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

case-control study

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This study assessed the effects of being born under the zodiac sign Pisces on mortality. For that purpose, a retrospective observational study was conducted of the data from 26 Scandinavian intensive care units between 2009 and 2011. Patients aged 18 years or older with severe sepsis and in need of fluid resuscitation were included from the Scandinavian Starch for Severe Sepsis/ Septic Shock (6S) trial. The main outcome measure was the 90-day mortality.

The researchers included all 798 patients in the study; 70 (9%) of them were born under the sign of Pisces. The primary outcome (death within 90 days) occurred in 25 patients (35.7%) in the Pisces group, compared with 348 patients (48%) in the non-Pisces group (relative risk, 0.75; 95% CI, 0.54-1.03; one-sided P = 0.03).

The authors concluded that in a multicentre randomised clinical trial of IV fluids, being born under the sign of Pisces was associated with a decreased risk of death. Our study shows that with convenient use of statistics and an enticing explanatory hypothesis, it is possible to achieve significant findings in post-hoc analyses of data from large trials.

This is an excellent paper! It showcases the sort of nonsense one can do with datasets, statistics, and post hoc hypotheses. The authors entitled their article “Gone fishing in a fluid trial”, and this title should ensure that there are not some astrology nutters who mistake correlation for causation

… I hope

… but, of course, I am an optimist.

Vertebral artery dissections (VAD) are a rare but important cause of ischemic stroke, especially in younger patients. Many etiologies have been identified, including motor vehicle accidents, cervical fractures, falls, physical exercise, and, as I have often discussed on this blog, cervical chiropractic manipulation. The goal of this study was to investigate the subgroup of patients who suffered a chiropractor-associated injury and determine how their prognosis compared to other-cause VAD.

The researchers, neurosurgeons from Chicago, conducted a retrospective chart review of 310 patients with vertebral artery dissections who presented at their institution between January 2004 and December 2018. Variables included demographic data, event characteristics, treatment, radiographic outcomes, and clinical outcomes measured using the modified Rankin Scale.

Overall, 34 out of our 310 patients suffered a chiropractor-associated injury. These patients tended to be younger (p = 0.01), female (p = 0.003), and have fewer comorbidities (p = 0.005) compared to patients with other-cause VADs. The characteristics of the injuries were similar, but chiropractor-associated injuries appeared to be milder at discharge and at follow-up. A higher proportion of the chiropractor-associated group had injuries in the 0-2 mRS range at discharge and at 3 months (p = 0.05, p = 0.04) and no patients suffered severe long-term neurologic consequences or death (0% vs. 9.8%, p = 0.05). However, when a multivariate binomial regression was performed, these effects dissipated and the only independent predictor of a worse injury at discharge was the presence of a cervical spine fracture (p < 0.001).

The authors concluded that chiropractor-associated injuries are similar to VADs of other causes, and apparent differences in the severity of the injury are likely due to demographic differences between the two populations.

The authors of the present paper are clear: “chiropractic manipulations are a risk factor for vertebral artery dissections.” This fact is further supported by a host of other investigations. For instance, the Canadian Stroke Consortium found that 28% of strokes following cervical artery dissection were preceded by chiropractic neck manipulation. Dziewas et al. obtained a similar rate in patients with vertebral artery dissections. Many chiropractors are in denial; however, this is merely due to their overt conflicts of interest.

My conclusions from the accumulated evidence are this:

Spinal manipulations of the upper spine should not be routinely used for any condition. Patients who nevertheless insist on having them must be made aware of the risks and give informed consent.

The objective of this systematic review was to examine whether back pain is associated with increased mortality risk and, if so, whether this association varies by age, sex, and back pain severity.

A systematic search of published literature was conducted and English-language prospective cohort studies evaluating the association of back pain with all-cause mortality with follow-up periods >5 years were included. Three reviewers independently screened studies, abstracted data, and appraised risk of bias using the Quality in Prognosis Studies (QUIPS) tool. A random-effects meta-analysis estimated combined odds ratios (OR) and 95% confidence intervals (CI), using the most adjusted model from each study. Potential effect modification by a priori hypothesized factors (age, sex, and back pain severity) was evaluated with meta-regression and stratified estimates.

