However, according to recently-published research, the benefits one would expect from regular exercise may be negated in those taking statin drugs.

In this research, 37 adults underwent 12 weeks of aerobic training. All participants, prior to the study, were sedentary and overweight or obese [1]. Fitness was assessed prior to the study starting, and at the end too.

Half of the group just participated in the exercise programme, while the other half took 40 mg of the statin simvastatin (Zocor) each day.

In those not taking statins, fitness increased by an average of 10 per cent of the 12-week study. However, in those taking simvastatin, fitness increased by only 1.5 per cent on average.

Mitochondrial activity was assessed by measuring activity of the enzyme citrate synthase (a key enzyme involved in energy production in the mitochondria). Citrate synthase activity increased by 13 per cent in those who adopted exercise, but actually fell by 4.5 per cent in those taking the drug.

It is possible, that these effects of statins have something to do with the fact that statins can deplete the body of the nutrient coenzyme Q10 which is essential for energy production in the mitochondria. I wrote about impact of statins on coenzyme Q10 levels recently here.

What seems clear from the research, is that statins have the ability to block some of the benefits exercise can bring. It’s yet another thing to add to the ever-lengthening list of potential unwanted effects of statins.

References:

1. Mikus CR, et al. Simvastatin impairs exercise training adaptations. Journal of the American College of Cardiology. Epub 10 April 2013

The pharmaceutical industry has not been slow out of the blocks in its attempt to develop HDL-boosting therapies. After all, if higher HDL levels are associated with improved health, then raising HDL levels in the blood should be good for health, right? While sometimes persuasive, this logic is flawed on more than one level.

To begin with, just because HDL is associated with improved health outcomes, that doesn’t mean that it’s actually responsible for those outcomes. It might be that HDL is not so much a protective factor in cardiovascular disease, but a marker for protection.

We know, for instance, that high-carbohydrate diets can push up blood sugar levels and induce changes such as raised triglyceride levels, inflammation and ‘oxidative stress’ (free radical damage) that likely increase the risk of cardiovascular disease. High carbohydrate diets also tend to lead to lower HDL. So, not surprisingly, lower carbohydrate diets tend to raise HDL levels, and lower triglyceride levels, inflammation and oxidative stress. In people eating a low-carb diet HDL may be pleasingly on the high side.

But are the improved health outcomes associated with this down to the HDL or other markers associated with low-carb eating? We don’t know, I think, and that means we cannot be too sure that a drug or agent that pushes up HDL levels are necessarily a good thing. Also, a drug or agent may have untoward effects. So, even if cyanide turns out to be a good HDL-boosting agent, on balance one might judge that it’s overall effects on healthy are negative.

What all this boils down to is that what we really need is studies that judge the impact of drugs not on ‘surrogate’ markers such as HDL levels, but on health.

In recent years, there has been focus on two main types of HDL-raising therapy: niacin (a form of vitamin B3) and what are known as CETP inhibitors. In the current edition of Current Opinions in Cardiology, two papers take a look at the state of the evidence in the area of HDL-raising therapy.

One of these papers comes from researchers based in Manchester, UK [1]. In their paper, the authors acknowledge work which suggests that in those with acceptable LDL levels, low levels of HDL is associated with elevated risk of cardiovascular disease. However, the authors also point out the presence of three recent ‘randomised controlled trials’ which find that neither niacin nor the CETP inhibitor dalcetrapib improved health outcomes. The authors of this paper make the point that, in the future, drugs will be required that actually have benefits for health (and don’t simply raise HDL levels).

The other paper comes from a researcher at the Mayo Clinic in Minnesota in the US [2]. The author of this study reviews, in essence, the same evidence as the authors of the first paper, and draws the same conclusions regarding the benefits (none). The author also draws our attention to the fact that niacin has been found to induce side-effects, and that the CETP inhibitor torcetrapib was found to increase the risk of death.

This review also draws our attention to the fact that two other CETP inhibitors (anacetrapib and evacetrapib) are being trialled but that the results will not be known for some years. Right now, though, given the overall adverse effects seen with HDL-boosting agents to date, I’d say that all bets are off.

References:

1. Schofield JD, et al. High-density lipoprotein cholesterol raising: does it matter? Curr Opin Cardiol. 2013;28(4):464-74

2. Wright RS. Recent clinical trials evaluating benefit of drug therapy for modification of HDL cholesterol. Curr Opin Cardiol. 2013;28(4):389-98

And I say rhetoric because, actually, quite a lot of evidence points away from the idea that melanoma is chiefly caused by sun exposure. Some of the most salient research was summarised by emeritus professor of dermatology Sam Shuster in the British Medical Journal [1]. You can read the full text of this piece here. You can read the counter arguments here.

In his piece, Sam Shuster points out that about 75 per cent of melanomas occur in relatively unexposed sites of the body. Elsewhere, he draws our attention to a form of melanoma known as acral lentiginous melanoma, where typical sites include the soles of the feet, palms of the hand and the inside of the mouth. The Daily Mail piece today even draws our attention to this paradox, including in its title which references ‘hotspots’ for cancers including the soles of the feet.

In his BMJ piece, Sam Schuster also draws our attention to the evidence showing that in Europe and the US, melanoma incidence and deaths due to melanoma fall as sun exposure increases.

