MD, PhD, FMedSci, FRSB, FRCP, FRCPEd

systematic review

I am sure, we have all heard it hundreds of times: THERE ARE IMPORTANT LINKS BETWEEN OUR DIET AND CERTAIN CANCERS. The evidence for this statement seems fairly compelling. Yet it also is complex and often confusing.

A recent review, for instance, suggested that fruits (particularly citrus) and vegetable consumption may be beneficial in the primary prevention of pancreatic cancer, the consumption of whole grains has been shown to reduce the risk and fortification of whole grains with folate may confer further protection. Red meat, cooked at high temperatures, should be avoided, and replaced with poultry or fish. Total fat should be reduced. The use of curcumin and other flavonoids should be encouraged in the diet. Another equally recent review, however, indicated that there is no conclusive evidence as an independent risk factor for isolated nutrients versus adoption of dietary patterns for cancer risk. Cancer colon risk derived from meat intake is influenced by both total intake and its frequency. The interaction of phenolic compounds on metabolic and signalling pathways seems to exert an inhibitory effect on cell proliferation and tumor metastasis and induces apoptosis in various types of cancer cells, including colon, lung, prostate, hepatocellular or breast cancer. A third recent review concluded that cruciferous vegetable intake protects against cancer of the colon, while a forth review suggested that the Mediterranean dietary pattern and diets composed largely of vegetables, fruit, fish, and soy are associated with a decreased risk of breast cancer. There was no evidence of an association between traditional dietary patterns and risk of breast cancer.

Not least based on these mixed messages from the scientific literature, an entire industry has developed selling uncounted alternative cancer-diets and dietary supplements to desperate patients and consumers. They promise much more than just cancer prevention, in fact, leave little doubt about the notion that cancer might be curable by diet. Here are just a few quotes from the thousands of websites promoting alternative cancer diets:

  • The Ketogenic Diet is believed capable of starving cancer cells to death, and thus capable of restricting tumour development.
  • a more alkaline body makes it difficult for tumors to grow.
  • Budwig diet: This diet was developed by Dr. Johanna Budwig who was nominated for the noble Prize sixth times. The diet is intended as a preventative as well as an alternative cancer treatment.
  • the Gerson Therapy naturally reactivates your body’s magnificent ability to heal itself – with no damaging side effects. This a powerful, natural treatment boosts the body’s own immune system to heal cancer, arthritis, heart disease, allergies, and many other degenerative diseases. Dr. Max Gerson developed the Gerson Therapy in the 1930s, initially as a treatment for his own debilitating migraines, and eventually as a treatment for degenerative diseases such as skin tuberculosis, diabetes and, most famously, cancer.
  • the concept of macrobiotics is much more than an alternative diet for cancer, or any other illness, but rather the ancient Chinese belief that all life, indeed the whole universe, is a balance of two opposing forces Yin and Yang.

Confused? Yes, I do worry how many cancer patients listen to these claims and pin their hopes on one of these diets. But what exactly does the evidence tell us about them?

A German team of researchers evaluated the following alternative cancer-diets: raw vegetables and fruits, alkaline diet, macrobiotics, Gerson’s regime, Budwig’s and low carbohydrate or ketogenic diet. Their extensive searches of the published literature failed to find clinical evidence supporting any of the diets. Furthermore, case reports and pre-clinical data pointed to the potential harm of some of these diets. The authors concluded that considering the lack of evidence of benefits from cancer diets and potential harm by malnutrition, oncologists should engage more in counselling cancer patients on such diets.

In other words, alternative cancer diets – and I mean not just the ones mentioned above, but all of them – are not supported by good evidence for efficacy as a treatment or prevention of any type of cancer. In addition, they might also cause harm.

What follows is obvious: cancer patients should take sound nutritional advice and adopt a healthy general life-style. But they should run a mile as soon as anyone suggests an alternative dietary cure for their disease.

There is not a discussion about homeopathy where an apologist would eventually state: HOMEOPATHY CANNOT BE A PLACEBO, BECAUSE IT WORKS IN ANIMALS!!! Those who are not well-versed in this subject tend to be impressed, and the argument has won many consumers over to the dark side, I am sure. But is it really correct?

The short answer to this question is NO.

