Author Archives: Dr. Malcolm Kendrick

About Dr. Malcolm Kendrick

Malcolm Kendrick is a Scottish doctor and author of The Great Cholesterol Con (2008). He has been a general practitioner for over 25 years and has worked with the European Society of Cardiology.

The Great Placebo scandal

25th February 2020

In this blog I am going to have a closer look at an issue that has niggled away at me for a long time. Placebos. In part I was stimulated to write on this following an article that Maryanne Demasi published on the CrossFit site ‘Sometimes a placebo is not a placebo.’ 1

There are many, many different issues about placebos. Most of which people don’t even consider. Such as, is there really such a thing as the placebo effect? And if there is, how come we haven’t managed to sort out what it actually might be? I know most people reading this will retort. ‘Of course, there’s a placebo effect. It’s a known thing.’ Personally, I am not so sure. Like many known things it begins to fall apart under a bit of critical examination.

For example:

‘Whether you know you’re taking a placebo pill or not, it will still have a beneficial effect, new research has revealed. Scientists from Harvard University and the University of Basel prescribed a group of minor burn victims with a “treatment” cream, telling only some of them that it was a placebo. After the cream was applied, both groups reported benefits, despite the placebo cream containing no medicine.

The study goes against traditional medical thinking surrounding the placebo effect, which has always revolved around the idea that it was necessary to deceive patients in order for “sugar pills” to be clinically effective.’ 2

In short, you get the placebo effect whether you know, or don’t know, that you are receiving a placebo. Which kind of blows a major hole in rationale underpinning double-blind, placebo controlled clinical trials.

However, I am not exploring that particular rabbit hole today.

Today I am going to look at the question. What is in a placebo? You may well believe you know the answer to this. A placebo is an inert formulation containing no active ingredients.

This is a reasonable assumption to make as the medical definition of a placebo, as taken from the Merriam-Webster medical dictionary, is:

‘1a: a usually pharmacologically inert preparation prescribed more for the mental relief of the patient than for its actual effect on a disorder

b: an inert or innocuous substance used especially in controlled experiments testing the efficacy of another substance (such as a drug)’

A few years ago, I was speaking to an investigative journalist from the Netherlands who was trying to get hold of the placebo tablets used in a particular clinical trial. He wanted to establish exactly what was in them, and if they were truly inert. No such luck, these placebos were very carefully guarded, as was any information about what they contained.

He gave up, but I did file his tale in my mind, recognising this was something that needed to be looked in greater detail at some point in the future. Can it be true that placebos are not actually inert?

Surely, it’s possible to ask the pharmaceutical company running the trial what’s in the placebo. Well, you can try. To quote a section of Maryanne’s article

‘The process of obtaining regulatory documents, however, is by no means straightforward. In fact, it is often complicated and time consuming. I have made multiple appeals to a European drug regulator (Medicines Evaluation Board) to obtain information (Certificate of Analysis) regarding the ingredients of a placebo used in a controversial statin study (JUPITER trial), but so far, they have fallen on deaf ears. So, too, have my requests to the trial’s lead investigator, Dr. Paul Ridker.

Medical journals will need to take responsibility and insist that published papers report on the methodological details of “inactive” placebos. Recently, Shader of Clinical Therapeutics stated, “It will no longer be sufficient to simply indicate that a placebo was used.”

“We will require that a full description of any placebo or matched control used in a clinical trial be given in the Methods section. This means that color; type (capsule or pill or liquid); contents (e.g, lactose), including dyes; taste (if there is any); and packaging (e.g, double-dummy) must be noted,” he stated. “We are instituting this change as part of our ongoing effort to facilitate replication of findings from trials. All too often this valuable information is omitted from published trial results.”

In short, you can’t find out what is contained within the placebos. Or at least, it is exceedingly difficult – to impossible.

This is very disturbing indeed, because it has become increasingly clear that placebos are often far from inactive or inert. In fact, they often contain some quite unpleasant substances. For example, here from an article in Medical News Today

‘The authors outline an example where a particular placebo skewed the results of several studies. In studies that investigated oseltamivir, which people may know by its brand name Tamiflu, scientists often added dehydrocholic acid to the placebo.

Dehydrocholic acid has a bitter taste, as does oseltamivir. The researchers chose to add this chemical to the placebo so that the participants would not know whether they had received the active drug or the placebo.