Some say that it’s not sunlight per se that causes melanoma but intermittent sun exposure and/or burning, especially in early life (the counter-argument piece argues this position). Sam Shuster pours cold water on this theory though, by writing that this theory: “is easily excluded, because the melanomas would then occur at the burn sites; there is no evidence for this, and it is unlikely that any will be found, because sunburn occurs in sun exposed sites, and these are not the sites at which melanomas occur.”

The BMJ allows people to comment on articles on-line in the form of ‘rapid responses’. One of the rapid responses comes from surgeon who suggests that Sam Shuster has taken leave of his senses. Here’s an extract:

As a newly qualified doctor who spent 8 weeks last year studying at the Sydney Melanoma centre I was dumbfounded by the claims made against a link between sun exposure and melanoma. Having spent time with endless patients reporting hours of sun exposure and sunburn in earlier years and now presenting with cancerous lesions I believe that Dr Shuster may benefit from a similar “elective” in order to change his mind on the melanoma theory! Rubbishing the claims that the high incidences of melanoma do not occur in sun bathed areas seems bizarre.

Oh, dear. Notice the complete absence of reference to relevant science here. The observations this doctor made fit his pre-conceived beliefs so, voila, the answer is obvious (to him). There is a term for this sort of (faulty) thinking: confirmation bias. This doctor suggests Sam Shuster could do with an educational trip down-under, but I suggest he himself might take a trip to a relevant textbook or the internet to read about the scientific method.

But don’t lose complete faith in medical professionals just yet. Compare and contrast that first response with a later one which comes from another surgeon:

We most certainly do NOT know for sure that sunlight exposure is directly responsible for melanoma. As Schuster so rightly states, debate based on opinion is precisely what we don’t need in this area. We need hard evidence, and our profession isn’t always the best at offering advice on this basis.

Good to see this doctor thinking straight, and not falling into the trap of propagating ideas that seem to be based more on folklore than fact.

References:

1. Shuster S. Is sun exposure a major cause of melanoma? No BMJ 2008;337:a764

One might argue then that forbidding certain foods or drinks in the name of healthy eating may encourage a somewhat unhealthy relationship with food. I think I’ve seen a few examples of this in my time, and it’s one reason why I generally give the advice that ‘it’s what we eat most of the time, not some of it, that’s most important’. So, even if someone were eating a decent ‘primal’ diet based on natural unprocessed foods, I’m generally relaxed about the occasional consumption of bread, pasta or pizza, for instance (assuming someone does not have a contraindication such as coeliac disease).

However, I also know that the ideal is really for people to get a to a place where they are ambivalent about whether they have a food or not. Because if someone is not fussed about whether they eat something, and has not particular drive to eat it either, then actually there’s no need to even think about forbidding the food – it’s largely a non-event.

One thing that tends to work well here is to avoid getting very hungry, because when we do, there’s often a tendency to crave or desire foods such as cake, biscuits/cookies, and doughnuts. Should we get such a craving, we are usually going to have to exert some considerable willpower to resist it. And willpower has been shown to be a bit like a muscle: once exercised, it is weaker for some time later. So, repeatedly using willpower to resist a food will usually make resisting it harder and harder over time.

Research has found that if individuals are given a sugary drink between two tests of self-control, they do better on the second one [2]. The same effect does not occur if the drink is artificially sweetened, suggesting that somehow sugar feeds the willpower ‘muscle’ and strengthens the resolve. Eating a diet that helps stabilise blood sugar levels regularly enough to keep hunger and low blood sugar at bay can, I think, go a long way to essentially putting a stop to cravings for sugary and none-too-healthy foods. It also likely strengthens the resolve.

But what is also interesting, I think, is that the very act of exerting willpower tends to cause blood sugar levels to drop [3]. So, a spot of hunger and low blood sugar may trigger the need for willpower and sap it at the same time. No wonder so many of us can find it almost impossible to resist sweet foodstuffs from time to time.

Again, the key to making life a lot easier is not really wanting the food in the first place, and blood sugar stability is critical here. But it can often help to supplement with key nutrients. Two supplements I use quite a lot in practice are:

1. L-glutamine. A pinch of the amino acid L-glutamine power allowed to dissolve under the tongue can, I find, reduce an intense craving for something sweet within a few minutes.

2. L-tryptophan. This amino acid is a precursor of the brain chemical serotonin, low levels of which can provoke cravings for sweet foods and perhaps other carbohydrates. Serotonin levels naturally fall during the day, which means some individuals find their problem time is in the evening here. 500-1,500 mg taken on an empty stomach in the mid-afternoon and early evening will often really help to reduce an unhealthy drive for carbohydrate.

References:

1. Truong G, et al. An unforgettable apple: Memory and attention for forbidden objects. Cogn Affect Behav Neurosci. 2013 May 24. [Epub ahead of print]

2. Gailliot MT, et al. Self-control relies on glucose as a limited energy source: willpower is more than a metaphor. J Pers Soc Psychol. 2007;92(2):325-36

3. Gailliot MT, et al. The physiology of willpower: linking blood glucose to self-control. Pers Soc Psychol Rev. 2007;11(4):303-27

Regular readers of this blog will know that, generally speaking, I’m all for transparency and patient empowerment. However, while the publication of surgeon mortality statistics may seem like an eminently good idea on the surface to some, I have to say I have some considerable concerns about it.