Pavlov discovered the phenomenon of ‘conditioning’ in animals, and ‘conditioning’ is considered to be a major part of the placebo-response. So, depending on the circumstances, animals do respond to placebo (my dog, for instance, used to go into a distinct depressive mood when he saw me packing a suitcase).

Then there is the fact that the animal’s response might be less important than the owner’s reaction to homeopathic treatment. This is particularly important with pets, of course. Homeopathy-believing pet owners might over-interpret the pet’s response and report that the homeopathic remedy has worked wonders when, in fact, it has made no difference.

Finally, there may be some situations where neither of the above two phenomena can play a decisive role. Homeopaths like to cite studies where entire herds of cows were treated homeopathically to prevent mastitis, a common problem in milk-cows. It is unlikely that conditioning or wishful thinking of the owner are decisive in such a study. Let’s see whether homeopathy-promoters will also be fond of this new study of exactly this subject.

New Zealand vets compared clinical and bacteriological cure rates of clinical mastitis following treatment with either antimicrobials or homeopathic preparations. They used 7 spring-calving herds from the Waikato region of New Zealand to source cases of clinical mastitis (n=263 glands) during the first 90 days following calving. Duplicate milk samples were collected for bacteriology from each clinically infected gland at diagnosis and 25 (SD 5.3) days after the initial treatment. Affected glands were treated with either an antimicrobial formulation or a homeopathic remedy. Generalised linear models with binomial error distribution and logit link were used to analyse the proportion of cows that presented clinical treatment cures and the proportion of glands that were classified as bacteriological cures, based on initial and post-treatment milk samples.

The results show that the mean cumulative incidence of clinical mastitis was 7% (range 2-13% across herds) of cows. Streptococcus uberis was the most common pathogen isolated from culture-positive samples from affected glands (140/209; 67%). The clinical cure rate was higher for cows treated with antimicrobials (107/113; 95%) than for cows treated with homeopathic remedies (72/114; 63%) (p<0.001) based on the observance of clinical signs following initial treatment. Across all pathogen types bacteriological cure rate at gland level was higher for those cows treated with antimicrobials (75/102; 74%) than for those treated with a homeopathic preparation (39/107; 36%) (p<0.001).

The authors conclude that homeopathic remedies had significantly lower clinical and bacteriological cure rates compared with antimicrobials when used to treat post-calving clinical mastitis where S. uberis was the most common pathogen. The proportion of cows that needed retreatment was significantly higher for the homeopathic treated cows. This, combined with lower bacteriological cure rates, has implications for duration of infection, individual cow somatic cell count, costs associated with treatment and animal welfare.

Yes, I know, this is just one single study, and we need to consider the totality of the reliable evidence. Currently, there are 203 clinical trials of homeopathic treatments of animals; and they are being reviewed at the very moment (unfortunately by a team that is not known for its objective stance on homeopathy). So, we will have to wait and see. When, in 1999, A. Vickers reviewed all per-clinical studies, including those on animals, he concluded that there is a lack of independent replication of any pre-clinical research in homoeopathy. In the few instances where a research team has set out to replicate the work of another, either the results were negative or the methodology was questionable.

All this is to say that, until truly convincing evidence to the contrary is available, the homeopaths’ argument ‘HOMEOPATHY CANNOT BE A PLACEBO, BECAUSE IT WORKS IN ANIMALS!!!’ is, in my view, as weak as the dilution of their remedies.

One of the questions I hear regularly is ‘HOW DO THE EFFECTS OF THIS ALTERNATIVE TREATMENT COMPARE TO THOSE OF CONVENTIONAL OPTIONS’? Take acupuncture in the management of osteoarthritis, for instance. There is some encouraging evidence suggesting it might help. The most recent systematic review that I know of concluded that “acupuncture provided significantly better relief from knee osteoarthritis pain and a larger improvement in function than sham acupuncture, standard care treatment, or waiting for further treatment.” However, in order to estimate its value in practice, we ought to know whether it is as good as or perhaps even better than standard treatments. In other words, what we really want to know is its relative effectiveness.

Data to evaluate the relative effectiveness of acupuncture or other alternative therapies are hard to come by. Ideally, one would require clinical trials which provide direct comparisons between the alternative and the conventional therapy. Sadly, such studies are scarce or even non-existent. Therefore we might have to rely on more indirect evidence. A new paper could be a step in the right direction.

The aim of this systematic review was to critically evaluate existing osteoarthritis (OA) management guidelines to better understand potential issues and barriers.

