Controlled clinical trials are methods for testing whether a treatment works better than whatever the control group is treated with (placebo, a standard therapy, or nothing at all). In order to minimise bias, they ought to be randomised. This means that the allocation of patients to the experimental and the control group must not be by choice but by chance. In the simplest case, a coin might be thrown – heads would signal one, tails the other group.
In so-called alternative medicine (SCAM) where preferences and expectations tend to be powerful, randomisation is particularly important. Without randomisation, the preference of patients for one or the other group would have considerable influence on the result. An ineffective therapy might thus appear to be effective in a biased study. The randomised clinical trial (RCT) is therefore seen as a ‘gold standard’ test of effectiveness, and most researchers of SCAM have realised that they ought to produce such evidence, if they want to be taken seriously.
But, knowingly or not, they often fool the system. There are many ways to conduct RCTs that are only seemingly rigorous but, in fact, are mere tricks to make an ineffective SCAM look effective. On this blog, I have often mentioned the A+B versus B study design which can achieve exactly that. Today, I want to discuss another way in which SCAM researchers can fool us (and even themselves) with seemingly rigorous studies: the de-randomised clinical trial (dRCT).
The trick is to use random allocation to the two study groups as described above; this means the researcher can proudly and honestly present his study as an RCT with all the kudos these three letters seem to afford. And subsequent to this randomisation process, the SCAM researcher simply de-randomises the two groups.
To understand how this is done, we need first to be clear about the purpose of randomisation. If done well, it generates two groups of patients that are similar in all factors that might impact on the results of the study. Perhaps the most obvious factor is disease severity; one could easily use other methods to make sure that both groups of an RCT are equally severely ill. But there are many other factors which we cannot always quantify or even know about. By using randomisation, we make sure that there is an similar distribution of ALL of them in the two study groups, even those factors we are not even aware of.
De-randomisation is thus a process whereby the two previously similar groups are made to differ in terms of any factor that impacts on the results of the trial. In SCAM, this is often surprisingly simple.
Let’s use a concrete example. For our study of spiritual healing, the 5 healers had opted during the planning period of the study to treat both the experimental group and the control group. In the experimental group, they wanted to use their full healing power, while in the control group they would not employ it (switch it off, so to speak). It was clear to me that this was likely to lead to de-randomisation: the healers would have (inadvertently or deliberately) behaved differently towards the two groups of patients. Before and during the therapy, they would have raised the expectation of the verum group (via verbal and non-verbal communication), while sending out the opposite signals to the control group. Thus the two previously equal groups would have become unequal in terms of their expectation. And who can deny that expectation is a major determinant of the outcome? Or who can deny that experienced clinicians can manipulate their patients’ expectation?
For our healing study, we therefore chose a different design and did all we could to keep the two groups comparable. Its findings thus turned out to show that healing is not more effective than placebo (It was concluded that a specific effect of face-to-face or distant healing on chronic pain could not be demonstrated over eight treatment sessions in these patients.). Had we not taken these precautions, I am sure the results would have been very different.
In RCTs of some SCAMs, this de-randomisation is difficult to avoid. Think of acupuncture, for instance. Even when using sham needles that do not penetrate the skin, the therapist is aware of the group allocation. Hoping to prove that his beloved acupuncture can be proven to work, acupuncturists will almost automatically de-randomise their patients before and during the therapy in the way described above. This is, I think, the main reason why some of the acupuncture RCTs using non-penetrating sham devices or similar sham-acupuncture methods suggest that acupuncture is more than a placebo therapy. Similar arguments also apply to many other SCAMs, including for instance chiropractic.
There are several ways of minimising this de-randomisation phenomenon. But the only sure way to avoid this de-randomisation is to blind not just the patient but also the therapists (and to check whether both remained blind throughout the study). And that is often not possible or exceedingly difficult in trials of SCAM. Therefore, I suggest we should always keep de-randomisation in mind. Whenever we are confronted with an RCT that suggest a result that is less than plausible, de-randomisation might be a possible explanation.