Is it always wise to place doctors in ‘league table’ of survival performance? Just imagine you take 100 surgeons, and all have very low and quite similar mortality statistics. All of them may be perfectly able and technically sound surgeons with acceptable mortality rates given the known risks of surgery. However, once put in a ‘league table’, half of them will be automatically ‘below average’, with all the stigma and judgment that may bring. Even the person last in the list could, technically speaking, be a perfectly adequately-performing surgeon. He or she, however, looks awful.

I had a conversation recently with a friend who is a cardiothoracic anaesthetist, and he told me that he was aware that a hospital in the UK recently decided to audit the performance of its anaesthetists. One anaesthetist stood out as having significantly worse outcomes than the rest. However, within the department, he was recognised as the most skilled and experienced anaesthetist. The probable explanation? That the surgeons were specifically seeking to have him as their anaesthetist when operating on the riskier cases were complications and poorer outcomes were more likely.

So, a surgeon’s mortality statistics may actually not accurately reflect his or her skill or expertise. Poorer statistics might reflect, for example, the fact that the surgeon attracts sicker people and riskier cases. Maybe, that surgeon is prepared to take on cases that other surgeons reject because they are view as ‘poor candidates’ for anaesthetic or surgery?

The statistics on surgeon’s performance are ‘risk adjusted’, which essentially means allowances are made for surgeons operating on more difficult and riskier cases. However, I wonder how reliable this process is, and even if it is reliable, I suspect some surgeons will have the league table system affect them (either consciously or unconsciously) in terms of their decision-making and the care they offer.

So, while these league tables may be designed to allow patients to make a more informed choice about who they have operate on them, this works both ways of course. Because, surgeons are quite within their rights to choose who they operate on too.

Put yourself in the shoes of a surgeon for a moment, and imagine you know your mortality statistics are to be published. You’re sitting in a clinic and see a patient who ‘needs’ an operation, but who in your view is a poor candidate. Do you think the fact that your mortality statistics are going to be published in any way might affect whether you take this patient on or not?

You can perhaps see what the problem might be here. And the end result might be doctors will be increasingly less inclined to take on challenging cases who may possibly end up being ‘left out in the cold’.

The league table idea is not new. In fact, in the UK, statistics for cardiothoracic surgeons has been available for several years. My friend (the cardiothoracic anaesthetist) works with some of them. He told me that one of his colleagues (by all accounts a very good surgeon) has said that he used to love his job, but now hates it. He feels under immense pressure. If ones of his patients dies that is beyond ‘the norm’ he gets a letter from his professional society. Another death within a year apparently triggers ‘a visit’. The risk is that he might be singled out for ‘observation’ and ‘retraining’. A my friend explained, none of the apparent problem with this surgeon’s performance may have to do with the surgeon’s performance, though. He just may have taken on more challenging cases, or maybe the aftercare was a problem, or maybe he was just unlucky (it can happen).

I can see the logic behind the publication of mortality statistics, but it’s clear that for some surgeons, this initiative will take the joy out of fixing people. And I reckon that if there’s a profession where being happy in your work is fundamentally important, it’s medicine.

The email reminded me that I had recently seen an piece of research in the American Journal of Clinical Nutrition where the authors had sought evidence for the blood type diet [1]. I don’t want to ruin it for you but the conclusion was there is none.

Now, this does not mean that the blood type diet does not work. The fact is, it’s not actually been studied properly at all. And, as the saying going, absence of evidence is not evidence of absence. If the diet was subjected to proper study, it might turn out to work just as Peter D’Adamo says it does.

However, if I am going to be honest, for a long time I have had my doubts about this diet. I don’t deny that it may help people. I just doubt the benefits have anything to do with someone’s blood type.

Dr D’Adamo’s reasoning is based on substances on the surface of foods known as ‘lectins’. Basically, lectins have the capacity to react with blood antigens, and this can cause red blood cells to clump together, which can lead to any number of ills including fatigue and chronic disease. According to Dr D’Adamo, the foods we react to are largely determined by the antigens to be found on our red blood cells. Those of O blood type (the original blood group) individuals are best suited to a diet devoid of grain and dairy products. Groups A, B and AB, he says, came later and are therefore better adapted, to varying degrees, to these more recent additions to our diet. Dr D’Adamo claims not only that different blood types developed at different points during our evolution, but that the predominant diet at their time of origin reflects the ideal diet for an individual of that blood type.

This may sound a decent enough theory, except I think there are a few problems with it. Firstly, it simply isn’t established when different blood groups came about, which casts considerable doubt on the validity of one the blood group diet’s major tenets. Also, if blood groups A, B and AB only came since we converted from hunter-gathering to farming, then their appearance was very recent in evolutionary terms. Evolution is a slow process, and I wonder if it’s likely that any of us are particularly well adapted to the diets assigned by Dr D’Adamo to those of blood types A, B and AB.