A systematic review of the literature in MEDLINE published from January 1, 2000 to April 1, 2013 was performed and supplemented by bibliographic reviews, following PRISMA guidelines and a written protocol. Following initial title and abstract screening, two authors independently reviewed full-text articles; a third settled disagreements. Two independent reviewers extracted data into a standardized form. Two authors independently assessed guideline quality; three generated summary recommendations based on the extracted guideline data.

Overall, 16 articles were included in the final review. There was broad agreement on recommendations by the various organizations. For non-pharmacologic modalities, education/self-management, exercise, weight loss if overweight, walking aids as indicated, and thermal modalities were widely recommended. For appropriate patients, joint replacement was recommended; arthroscopy with debridement was not recommended for symptomatic knee OA. Pharmacologic modalities most recommended included acetaminophen/paracetamol for first line treatment and oral or topical NSAIDs for second line therapy. Intra-articular corticosteroids were generally recommended for hip and knee OA. Controversy remains about the use of acupuncture, knee braces, heel wedges, intra-articular hyaluronans, and glucosamine/chondroitin.

I think that this tells us fairly clearly that, compared to other options, acupuncture is not considered to be an overwhelmingly effective treatment for osteoarthritis by those who understand that condition best. Several other therapies seem to be preferable because the evidence is clearer and stronger and their effect sizes is larger. This, I think begs the question whether it is in the best interest of patients or indeed ethical to ignore this knowledge and recommend acupuncture as a treatment of osteoarthritis.

More generally speaking, we should always bear in mind that it is not enough proving a therapy to be effective; we usually also need to consider what else is on offer. And if you think that this is rather complex, you are, of course, correct – but wait until someone mentions issues such as safety and cost of all the relevant therapeutic options.

Cancer patients are understandably desperate and leave no stone unturned to improve their prognosis. Thus they become easy prey of charlatans who claim that this or that alternative therapy will cure them or improve their outlook. One of the most popular alternative cancer therapies is mistletoe, a treatment dreamt up by Rudolf Steiner on the basis of the ‘like cures like’ principle: the mistletoe plant grows on a host tree like a cancer in the human body. One of many websites on this subject, for instance, states:

Mistletoe therapy

  • integrates with conventional cancer treatments
  • can be used for a wide range of cancers
  • may be started at any stage of the illness….

potential benefits…include:

  • Improved quality of life
  • generally feeling better
  • increased appetite and weight
  • less tired/more energy
  • reduced pain
  • better sleep pattern
  • felling more hopeful and motivated
  • reduced adverse effects from chemo and radiotherapy
  • reduced risk of cancer spread and recurrence
  • increased life expectancy.

Mistletoe extracts have been shown in studies to:

  • stimulate the immune system
  • cause cancer cell death
  • protect healthy cells against harmful effects of radiation and chemotherapy.

In fact, the debate about the efficacy of mistletoe either as a cancer cure, a supportive therapy, or a palliative measure is often less than rational and seems never-ending.

The latest contribution to this saga comes from US oncologists who published a phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC). The trial was aimed at evaluating: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM.

A total of 44 study participants were enrolled; 20 were treated in stage I (mistletoe dose escalation phase) and 24 in stage II (gemcitabine dose escalation phase). All patients had stage IV disease; the majority had received previous chemo-, hormonal, immunological, or radiation therapy, and 23% were chemotherapy-naïve.

Patients were treated with increasing doses of a mistletoe-extract (HELIXOR Apis (A), growing on fir trees) plus a fixed GEM dose in stage I, and with increasing doses of GEM plus a fixed dose of mistletoe in stage II. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery.

The results show that dose-limiting toxicities were neutropenia, thrombocytopenia, acute renal failure, and cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of the 44 patients, 24 developed non-neutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation.

6% of patients showed a partial response, and 42% had stable disease. Of the 44 study participants, three died during the study, 10 participants requested to terminate the study, 23 participants progressed while on study, one terminated the study due to a dose limiting toxicity, 6 left due to complicating disease issues which may be tied to progression, and one voluntarily withdrew.

An attempt was made to follow study subjects once they terminated study treatment until death. At the last attempt to contact former participants, three were still alive and five others were lost to follow-up. The median time to death of any cause was approximately 200 days. Compliance with mistletoe injections was high.