On Twitter, I recently found this remarkable advertisement:
Naturally, it interested me. The implication seemed to be that we can boost our immune system and thus protect ourselves from colds, the flu and other infections by using this supplement. With the flu season approaching, this might be important. On the other hand, the supplement might be unsafe for many other patients. As I had done a bit of research in this area, I needed to know more.
According to the manufacturer’s information sheet, Viracid
- Provides Support for Immune Challenges
- Strengthens Immune Function
- Maintains Normal Inflammatory Balance
The manufacurer furthermore states the following:
Our body’s immune system is a complex and dynamic defense system that comes to our rescue at the first sign of exposure to an outside invader. The dynamic nature of the immune system means that all factors that affect health need to be addressed in order for it to function at peak performance. The immune system is very sensitive to nutrient deficiencies. While vitamin deficiencies can compromise the immune system, consuming immune enhancing nutrients and botanicals can support and strengthen your body’s immune response. Viracid’s synergistic formula significantly boosts immune cell function including antibody response, natural killer (NK) cell activity, thymus hormone secretions, and T-cell activation. Viracid also helps soothe throat irritations and nasal secretions, and maintains normal inflammatory balance by increasing antioxidant levels throughout the body.
This sounds impressive. Viracid could thus play an important role in keeping us healthy. It could also be contra-indicated to lots of patients who suffer from autoimmune and other conditions. In any case, it is worth having a closer look at this dietary supplement. The ingredients of the product include:
- Vitamin A,
- Vitamin C,
- Vitamin B12,
- Pantothenic Acid,
- L-Lysine Hydrochloride,
- Echinacea purpurea Extract,
- Acerola Fruit,
- Andrographis paniculata,
- European Elder,
- Berry Extract,
- Astragalus membranaceus Root Extract
Next, I conducted several literature searches. Here is what I did NOT find:
- any clinical trial of Viracid,
- any indication that its ingredients work synergistically,
- any proof of Viracid inducing an antibody response,
- or enhancing natural killer (NK) cell activity,
- or thymus hormone secretions,
- or T-cell activation,
- or soothing throat irritations,
- or controlling nasal secretions,
- or maintaining normal inflammatory balance,
- any mention of contra-indications,
- any reliable information about the risks of taking Viracid.
There are, of course, two explanations for this void of information. Either I did not search well enough, or the claims that are being made for Viracid by the manufacturer are unsubstantiated and therefore bogus.
Which of the two explanations apply?
Please, someone – preferably the manufacturer – tell me.
The ‘College of Medicine and Integrated Health’ (CMIH) has been the subject of several previous blog posts (see for instance here, here and here). Recently, they have come up with something new that, in my view, deserves a further comment.
The new ‘SELF CARE TOOL KIT’ began, according to the CMIH, in 2009 with a national multi-centre project commissioned by the UK Department of Health, to consider the best way to integrate self care into family practice. The project involved two large family health centres and two university departments. One output was the Self Care Library (SCL).
The Self Care Library (SCL) is an online patient resource providing free evidence-based information about self-care. The funding for the SCL did, however, not survive, and the facility was assigned to the CMIH. Thanks to funding from ‘Pukka Herbs Vitamins, Herbal Remedies & Health Supplements‘, the CMIH was able to transfer the content and to begin updating entries. Simon Mills, the coordinator of the original project who is now employed by Pukka, has led this transformation and helped the College set up the new parent portal, Our Health Directory.
The Self Care Toolkit is thus the new SCL. All concerned with this project are experienced in clinical practice and can separate the theory from real life needs. We all have academic lives as well so can be hard-nosed with the evidence base as well.
The above text is essentially based on the information provided by the CMIH. A few critical remarks and clarifications might therefore be in order:
- What does ‘separate the theory from real life needs’ mean? Does it mean that the scientific evidence can be interpreted liberally (see below)?
- Is it a good idea to have a commercial sponsor for such a project?
- Is it wise that the main person in charge is on the payroll of a manufacturer of dietary supplements?
- Is there any oversight to minimise undue bias and prevent the public from being misled?
- Is it really true that all people involved have academic lives? Simon Mills (who once was a member of my team) has no longer an academic appointment, as far as I know.
