of acupuncture is point specific. Future research should investigate whether there is a biological effect of needling on hot flushes or not, whether tailored treatment is superior to standardised treatment, and ways of delivering treatment that causes least discomfort and least cost. (2010) P
- Acupuncture can contribute to a more rapid reduction in vasomotor symptoms and increase in health-related quality of life in postmenopausal women but probably has no long-term effects. (2010) P
- within the context of this pilot study, the sham acupuncture intervention was found to be a credible control for acupuncture. This supports its use in a planned, definitive, randomised controlled trial on a similar whiplash injured population. (2009) N/P
- factors other than the TCM syndrome diagnoses and the point selection may be of importance regarding the outcome of the treatment. (2009) N/P
- Acupuncture plus self-care can contribute to a clinically relevant reduction in hot flashes and increased health-related quality of life in postmenopausal women. (2009) P
- the authors conclude that acupuncture could be a valuable non-pharmacological tool in patients with frequent episodic or chronic tension-type headaches. (2009) P
- there is consistent evidence that acupuncture provides additional benefit to treatment of acute migraine attacks only or to routine care. There is no evidence for an effect of ‘true’ acupuncture over sham interventions, though this is difficult to interpret, as exact point location could be of limited importance. Available studies suggest that acupuncture is at least as effective as, or possibly more effective than, prophylactic drug treatment, and has fewer adverse effects. Acupuncture should be considered a treatment option for patients willing to undergo this treatment. (2009) P
- We have conducted the first survey of the effects of provision of acupuncture in UK general practice, using data provided by the NHS, and uncovered a wide variation in the availability of the service in different areas. We have been unable to demonstrate any consistent differences in the prescribing or referral rates that could be due to the use of acupuncture in these practices. The wide variation in the data means that if such a trend exists, a very large survey would be needed to identify it. However, we discovered inaccuracies and variations in presentation of data by the PCTs which have made the numerical input, and hence our results, unreliable. Thus the practicalities of access to data and the problems with data accuracy would preclude a nationwide survey. (2008) P
- In conclusion, there is limited evidence deriving from one study that deep needling directly into myofascial trigger points has an overall treatment effect when compared with standardised care. Whilst the result of the meta-analysis of needling compared with placebo controls does not attain statistically significant, the overall direction could be compatible with a treatment effect of dry needling on myofascial trigger point pain. However, the limited sample size and poor quality of these studies highlights and supports the need for large scale, good quality placebo controlled trials in this area. (2009) P
- We conclude that limited evidence supports acupuncture use in treating pregnancy-related pelvic and back pain. Additional high-quality trials are needed to test the existing promising evidence for this relatively safe and popular complementary therapy. (2008) P
- Acupuncture appears to offer symptomatic improvement to some patients with fibromyalgia in a tertiary clinic who have failed to respond to other treatments. In view of its safety, further acupuncture research is justified in this population. (2007) P
- It is speculated that optimal results from acupuncture treatment for osteoarthritis of the knee may involve: climatic factors, particularly high temperature; high expectations of patients; minimum of four needles; electroacupuncture rather than manual acupuncture, and particularly, strong electrical stimulation to needles placed in muscle; and a course of at least 10 treatments. These factors offer some support to criteria for adequate acupuncture used in the recent review. In addition, ethnic and cultural factors may influence patients’ reporting of their symptoms, and different versions of an outcome measure are likely to differ in their sensitivity – both factors which may lead to apparent rather than real differences between studies. The many variables in a study are likely to be more tightly controlled in a single centre study than in multicentre studies. (2007) P
- Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested. (2007) P
- Auricular acupuncture appears to be effective for smoking cessation, but the effect may not depend on point location. This calls into question the somatotopic model underlying auricular acupuncture and suggests a need to re-evaluate sham controlled studies which have used ‘incorrect’ points. Further experiments are necessary to confirm or refute these observational conclusions. (2006) P