The authors explain that a partial response rate of 6% is comparable to what would be expected from single agent gemcitabine in this population of patients with advanced, mostly heavily pretreated carcinomas. The median survival from study enrollment of about 200 days is within the range of what would be expected from single agent gemcitabine.

The authors concluded that GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response  is similar to GEM alone.

These results are hardly encouraging but they originate from just one (not particularly rigorous) study and might thus not be reliable. So, what does the totality of the reliable evidence tell us? Our 2003 systematic review of 10 RCTs found that none of the methodologically stronger trials exhibited efficacy in terms of quality of life, survival or other outcome measures. Rigorous trials of mistletoe extracts fail to demonstrate efficacy of this therapy.

Will this stop the highly lucrative trade in mistletoe extracts? will it prevent desperate cancer patients being misled about the value of mistletoe treatment? I fear not.

Times of celebration are often also times of over-indulgence and subsequent suffering. Who would not know, for instance, how a hangover can spoil one’s pleasure at the start of a new year? But where is the research that addresses this problem? Scientists seem to be cynically devoid of sympathy for the hangover-victim – well, not all scientists.

During the course of my research-career, I must have conducted well over 60 clinical trials, but none was remotely as entertaining as the one my Exeter-team did several years ago to test whether an artichoke extract is effective in preventing the signs and symptoms of alcohol-induced hangover.

We recruited healthy adult volunteers from our own ranks to participate in a randomized double-blind crossover trial. Participants received either 3 capsules of commercially available standardized artichoke extract or indistinguishable, inert placebo capsules immediately before and after alcohol exposure. After a 1-week washout period the volunteers received the opposite treatment. Each participant predefined the type and amount of alcoholic beverage that would give him/her a hangover and ate the same meal before commencing alcohol consumption on the two study days. The primary outcome measure was the difference in hangover severity scores between the artichoke extract and placebo interventions. Secondary outcome measures were differences between the interventions in scores using a mood profile questionnaire and cognitive performance tests administered 1 hour before and 10 hours after alcohol exposure.

The mean number of alcohol units consumed per person during treatment with artichoke extract and placebo were  10.7 and 10.5 respectively, equivalent to 1.2 g of alcohol per kilogram body weight. The volume of non-alcoholic drink consumed and the duration of sleep after the binge were similar during the artichoke extract and placebo interventions. The hangovers we experienced the mornings after our alcohol exposure were monumental but unaffected by the treatments. None of the outcome measures differed significantly between interventions. Adverse events of the treatment were rare and were mild and transient. Our results therefore suggested that artichoke extract is not effective in preventing the signs and symptoms of alcohol-induced hangover.

While it was great fun to obtain ethic’s approval and run this trial, the results of our two binges in the name of science were, of course, a disappointment. As diligent researchers we felt we had to do a little more for the poor victims of over-indulgence.

We thus decided to conduct a systematic review aimed at assessing the clinical evidence on the effectiveness of any medical intervention for preventing or treating alcohol hangover. We conducted systematic searches to identify all RCTs of any medical intervention for preventing or treating alcohol hangover. Fifteen potentially relevant trials were found. Seven publications failed to meet all inclusion criteria. Eight RCTs assessing 8 different interventions were reviewed. The agents tested were propranolol, tropisetron, tolfenamic acid, fructose or glucose as well as the dietary supplements Borago officinalis (borage), Cynara scolymus (artichoke), Opuntia ficus-indica (prickly pear), and a yeast based preparation. All studies were double blind. Significant intergroup differences for overall symptom scores and individual symptoms were reported only for tolfenamic acid, gamma linolenic acid from borage, and a yeast based preparation.

We concluded that the most effective way to avoid the symptoms of alcohol induced hangover is to practise abstinence or moderation.

WISE WORDS PERHAPS, BUT EASIER SAID THAN DONE, I’M SURE.

Many dietary supplements are heavily promoted for the prevention of chronic diseases, including cardiovascular disease (CVD) and cancer. But do they actually work or are they just raising false hopes? The evidence on this subject is confusing and proponents of both camps produce data which seemingly support their claims. In this situation, we need an independent analysis of the totality of the evidence to guide us. And one such review has just become available

The purpose of this article was to systematically review evidence for the use of multivitamins or single nutrients and functionally related nutrient pairs for the primary prevention of CVD and cancer in the general population.