But, you are right, these are perhaps mere trivialities. Let’s see what the ‘Self Care Tool Kit’ actually delivers. I have chosen the entry on DEPRESSION to check its validity. Here it is:
It isn’t likely that taking extra vitamins will make much difference to low mood or depression. It is true that many people don’t get quite enough B, C and D vitamins in their food. And it’s also true that the brain and nervous system need these vitamins. Because they don’t get stored in the body, our daily diet has to supply them. Research has shown that people with low blood levels of the B vitamin folic acid are more likely to be depressed and less likely to do well on anti-depressant medicines. So, if you are eating a very poor diet, taking extra vitamins just might help. It’s also worth remembering that alcohol, refined sugars, nicotine and caffeine all take these vitamins out of the body. Yet most people who feel depressed probably won’t benefit from taking vitamins alone. To ensure that you get a good balance of these vitamins, try to eat more whole-foods, fruits, vegetables, nuts and seeds.
Some people say that taking high doses of vitamin C (1-2 g and more a day) helps lift their mood. There is a little research to support this and none showing that high doses of vitamin C actually help clinical depression. Vitamin C levels fall after surgery or inflammatory disease. The body needs more vitamin C when coping with stress, pregnancy and breast feeding. Aspirin, tetracycline and contraceptive pills take vitamin C out of the body. Smokers also need extra vitamin C because nicotine removes it. Fresh fruit and vegetables are the best sources of vitamin C.
Doctors are increasingly concerned about low vitamin D, especially in the Asian community. A lack of vitamin D can lead to depression. Oily fish and dairy products are good sources of vitamin D, and sunlight helps the body make vitamin D. Do you get enough sunshine and eat a good diet? It is estimated that worldwide over 1 billion people get too little vitamin D.
Taking supplements of vitamins B and D might help some people, whose diet is poor, but more research is needed.
Very high doses of vitamins and minerals can upset the body and cause side-effects. Get medical advice if you intend to take large doses. To ensure that you get a good balance of these vitamins, try to eat more whole-foods, fruits, vegetables, nuts and seeds.
If your diet is poor and you don’t get into the sun, ask your doctor about a vitamin D blood test. If it’s normal, there’s no point in taking vitamin D. If it’s low, your GP will prescribe it for you or you can buy a vitamin D supplement.
In my view, this text begs several questions:
1) Am I right in thinking that phraseology such as the one below will encourage patients suffering from depression to try the supplements mentioned?
- people with low blood levels of the B vitamin folic acid are more likely to be depressed and less likely to do well on anti-depressant medicines..
- Some people say that taking high doses of vitamin C (1-2 g and more a day) helps lift their mood…
- There is a little research to support this and none showing that high doses of vitamin C actually help clinical depression…
- A lack of vitamin D can lead to depression.
- Taking supplements of vitamins B and D might help some people…
- … your GP will prescribe it for you or you can buy a vitamin D supplement.
2) How does that tally with the latest evidence? For instance:
- No significant reduction in depression was seen after vitamin D supplementation compared to placebo
- No additional effects from nutritional supplementation were detected
- Adding vitamin C to citalopram did not increase the efficacy of citalopram in MDD patients.
3) The CMIH state: ‘This site gives you information NOT medical advice.’ But, in view of the actual text above, is this true?
4) Depression is a life-threatening condition. Is there a risk that patients trust the CMHI’s (non-) advice and commit suicide because of its ineffectiveness?
5) Do Pukka, the sponsor of all this, happen to supply most of the self care remedies promoted in the ‘Self Care Tool Kit’?
The answer to the last question, I am afraid, is YES!