- Acupuncture that meets criteria for adequate treatment is significantly superior to sham acupuncture and to no additional intervention in improving pain and function in patients with chronic knee pain. Due to the heterogeneity in the results, however, further research is required to confirm these findings and provide more information on long-term effects. (2007) P
- There is no consistent evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation, but methodological problems mean that no firm conclusions can be drawn. Further research using frequent or continuous stimulation is justified. (2006) N/P
- Acupuncture is not superior to sham treatment for recovery in activities of daily living and health-related quality of life after stroke, although there may be a limited effect on leg function in more severely affected patients. (2005) N
- The evidence from controlled trials is insufficient to conclude whether acupuncture is an effective treatment for depression, but justifies further trials of electroacupuncture. (2005) N
- Acupuncture effectively relieves chronic low back pain. No evidence suggests that acupuncture is more effective than other active therapies. (2005) N/P
- In view of the small number of studies and their variable quality, doubt remains about the effectiveness of acupuncture for gynaecological conditions. Acupuncture and acupressure appear promising for dysmenorrhoea, and acupuncture for infertility, and further studies are justified. (2003) N
- In conclusion, the results suggest that the procedure using the new device is indistinguishable from the same procedure using real needles in acupuncture naïve subjects, and is inactive, where the specific needle sensation (de qi) is taken as a surrogate measure of activity. It is therefore a valid control for acupuncture trials. The findings also lend support to the existence of de qi, a major concept underlying traditional Chinese acupuncture. (2002) N/P
- There is no clear evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation. (2002) N
- Collectively, these data imply that acupuncture is superior to various control interventions, although there is insufficient evidence to state whether it is superior to placebo. (2002) N/P
- In conclusion, the incidence of adverse events following acupuncture performed by doctors and physiotherapists can be classified as minimal; some avoidable events do occur. Acupuncture seems, in skilled hands, one of the safer forms of medical intervention. (2001) N/P
- Based on the evidence of rigorous randomised controlled trials, there is no compelling evidence to show that acupuncture is effective in stroke rehabilitation. Further, better-designed studies are warranted. (2001) N
- Although it has already been demonstrated that severe adverse events seem to be uncommon in standard practice, many serious cases of negligence have been found in the present review, suggesting that training system for acupuncturists (including medical doctors) should be improved and that unsupervised self-treatment should be discouraged. (2001) N
- Direct needling of myofascial trigger points appears to be an effective treatment, but the hypothesis that needling therapies have efficacy beyond placebo is neither supported nor refuted by the evidence from clinical trials. Any effect of these therapies is likely because of the needle or placebo rather than the injection of either saline or active drug. Controlled trials are needed to investigate whether needling has an effect beyond placebo on myofascial trigger point pain. (2001) N/P
- Although the incidence of minor adverse events associated with acupuncture may be considerable, serious adverse events are rare. Those responsible for establishing competence in acupuncture should consider how to reduce these risks. (2001) N
- In conclusion, this study does not provide evidence that this form of acupuncture is effective in the prevention of episodic tension-type headache. (2000) N
- The present study provides no strong evidence to support the hypothesis that the acupuncture point SP6 is more tender in women and in men. Recommendations for further investigations are discussed. (2000) N
- Acupuncture has not been demonstrated to be efficacious as a treatment for tinnitus on the evidence of rigorous randomized controlled trials. (2000) N
- We conclude that acupuncture continues to be associated with occasional, serious adverse events and fatalities. These events have no geographical limits. Most of these events are due to negligence. Everyone concerned with setting standards, delivering training, and maintaining competence in acupuncture should familiarise themselves with the lessons to be learnt from these untoward events. (2000) N
- Overall, the existing evidence suggests that acupuncture has a role in the treatment of recurrent headaches. However, the quality and amount of evidence is not fully convincing. There is urgent need for well-planned, large-scale studies to assess effectiveness and efficiency of acupuncture under real life conditions. (1999) N/P