The authors searched 5 databases to identify literature that was published between 2005 and January 29, 2013. They also examined the references from the previous reviews and other relevant articles to identify additional studies. In addition, they searched Web sites of government agencies and other organizations for grey literature. Two investigators independently reviewed identified abstracts and full-text articles against a set of a priori inclusion and quality criteria. One investigator abstracted data into an evidence table and a second investigator checked these data. The researchers then qualitatively and quantitatively synthesized the results for 4 key questions and grouped the included studies by study supplement. Finally, they conducted meta-analyses using Mantel-Haenzel fixed effects models for overall cancer incidence, CVD incidence, and all-cause mortality.

103 articles representing 26 unique studies met the inclusion criteria. Very few studies examined the use of multivitamin supplements. Two trials showed a protective effect against cancer in men; only one of these trials included women and found no effect. No effects of treatment were seen on CVD or all-cause mortality.

Beta-carotene showed a negative effect on lung cancer incidence and mortality among individuals at high risk for lung cancer at baseline (i.e., smokers and asbestos-exposed workers); this effect was persistent even when combined with vitamin A or E. Trials of vitamin E supplementation showed mixed results and altogether had no overall effect on cancer, CVD, or all-cause mortality. Only one of two studies included selenium trials showed a beneficial effect for colorectal and prostate cancer; however, this trial had a small sample size. The few studies addressing folic acid, vitamin C, and vitamin A showed no effect on CVD, cancer, and mortality. Vitamin D and/or calcium supplementation also showed no overall effect on CVD, cancer, and mortality. Harms were infrequently reported and aside from limited paradoxical effects for some supplements, were not considered serious.

The authors’ conclusion are less than encouraging: there are a limited number of trials examining the effects of dietary supplements on the primary prevention of CVD and cancer; the majority showed no effect in healthy populations. Clinical heterogeneity of included studies limits generalizability of results to the general primary care population. Results from trials in at-risk populations discourage additional studies for particular supplements (e.g., beta-carotene); however, future research in general primary care populations and on other supplements is required to address research gaps.

A brand-new RCT provides further information, specifically on the question whether oral multivitamins are effective for the secondary prevention of cardiovascular events. In total, 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier with elevated serum creatinine levels were randomly assigned to an oral, 28-component, high-dose multivitamin and multi-mineral mixture or placebo. The primary end point was time to death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. Median follow-up was 55 months. Patients received treatments for a median of 31 months in the vitamin group and 35 months in the placebo group. 76% and 76% patients in the vitamin and placebo groups completed at least 1 year of oral therapy, and 47% and 50% patients completed at least 3 years. Totals of 46% and 46% patients in both groups discontinued the vitamin regimen, and 17% of patients withdrew from the study.

The primary end point occurred in 27% patients in the vitamin group and 30% in the placebo group. No evidence suggested harm from vitamin therapy in any category of adverse events. The authors of this RCT concluded that high-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate.

These findings are sobering and in stark contrast to what the multi-billion dollar supplement industry promotes. The misinformation in this area is monumental. Here is what one site advertises for heart disease:

Vitamin C could be helpful, limit dosage to 100 to 500 mg a day.

Vitamin E works better with CoQ10 to reduce inflammation in heart disease. Limit vitamin E to maximum 30 to 200 units a few times a week. Use a natural vitamin E complex rather than synthetic products.

CoQ10 may be helpful in heart disease, especially in combination with vitamin E. I would recommend limiting the dosage of Coenzyme Q10 to 30 mg daily or 50 mg three or four times a week.

B complex vitamins reduce levels of homocysteine. Keep the vitamin B dosages low, perhaps one or two times the RDA. Taking higher amounts may not necessary be a healthier approach.

Curcumin protects rat heart tissue against damage from low oxygen supply, and the protective effect could be attributed to its antioxidant properties. Curcumin is derived from turmeric, which is often used in curries.

Garlic could be an effective treatment for lowering cholesterol and triglyceride levels for patients with a history or risk of cardiovascular disease, especially as a long term strategy.

Terminalia arjuna, an Indian medicinal plant, has been reported to have beneficial effects in patients with ischemic heart disease in a number of small studies. Arjuna has been tested in angina and could help reduce chest pain.
Magnesium is a mineral that could help some individuals. It is reasonable to encourage diets high in magnesium as a potential means to lower the risk of coronary heart disease.