Another deficiency of this diet relates to the blood types themselves. The ABO group of antigens are just one way to type blood, but there are literally dozens of other antigens on the surface of the blood cells. Following Dr D’Adamo’s logic, is it not possible that these also developed at different times and therefore influence our dietary requirements? This possibility and the muddied waters it brings is not address by the approach taken in the book.

Another issue with the blood type approach is that it seems to be based on experiments in which lectins from food have been mixed with blood in the test-tube. This is important because these experiments do not reflect what happens in nature. Under normal circumstances lectins are not injected into the bloodstream, but are eaten. This gives the body an opportunity to inactivate the lectins through the process of digestion. Also, the gut wall may provide some protection by providing a physical barrier against the absorption of lectins into the system. Lectins may also be deactivated even before they get into the gut through the way in which foods are prepared and cooked.

There is no doubt in my mind, however, that food sensitivity issues do exist. It’s just that mixing lectins with blood cells in a test tube may not be the best way to test for them.

Another potential deficiency of the blood type approach is that while it focuses on lectins, there are several other ways in which the body can react to foods. For example, the body can react directly to foods with white blood cells known as T-cells, and can also produce antibodies of more than one type (the two main types in this regard are known as IgE and IgG antibodies). Such reactions, that are clearly important for assessing food suitability, are just not taken into consideration in the lectin-based ‘blood group’ approach.

None of this means that applying the principles of the blood type diet will not help individuals. The most common blood group, ‘O’, is advised to eat what amounts to a dairy and grain-free diet. Bearing in mind the very frequent role these foods play in health issues generally, then the type O approach is likely to help a lot of people. Also, Dr D’Adamo advises not just the O’s but also the A’s and B’s to eliminate major offenders in the diet such as commercially-produced bread, biscuits, pasta and cereals. These foods are generally bad for health for a myriad of reasons, and perhaps it’s no wonder that individuals feel better for getting them out of the diet.

There is no doubt in my mind that there is metabolic individuality, and some people suit certain dietary approaches more than others. For the reasons about, though, I doubt if this has anything at all to do with blood type.

References:

1. Cusack L, et al. Blood type diets lack supporting evidence: a systematic review. Am J Clin Nutr epub 22 May 2013

The site is selling what is essentially a strap that keeps the mouth closed during sleep. It is claimed to have the ability to stop snoring and sleep apnoea (see below). At first sight, it may look to many as a gimmick. The price also might seem steep. But before you reject this product, let me explain why I think it, and the idea behind it, at least deserve consideration.

It’s believed that a major cause of snoring is when the soft palate at the back of the mouth blocks the entrance to the airways. This mostly happens when the mouth is open. If it’s bad enough, it may block the airways enough to stop breathing altogether for a few seconds or longer. This problem (sleep apnoea) is potentially a health hazard, and can cause people to wake feeling quite unrefreshed and even downright groggy, despite having slept for a good amount of time.

Even if someone does not snore, there’s a theoretical risk to breathing through an open mouth. This may increase the risk of ‘over-breathing’ (too much air going into and out of the lungs). The potential problem here is that it might cause carbon dioxide levels to drop to a lower level than is optimal. This can cause blood vessels to constrict but also means that less oxygen will be delivered to the tissues (if you’re interested in the physiology of this, look up ‘the Bohr effect’).

One reason for people breathing through their mouth, including at night, is a blocked nose. So, in the past, a lot of advice I have given about snoring has been geared to approaches to prevent nasal congestion. Eliminating or significantly cutting down on dairy products often helps (no, this is not an urban myth – I’ve found in practice that dairy is a quite common cause of nasal congestion, excess mucus and catarrh). Also, red wine quite commonly causes problems (apparently, it’s high in histamine, though the usually yeasty nature of this drink might not help either).

The thing is, though, even if someone’s nasal passages are beautifully clear, it is still possible for them to have their mouth drop open during sleep, particularly if they lie on their back. This, by the way, is the basis of an old remedy for snoring which involved sewing a tennis ball into the back of the sufferer’s pyjama jacket or nightdress. The idea is that lying on one’s back was made so uncomfortable that, even when asleep, the natural tendency would be to find another position.

Until today, the idea of dealing with snoring by doing something to keep the mouth shut did not occur to me. It probably should have, but it didn’t. And when I saw the ‘jaw supporter’ my instant reaction was not ‘what rubbish’ but ‘what a good idea and why didn’t I (or someone else) think of that soon?’

I have nothing to do with the company, haven’t trialled the product, and have no plans to either (I sleep with my mouth closed and don’t snore, I am reliably informed). However, my intuitive feeling about the product is that for people who snore and those with sleep apnoea, this product is in the ‘definitely worth a go’ category.

However, it also occurs to me that investing in this piece of kit may not be necessary at all. Ingenious and practical folks may want to fashion their own versions of the ‘jaw supporter’. Please send photos if you wish and feel free to share and personal snoring success stories below.

All of us need could do with maintaining coenzyme Q10 levels, and this has particular relevance to individuals who take statins: these drugs impair the product of coenzyme Q10. There is plenty of evidence in animals and humans that statins can indeed deplete the body of coeynzme Q10 [1].