- While the frequency of adverse effects of acupuncture is unknown and they may be rare, knowledge of normal anatomy and anatomical variations is essential for safe practice and should be reviewed by regulatory bodies and those responsible for training courses. (1999) N
- In conclusion, the hypothesis that acupuncture is efficacious in the treatment of neck pain is not based on the available evidence from sound clinical trials. Further studies are justified. (1999) N
- Even though all studies are in accordance with the notion that acupuncture is effective for temporomandibular joint dysfunction, this hypothesis requires confirmation through more rigorous investigations. (1999) N
- Acupuncture is not free of risks. All adverse events reported in 1997 would have been avoidable. The absolute number of cases is small, but the degree of underreporting remains unknown. (1999) N
- This form of electroacupuncture is no more effective than placebo in reducing nicotine withdrawal symptoms. (1998) N
- Acupuncture was shown to be superior to various control interventions, although there is insufficient evidence to state whether it is superior to placebo. (1998) N/P
- Considerable variation was observed in the scores awarded by the acupuncture experts. (1998) N
- It is therefore concluded that, according to the data published to date, the evidence that acupuncture is a useful adjunct for stroke rehabilitation is encouraging but not compelling. More and better trials are required to clarify this highly relevant issue. (1996) N
The results are remarkable (particularly considering that one would not expect unbiased studies or reviews of acupuncture to generate plenty of positive conclusions):
0 times N, 5 times N/P, 22 times P – after Adrian had left my department,
17 times N, 7 times N/P, 0 times P – while Adrian worked in my department.
From these figures, it is tempting to calculate the ratios for both periods of negative : positive conclusions:
zero versus infinite
If that is not impressive, I don’t know what is!
Looking just at the positive and the negative papers over the years:
One could discuss these papers in more detail, but I think this is hardly necessary. Just a few highlights perhaps: look at articles No 5, 20 and 27 for examples of turning an essentially negative finding into a positive conclusion. Notice that Adrian conducted a clinical trial of acupuncture for smoking cessation (No 49) while working with me and later published uncritical positive reviews on the subject. Does this not indicate that he distrusted his own study because it had not generated the result he had hoped for?
Of course, my analysis is merely a case study and therefore my findings are not generalisable. However, in my personal experience, the described phenomenon is by no means an exception in SCAM research. I have observed similar phenomena over and over again. Just look at the ALTERNATIVE MEDICINE HALL OF FAME that I created for this blog:
- John Weeks (editor of JCAM)
- Deepak Chopra (US entrepreneur)
- Cheryl Hawk (US chiropractor)
- David Peters (osteopathy, homeopathy, UK)
- Nicola Robinson (TCM, UK)
- Peter Fisher (homeopathy, UK)
- Simon Mills (herbal medicine, UK)
- Gustav Dobos (various, Germany)
- Claudia Witt (homeopathy, Germany and Switzerland)
- George Lewith (acupuncture, UK)
- John Licciardone (osteopathy, US)
But Adrian’s case might be unique because it allows us to make a longitudinal observation over two decades. And it suggests to me that an ideological bias can (and often is) so strong and indistructable that is re-emerges as soon as it is no longer kept under strict control.
I have long suspected that ideological conflicts of interest have a much more powerful influence in SCAM research than financial ones. Such an overpowering influence might even be characteristic to much of SCAM research. And because it can be so dominant, it seems important to know about. People reading research need to be aware that it originates from a biased source, and funders who finance research would be wise to think twice about supporting researchers who are likely to generate findings that are biased and therefore false-positive. In the final analysis, such research is worse than no research at all.
Thirty years ago, I had just been appointed chair of PHYSICAL MEDICINE AND REHABILITATION at the University of Vienna and was about to move – as the first clinical department – into the brand new AKH (General Hospital) of Vienna thus gradually enlarging the team I had taken over from about 20 to 120 co-workers. During this period, I found little time to do original research; however, I did manage to finally write up and publish a study, we had conducted several years before while I was still in Munich. As it is (almost) on the subject of so-called alternative medicine (SCAM), and as it relates to the prevention of a viral infection, I think it might be of interest to give it another outing.