Danshen used in China for heart conditions.

And in the area of cancer, the choice is even more wide and audacious as this web-site for example demonstrates.

So, the picture that emerges from all this seems fairly clear. Despite thousands of claims to the contrary, dietary supplements are useless in preventing cardiovascular diseases or cancer. All they do produce, I am afraid, is rather expensive urine.

Hypercholesterolemia is an important, independent risk factor for cardiovascular disease, according to a generally accepted wisdom. Measures to normalise elevated blood lipids include diet, exercise and drugs, of which statins are the most widely prescribed. But many people have become somewhat sceptical about the wide-spread use of statins: Traditionally, doctors have viewed statin drugs as the most effective way to lower high LDL cholesterol. But today researchers are starting to believe that statins may not be the magic bullet they’ve always been made out to be. Statins can cause severe adverse effects and some experts have questioned whether they generate more benefit than harm and suggested that ‘BIG PHARMA’ are pushing statins not for the benefit of public health but for maximising profit.

This begs the question: is there an alternative?

This RCT tested the efficacy of a dietary supplement providing 1.8 g/day esterified plant sterols and stanols to improve the fasting lipid profile of men and women with primary hypercholesterolemia. Repeated measures analysis of covariance was used to compare outcomes for sterol/stanol and placebo treatment conditions using the baseline value as a covariate. Thirty subjects were randomized and all of them completed the trial.

Baseline (mean±standard error of the mean) plasma lipid concentrations were: total cholesterol 236.6±4.2 mg/dL (6.11±0.11 mmol/L), high-density lipoprotein (HDL) cholesterol 56.8±3.0 mg/dL (1.47±0.08 mmol/L), LDL cholesterol 151.6±3.3 mg/dL (3.92±0.09 mmol/L), non-HDL cholesterol 179.7±4.6 mg/dL (4.64±0.12 mmol/L), and triglycerides 144.5±14.3 mg/dL (1.63±0.16 mmol/L). Mean placebo-adjusted reductions in plasma lipid levels were significant (P<0.01) for LDL cholesterol (-4.3%), non-HDL cholesterol (-4.1%), and total cholesterol (-3.5%), but not for triglycerides or HDL cholesterol.

The authors conclude that these results support the efficacy of 1.8 g/day esterified plant sterols/stanols in softgel capsules, administered as an adjunct to the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to augment reductions in atherogenic lipid levels in individuals with hypercholesterolemia.

These findings are encouraging but certainly not rock solid. The study was too small, and the effect sizes were less than impressive. A brand-new systematic review, however, provides much more convincing data.

Its aim was to quantify the LDL-cholesterol-lowering effect of plant sterols/stanols as supplements. Eight eligible clinical trials were identified. Among the trials with a duration between 4 and 6 weeks, plant sterol/stanol dose ranged from 1.0 to 3.0 g/day administrated mainly with the main meals (2 or 3 times/day). Intake of plant sterol/stanol supplements decreased LDL-cholesterol concentrations by 12 mg/dL (0.31 mmol/L) compared with placebo. Further analysis showed no significant difference between the LDL-cholesterol-lowering action of plant sterols/stanols supplements vs foods enriched with plant sterols/stanols. The authors concluded that plant sterol/stanol supplements as part of a healthy diet represent an effective means of delivering LDL-cholesterol-lowering similar to plant sterols/stanols delivered in various food formats.

Crucially, this positive verdict does not stand alone. Another recent review included 5 trials and concluded that a dose-effect relationship of plant stanols in higher doses than currently recommended has been demonstrated by recent clinical studies and a meta-analysis.

Plant sterols seem to be not just effective but also safe: none of the trials published to date reported significant adverse effects. The only concern is the potential decrease in the concentrations of lipid-soluble antioxidants and vitamins, including β-carotene, α-tocopherol, lutein, and α-carotene. It is currently not clear whether these effects are clinically relevant.

The relative merits of phytosterols versus statins are not easy to evaluate. We have hundreds of studies of statins but just a few of sterols. This means our knowledge in this area is incomplete. Statins can cause serious adverse effects but their effects on blood lipids is about one order of magnitude larger that those of sterols. There is plenty of evidence to show that statins lower the risk of cardiovascular disease, while such data are missing for phytosterols.