We have looked at curcumin several (tumeric) times before (see here, here and here). It seems to have a fascinating spectrum of pharmacological activities. But do they translate into clinical usefulness? To answer this question, we obviously need clinical trials. Unfortunately, not many have become available. Here are two recent studies:
Due to the potential benefits of curcumin in the ischemic heart disease, this study was performed to evaluate whether pretreatment with curcumin may reduce myocardial injury following elective percutaneous coronary intervention (PCI). A randomized clinical trial was performed on 110 patients undergoing elective PCI. The intervention group (n = 55) received a single dose of 480 mg nanomicelle curcumin orally and the standard treatment before PCI, while the control group (n = 55) received only the standard treatment., Serum concentrations of CK-MB and troponin I was measured before, 8 and 24 h after the procedure to assess myocardial damage during PCI. The results showed that the raise of CK-MB in curcumin group was half of the control group (4 vs. 8 cases) but was not significant. There were no significant differences in CK-MB levels at 8 (P = .24) and 24 h (P = .37) after PCI between the curcumin and the control group. No significant difference was also found in troponin I levels at 8 (P = 1.0) and 24 h (P = .35) after PCI between the groups. This study did not support the potential cardioprotective benefit of curcumin against pre-procedural myocardial injury in patients undergoing elective PCI.
Inflammation along with oxidative stress has an important role in the pathophysiology of unstable angina which leads to acute myocardial infarction, arrhythmias and eventually heart failure. Curcumin has anti-inflammatory and anti-oxidant effects and thereby, it may reduce cardiovascular complications. This randomized controlled trial aimed to investigate the effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina.
Materials and Methods:
Forty patients with unstable angina who met the trial inclusion and exclusion criteria, participated in this double-blind randomized clinical trial. The patients were randomized into two groups: curcumin (80 mg/day for 5days) and placebo (80 mg/day for 5days). Cardiac function was evaluated by two-dimensional echocardiography devices at baseline (immediately after hospitalization) and 5 days after the onset of the trial. Atrial and ventricular arrhythmias were recorded by Holter monitors in cardiology ward, Ghaem academic hospital, Mashhad, Iran. Progression to heart failure, myocardial infarction, and pulmonary and cardiopulmonary resuscitation events as well as mortality were recorded daily throughout the study.
There were no significant differences between the two groups in atrial and ventricular arrhythmias (p=0.2), and other echocardiographic parameters (Ejection fraction, E, A, E/A ratio, Em, and pulmonary artery pressure) at baseline and five days after the start of the trial.
Nanocurcumin administered at the dose of 80 mg/day for five days had no effect in the incidence of cardiovascular complications in patients with unstable angina.
Clinical trials are not a good tool for proving a negative; they rarely can prove that a therapy is totally useless. Therefore, we cannot be sure that the many fascinating pharmacological activities of curcumin do not, after all, translate into some clinical benefit. However, what we can say with a high degree of certainty is this: currently there is no good evidence to show that curcumin is effective in treating any human condition.
Perhaps there is a more general lesson here about herbal medicine. Many plants have exiting pharmacological activities such as anti-biotic or anti-cancer activity which can be shown in-vitro. These are then hyped by entrepreneurs and enthusiasts of so-called alternative medicine (SCAM). Such hype fools many consumers and is thus good for business. But in-vitro activity does not necessarily mean that the therapy is clinically useful. There are many reasons for this, e.g. toxicity, lack of absorption. The essential test is always the clinical trial.
Facebook and YouTube have in the past been Eldorados for quacks who used it to promote their nonsensical products, false messages, and bogus treatments. A recent article in the Washington Post explained that this might be about to change.
Hundreds of thousands of enthusiasts of so-called alternative medicine (SCAM) persuade each other on Facebook that baking soda, apple cider vinegar, frankincense, apricot kernels, tiger bones, Essiac, bleach, homeopathics, Bach flower remedies etc. are cures that doctors don’t want you to know about. But recently Facebook announced that it is taking steps to limit the reach of false and sometimes dangerous therapeutic claims by treating them similar to clickbait or spam.
Facebook will “down-rank” posts that contain certain types of health misinformation, meaning those posts will appear in the news feeds of fewer users, and less prominently. The down-ranking process will use keywords and phrases that commonly appear in posts containing exaggerated or false health claims, but tend to be absent in posts containing accurate information on the same topics. Facebook’s News Feed algorithms will use those suspicious phrases, which the company has identified with the help of health-care professionals, to predict which posts might contain sensational health claims.