Here is its abstract:
The high morbidity of common colds means that their economic importance is considerable, with colds causing more loss of productivity than any other infection. As no effective prophylaxis is available, this trial was to test the hypothesis that sauna bathing can reduce the incidence of common colds. Twenty-five volunteers were submitted to sauna bathing, with 25 controls abstaining from this or comparable procedures. In both groups the frequency, duration and severity of common colds were recorded for six months. There were significantly fewer episodes of common cold in the sauna group. This was found particularly during the last three months of the study period when the incidence was roughly halved compared to controls. The mean duration and average severity of common colds did not differ significantly between the groups. It is concluded that regular sauna bathing probably reduces the incidence of common colds, but further studies are needed to prove this.
In the discussion section of the paper, we stated the following:
Preventive methods with comparable efficacy have not been described in the literature (2, 12). Vitamin C is of doubtful value (7, 15, 16); vaccination is not feasible since far too many virus types exist (2, 17); virucidal kerchiefs are effective (8, 18) but not available commercially and protect only the environment of a common cold sufferer rather than the sufferer him-/herself.
I believe most of this is still true today (but I might be wrong, as I did not keep up with this particular line of research). Re-reading the paper, I find that our trial was far from optimal:
- we had to conduct it with zero funding,
- it was small,
- it was not randomised,
- it lacked objective endpoints.
Anyway, sauna bathing is most agreeable, and I can recommend it just for this reason. However, I would doubt that public saunas are a good idea during the present health crisis.
Please, stay safe!
In 2012, we published a systematic review of adverse effects of homeopathy. Here is its abstract:
Aim: The aim of this systematic review was to critically evaluate the evidence regarding the adverse effects (AEs) of homeopathy.
Method: Five electronic databases were searched to identify all relevant case reports and case series.
Results: In total, 38 primary reports met our inclusion criteria. Of those, 30 pertained to direct AEs of homeopathic remedies; and eight were related to AEs caused by the substitution of conventional medicine with homeopathy. The total number of patients who experienced AEs of homeopathy amounted to 1159. Overall, AEs ranged from mild-to-severe and included four fatalities. The most common AEs were allergic reactions and intoxications. Rhus toxidendron was the most frequently implicated homeopathic remedy.
Conclusion: Homeopathy has the potential to harm patients and consumers in both direct and indirect ways. Clinicians should be aware of its risks and advise their patients accordingly.
The paper prompted a number of angry reactions from proponents of homeopathy who claimed, for instance, that homeopathic remedies are highly diluted and thus safe. We responded that homeopaths can nevertheless be dangerous to patients through neglect and bad advice by homeopaths, and that not all homeopathic remedies are highly diluted, and that some might be toxic because of poor quality control of the manufacturing process.
Now, a different group of researchers have looked at the problem from a slightly different angle and with different methodologies. This systematic review and meta-analysis by researchers from NAFKAM focused on observational studies, as a substantial amount of the research base for homeopathy are observational.
Eight electronic databases, central webpages and journals were searched for eligible studies, and a total of 1,169 studies were identified, 41 were included in this review. Eighteen studies were included in a meta-analysis that made an overall comparison between homeopathy and control (conventional medicine and herbs).
Eighty-seven percent (n = 35) of the studies reported adverse effects. They were graded as CTCAE 1, 2 or 3 and equally distributed between the intervention and control groups. Homeopathic aggravations (homeopaths believe that, when the optimal remedy is given, patients will experience an aggravation of their presenting symptoms) were reported in 22,5% (n = 9) of the studies and graded as CTCAE 1 or 2. The frequency of adverse effects for control versus homeopathy was statistically significant (P < 0.0001). Analysis of sub-groups indicated that, compared to homeopathy, the number of adverse effects was significantly higher for conventional medicine (P = 0.0001), as well as other complementary therapies (P = 0.05).
The authors concluded that adverse effects of homeopathic remedies are consistently reported in observational studies, while homeopathic aggravations are less documented. This meta-analysis revealed that the proportion of patients experiencing adverse effects was significantly higher when receiving conventional medicine and herbs, compared to patients receiving homeopathy. Nonetheless, the development and implementation of a standardized reporting system of adverse effects in homeopathic studies is warranted in order to facilitate future risk assessments.