The heart is a muscle, the cells of which contain mitochondria which depend on coenzyme Q10. Back in January, I wrote a post which explored the possibility that statins may be contributing to increasing incidence of heart failure (weakened heart function that can lead to symptoms such as fatigue, breathlessness and swelling in the legs).

The role of coenzyme Q10 depletion in heart has been highlighted by studies in which supplementation with it has been found to improve heart function [2]. Recently, though, there were reports (example here) of a new study which appears to have found that coenzyme Q10 supplementation can prevent major cardiovascular events (such as heart attacks) and save lives.

The research was led by Professor Svend Mortensen from Copenhagen, Denmark. In the study, individuals with severe heart failure were given 100 mg of coenzyme Q10, three times a day in addition to their normal care for 2 years. Outcomes were compared with a similar group receiving normal care and a placebo.

According to the report, coenzyme Q10 therapy essentially halved the number of ‘major adverse cardiovascular events’. It also, apparently, halved the overall risk of death too.

If you follow this trail of evidence, it’s not too far-fetched to suggest that while statins may ‘save lives’ in the relative short-term by reducing the risk of, say, heart attacks, they may possibly cause some people to perish in the long term as a result of chronic coenzyme Q10 depletion and associated heart failure.

One of the studies referred to above [1] contains a notable quote:

Statin-induced CoQ10 deficiency is completely preventable with supplemental CoQ10 with no adverse impact on the cholesterol lowering or anti-inflammatory properties of the statin drugs. We are currently in the midst of a congestive heart failure epidemic in the United States, the cause or causes of which are unclear. As physicians, it is our duty to be absolutely certain that we are not inadvertently doing harm to our patients by creating a wide-spread deficiency of a nutrient critically important for normal heart function.

The authors of this study make a good point, I think, and it’s perhaps something we doctors should take heed of.

References:

1. Langsjoen PH, et al. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications. Biofactors 2003;18(1-4):101-11

2. Fotino AD, Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2013;97(2):268-75

I don’t have access to details of the poll or how it was done, but the tone of the article is that young children often have a reckless attitude to the sun. Here’s a quote from the piece:

These findings are really alarming as they show that children have little regard or knowledge of the dangers of the sun, or the consequences of spending time in the burning sun without protection.

This quote comes from Richard Cryne – Superdrug’s ‘sun care buyer’. And we all know how important it is to take sun exposure advice from a person whose job is to ensure his pharmacy’s shelves are stocked with sun care products.

Numerous times on this site I have written about the broad benefits of sunlight exposure. While increased exposure is associated with an increased risk of certain skin cancers, it’s also associated with a reduced risk of lots of other forms of cancer, as well as protection from other chronic diseases including cardiovascular disease and multiple sclerosis.

Quite a lot of evidence links these benefits to higher levels of vitamin D. Suncreens can block vitamin D production. They’re also quite chemicalised. They also might prevent burning but be used to extend time in the sun and allow increased exposure to potentially harmful rays. For more about this, see my blog post ‘The Dark Side of Sunscreens’. You can read there about some evidence which links sunscreen use with an increased risk of melanoma.

A couple of years back, I featured a BMJ column written by GP (family doctor) Des Spence on the very subject of sun exposure in kids. In this piece, he writes about the importance of vitamin D, as well as how increasing rates of melanoma are probably the result of ‘over-diagnosis’. He even refers to evidence which casts doubt on the idea that melanoma is chiefly caused by sunlight exposure. Here’s an extract from Dr Spence’s original piece:

Melanoma most commonly occurs in areas that are less sun exposed. It is 50% more common in social class one, despite the fact that manual workers are more likely to work outside and use sun beds.

The most conflicting evidence, however, is that despite a reported tripling of incidence, the actual death rate under 65 has remained unchanged. This observation cannot be explained by better treatment, because melanoma remains resistant to chemotherapy.

None of the doubts over the relationship between melanoma and sunlight or the safety and effectiveness of sunscreens make their way into the Daily Mail piece. We do learn, however, that the poll was a joint initiative between Superdrug and the skin cancer charity Skcin. See here for its corporate sponsors. Should you bother clicking on that link, I trust you won’t fall off your chair when you see sunscreen manufacturers there.

You may notice, also, that the author of the piece appears as ‘Daily Mail Reporter’. Why has no writer put their name to this piece? Because, I suspect, no journalist actually wrote it. I think it’s a ‘cut and paste job’. It’s not editorial or even news. It is, I think, just a press release.

This conversation came back to me this week on reading the summary of study in which young men spent two weeks on each of two eating regimes [1]:

1. normal eating

2. normal eating except no food between 7.00 pm and the following 6.00 am

Food intake and weight was calculated in both settings.

Here are the main findings of the study:

• In setting 1, individuals ate an average of 700 calories each day between 7.00 pm and 6.00 am.
• In setting 2, individuals ate no calories during this time period (as instructed).
• Over the course of the whole day, individuals in setting 1 ate an average of about 2660 calories each day.
• In setting 2, average daily intake was about 2420 (about 240 calories less than in setting 1).
• In setting 1, average weight change was a gain of 0.6 kg, while in setting 2, there was an average loss of 0.4 kg.

This is a small study, in a quite confined subset of people (young, healthy men) and relatively short in duration. However, it does provide evidence which suggests that cutting out evening eating may not be fully compensated for by additional eating at other times of the day, and may promote weight loss.