“Misleading health content is particularly bad for our community,” Travis Yeh, a Facebook product manager, wrote in a blog post. “So, last month we made two ranking updates to reduce (1) posts with exaggerated or sensational health claims and (2) posts attempting to sell products or services based on health-related claims.”
In a media statement, YouTube said: “Misinformation is a difficult challenge and any misinformation on medical topics is especially concerning … We’ve taken a number of steps to address this, including surfacing more authoritative content across our site. Our systems are not perfect, but we’ve seen progress within this space.”
Without question, these moves are a steps in the right direction. Whether they amount to more than a lip-service, whether they are able to out-smart the quacks, and whether they will make a real difference to the ubiquitous promotion of quackery, has to be seen.
This image caught my eye on facebook. It links to an article that makes a multitude of claims for a dietary supplement by the name of ‘smarter curcumin’:
Promotes Comfort & Flexibility
Studies have shown that curcumin may work by reducing certain key inflammation-promoting enzymes in the body. In some studies curcumin performed well in promoting comfort and flexibility without the side-effects; providing a natural supplement alternative. Athletes and weekend warriors alike are also using it for muscle and joint health recovery, too.
Supports Healthy Joints
Antioxidants play a role in keeping our joints healthy. Your body uses antioxidants to combat free radicals. Free radicals are unstable particles that are created as a result of millions of chemical reactions in the body. They can cause oxidative stress and damage on a cellular level. When scientists examine the blood and joint fluid of patients that are suffering with joint discomfort, often times there is an increased activity of free radicals and lower levels of antioxidants. Curcumin being rich in antioxidants, can give you a healthy supply.
Age-Reducing Beauty – Skin, Hair, and Body
Curcumin, being a very powerful natural antioxidant, helps reduce and neutralize free radicals, which damage and destroy your cells and DNA causing accelerated aging. Since most ageing disorders are driven by oxidative stress, this makes curcumin a very important daily supplement for aging adults.
Healthy Immune Balance
Your immune system is a network of various organs, tissues, and cells that work together to protect your body. Curcumin not only helps to enhance the responses of certain antibodies and cells within the immune system but may also help downregulate the expression of certain proinflammatory substances.
Promotes Cardio Health
A healthy heart consists of many factors, especially eating healthy and routine exercise. Adding curcumin as part of your healthy diet may have many benefits to protect your heart. Oxidized LDL (Low-density lipoprotein) particles (that have been disrupted by free radicals) may produce inflammation in the cardiovascular system. Studies suggest that the antioxidant effects of curcumin can help fight those free radicals.
Curcumin has been shown to calm the digestive system, helping to relieve gas, bloating, and other stomach and bowel issues. It works differently than probiotics or enzymes – naturally soothing the gut, and reducing the overproduction of acid.
Support Liver Health
Your liver plays an important role in stabilizing and balancing the maintenance of your body. The health of your liver can be directly related to oxidative stress and proinflammatory substances. Curcumin may help boost antioxidant defenses to help the liver detoxify and restore balance.
Supports Brain Health
The connection between inflammation and cognitive health cannot be overstated. Neurons are especially susceptible to inflammation and the release of inflammatory compounds in the body can be neurotoxic. Curcumin may help protect those precious brain cells.
What fascinates me here is not so much the plethora of therapeutic claims. As far as I can see, most of them are not supported by what I would call good evidence. But I have grown so used to bogus claims in SCAM, that they rarely make me bat an eyelash.
What fascinates me most is the extraordinary picture evidently designed to attract our attention. Many people might have no idea what it depicts, other than a running leopard in a strange environment. Others will realise that the environment is an artery, and the chasing animal therefore seems to imply that the supplement enhances arterial blood flow.
But why? There is no evidence that curcumin has this effect, and the above therapeutic claims are largely unrelated to improvements of the blood circulation.
The artery is filled with red cells in their typical disc shape. It is, however, a shape red cells never have while submitted to flow in arteries. While circulating, they tend to attain a parachute-like shape:
Red cells form a disc shape only when they are motionless. Perhaps the picture really implies that curcumin generates a stagnation of blood flow? No, this is also not in line with reality; in stagnant blood, red cells aggregate and look like this:
So, you see why this image is puzzling. It seems to be aimed at people who are aware that it depicts something medical, yet too ignorant to realise that almost everything is wrong with it.