Eleven studies with a total of 81,337 participants were included. Follow-up periods ranged from 5 to 23 years. The presence of any back pain, compared to none, was not associated with an increase in mortality (OR, 1.06; 95% CI, 0.97 to 1.16). However, back pain was associated with mortality in studies of women (OR, 1.22; 95% CI, 1.02 to 1.46) and among adults with more severe back pain (OR, 1.26; 95% CI, 1.14 to 1.40).

The authors concluded that back pain was associated with a modest increase in all-cause mortality among women and those with more severe back pain.

I bet that back pain is associated with hundreds of things. The question is whether there might be a causal association; could it be that people die earlier BECAUSE of back pain?

Unless someone’s back pain is so unbearable that she commits suicide, I cannot see how the two can be directly linked in a cause/effect relationship. But there could be indirect causal links. For instance, certain cancers can cause both back pain and death. Or someone’s back pain might make him take treatment against a life-threatening condition less seriously and thus hasten his death.

It has also occurred to me that chiropractors might jump on the bandwagon and use the association between back pain and mortality for boosting their business. Something like this:

Back pain is a risk factor for premature death.

Come to us, and we treat your back pain.

This will make you live longer.

Chiropractic prolongs life!

That would, of course, be daft. Firstly, chiropractic is not all that effective for back pain (or anything else). Secondly, getting rid of back pain is unlikely to prolong your life.

Correlation is not causation!

 

Mind-body interventions (MBIs) are one of the top ten so-called alternative medicine (SCAM) approaches utilized in pediatrics, but there is limited knowledge on associated adverse events (AE). The objective of this review was to systematically review AEs reported in association with MBIs in children.

Electronic databases MEDLINE, Embase, CINAHL, CDSR, and CCRCT were searched from inception to August 2018. The authors included primary studies on participants ≤ 21 years of age that used an MBI. Experimental studies were assessed for whether AEs were reported on or not, and all other study designs were included only if they reported an AE.

A total of 441 were included as primary pediatric MBI studies. Of these, 377 (85.5%) did not explicitly report the presence/absence of AEs or a safety assessment. In total, there were 64 included studies: 43 experimental studies reported that no AE occurred, and 21 studies reported AEs. A total of 37 AEs were found, of which the most serious were grade 3. Most of the studies reporting AEs did not report on severity (81.0%) or duration of AEs (52.4%).

The authors concluded that MBIs are popularly used in children; however associated harms are often not reported and lack important information for meaningful assessment.

SCAM is far too often considered to be risk-free. This phenomenon is particularly stark if the SCAM in question does not involve physical or pharmacological treatments. Thus MBIs are seen and often waved through as especially safe. Consequently, many researchers do not even bother to monitor AEs in their clinical trials. This might be understandable, but it is nevertheless a violation of research ethics.

This new review is important in that it highlights these issues. It is high time that we stop giving researchers in SCAM the benefit of the doubt. They may or may not make honest mistakes when not reporting AEs. In any case, it is clear that they are not properly trained and supervised. All too often, we still see clinical trials run by amateurs who have little idea of methodology and even less of ethics. The harm this phenomenon does is difficult to quantify, but I fear it is huge.

Epidemiological studies on the association between coffee intake, arguably a herbal remedy, and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, researchers conducted an umbrella review of existing findings from meta-analyses of observational studies.

They searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, they estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias.

Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10− 6). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I2 ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when the researchers restricted analyses to a meta-analysis of cohort studies.

The authors concluded that there is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites.

This is an interesting analysis that begs many questions. Let me just make four brief points:

  1. Correlation is not causation! Epidemiological studies throw up all sorts of associations that are too often mistaken as causal relationships. The question of whether coffee causes a decrease in the risk of certain cancers is as yet unanswered. The authors mention dose relationships which would, of course, increase the likelihood of a causal effect. Yet, they do not prove it.
  2. Another argument that would strengthen the possibility of a causal effect would be a plausible mechanism of action. However, the biological mechanism of how coffee might affect the risk remains unclear. Coffee contains a range of biologically active chemicals, including caffeine and phenolic compounds. In so-called alternative medicine (SCAM), coffee is also claimed to be a ‘detox‘ remedy. Yet it is unclear how exactly they might reduce the risk.
  3. The studies were all about the oral consumption of coffee. None considered anal application, like in Gerson therapy.
  4. The only way to find out whether coffee does, in fact, reduce the risk of certain cancers is to conduct prospective controlled clinical trials. Such studies are, however, not easy to conduct, particularly if designed such that their findings are truly reliable.