Another way of looking at this dietary tactic is as a form of intermittent fasting which I’ve written about here.

References:

1. Le Cheminant JD, et al. Restricting night-time eating reduces daily energy intake in healthy young men: a short-term cross-over study British

The British Medical Journal if waging a campaign for Roche to cough up the relevant information, and provided an update on the situation recently [1]. It is reported that on 2 April Roche informed researchers that it would give them 74 clinical study reports on Tamiflu over the next few months. To date, though, none of them have materialised.

If an when then critical information is yielded, then it may still prove difficult for researchers to perform a full analysis. I say this, because as the recent BMJ report details, another drug company has recently given up some data on its own flu drug, and the nature of this information has left a lot to be desired.

Drug company GlaxoSmithKline (GSK) gave researchers 30 reports relating to its flu drug zanamivir (Relenza) at the end of April. These reports hold vast amounts of information on the conduct of Relenza trials, outcomes and adverse events. The only problem is GSK has chosen to redact much critical information, including descriptions of serious adverse events and the start and stop dates of the trials.

The researchers who received the data have written to GSK and asked:

What type of independent research does GSK think this kind of release enables?

The true answer, I think, is probably: “Research that cannot reveal the full truth about the safety and effectiveness of Relenza.”

What we appear to have here is two drug companies making similar flu drugs that appear to be doing their damndest to ensure independent researchers are unable to assess these drugs properly.

Meanwhile, it has recently come to light that, partly due to poor record-keeping by the UK Department of Health, £74 million was wasted on Tamiflu.

This drug has been stockpiled by the British Government even though (as detailed above) the Government does not have all the data on it and what data we have shows that it really doesn’t work very well.

One might ask how it seems authorities have (literally) bought into flu drugs that aren’t particularly effective and on which the relevant data has not been made available. Back in 2010, the BMJ revealed potential conflicts of interest in the World Health Organization that may go some way to explain these anomalies. Here’s an extract from the report:

A joint investigation by the BMJ and the Bureau of Investigative Journalism has uncovered evidence that raises troubling questions about how WHO managed conflicts of interest among the scientists who advised its pandemic planning, and about the transparency of the science underlying its advice to governments. Was it appropriate for WHO to take advice from experts who had declarable financial and research ties with pharmaceutical companies producing antivirals and influenza vaccines? Why was key WHO guidance authored by an influenza expert who had received payment for other work from Roche, manufacturers of oseltamivir, and GlaxoSmithKline, manufacturers of zanamivir? And why does the composition of the emergency committee from which Chan sought guidance remain a secret known only to those within WHO? We are left wondering whether major public health organisations are able to effectively manage the conflicts of interest that are inherent in medical science.

The more one delves into the politics of flu medication, the murkier it get, it seems. One wonders what the drug companies might have to hide.

References:

BMJ 2013;346:f3190

The presumed mechanism involved here concerns the amino acid homocysteine – raised levels of which are associated with an increased risk of dementia. Vitamin B6 and B12 and folic acid have the capacity to lower homocysteine levels in the body. Interestingly, the previous research found that supplementation benefitted those who, prior to the study, had elevated levels of homocysteine, but not those with normal levels. This finding does support the idea that elevated levels of homocysteine can damage the brain, and that bringing levels down helps preserve brain functioning.

This week saw the publication of another follow-up study regarding this research. In this study, the impact of supplementation on the brain areas particularly affected by Alzheimer’s disease including the grey matter (outermost part of the brain) in a part of the brain known as the medial temporal lobe [3]. Compared to people taking placebo (inactive pills), atrophy here in those taking B vitamins was reduced by 90 per cent.

In summary, the research shows:

• B12, B6 and folic acid found to reduce brain atrophy in those with elevated levels of homocysteine
• In these people, B12, B6 and folic acid supplementation was found to improve brain function
• In these people, B12, B6 and folic acid supplementation was found to dramatically reduce brain shrinkage in the part of the brain most affected in Alzheimer’s disease

Lead researcher in this work, Professor David Smith, is listed as an inventor on patents held by Oxford University for B vitamin formulations to treat mild cognitive impairment and Alzheimer’s disease. However, taking the research at face value, what we have here is evidence that B-vitamin supplementation is a legitimate strategy for those suffering with mild cognitive impairment and raised homocysteine levels (the level of homocysteine used as the threshold for ‘raised’ homocysteine in these studies was 11 µmol/L).

What is strange about this research, I think, is how little impact it has had in some quarters of the medical and scientific communities. UK journalist Jerome Burne has been following the story throughout, and wrote this week about this latest study on his blog. Jerome, in his post, also examines some of the political reasons which might explain why the reaction to this research which has enormous implications has been somewhat lukewarm. You can read Jerome’s post here.

References:

1. Smith AD, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010;5(9):e12244.

2. de Jager CA, et al. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012;27(6):592-600

3. Douaud G, et al. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. PNAS published 20 May 2013

This sort of ‘epidemiological’ study cannot, however, prove that cannabis use brings these benefits for health, and only tell us that it’s associated with these benefits. At first sight, the findings actually appear to fly in the face of common sense. As the authors point out, marijuana users tend to consume more calories than non-users. The authors also refer to an increase in ‘acute intake’ with marijuana use (meaning that using marijuana can cause people to eat or drink more shortly after). Back in the day, we referred to this ‘increase in acute intake’ as ‘the munchies’.