And why would anyone design an image like this? Could it be that only people naïve enough to think this picture makes any sense are likely to believe the tall tales offered in the text?
Green tea is said to have numerous health benefits. Recently, a special green tea, matcha tea, is gaining popularity and is claimed to be more powerful than simple green tea. Matcha tea consumption is said to lead to higher intake of green tea phytochemicals compared to regular green tea.
But what is matcha tea? This article explains:
The word matcha literally means “powdered tea”. Drinking a cup or two of the tea made from this powder could help you tackle your day feeling clear, motivated and energized, rather than foggy, stressed out, and succumbing to chaos.
Matcha tea leaves are thrown a lot of shade (literally). They’re grown in the dark. The shade growing process increases matcha’s nutrients, especially chlorophyll, a green plant pigment that allows plants to absorb energy from sunlight. Chlorophyll is rich in antioxidants, and gives matcha it’s electrifying green colour. Shade growing also increases the amount of L-theanine, which is the amino acid known for promoting mental clarity, focus, and a sense of calm. It’s called nature’s “Xanax” for a reason.
The high amino acid content is also what gives matcha it’s signature umami taste. Umami is the “fifth” taste that describes the savory flavor of foods like miso, parmesan cheese, chicken broth, spinach, and soy sauce. You know you’ve got a premium matcha when you taste balanced umami flavors, hints of creaminess, and the slightest taste of fresh cut grass. You shouldn’t need to add any sweetener to enjoy sipping it. When choosing a high quality matcha powder, it’s important to remember: a strong umami flavour = higher in amino acids = the more L-theanine you’ll receive.
Once matcha leaves are harvested, they get steamed, dried, and ground up into a fine powder that you can mix with hot or cold water. The key difference here is that you’re actually consuming the nutrients from the entire leaf— which is most concentrated in antioxidants, amino acids, and umami flavour. This is unlike traditional brewed tea, where you’re only drinking the dissolvable portions of the leaf that have been steeped in water.
The article also names 5 effects of matcha tea:
1. Promotes Relaxation, Mood, and Mental Focus
2. Supports Healthy Cognitive Function
3. Supports Detoxification
4. Fights Physical Signs of Aging
5. Promotes a Healthy Heart
None of the sources provided do actually confirm that matcha tea conveys any of these benefits in humans. My favourite reference provided by the author is the one that is supposed to show that matcha tea is a detox remedy for humans. The article provided is entitled Low-dose dietary chlorophyll inhibits multi-organ carcinogenesis in the rainbow trout. Who said that SCAM-peddlers have no sense of humour?
Joking aside, is there any evidence at all to show that matcha tea has any health effects in humans? I found two clinical trials that tested this hypothesis.
Intake of the catechin epigallocatechin gallate and caffeine has been shown to enhance exercise-induced fat oxidation. Matcha green tea powder contains catechins and caffeine and is consumed as a drink. We examined the effect of Matcha green tea drinks on metabolic, physiological, and perceived intensity responses during brisk walking. A total of 13 females (age: 27 ± 8 years, body mass: 65 ± 7 kg, height: 166 ± 6 cm) volunteered to participate in the study. Resting metabolic equivalent (1-MET) was measured using Douglas bags (1-MET: 3.4 ± 0.3 ml·kg-1·min-1). Participants completed an incremental walking protocol to establish the relationship between walking speed and oxygen uptake and individualize the walking speed at 5- or 6-MET. A randomized, crossover design was used with participants tested between Days 9 and 11 of the menstrual cycle (follicular phase). Participants consumed three drinks (each drink made with 1 g of Matcha premium grade; OMGTea Ltd., Brighton, UK) the day before and one drink 2 hr before the 30-min walk at 5- (n = 10) or 6-MET (walking speed: 5.8 ± 0.4 km/hr) with responses measured at 8-10, 18-20, and 28-30 min. Matcha had no effect on physiological and perceived intensity responses. Matcha resulted in lower respiratory exchange ratio (control: 0.84 ± 0.04; Matcha: 0.82 ± 0.04; p < .01) and enhanced fat oxidation during a 30-min brisk walk (control: 0.31 ± 0.10; Matcha: 0.35 ± 0.11 g/min; p < .01). Matcha green tea drinking can enhance exercise-induced fat oxidation in females. However, when regular brisk walking with 30-min bouts is being undertaken as part of a weight loss program, the metabolic effects of Matcha should not be overstated.