However, both dehydrocholic acid and oseltamivir cause gastrointestinal side effects. When scientists attempted to calculate the rate of gastrointestinal side effects due to oseltamivir, they compared them with side effects from the placebo.

As the placebo also caused these types of symptoms, scientists underestimated the overall gastrointestinal side effect rate for oseltamivir.3

Essentially, and you may find this rather shocking, a company doing a clinical trial can stick almost any nasty substance they like into a placebo and tell no-one. There are no regulations to prevent this happening, or at least none that I can find.

From time to time, however, the secret ingredients are revealed, or discovered, such as dehydrocholic acid. Here is Maryanne on the Gardasil (HPV) vaccine. In this case the ‘secret ingredient’ in the placebo was also identified.

‘In trials of the human papilloma virus (HPV) vaccine, participants were told they were either receiving a “vaccine or placebo.” The vaccine manufacturer defines a placebo as an “inactive pill, liquid, or powder that has no treatment value.”

However, participants in the placebo group did not receive an inactive substance of no treatment value. “Instead,” RIAT researchers state in the BMJ, “they received an injection containing amorphous aluminium hydroxyphosphate (AAHS), a proprietary adjuvant system used in the Gardasil vaccine to boost immune response.” 4

[RIAT = Restoring invisible and abandoned trials. Good people]

This is worrying. Many of those who are concerned about the potential for vaccine damage, believe it may well be the amorphous aluminium hydroxyphosphate (AAHS) itself which is the substance that can cause the adverse effects seen with many vaccines.

If both placebo, and vaccine, contain this adjuvant, then… it’s a free pass for the vaccine. In order to hide adverse effects with the vaccine, the placebo contained the substance suspected to cause adverse effects. Anyone who thinks that is remotely acceptable needs a long hard look in the mirror…

However, important thought it may be, it is time to move onto my favourite subject, statins – and placebos. For years I been highly suspicious of the adverse effect rates seen in the statin clinical trials. My concerns, and the concerns of others, formed part of a letter written to the then Health Secretary (Jeremy Hunt), and also to the National Institute for Health and Care Excellence 5

Here was the section on adverse events:

  1. Conflicting levels of adverse events

In emphasising the cost per Quality Adjusted Life Year (QALY), NICE is clearly making a major assumption that the key issue is mortality reduction, and that statins lead to very few adverse effects. We would question this very strongly.

The levels of adverse events reported in the statin trials contain worrying anomalies. For example, in the West of Scotland Coronary Prevention Study (WOSCOPS, the first primary prevention study done), the cumulative incidence of myalgia was 0.6% in the statin arm, and 0.6% in the placebo arm*

However, the METEOR study found an incidence of myalgia of 12.7% in the Rosuvastatin arm, and 12.1% in the placebo arm

Whilst it can be understood that a different formulation of statin could cause a different rate of myalgia, it is difficult to see how the placebo could, in one study, cause a rate of myalgia of 0.6%, and 12.1% in another. This is a twenty-fold difference in a trial lasting less than half as long*.

Furthermore, the rate of adverse effects in the statin and placebo arms of all the trials has been almost identical. Exact comparison between trials is not possible, due to lack of complete data, and various measures of adverse effects are used, in different ways.

However, here is a short selection of major statins studies.

AFCAPS/TEXCAPS: Total adverse effects lovastatin 13.6%: Placebo 13.8%

4S: Total adverse effects simvastatin 6%: Placebo 6%

CARDS: Total adverse effects atorvastatin 25%: Placebo 24%

HPS: Discontinuation rates simvastatin 4.5%: Placebo 5.1%

METEOR: Total adverse effects rosuvastatin 83.3%: Placebo 80.4%

LIPID: Total adverse effects 3.2% Pravastatin: Placebo 2.7%

JUPITER: Discontinuation rate of drug 25% Rosuvastatin 25% placebo. Serious Adverse events 15 % Rosuvastatin 15.5% placebo

WOSCOPS: Total adverse effects. Pravastatin 7.8%: Placebo 7.0%

Curiously, the adverse effect rate of the statin is always very similar to that of placebo. However, placebo adverse effect rates range from 2.7% to 80.4%, a thirty-fold difference.

How can the adverse effects of placebo range from 2.7% to 80.4%? Yes, there can be differences in the way that adverse effects are recorded, and that could explain, perhaps a five-fold difference – being extremely generous. But a thirty-fold difference?