While these results are interesting, they have to be taken with a pinch of salt and beg a number of questions:
- Is there proof that aggravations exist at all?
- How can one differentiate them from adverse effects?
- As even placebos are known to cause adverse effects (nocebo effects), how can one be sure that the adverse effects of homeopathy are not nocebo effects?
- Is it a good reason to focus on largely inconclusive observational studies, because a substantial amount of the research base for homeopathy are observational?
- Can one produce conclusive results by meta-analysing inconclusive studies?
For me, the most impressive findings of this review is that in total 86 studies had to be excluded by the authors because they reported no adverse effects or aggravations. I think this renders the interpretation of the evidence from the 41 studies they did include even more flimsy. In fact, I don’t see how any meaningful conclusion can be drawn at all – except of course that many researchers of homeopathy violate the rules of research ethics by not reporting adverse effects in their studies.
As to aggravations, we clearly need to rely on placebo controlled studies, if we want to find out whether they exist at all. This we have done in our 2003 paper:
Homeopathic aggravations have often been described anecdotally. However, few attempts have been made to scientifically verify their existence. This systematic review aimed at comparing the frequency of homeopathic aggravations in the placebo and verum groups of double-blind, randomised clinical trials. Eight independent literature searches were carried out to identify all such trials mentioning either adverse effects or aggravations. All studies thus found were validated and data were extracted by both authors. Twenty-four trials could be included. The average number of aggravations was low. In total, 50 aggravations were attributed to patients treated with placebo and 63 to patients treated with homoeopathically diluted remedies. We conclude that this systematic review does not provide clear evidence that the phenomenon of homeopathic aggravations exists.
What is interesting, from my perspective, is the fact that the NAFKAM authors chose to ignore our 2012 paper completely (even though it is highly relevant to their paper and was not published in an obscure journal) and elected to completely misinterpret the findings of our 2003 paper (stating this about it: Grabia and Ernst reported a total of 103 cases of homeopathic aggravations in 3437 participants (3%), while, in fact, our paper demonstrated that aggravations are a homeopathic figment of imagination).
I wonder why.
In the past, NAFKAM did not have the reputation of doing research that was overtly biased towards homeopathy. Recently, the head of the team retired and was replaced by Miek C. Jong who is a co-author of the present review (plus head of CAMcancer, an organisation of which I am a founding member and which did, I think, some good work in the past). She happens to have a long history as a homeopath or homeopathic researcher and is co-author of many papers in this area. Here are three of her conclusions:
- The prognostic questionnaire proved a reliable tool to rank 11 homeopathic medicines by total scores, based on keynote symptoms. This PMS algorithm can be used for the treatment of PMS/PMDD in clinical practice.
- Both complex homeopathic products led to a comparable reduction of URTIs. In the CalSuli-4-02 group, significantly less URTI-related complaints and symptoms and higher treatment satisfaction and tolerability were detected. The observation that the use of antibiotics was reduced upon treatment with the complex homeopathic medications, without the occurrence of complications, is interesting and warrants further investigations on the potential of CalSuli-4-02 as an antibiotic sparing option.
- Our systematic evaluation demonstrated that the reporting rate of ADRs associated with anthroposophic and homeopathic solutions for injection is very low. Most reported ADRs were listed, and one quarter consisted of local reactions. These findings suggest a low risk profile for solutions for injection as therapeutically applied in anthroposophic medicine and homeopathy.
Could it be that, within NAFKAM, the attitude towards homeopathy has changed?
This systematic review and meta-analysis was aimed at investigating the effect and safety of acupuncture for the treatment of chronic spinal pain.
The authors included 22 randomized controlled trials (RCTs) involving patients with chronic spinal pain treated by acupuncture versus sham acupuncture, no treatment, or another treatment were included. Chronic spinal pain was defined as:
- chronic neck pain,
- chronic low back pain,
- or sciatica for more than 3 months.