So, the answer to the question DOES COFFEE CONSUMPTION PREVENT CANCER? will remain unanswered for some time, I am afraid. Meanwhile, I suggest we enjoy our coffee per oral (and avoid it per anal).

The use of so-called alternative medicine (SCAM) is common among breast cancer patients, but less is known about whether SCAM influences breast cancer survival. The primary aim of this recent study from Tunesia was to determine the impact of self-use of herbs on the overall survival of women with breast cancer.

The researchers conducted a prospective study including 110 patients with breast cancer. All patients were questioned about their usage of herbal remedies. The demographic data and the overall survival of the patients were then analyzed.

The average age was 51 years (30-80 years old). In total, 37 had metastatic disease (33.6%), and 48 patients had taken plant-based treatments (43.6%). Of those women, 19 patients consumed Graviola (39.6%) and 29 Alenda (60.4%). Overall survival rates at 3 years and at 5 years were 96.2% and 82.4% in the absence of herbal medicine usage versus 78.5% and 78.5% in the presence of herbal medicine use (p = 0.015).

The authors concluded that self-medication with Graviola or Alenda may be associated with an increase of death risk in patients with breast cancer. Further studies are needed to confirm these results.

This is only a small and not very rigorous case-control study. In itself, it would be far from conclusive. What renders it relevant, however, is the fact that its findings do by no means stand alone. We have seen several times on this blog that SCAM use can shorten the life of cancer patients, e.g.:

So, perhaps it is true? Perhaps using SCAM is not such a good idea, if you are suffering from cancer!

The mechanisms of such detrimental effects are not difficult to imagine. They might include direct effects on the cancer, interactions with prescribed drugs, delay of cancer diagnosis, or less strict adherence to the anti-cancer treatments.

 This study aimed to evaluate the effect of Traditional Chinese Medicine (TCM) on patients with gastric cancer following surgery and adjuvant chemotherapy in Taiwan. The cohort sampling data set was obtained from the Registry of Catastrophic Illness Patient Database, a research database of patients with severe illnesses from the National Health Insurance Research Database, Taiwan. Patients who had received a new diagnosis of gastric cancer and had undergone surgery were enrolled. the researchers matched TCM users and nonusers at a ratio of 1 : 3 based on the propensity score, and TCM users were also grouped into short-term and long-term users.

The number of TCM users and nonusers was 1701 and 5103 after applying the propensity score at a ratio of 1 : 3. Short-term users and long-term TCM users were independently associated with a decreased risk of death with HRs of 0.59 (95% confidence interval (CI), 0.55-0.65) and 0.41 (95% CI, 0.36-0.47), respectively, compared with TCM nonusers. The researchers also obtained similar results when they adjusted for covariates in the main model, as well as each of the additional listed covariates. They also observed similar HR trends in short-term users and long-term TCM users among men and women aged <65 years and ≥65 years. The most commonly prescribed single herb and herbal formula in our cohort were Hwang-Chyi (Radix Hedysari; 11.8%) and Xiang-Sha-Liu-Jun-Zi-Tang (15.5%), respectively.

The authors concluded that TCM use was associated with higher survival in patients with gastric cancer after surgery and adjuvant chemotherapy. TCM could be used as a complementary and alternative therapy in patients with gastric cancer after surgery and adjuvant chemotherapy.

This is an interesting study which seems well-done – except for one fatal mistake: even in the title, the authors imply a causal relationship between TCM and survival. Their conclusion has two sentences; the first one speaks correctly of an association. The second, however, not only implies causality but goes much further in suggesting that TCM should be used to prolong the life of patients. Yet, there are, of course, dozens of factors that could interfere with the findings or be the true cause of the observed outcome.

Anyone with a minimum of critical thinking ability should know that CORRELATION IS NOT CAUSATION; sadly, the authors of this study seem to be the exception.