Also, how can it be possible that the adverse effects of the placebo, and the statin, are always, almost exactly the same, in all trails – no matter the absolute figure. I believe that this could not possibly occur unless:

  • The placebos in each trial were carefully formulated to cause adverse effects at the same rate as the statin
  • The statistics on adverse effects were manipulated

Neither possibility should fill anyone with joy, nor confidence in the regulatory systems.

I have raised this issue with a number of different people, but they all seem determinedly disinterested. I suppose that if either of my two statements are true, it means that the entire database of randomised double-blind placebo-controlled trials can no longer be trusted. This is not a nettle to be grasped. It is a fifty-thousand-volt power line with a sign reading ‘Danger of Death!’ attached.

I can well understand the reluctance to investigate. However, I do not believe that we can possibly allow the formulation of placebos to remain a well-kept secret in future, current, or past trials.

If my suspicions about placebos are wrong, then can someone please prove me wrong.

*in the letter I had calculated this figure wrongly. It was not 0.06%, it was 0.6%. So, I have changed the text in the blog to reflect that.






A podcast you may want to listen to

9th February 2020

The good thing about having different ideas about diet, obesity, diabetes and heart disease and suchlike, is that you get to meet with such interesting people. Steve Bennett is one such. He set up successful businesses, that have nothing whatsoever to do with health, and only came to diet and health from his own interest and passion.

He then established a brand called Primal Living, based on eating food that we used to eat in the past. Woolly mammoths and suchlike and avoiding processed foods and carbs. In addition taking supplements that have been removed from our diet by the mass food manufacturing industry. It has improved his own health, and the health of many others.

He is, essentially, on the same pathway as Aseem Malhotra, Tim Noakes, Ivor Cummins, Zoe Harcombe, Gary Taubes, David Unwin – and anyone else who has looked at diet, and health, and possess a fully functioning brain.

They have all – we have all – recognised that the current dietary guidelines are complete dangerous bunk, doing harm rather than providing benefit.

He was also good enough to allow me to outline my ideas on CVD, and the process of CVD, which his team has put together into a podcast. It can now be seen here

As always, I feel I have not really explained things as well as I can, but I hope you find it interesting, and I would welcome feedback and constructive criticism. I would further recommend looking at the other podcasts under the ‘Fat and Furious’ banner.

Coronary artery calcification (CAC)

17th January 2020

I thought I should write a blog on coronary artery calcification (CAC), as it has become the latest hot topic. CAC scans, and CAC scoring are now increasingly popular, and the results are worrying lots of people who wonder what they mean, and exactly how worried they should be. I get many e-mails on this issue from people who have been scared witless, or another word ending in***tless, by having a high CAC score.

What is coronary artery calcification

Coronary artery calcification (CAC) is the deposition of calcium in artery walls. It represents the final stages in the life cycle of some/many/most atherosclerotic plaques. At the risk of oversimplification, it is generally accepted that atherosclerotic plaques go through four stages

  • Small
  • Bigger
  • Vulnerable
  • Calcified

Forget small and bigger. The important ones are vulnerable and calcified. What is a vulnerable plaque? It is a plaque that reaches a certain size (undefined) containing an almost liquid core, with a thin cap. If this thin cap ruptures, it exposes the liquid core to the bloodstream triggering a major blood clot than can fully block a coronary artery and cause a myocardial infarction.

This is generally described as plaque rupture. If it happens in an artery in the neck, a carotid artery, the clot will normally not be big enough to block the artery. But it can break off and head up into the brain, causing a stroke.

Which means that it is these ‘vulnerable’ plaques that are dangerous, and these are often not calcified, and therefore cannot be seen on a CAC scan.

Over time, assuming the vulnerable plaques do not rupture and kill you, some of them (all of them?) shrink down in size, become more solid and start to calcify. At which point they are less likely to rupture and may be considered relatively benign.

Calcification of areas of damage in the body is not restricted to atherosclerotic plaques. Almost any damaged area in the body, that is not perfectly repaired, is likely to calcify to some extent or another. Scars tend to be white, and the white is calcium.

At the extreme end of calcification is a condition called myositis ossificans, whereby almost any damage ends up becoming bone. With damaged muscle turning into bone. This does not end well.

Anyway, assuming you have plaques developing and growing in your arteries, they will in time calcify. Or at least some of them will. Are some people genetically more likely to get calcification than others? Almost certainly.