Fourteen studies had a high risk of bias, 5 studies had a low risk of bias, and 5 studies had an unclear risk of bias. Pooled analysis revealed that:
- acupuncture can reduce chronic spinal pain compared to sham acupuncture (weighted mean difference [WMD] -12.05, 95% confidence interval [CI] -15.86 to -8.24),
- acupuncture can reduce chronic spinal pain compared to mediation control (WMD -18.27, 95% CI -28.18 to -8.37),
- acupuncture can reduce chronic spinal pain compared to usual care control (WMD -9.57, 95% CI -13.48 to -9.44),
- acupuncture can reduce chronic spinal pain compared to no treatment control (WMD -17.10, 95% CI -24.83 to -9.37).
In terms of functional disability, acupuncture can improve physical function at
- immediate-term follow-up (standardized mean difference [SMD] -1.74, 95% CI -2.04 to -1.44),
- short-term follow-up (SMD -0.89, 95% CI -1.15 to -0.62),
- long-term follow-up (SMD -1.25, 95% CI -1.48 to -1.03).
Trials assessed as having a high risk of bias (WMD −13.45, 95% CI −17.23 to −9.66, I 2 96.2%, moderate-quality evidence, including 14 studies and 1379 patients) found greater effects of acupuncture treatment than trials assessed as having a low risk of bias (WMD −11.99, 95% CI −13.94 to −10.03, I 2 44.6%, high-quality evidence, including 4 studies and 432 patients), but smaller effects than trials assessed as having an unclear risk of bias (WMD −14.51, 95% CI −17.25 to −11.78, I 2 0%, high-quality evidence, including 3 studies and 190 patients).
Only 6 trials provided information on adverse events. No trial reported data on serious adverse events during acupuncture treatment. The most frequent adverse events were temporarily worsened pain and needle pain at the acupuncture site, which can decrease quickly after a short period of rest.
The authors concluded that compared to no treatment, sham acupuncture, or conventional therapy such as medication, massage, and physical exercise, acupuncture has a significantly superior effect on the reduction in chronic spinal pain and function improvement. Acupuncture might be an effective treatment for patients with chronic spinal pain and it is a safe therapy.
I think this is a thorough review which produced interesting findings. I agree with most of what the authors report, except with their conclusions which I find too optimistic. In view of the facts that
- only 5 RCTs had a low risk of bias,
- collectively, the rigorous trials reported smaller effect sizes,
- the majority of trials failed to mention adverse effects which, in my view, casts considerable doubt on their quality and ethical standard,
I would have phrased the conclusion differently: compared to no treatment, sham acupuncture, or conventional therapies, acupuncture seems to have a significantly superior effect on pain and function. Due to the lack rigour of most studies, these effects are less certain than one would have wished. Many trials fail to report adverse effects which reflects poorly on their quality and ethics and prevents conclusions about the safety of acupuncture. In essence, this means that the effectiveness and safety of acupuncture as a treatment of chronic spinal pain remains uncertain.
Bloodletting has been used for centuries in many cultures. Its principle, it was assumed, consisted in re-balancing the body’s four humours. Bloodletting had a detrimental effect on most diseases and must have killed millions. It is a good historical example of the harm that ensues, if healthcare adheres to dogma. Today, we know that bloodletting is useful only in rare conditions such as polycythaemia vera or haemochromatosis (and some 30 years ago, a variation of bloodletting, isovolaemic haemodilution, was being discussed as a treatment for circulatory diseases such as intermittent claudication or stroke).
Yet, in so-called alternative medicine (SCAM), there are some practitioners who seem to find it hard to concede that ancient treatments might be not as good as they think. Thus, bloodletting has survived in this realm as a therapy for a wide range of conditions. This study assessed the efficacy of bloodletting therapy (acupoint pricking and cupping) in patients with chronic idiopathic urticaria (CIU) in a randomized, control, parallel-group trial.
A total of 174 patients with CIU were randomized into three groups:
- group A was treated with bloodletting therapy and ebastine (an anti-histamine),
- group B was treated with placebo treatment (acupoint pseudopricking and cupping) and ebastine,
- group C was treated with ebastine only.
The treatment period lasted 4 weeks. An intention-to-treat analysis was conducted, and the primary outcome was the effective rate of UAS7 score being reduced to 7 or below after treatment phase.