The choice between statins and plant sterols is thus not easy, particularly considering the often emotional arguments and hype used in the ‘cholesterol-debate’. Phytosterols offer one more alternative therapy for lowering LDL-cholesterol levels. They seem safe and have the added attraction of being ‘natural’ – but the lipid-effects are relatively small, the impact on cardiovascular morbidity and mortality is uncertain, and fairly high doses are required to see any lipid-lowering at all.

There are numerous types and styles of acupuncture, and the discussion whether one is better than the other has been long, tedious and frustrating. Traditional acupuncturists, for instance, individualise their approach according to their findings of pulse and tongue diagnoses as well as other non-validated diagnostic criteria. Western acupuncturists, by contrast, tend to use formula or standardised treatments according to conventional diagnoses.

This study aimed to compare the effectiveness of standardized and individualized acupuncture treatment in patients with chronic low back pain. A single-center randomized controlled single-blind trial was performed in a general medical practice of a Chinese-born medical doctor trained in both western and Chinese medicine. One hundred and fifty outpatients with chronic low back pain were randomly allocated to two groups who received either standardized acupuncture or individualized acupuncture. 10 to 15 treatments based on individual symptoms were given with two treatments per week.

The main outcome measure was the area under the curve (AUC) summarizing eight weeks of daily rated pain severity measured with a visual analogue scale. No significant differences between groups were observed for the AUC (individualized acupuncture mean: 1768.7; standardized acupuncture 1482.9; group difference, 285.8).

The authors concluded that individualized acupuncture was not superior to standardized acupuncture for patients suffering from chronic pain.

But perhaps it matters whether the acupuncturist is thoroughly trained or has just picked up his/her skills during a weekend course? I am afraid not: this analysis of a total of 4,084 patients with chronic headache, lower back pain or arthritic pain treated by 1,838 acupuncturists suggested otherwise. There were no differences in success for patients treated by physicians passing through shorter (A diploma) or longer (B diploma) training courses in acupuncture.

But these are just one single trial and one post-hoc analysis of another study which, by definition, cannot be fully definitive. Fortunately, we have more evidence based on much larger numbers. This brand-new meta-analysis aimed to evaluate whether there are characteristics of acupuncture or acupuncturists that are associated with better or worse outcomes.

An existing dataset, developed by the Acupuncture Trialists’ Collaboration, included 29 trials of acupuncture for chronic pain with individual data involving 17,922 patients. The available data on characteristics of acupuncture included style of acupuncture, point prescription, location of needles, use of electrical stimulation and moxibustion, number, frequency and duration of sessions, number of needles used and acupuncturist experience. Random-effects meta-regression was used to test the effect of each characteristic on the main effect estimate of pain. Where sufficient patient-level data were available, patient-level analyses were conducted.

When comparing acupuncture to sham controls, there was little evidence that the effects of acupuncture on pain were modified by any of the acupuncture characteristics evaluated, including style of acupuncture, the number or placement of needles, the number, frequency or duration of sessions, patient-practitioner interactions and the experience of the acupuncturist. When comparing acupuncture to non-acupuncture controls, there was little evidence that these characteristics modified the effect of acupuncture, except better pain outcomes were observed when more needles were used and, from patient level analysis involving a sub-set of 5 trials, when a higher number of acupuncture treatment sessions were provided.

The authors of this meta-analysis concluded that there was little evidence that different characteristics of acupuncture or acupuncturists modified the effect of treatment on pain outcomes. Increased number of needles and more sessions appear to be associated with better outcomes when comparing acupuncture to non-acupuncture controls, suggesting that dose is important. Potential confounders include differences in control group and sample size between trials. Trials to evaluate potentially small differences in outcome associated with different acupuncture characteristics are likely to require large sample sizes.

My reading of these collective findings is that it does not matter which type of acupuncture you use nor who uses it; the clinical effects are similar regardless of the most obvious potential determinants. Hardly surprising! In fact, one would expect such results, if one considered that acupuncture is a placebo-treatment.

What is ear acupressure?

Proponents claim that ear-acupressure is commonly used by Chinese medicine practitioners… It is like acupuncture but does not use needles. Instead, small round pellets are taped to points on one ear. Ear-acupressure is a non-invasive, painless, low cost therapy and no significant side effects have been reported.

Ok, but does it work?