The objective of this survey was to determine

  1. which patients’ characteristics are associated with the use of so-called alternative medicine (SCAM) during cancer treatment,
  2. their pattern of use,
  3. and if it has any association with its safety profile.

A total of 316 patients undergoing chemotherapy treatment in cancer centers in Poland between 2017 and 2019 were asked about their use of SCAM.

Patients’ opinion regarding the safety of unconventional methods is related to the use of SCAM. Moreover, patients’ thinking that SCAM can replace conventional therapy was correlated with his/her education. Moreover, the researchers performed analyses to determine factors associated with SCAM use including sociodemographic and clinical characteristics.

Crucially, they also conducted a survival analysis of patients undergoing chemotherapy with 42 months of follow-up. Using Kaplan-Meier curves and log-rank analysis, they found no statistical difference in overall survival between the groups that used and did not use any form of SCAM.

The authors concluded that SCAM use is common among patients undergoing chemotherapy treatment and should be considered by medical teams as some agents may interact with chemotherapy drugs and affect their efficacy or cause adverse effects.

As I have stated before, I find most surveys of SCAM use meaningless. This article is no exception – except for the survival analysis. It would have merited a separate, more detailed paper, yet the authors hardly comment on it. The analysis shows that SCAM users do not live longer than non-users. Previously, we have discussed several studies that suggested they live less long than non-users.

While this aspect of the new study is interesting, it proves very little. There are, of course, multiple factors involved in the survival of cancer patients, and even if SCAM use were a determinant, it is surely less important than many other factors. To get a better impression of the role SCAM plays, we need studies that carefully match patients according to the most obvious prognostic variables (RCTs would be problematic, difficult to do and unethical). Such studies do exist and they too fail to show that SCAM use prolongs survival, some even suggest it might shorten survival.

I was criticised for not referencing this article in a recent post on adverse effects of spinal manipulation. In fact the commentator wrote: Shame on you Prof. Ernst. You get an “E” for effort and I hope you can do better next time. The paper was published in a third-class journal, but I will nevertheless quote the ‘key messages’ from this paper, because they are in many ways remarkable.

  • Adverse events from manual therapy are few, mild, and transient. Common AEs include local tenderness, tiredness, and headache. Other moderate and severe adverse events (AEs) are rare, while serious AEs are very rare.
  • Serious AEs can include spinal cord injuries with severe neurological consequences and cervical artery dissection (CAD), but the rarity of such events makes the provision of epidemiological evidence challenging.
  • Sports-related practice is often time sensitive; thus, the manual therapist needs to be aware of common and rare AEs specifically associated with spinal manipulative therapy (SMT) to fully evaluate the risk-benefit ratio.

The author of this paper is Aleksander Chaibi, PT, DC, PhD who holds several positions in the Norwegian Chiropractors’ Association, and currently holds a position as an expert advisor in the field of biomedical brain research for the Brain Foundation of the Netherlands. I feel that he might benefit from reading some more critical texts on the subject. In fact, I recommend my own 2020 book. Here are a few passages dealing with the safety of SMT:

Relatively minor AEs after SMT are extremely common. Our own systematic review of 2002 found that they occur in approximately half of all patients receiving SMT. A more recent study of 771 Finish patients having chiropractic SMT showed an even higher rate; AEs were reported in 81% of women and 66% of men, and a total of 178 AEs were rated as moderate to severe. Two further studies reported that such AEs occur in 61% and 30% of patients. Local or radiating pain, headache, and tiredness are the most frequent adverse effects…

A 2017 systematic review identified the characteristics of AEs occurring after cervical spinal manipulation or cervical mobilization. A total of 227 cases were found; 66% of them had been treated by chiropractors. Manipulation was reported in 95% of the cases, and neck pain was the most frequent indication for the treatment. Cervical arterial dissection (CAD) was reported in 57%, and 46% had immediate onset symptoms. The authors of this review concluded that there seems to be under-reporting of cases. Further research should focus on a more uniform and complete registration of AEs using standardized terminology…

In 2005, I published a systematic review of ophthalmic AEs after SMT. At the time, there were 14 published case reports. Clinical symptoms and signs included:

  • central retinal artery occlusion,
  • nystagmus,
  • Wallenberg syndrome,
  • ptosis,
  • loss of vision,
  • ophthalmoplegia,
  • diplopia,
  • Horner’s syndrome…

Vascular accidents are the most frequent serious AEs after chiropractic SMT, but they are certainly not the only complications that have been reported. Other AEs include:

  • atlantoaxial dislocation,
  • cauda equina syndrome,
  • cervical radiculopathy,
  • diaphragmatic paralysis,
  • disrupted fracture healing,
  • dural sleeve injury,
  • haematoma,
  • haematothorax,
  • haemorrhagic cysts,
  • muscle abscess,
  • muscle abscess,
  • myelopathy,
  • neurologic compromise,
  • oesophageal rupture
  • pneumothorax,
  • pseudoaneurysm,
  • soft tissue trauma,
  • spinal cord injury,
  • vertebral disc herniation,
  • vertebral fracture…

In 2010, I reviewed all the reports of deaths after chiropractic treatments published in the medical literature. My article covered 26 fatalities but it is important to stress that many more might have remained unpublished. The cause usually was a vascular accident involving the dissection of a vertebral artery (see above). The review also makes the following important points:

  • … numerous deaths have been associated with chiropractic. Usually high-velocity, short-lever thrusts of the upper spine with rotation are implicated. They are believed to cause vertebral arterial dissection in predisposed individuals which, in turn, can lead to a chain of events including stroke and death. Many chiropractors claim that, because arterial dissection can also occur spontaneously, causality between the chiropractic intervention and arterial dissection is not proven. However, when carefully evaluating the known facts, one does arrive at the conclusion that causality is at least likely. Even if it were merely a remote possibility, the precautionary principle in healthcare would mean that neck manipulations should be considered unsafe until proven otherwise. Moreover, there is no good evidence for assuming that neck manipulation is an effective therapy for any medical condition. Thus, the risk-benefit balance for chiropractic neck manipulation fails to be positive.
  • Reliable estimates of the frequency of vascular accidents are prevented by the fact that underreporting is known to be substantial. In a survey of UK neurologists, for instance, under-reporting of serious complications was 100%. Those cases which are published often turn out to be incomplete. Of 40 case reports of serious adverse effects associated with spinal manipulation, nine failed to provide any information about the clinical outcome. Incomplete reporting of outcomes might therefore further increase the true number of fatalities.
  • This review is focussed on deaths after chiropractic, yet neck manipulations are, of course, used by other healthcare professionals as well. The reason for this focus is simple: chiropractors are more frequently associated with serious manipulation-related adverse effects than osteopaths, physiotherapists, doctors or other professionals. Of the 40 cases of serious adverse effects mentioned above, 28 can be traced back to a chiropractor and none to a osteopath. A review of complications after spinal manipulations by any type of healthcare professional included three deaths related to osteopaths, nine to medical practitioners, none to a physiotherapist, one to a naturopath and 17 to chiropractors. This article also summarised a total of 265 vascular accidents of which 142 were linked to chiropractors. Another review of complications after neck manipulations published by 1997 included 177 vascular accidents, 32 of which were fatal. The vast majority of these cases were associated with chiropractic and none with physiotherapy. The most obvious explanation for the dominance of chiropractic is that chiropractors routinely employ high-velocity, short-lever thrusts on the upper spine with a rotational element, while the other healthcare professionals use them much more sparingly.

Another review summarised published cases of injuries associated with cervical manipulation in China. A total of 156 cases were found. They included the following problems:

  • syncope (45 cases),
  • mild spinal cord injury or compression (34 cases),
  • nerve root injury (24 cases),
  • ineffective treatment/symptom increased (11 cases),
  • cervical spine fracture (11 cases),
  • dislocation or semi-luxation (6 cases),
  • soft tissue injury (3 cases),
  • serious accident (22 cases) including paralysis, deaths and cerebrovascular accidents.

Manipulation including rotation was involved in 42% of all cases. In total, 5 patients died…

To sum up … chiropractic SMT can cause a wide range of very serious complications which occasionally can even be fatal. As there is no AE reporting system of such events, we nobody can be sure how frequently they occur.