The effective rates at the end of treatment phase were different among the three groups, which were
- 73.7% in group A,
- 45.6% in group B,
- and 42.9% in group C.
Multiple analysis indicated differences between groups A and B (P < 0.0125) and groups A and C (P < 0.0125) and no difference between groups B and C (P > 0.0125). No severe bloodletting therapy-related adverse events were observed.
The authors concluded that one month of bloodletting therapy combined with ebastine is clinically beneficial compared with placebo treatment combined with ebastine and treatment with ebastine only. Thus, bloodletting therapy can be an effective complementary treatment in CIU.
How on earth might bloodletting help for CIU? Luckily, the authors have an answer to this question:
The clinical feature of urticaria with wheals and pruritus coming and going quickly is the manifestation of wind-evil that lurks in and circulates with blood. Hence, in the treatment of urticaria, dispersing wind is the one of the principle methods, and treating blood before wind is an important procedure because when blood flows fluently , wind-evil will resolve spontaneously. Bloodletting therapy is a direct and effective way of regulating blood.
You see, it’s all perfectly clear!
In this case, the results must be true. And the argument that patients might have known in which treatment group they had ended up (and were thus not blinded) can be discarded.
Acupuncture-moxibustion therapy (AMT) is a so-called alternative medicine (SCAM) that has been used for centuries in treatment of numerous diseases. Some enthusiasts even seem to advocate it for chemotherapy-induced leukopenia (CIL) The purpose of this review was to evaluate the efficacy and safety of acupuncture-moxibustion therapy in treating CIL.
Relevant studies were searched in 9 databases up to September 19, 2020. Two reviewers independently screened the studies for eligibility, extracted data, and assessed the methodological quality of selected studies. Meta-analysis of the pooled mean difference (MD) and risk ratio (RR) with their respective 95% confidence intervals (CI) were calculated.
Seventeen studies (1206 patients) were included, and the overall quality of the included studies was moderate. In comparison with medical therapy, AMT has a better clinical efficacy for CIL (RR, 1.24; 95% CI, 1.17-1.32; P < 0.00001) and presents advantages in increasing leukocyte count (MD, 1.10; 95% CI, 0.67-1.53; P < 0.00001). Also, the statistical results show that AMT performs better in improving the CIL patients’ Karnofsky performance score (MD, 5.92; 95% CI, 3.03-8.81; P < 0.00001).
The authors concluded that this systematic review and meta-analysis provides updated evidence that AMT is a safe and effective alternative for the patients who suffered from CIL.
A CIL is a serious complication. If I ever were afflicted by it, I would swiftly send any acupuncturist approaching my sickbed packing.
But this is not an evidence-based attitude!!!, I hear some TCM-fans mutter. What more do you want that a systematic review showing it works?
I beg to differ. Why? Because the ‘evidence’ is hardly what critical thinkers can accept as evidence. Have a look at the list of the primary studies included in this review:
- Lin Z. T., Wang Q., Yu Y. N., Lu J. S. Clinical observation of post-chemotherapy-leukopenia treated with ShenMai injectionon ST36. World Journal of Integrated Traditional and Western Medicine. 2010;5(10):873–876. [Google Scholar]
- Wang H. Clinical Observation of Acupoint Moxibustion on Leukopenia Caused by Chemotherapy. Beijing, China: Beijing University of Chinese Medicine; 2011. [Google Scholar]
- Fan J. Y. Coupling of Yin and Yang between Ginger Moxibustion Improve the Clinical Effect of the Treatment of Chemotherapy Adverse Reaction. Henan, China: Henan University of Chinese Medicine; 2013. [Google Scholar]
- Lu D. R., Lu D. X., Wei M., et al. Acupoint injection with addie injection for patients of nausea and vomiting with cisplatin induced by chemotherapy. Journal of Clinical Acupuncture and Moxibustion. 2013;29(10):33–38. [Google Scholar]