There is a lot of money being made with the claim that ear acupressure (EAP) is effective, especially for smoking cessation; entrepreneurs sell gadgets for applying the pressure on the ear, and practitioners earn their living through telling their patients that this therapy is helpful. There are hundreds of websites with claims like this one: Auricular therapy (Acupressure therapy of the ear region) has been used successfully for Smoking cessation. Auriculotherapy is thought to be 7 times more powerful than other methods used for smoking cessation; a single auriculotherapy treatment has been shown to reduce smoking from 20 or more cigarettes a day down to 3 to 5 a day.

But what does the evidence show?

This new study investigated the efficacy of EAP as a stand-alone intervention for smoking cessation. Adult smokers were randomised to receive EAP specific for smoking cessation (SSEAP) or a non-specific EAP (NSEAP) intervention, EAP at points not typically used for smoking cessation. Participants received 8 weekly treatments and were requested to press the five pellets taped to one ear at least three times per day. Participants were followed up for three months. The primary outcome measures were a 7-day point-prevalence cessation rate confirmed by exhaled carbon monoxide and relief of nicotine withdrawal symptoms (NWS).

Forty-three adult smokers were randomly assigned to SSEAP (n = 20) or NSEAP (n = 23) groups. The dropout rate was high with 19 participants completing the treatments and 12 remaining at followup. One participant from the SSEAP group had confirmed cessation at week 8 and end of followup (5%), but there was no difference between groups for confirmed cessation or NWS. Adverse events were few and minor.

And is there a systematic review of the totality of the evidence?

Sure, the current Cochrane review arrives at the following conclusion: There is no consistent, bias-free evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation…

So?

Yes, we may well ask! If most TCM practitioners use EAP or acupuncture for smoking cessation telling their customers that it works (and earning good money when doing so), while the evidence fails to show that this is true, what should we say about such behaviour? I don’t know about you, but I find it thoroughly dishonest.

Pyruvate, a ketone and an alpha-keto acid, occurs naturally in the body when glucose is converted into energy. It is part of the Krebs cycle, the complex chain of reactions in which nutrients are metabolised to provide energy. High doses of pyruvate seem to stimulate the breakdown of fat in the body. It is therefore not surprising that pyruvate is used in all sorts of slimming aids; and if the advertising for ‘fat burners’ is to be believed, pyruvate is just the ticket for the desperate slimmer.

One such product advertisement, for instance, claims that sodium pyruvate and potassium pyruvate, which can act as a stimulant for the metabolism, adding to the thermogenesis process. Pyruvates have been found in studies to reduced the storage of fat in the body and convert the food source into calories which are then burned off in the production of heat. In one study, rats were injected with three fat burners, including pyruvates, and the rats given the pyruvates burned the greatest amount of fat by increasing the rat’s resting metabolic rate. With the elevated resting metabolic rate, the body burned more fat in individuals, which makes pyruvate an excellent source for weight maintenance.

So, maybe pyruvate works for rats – but does it really help those of us who would like to lose a few kilos? Some studies seem to say so, but others don’t. What do we conclude? There can only be one solution: we need a systematic review of the totality of the available trial evidence – and you probably guessed it: we have just published such an article.

The objective of our systematic review was to examine the efficacy of pyruvate in reducing body weight. Extensive literature searches identifies 9 RCTs of which 6 were met our inclusion criteria. All had methodological weaknesses. The meta-analysis revealed a statistically significant difference of 0.72 kg in body weight with pyruvate compared to placebo. The magnitude of the effect is small, and its clinical relevance is therefore uncertain. Adverse events included gas, bloating, diarrhoea, and increase in low-density lipoprotein cholesterol.

Our conclusion: The evidence from randomized clinical trials does not convincingly show that pyruvate is efficacious in reducing body weight. Limited evidence exists about the safety of pyruvate. Future trials involving the use of this supplement should be more rigorous and better reported.

Pyruvate supplements are popular; people who want to lose weight are misled into believing that they are effective. Bodybuilders as well as other athletes tend to take them because pyruvate is claimed to reduce body fat and enhance the ability to use energy more efficiently. None of these assumptions is based on sound evidence. Regardless of the evidence, a whole industry is exploiting the gullible and doing very well on it.

As these ‘fat burners’ are by no means cheap, I recommend a more efficient and more economical method for normalising body weight: eat a little less and move a bit more – I know it’s naff, but it works!

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