Matcha tea is gaining popularity throughout the world in recent years and is frequently referred to as a mood-and-brain food. Previous research has demonstrated that three constituents present in matcha tea, l-theanine, epigallocatechin gallate (EGCG), and caffeine, affect mood and cognitive performance. However, to date there are no studies assessing the effect of matcha tea itself. The present study investigates these effects by means of a human intervention study administering matcha tea and a matcha containing product. Using a randomized, placebo-controlled, single-blind study, 23 consumers participated in four test sessions. In each session, participants consumed one of the four test products: matcha tea, matcha tea bar (each containing 4g matcha tea powder), placebo tea, or placebo bar. The assessment was performed at baseline and 60min post-treatment. The participants performed a set of cognitive tests assessing attention, information processing, working memory, and episodic memory. The mood state was measured by means of a Profile of Mood States (POMS). After consuming the matcha products compared to placebo versions, there were mainly significant improvements in tasks measuring basic attention abilities and psychomotor speed in response to stimuli over a defined period of time. In contrast to expectations, the effect was barely present in the other cognitive tasks. The POMS results revealed no significant changes in mood. The influence of the food matrix was demonstrated by the fact that on most cognitive performance measures the drink format outperformed the bar format, particularly in tasks measuring speed of spatial working memory and delayed picture recognition. This study suggests that matcha tea consumed in a realistic dose can induce slight effects on speed of attention and episodic secondary memory to a low degree. Further studies are required to elucidate the influences of the food matrix.
However, I was impressed when I looked up the costs of matcha tea: £17.95 for 30 g of powder does not exactly seem to be a bargain. So, matcha tea does after all help some people, namely all those engaged in flogging it to the gullible SCAM fraternity.
‘Acute-on-chronic liver failure’ (ACLF) is an acute deterioration of liver function in patients with pre-existing liver disease. It is usually associated with a precipitating event and results in the failure of one or more organs and high short term mortality.
An international team of researchers published a analysis examining data regarding drugs producing ACLF. They evaluated clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. They identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation.
Of the 3,132 patients with ACLF, drugs were implicated as a cause in 10.5% of all cases and other non-drug causes in 89.5%. Within the first group, so-called alternative medications (SCAMs) were the commonest cause (71.7%), followed by combination anti-tuberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%).
The authors concluded that drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by anti-tuberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.
Systematic literature searches were performed on Medline, Embase, The Cochrane Library, Amed and Ciscom. To identify additional data, searches were conducted by hand in relevant medical journals and in our own files. The screening and selection of articles and the extraction of data were performed independently by the two authors. There were no restrictions regarding the language of publication. In order to be included articles were required to report data on hepatotoxic events associated with the therapeutic use of herbal medicinal products.
Single medicinal herbs and combination preparations are associated with hepatotoxic events. Clinically, the spectrum ranges from transient elevations of liver enzyme levels to fulminant liver failure and death. In most instances hepatotoxic herbal constituents are believed to be the cause, while others may be due to herb-drug interactions, contamination and/or adulteration.
A number of herbal medicinal products are associated with serious hepatotoxic events. Incidence figures are largely unknown, and in most cases a causal attribution is not established. The challenge for the future is to systematically research this area, educate all parties involved, and minimize patient risk.
Despite these warnings, progress is almost non-existent. If anything the problem seems to increase in proportion with the rise in the use of SCAM. Hence, one cannot but agree with the conclusion of a more recent overview: The actual incidence and prevalence of herb-induced liver injury in developing nations remain largely unknown due to both poor pharmacovigilance programs and non-application of emerging technologies. Improving education and public awareness of the potential risks of herbals and herbal products is desirable to ensure that suspected adverse effects are formally reported. There is need for stricter regulations and pre-clinical studies necessary for efficacy and safety.