- Yang J. E. The Clinical Observation on Treatment of Leukopenia after Chemotherapy with Needle Warming Moxibustion. Hubei, China: Hubei University of Chinese Medicine; 2013. [Google Scholar]
- Fu Y. H., Chi C. Y., Zhang C. Y. Clinical effect of acupuncture and moxibustion on leukopenia after chemotherapy of malignant tumor. Guide of China Medicine. 2014;12(12) [Google Scholar]
- Wang J. N., Zhang W. X., Gu Q. H., Jiao J. P., Liu L., Wei P. K. Protection of herb-partitioned moxibustion on bone marrow suppression of gastric cancer patients in chemotherapy period. Chinese Archives of Traditional Chinese Medicine. 2014;32(12):110–113. [Google Scholar]
- Zhang J. The Clinical Research on Myelosuppression and Quality of Life after Chemotherapy Treated by Grain-Sized Moxibustion. Nanjing, China: Nanjing University of Chinese Medicine; 2014. [Google Scholar]
- Tian H., Lin H., Zhang L., Fan Z. N., Zhang Z. L. Effective research on treating leukopenia following chemotherapy by moxibustion. Clinical Journal of Chinese Medicine. 2015;7(10):35–38. [Google Scholar]
- Hu G. W., Wang J. D., Zhao C. Y. Effect of acupuncture on the first WBC reduction after chemotherapy for breast cancer. Beijing Journal of Traditional Chinese Medicine. 2016;35(8):777–779. [Google Scholar]
- Zhu D. L., Lu H. Y., Lu Y. Y., Wu L. J. Clinical observation of Qi-blood-supplementing needling for leukopenia after chemotherapy for breast cancer. Shanghai Journal of Acupuncture and Moxibustion. 2016;35(8):964–966. [Google Scholar]
- Chen L, Xu G. Y. Observation on the prevention and treatment of chemotherapy-induced leukopenia by moxibustion therapy. Zhejiang Journal of Traditional Chinese Medicine. 2016;51(8):p. 600. [Google Scholar]
- Mo T., Tian H., Yue S. B., Fan Z. N., Zhang Z. L. Clinical observation of acupoint moxibustion on leukocytopenia caused by tumor chemotherapy. World Chinese Medicine. 2016;11(10):2120–2122. [Google Scholar]
- Nie C. M. Nursing observation of acupoint moxibustion in the treatment of leucopenia after chemotherapy. Today Nurse. 2017;4:93–95. [Google Scholar]
- Wang D. Y. Clinical Research on Post-chemotherapy-leukopenia with Spleen-Kidney Yang Deficiency in Colorectal Cancer Treated with Point-Injection. Yunnan, China: Yunnan University of Chinese Medicine; 2017. [Google Scholar]
- Gong Y. Q, Zhang M. Q, Zhang B. C. Prevention and treatment of leucocytopenia after chemotherapy in patients with malignant tumor with ginger partitioned moxibustion. Chinese Medicine Modern Distance Education of China. 2018;16(21):135–137. [Google Scholar]
- Li Z. C., Lian M. J., Miao F. G. Clinical observation of fuzheng moxibustion combined with wenyang shengbai decoction in the treatment of 80 cases of leukopenia after chemotherapy. Hunan Journal of Traditional Chinese Medicine. 2019;35(3):64–66. [Google Scholar]
Notice anything peculiar?
- The studies are all from China where data fabrication was reported to be rife.
- They are mostly unavailable for checking (why the published adds links that go nowhere is beyond me).
- Many do not look at all like randomised clinical trials (which, according to the authors, was an inclusion criterion).
- Many do not look as though their primary endpoint was the leukocyte count (which, according to the authors, was another inclusion criterion).
Intriguingly, the authors conclude that AMT is not just effective but also ‘safe’. How do they know? According to their own data extraction table, most studies failed to mention adverse effects. And how exactly is acupuncture supposed to increase my leukocyte count? Here is what the authors offer as a mode of action:
I think it is high time that we stop tolerating that the medical literature gets polluted with such nonsense (helped, of course, by journals that are beyond the pale) – someone might actually believe it, in which case it would surely hasten the death of vulnerable patients.
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.