Some things are known to increase the rate of calcification. Statins, for example. Here from the Cleveland clinic:

  • Patients with coronary artery disease (CAD) who are treated with statins experience an increase in coronary calcification, an effect that is independent of plaque progression or regression.
  • Paradoxically, high-intensity statin therapy is associated with the largest increases in coronary calcification despite promoting atheroma regression 1

With statins the plaques get smaller and the calcium load gets bigger.

Another drug that whacks up the rate of calcification is warfarin (often called coumadin in the US).

‘The vitamin K antagonist, warfarin, is the most commonly prescribed oral anticoagulant. Use of warfarin is associated with an increase in systemic calcification, including in the coronary and peripheral vasculature. This increase in vascular calcification is due to inhibition of the enzyme matrix gamma-carboxyglutamate Gla protein (MGP). MGP is a vitamin K-dependent protein that ordinarily prevents systemic calcification by scavenging calcium phosphate in the tissues.’ 2

High intensity exercise also stimulates CAC.

‘Emerging evidence from epidemiological studies and observations in cohorts of endurance athletes suggest that potentially adverse cardiovascular manifestations may occur following high-volume and/or high-intensity long-term exercise training, which may attenuate the health benefits of a physically active lifestyle. Accelerated coronary artery calcification, exercise-induced cardiac biomarker release, myocardial fibrosis, atrial fibrillation, and even higher risk of sudden cardiac death have been reported in athletes.’ 3

An interesting mix, I think.

  • Statins increase calcification
  • Warfarin increases calcification
  • Intense exercise increases calcification

Yet, all three reduce the risk of dying of cardiovascular disease. Yes, even statins – a bit.

But, let’s turn this around for a second. If you have no calcification in your arteries, you have a greatly reduced risk of dying of cardiovascular disease. Which means that calcification can be both good, and bad? Yes, you are right, this area is not straightforward at all.

Even if you look at non-calcified atherosclerosis, or pre-calcified atherosclerosis, the picture is complex.

For many years I have studied the Masai villagers, on and off. They are fascinating because, amongst Masai males, the diet almost entirely consists of cholesterol and saturated fat – or at least it did. Nowadays, I believe it is more McDonalds and Subway.

Despite their previous super-high saturated fat and cholesterol diet, their cholesterol levels were the lowest of any population studied. However, they developed atherosclerosis at around the same rate as any Western male of the same age.

Added to this, and just to make things even more complicated, there were no recorded cases of any male Masai villagers dying of CVD. Which made me think, at one time, that atherosclerosis and death from CVD must be unrelated phenomenon.

You think not? Here, for example, is a study on the Masai from 1971 by George Mann (who helped to set up the Framingham Study and then became a trenchant critic of the cholesterol hypothesis).

Atherosclerosis in the Masai

‘Do the Masai not develop atherosclerosis or do they have it but remain immune to occlusive disease because of some other protective circumstances? The question was answered with autopsy material collected over a five-year period. The Masai do have atherosclerosis but they are almost immune to occlusive disease.’ 4

Now, if we bring these facts together, what do they tell us. At the risk of running the thinking too fast, these facts tell us that atherosclerosis, calcified or not, is necessary for someone to die from CVD. However, it is not sufficient, by itself, to cause death from occlusive disease.

In epidemiology this is the well-recognised concept of ‘necessary but not sufficient’. It actually applies to many/most diseases. For example, you cannot get TB, or die of TB, without infection with the tuberculous bacillus. However, you can be exposed to the bacillus and not have TB.

Why, because your immune system fought it off. Which means that the tuberculous bacillus is necessary but not sufficient, to cause infection and death from TB. As a slight aside, one sign of TB is calcified nodes in the lungs. Which can mean that you have active TB. Alternatively, it can mean that you had active TB, which has now been cleared out, leaving only calcification.

Turning back to atherosclerosis, and using the Masai as one example, it is clear that you can get atherosclerosis, and calcified atherosclerosis, and not die of CVD, or even have an increased risk of CVD. Why, because other factors are required to kill you. Which is why it can be said that atherosclerosis is necessary, but not sufficient, to cause heart attacks and strokes.

To put this another way, you are exceedingly unlikely to die from an acute blockage to an artery without any atherosclerosis [or at least this is vanishingly rare], but just having atherosclerosis is not sufficient to cause heart attacks and strokes.

Which means that for example, if your atherosclerosis is (only) caused by intense exercise you are at no significant increased risk of dying CVD. In this case your calcified atherosclerosis is not sufficient to cause CVD.