I can certainly bear personal testament to this phenomenon. I still have vivid recollections of smoking pot in a former life (well, I was at medical school for 6 years) and the effect this had on me. After initially feeling ‘bombed out’, I would find something hilariously funny (that, in the cold light of day could only really be viewed as mildly amusing). Shortly after, I’d be driven to consume industrial quantities of, say, chocolate Hob Nobs (a type of biscuit/cookie) and tinned custard. How, on heaven’s earth could carb- and calorie-fest which invariably came as part and parcel of dope-smoking possibly lead to lower weight, reduced waist circumference and improved markers for diabetes, one might ask?

The authors of this research suggest some mechanisms that have to do with substances (such as cannabidiol) which bind to ‘cannabinoid’ receptors in the brain and may influence physiological factors. It’s been found, for instance, that mice genetically bred to lack one of the two main cannabinoid receptors (receptor number 1) are resistant to weight gain, suggesting a role for this receptor in obesity. Cannabidiol partially blocks cannabinoid receptors which might have some role in any weight reducing effect marijuana has. Adding strength to this idea is the findings of research which finds that giving cannabidiol to mice induces weight loss [2]. Also, giving cannabis to obese rats has been shown to have the same effect [3].

Unless these studies are replicated in humans, then we’re still in the dark about the effect cannabis has on weight and associated aspects of health. And, of course, there’s always the possibility that even if beneficial from these perspectives, cannabis may have the potential for harm too. Notably, there is some thought that cannabis has some ability to trigger psychotic illness.

However, there exists evidence that cannabis (and in particular cannabinoid substances found in it) offers the potential of doing more good than harm. Here’s an extract from a summary of an article about the impact of cannabinoids on health [4]:

Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson’s disease, Huntington’s disease, Tourette’s syndrome, Alzheimer’s disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable…

In a way, one might possibly think of cannabis or cannabinoids in a way similar to our general attitude to licenced ‘drugs’ or other conventional therapies (such as surgery): these invariably pose risks, but have considerable benefits to offer too.

References:

1. Penner EA, et al. The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults. Am J Med [epub 16 May 2013]

2. Weiss L, et al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006;39:143–151

3. Levendal R, et al. Cannabis exposure associated with weight reduction and β-cell protection in an obese rat model. Phytomedicine. 2012;19:575–582

4. Kogan NM, et al. Cannabinoids in health and disease. Dialogues Clin Neurosci. 2007;9(4):413-30

Taking a look around the internet I notice that there are ever-increasingly numbers of reports from individuals who appear to have suffered at the hands of statins. I see the same thing in my practice too. Not uncommonly, I’ve seen individuals who have symptoms such as fatigue and muscle pain who have seen these disappear or improve considerably on stopping their statin, only to return on resumption of it. Maybe these people have imagined these changes or it’s some sort of placebo effect going on, but I tend to take people at face value and believe their experience is what matters here. I also happen to believe, as I alluded to above, that statin side effects are more common than some would have us believe.

Another common symptom that crops up in statin-takers is ‘fuzzy thinking’ or ‘brain fog’. I was interested to read about a recent study [1] (report here) which found statins can have a very unusual effect on nerve cells (neurons).

The research, conducted at the University of Arizona, involved exposing nerve cells from the fruit fly to over 1,000 drugs in blind fashion (meaning that the researchers did not know what drugs were being added to the nerve cell cultures). At the end of the experiments, in four instances, the nerve cells developed an appearance of ‘beads on a string’. Here’s a ‘before (left) and after (right)’ photo.

It is believed that these bead-like growths within the nerve cells would hamper nerve transmission. So, here’s the kicker: in all four instances where this change occurred, the drug to which the nerve cells were exposed was a statin.

In the report about this study I linked to, the researchers involved in this study point out that there’s a chance that some people are more genetically susceptible to neurological statins than others, and that’s certainly valid in my opinion. Also, it should perhaps be borne in mind that culturing fruit fly cells with drugs in the laboratory does not necessarily mirror what happens when human beings take statin drugs orally.

However, it is known that certain statins are able to be absorbed into the brain (across the ‘blood brain barrier’) where, potentially, they may exert harmful effects. The statins which confer the greatest risk in this respect are described as ‘lipophilic’ (attracted to fat) statins and include commonly prescribed agents such as atorvastatin (Lipitor) and simvastatin (Zocor).

References:

1. Kraft R, etal. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions. Disease Models & Mechanisms 2012;6(1): 217

There are a number of reasons why conventional ‘dieting’ (using, say, a diet that is consciously restricted in calories and dietary fat) is unlikely to lead to lasting weight loss. One obvious issue is hunger. Consciously restricting calories will usually mean someone is hungrier than they would like, but weight loss seems to heighten this hunger, as evidenced by the fact that when individuals start to eat in a less restricted way, they can find themselves driven to eat larger quantities of food than they were eating before, at least until their weight ‘normalises’.