[references from my text can be found in the book]

Despite reported widespread use of dietary supplements by cancer patients, few empirical data with regard to their safety or efficacy exist. Because of concerns that antioxidants could reduce the cytotoxicity of chemotherapy, a prospective study was carried out to evaluate associations between supplement use and breast cancer outcomes.

Patients with breast cancer randomly assigned to an intergroup metronomic trial of cyclophosphamide, doxorubicin, and paclitaxel were queried on their use of supplements at registration and during treatment (n =1,134). Cancer recurrence and survival were indexed at 6 months after enrollment.

There were indications that use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment was associated with an increased hazard of recurrence and, to a lesser extent, death. Relationships with individual antioxidants were weaker perhaps because of small numbers. For non-antioxidants, vitamin B12 use both before and during chemotherapy was significantly associated with poorer disease-free survival and overall survival. Use of iron during chemotherapy was significantly associated with recurrence as was use both before and during treatment. Results were similar for overall survival. Multivitamin use was not associated with survival outcomes.

The authors concluded that associations between survival outcomes and use of antioxidant and other dietary supplements both before and during chemotherapy are consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.

These data are interesting but, for a range of reasons, not compelling. There might have been several important confounding factors distorting the findings. Even though clinical and life-style variables were statistically adjusted for in this study, it might still be possible that supplement users and non-users were not comparable in impotant prognostic variables. Simply put, sicker patients might be more likely to use supplements and would then have worse outcomes not because of the supplements but their disease severity.

Moreover, it seems important to note that other research showed the opposite effects. For instance, a study prospectively examined the associations between antioxidant use after breast cancer (BC) diagnosis and BC outcomes in 2264 women. The cohort included women who were diagnosed with early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years postdiagnosis. Baseline data were collected on antioxidant supplement use since diagnosis and other factors. BC recurrence and mortality were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated.

Antioxidant supplement use after diagnosis was reported by 81% of women. Among antioxidant users, frequent use of vitamin C and vitamin E was associated with a decreased risk of BC recurrence. Vitamin E use was associated with a decreased risk of all-cause mortality. Conversely, frequent use of combination carotenoids was associated with increased risk of death from BC and all-cause mortality.

The authors concluded that frequent use of vitamin C and vitamin E in the period after BC diagnosis was associated with a decreased likelihood of recurrence, whereas frequent use of combination carotenoids was associated with increased mortality. The effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant.

Yet another study provided limited support for the hypothesis that antioxidant supplements may reduce the risk of breast cancer recurrence or breast cancer-related mortality.

Confused?

Me too!

What is needed, it seems, is a systematic review of all these contradicting studies. A 2009 review is available of the associations between antioxidant supplement use during breast cancer treatment and patient outcomes.

Inclusion criteria were: two or more subjects; clinical trial or observational study design; use of antioxidant supplements (vitamin C, vitamin E, antioxidant combinations, multivitamins, glutamine, glutathione, melatonin, or soy isoflavones) during chemotherapy, radiation therapy, and/or hormonal therapy for breast cancer as exposures; treatment toxicities, tumor response, recurrence, or survival as outcomes.

A total of 22 articles met the criteria. Their findings did not support any conclusions regarding the effects of individual antioxidant supplements during conventional breast cancer treatment on toxicities, tumor response, recurrence, or survival. A few studies suggested that antioxidant supplements might decrease side effects associated with treatment, including vitamin E for hot flashes due to hormonal therapy and glutamine for oral mucositis during chemotherapy. Underpowered trials suggest that melatonin may enhance tumor response during treatment.

The authors concluded that the evidence is currently insufficient to inform clinician and patient guidelines on the use of antioxidant supplements during breast cancer treatment. Thus, well designed clinical trials and observational studies are needed to determine the short- and long-term effects of such agents.

Still confused?

Me too!

Antioxidants seem to have evolved as parts of elaborate networks in which each substance plays slightly different roles. This means that each antioxidant has a different spectrum of actions. And this means that it is probably not very constructive to lump them all together and excect to see uniform effects. What we would need to create more clarity is a series of RCTs on single antioxidants. But who is going to fund them? We might be waiting a long time for more clarity. Meanwhile, consuming a healthy and well-balanced diet might be the best advice for cancer patients and everyone else.

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