‘A new study of mostly middle-aged men in JAMA Cardiology found the most avid exercisers—averaging eight hours per week of vigorous exercise—did indeed show greater levels of coronary artery calcium (CAC). Nevertheless, they were less prone to dying over the average follow-up period of 10.4 years compared to men who exercised less, suggesting they can safely continue their workout regimens. 5

However, if your CAC score has gone through the roof because of say: diabetes, smoking, steroid use, air pollution, heavy metal toxicity, high Lp(a), lack of various nutrients etc. then you are at great risk of dying of CVD, and you need to do something about it.

Further complications

At one time atherosclerosis was defined as either athero…sclerosis, or arterio…sclerosis, in acknowledgement that there seem to be two distinct and different type of …sclerosis in your arteries. This concept seems to have fallen by the wayside.

This may be a mistake. Some years ago, the AHA tried to define all the different types of lesion* that could be found in arteries. The report was so big, that it got split in two 6.7. Then it got ever bigger, and then they gave the project up. The reports are long, and mind splittingly boring. One of them was a ‘twenty cups of coffee’ read. Followed by three Red Bulls.

(*lesion = abnormal thing)

What I learned, I think, in the moments when I was still conscious, was that atherosclerotic plaques are most certainly not all the same. Which lead me to think that we should attempt to bring back arteriosclerosis as a concept.

By which I mean the idea that some plaques develop, primarily, in response to biomechanical stress – such as is caused by physical exercise. On the other hand, some plaques develop in response to factors that independently damage the endothelium – such as a high blood sugar level, or smoking. With the addition of high clotting factors.

Whilst all plaques are now called atherosclerotic plaques, they do not all look the same, and they probably do not act the same. The arteriosclerotic lesions are thinner and more fibrous, they have no real lipid core and are very unlikely to rupture. They are, still, sometimes called fibroatheroma.

On the other hand atherosclerotic lesions are thicker, have a lipid core, more likely to narrow the artery and are also more likely to rupture, causing an occlusive blockage – leading to a stroke and/or heart attack.

Which is why the Masai (the most heavily exercising population on the planet – at the time) had …sclerosis yet remained ‘almost immune to occlusive disease’. Which is also why people who exercise intensely can develop …sclerosis and calcification but are not at an increased risk of dying of CVD.

However, both arterio and athero… sclerosis can calcify. So, they (probably) look much the same on the CAC san.

Moving on, again.

Sensitivity and specificity

Getting back to the CAC test, and what it means. The next issue is one that plagues all screening tests. Namely, what is the sensitivity, and what is the specificity? Something I always get the wrong way around in my head, then I must go back and look it up, to get it clear again.

To explain. A perfect screening test is one that is 100% sensitive and 100% specific. No test has ever achieved that, and I doubt any test ever will.

Sensitivity means, how good is the test at picking up that someone with the disease is identified as having the disease. Specificity means, how good is the test at making sure that people who do not have the disease are accurately told that they do not.

If we look at breast cancer, the first sign of breast cancer can often be that a woman feels a lump in her breast. However, many things that are not breast cancer, can cause a lump in the breast. Let us say 50% of palpable lumps are not breast cancer. If this is true, then the specificity of manual examination of the breast, in detecting breast cancer, would be 50%.

What of mammography? While it is clearly much better than manual palpation (from a sensitivity point of view) many cancers that cannot be felt, can still be seen on a scan, but it is actually worse from a specificity point of view.

This is because many/most ‘abnormal’ things seen on a mammogram will turn out to be benign. Sensitivity and specificity are often inversely related.

Some things sit in an intermediate area. In breast cancer screening a lot of women are told they may have breast cancer, but what has been detected is an abnormality called ductal carcinoma in situ (DCIS). This is something that may, or far more likely may not, progress to become a significant breast cancer. Should it be treated, or not?

The specificity problem is a problem for almost all screening tests. You have managed to find something abnormal on your test. Is it really abnormal? Does it need treatment? Would it have been better not to have found this ‘abnormality’ at all.

This is not a simple argument. Although it is usually presented in the most black and white terms if you question the breast cancer screening programmes. ‘Do you want women to die of breast cancer?’ Is a statement I have often heard from the pro-screening side. How does one answer this? ‘Well, of course I do. I see it as my role, as a doctor, to ensure that as many women as possible die from breast cancer.’

The real debate, of course, is far more complex and nuanced. Do the harms of finding benign abnormalities (with all the anxiety, further investigations, possible mastectomies etc. that this causes) outweigh the benefits of finding breast cancer at an early stage? Currently, the answer seems to be … yes.