Another fundamental issue concerns the metabolic rate. We expect this to decline as the body loses weight. However, there is evidence that metabolic rates tend to decline significantly more than would be expected as a result of weight loss alone. For example, in the first controlled trial of the effect of calorie restriction on weight (the Minnesota Experiment), while weights declined by 20-26 per cent, energy expenditure fell by almost 40 per cent. This dwindling of the metabolism can cause people to plateau at a weight significantly higher than the one they were aiming for, and may also contribute to weight going back on scarily quickly once ‘diet’ is relaxed.

Without access to sophisticated testing equipment, it’s not possible to accurately gauge the impact of any diet on the metabolism. However, for those looking to lose weight in the long term, I generally advise people to avoid undue hunger. If we’re able to eat and live in a way that does not allow us to be unduly hungry then this suggests (though doesn’t prove) that the body is not being metabolically starved either.

Some people wonder how it is possible to lose weight without hunger. Well, my experience tells me this is entirely possible with most people as long as they choose the right foods. In general terms,  protein-rich are, calorie for calorie, more sating than carbohydrate rich ones. Carbohydrate-rich foods also have the added disadvantage of often destabilising blood sugar levels in a way which can drive hunger and food cravings.

There is also a theory that lower carbohydrate diets allow more ready release of fat from fat cells which can then be metabolised. The idea here is that those on a low-carb diet may be able to supplement what they’re not eating with their own fat, and may be less hungry as a result. This fatty fuel, of course, may also help to maintain the metabolism (just like putting a bit more coal on a fire would).

Recently, I came across a study which appears to support the idea that lower-carbohydrate diets are better for maintaining the metabolism than, say, low-fat ones, particularly in the context of weight loss [1].

In this study, overweight or obese aged 18-40 were assessed for a range of body measurements including ‘resting energy expenditure’ (the amount of energy burned at rest over 24 hours) and ‘total energy expenditure’ (the total amount of energy burned over 24 hours). The participants were then put on a weight-reducing diet until they had lost 10-15 per cent of their weight over a 12-week period.

Then, the study participants were monitored on the same diet but adjusted to ensure weight-stability rather than further weight loss.

After this, each participant ate three different diets in random order for four weeks each. The nature of each of the three diets was:

1. low-fat
2. low glycaemic index (emphasising foods that do not cause great disruption in blood sugar levels)
3. very low carbohydrate diet

Here’s a table which shows the dietary make-up of all four diets used in this study:

Body measurements, including resting energy expenditure and total energy expenditure were assessed at the end of each 4-week diet period. 21 participants completed the study.

One of the major things this study tested was the effect of different diets on the metabolic rates of individuals assessed before any weight loss. In this context, diets that led to the smallest reductions in metabolic rate would be generally view as superior.

Here’s the results from this experiment (REE = resting energy expenditure TEE = total energy expenditure).

You can see from this that the decline in REE and TEE was smallest with the very low carb diet and was biggest for the low-fat diet. The results were statistically significant.

If we focus on the total energy expenditure for a moment we can see that the low-carb diet preserved more than 300 kcals a day in expenditure compared to the low-fat one, which the authors describe as “…an effect corresponding to the amount of energy typically expended in 1 hour of moderate-intensity physical activity.”

However, not all the news was good about the very low carbohydrate diet, as it induced the highest levels of cortisol (a key stress hormone) and the inflammatory marker CRP (C-reactive protein). Against this, though, it perhaps considering that carbohydrate controlled diets have been shown to bring positive changes in a range of markers for chronic disease including improved blood sugar control, lower blood pressure, higher levels of ‘good’ (HDL) cholesterol and lower levels of blood fats known as triglycerides.

The reasons for the differences in resting energy expenditure and total energy expenditure are not easily explained. Factors such as physical activity, the thermogenic effect of food (the increase in energy expenditure arising from digestive and metabolic processes) and changes in the thyroid hormone T3 did not appear to provide the answer.

One potential explanation mooted by the authors concerns the hormone leptin. Leptin is secreted by fat cells and acts in the brain to quell appetite but also stimulate the metabolism. Leptin insensitivity (a failure of leptin to act efficiently) has been suggested to be a potential underlying mechanism in overweight and obesity (something that I explore in Escape the Diet Trap).

One way of gauging leptin sensitivity is be dividing energy expenditure by the level of leptin. The higher this number, the better leptin sensitivity is believed to be. In this study, the very low-carb diet produced the best leptin sensitivity, with the low-fat diet producing the worst.

This was a relatively small study and the test diets were relatively brief (4 weeks) in duration so we should perhaps not draw too many conclusions from it. However, there is some evidence here that diet lower in carbohydrate and richer in protein and fat may offer benefits over the long term for weight loss maintenance on account of their ability to help maintain the metabolism.

Another thing worth bearing in mind is that in this study, individuals were asked to eat calorie-counted quantities of food each day. In the real World, though, what makes a new way of eating easier and more sustainable is if it allows individuals to lose weight and maintain their weight loss without hunger and the need to consciously control how much they eat. As a general rule, as I alluded to above, here again diets relatively rich in fat and protein tend to win out over those based on carbohydrate.

References:

1. Ebbeling CB, et al. Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA. 2012;307(24):2627-34