“Eating elderberries can help minimise influenza symptoms.” This statement comes from a press release by the University of Sydney. As it turned out, the announcement was not just erroneous but it also had concealed that the in-vitro study that formed the basis for the press-release was part-funded by the very company, Pharmacare, which sells elderberry-based flu remedies.
“This is an appalling misrepresentation of this Pharmacare-funded in-vitro study,” said associate professor Ken Harvey, president of Friends of Science in Medicine. “It was inappropriate and misleading to imply from this study that an extract was ‘proven to fight flu’.” A University of Sydney spokeswoman confirmed Pharmacare was shown a copy of the press release before it was published.
This is an embarrassing turn of events, no doubt. But what about elderberry (Sambucus nigra) and the flu? Is there any evidence?
A systematic review quantified the effects of elderberry supplementation. Supplementation with elderberry was found to substantially reduce upper respiratory symptoms. The quantitative synthesis of the effects yielded a large mean effect size. The authors concluded that these findings present an alternative to antibiotic misuse for upper respiratory symptoms due to viral infections, and a potentially safer alternative to prescription drugs for routine cases of the common cold and influenza.
The alternative to antibiotic misuse can only be the correct use of antibiotics. And, in the case of viral infections such as the flu, this can only be the non-use of antibiotics. My trust in this review, published in a SCAM journal of dubious repute, has instantly dropped to zero.
Perhaps a recent overview recently published in THE MEDICAL LETTER provides a more trustworthy picture:
No large randomized, controlled trials evaluating the effectiveness of elderberry for prevention or treatment of influenza have been conducted to date. Elderberry appears to have some activity against influenza virus strains in vitro. In two small studies (conducted outside the US), adults with influenza A or B virus infection taking elderberry extract reported a shorter duration of symptoms compared to those taking placebo. Consuming uncooked blue or black elderberries can cause nausea and vomiting. The rest of the plant (bark, stems, leaves, and root) contains sambunigrin, which can release cyanide. No data are available on the safety of elderberry use during pregnancy or while breastfeeding. CONCLUSION — Prompt treatment with an antiviral drug such as oseltamivir (Tamiflu, and generics) has been shown to be effective in large randomized, controlled trials in reducing the duration of influenza symptoms, and it may reduce the risk of influenza-related complications. There is no acceptable evidence to date that elderberry is effective for prevention or treatment of influenza and its safety is unclear.
Any take-home messages?
- Elderberry supplements are not of proven effectiveness against the flu.
- The press officers at universities should be more cautious when writing press-releases.
- They should involve the scientists and avoid the sponsors of the research.
- In-vitro studies can never tell us anything about clinical effectiveness.
- SCAM-journals’ articles must be taken with a pinch of salt.
- Consumers are being misled left, right and centre.
Glucosamine supplements are often advocated for the treatment of osteoarthritis. But there is evidence that they might convey other benefits as well. This prospective observational study assessed the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events. The UK Biobank data of 466 039 participants without CVD at baseline was used. They completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016. The main outcome measures were incident CVD events, including CVD death, coronary heart disease, and stroke.
During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00).
The authors concluded that habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events.
This is an impressive study! It incorporates both a huge sample size and a long observation period. Moreover, the authors analysed the data expertly and interpreted their results with the necessary caution.
The association between glucosamine intake and CVD risk were independent of CVD risk factors, such as gender, age, income, body mass index, physical activity, healthy diet, alcohol intake, smoking status, diabetes, hypertension, high cholesterol, arthritis, drug use, and other supplement use. Moreover, the findings are in line with several previous studies that show inverse associations of glucosamine use with CVD risk and mortality. And finally, the authors discuss several biologically plausible mechanisms that could explain the observed findings.
Yet, it is conceivable that the association is not of a causal nature. There might be a host of confounders responsible for the finding. Therefore, before we now all rush to the next health-food store to buy glucosamine supplements – they are not all that cheap! – we should perhaps wait for further independent replications and research.