If you want a far more detailed review of this area, you could buy the book ‘Mammography Screening’ by Peter Gøtzsche.

‘If Peter Gøtzsche did not exist, there would be a need to invent him … It may still take time for the limitations and harms of screening to be properly acknowledged and for women to be enabled to make adequately informed decisions. When this happens, it will almost entirely due to the intellectual rigour and determination of Peter Gøtzsche.’ Iona Health President RCGP (Royal College of General Practitioners)

Screening and scanning always seems a fantastic idea. Pick up a disease early, then you can treat it, even cure it. Presented in this, the simplest form, who could argue against it?

But it is not simple, in medicine very few things are. Breast cancer screening – in fact most cancer screening programmes – are far from black and white. You can argue for them, you can argue against them.

And, at present, cancer screening programmes are much better than CAC screening, for many other reasons. I will only deal with the most important one. Which is that… We don’t know what to do about the finding!

If you find a small, early stage, not yet spread anywhere, breast cancer you can remove it. It is gone, never to return. But what are you going to do with calcified plaques? You certainly can’t remove them. You do not know if they are going to rupture. They probably won’t. If you manage to stop the calcification getting worse, are you doing any good. Who knows? What caused them in the first place?

It is not even the calcified plaque that is the problem. The calcified plaque is only really a marker for earlier stage vulnerable plaques. If these start to calcify, this is probably a good thing, but whilst calcification is going on, the CAC score will be getting worse – while your risk of suffering a myocardial infarction is falling.

Sensitivity and specificity, false positives – and CAC scans (Pandora’s box)

My first general comment here is that you should never start screening and scanning until you are extremely certain, based on strong evidence, that you understand the natural history of the disease you are screening for.

Also, that you fully understand what the results of your test mean. And that you have an effective treatment for any abnormality you find.

These criteria are all missing with CAC scans.

Yes, a negative scan – no calcium detected – has reassurance value. If you have no calcium in your arteries, you almost certainly do not have any type of …sclerosis in your arteries. So, your risk of CVD is low.

However, positive scans, like positive mammograms, will include a very high number of false positives. Then what? You have been told you have significant calcification in your arteries. But it is ‘good’ calcification, or ‘bad’ calcification. Are you at increased risk, or not? This, no-one can tell you, for sure.

Equally, if you have calcification in your arteries, what are you going to do about it? Take statins… that makes it worse. Do more exercise…. that makes it worse. If you don’t know why you have calcification in the first place, it becomes impossible to take steps to do anything about it.

This is somewhat analogous to having a genetic test to discover if you have Huntington’s Chorea – if one of your parents had it. Do you want to find out that you have a disease – which will kill you – that you can do absolutely nothing about?

In a similar way should you have a test for Alzheimer’s, to find out if you are going to get the disease. Do you really want to know that you are going to have a terrible and devastating disease, and that there is nothing that can be done to prevent it?

In fact, CAC scans meet most of my criteria for ‘a bloody awful test that should not be done.’ It may or may not mean anything, there is no clear guidance as to what you can do about it if it is positive, and it spreads fear and anxiety in many, many, people. I should know, my inbox is stuffed with e-mails from people terrified by their CAC score.


My first recommendation is that, if you have not had a CAC scan, do not have one.

My second recommendation is that, if you have had a CAC scan, and it shows no calcification, good. Do not have another one.

If, however, you have had a CAC scan and it shows significant calcification. What then? What then indeed? You may want to read this paper: ‘Non-invasive vulnerable plaque imaging: how do we know that treatment works?’

‘Atherosclerosis is an inflammatory disorder that can evolve into an acute clinical event by plaque development, rupture, and thrombosis. Plaque vulnerability represents the susceptibility of a plaque to rupture and to result in an acute cardiovascular event. Nevertheless, plaque vulnerability is not an established medical diagnosis, but rather an evolving concept that has gained attention to improve risk prediction. The availability of high-resolution imaging modalities has significantly facilitated the possibility of performing in vivo regression studies and documenting serial changes in plaque stability. This review summarizes the currently available non-invasive methods to identify vulnerable plaques and to evaluate the effects of the current cardiovascular treatments on plaque evolution.’ 8

It will, at least, give you some idea of the other forms of investigation that are available.

Or, you might want to read this one: ‘New methods to image unstable atherosclerotic plaques.’

‘Atherosclerotic plaque rupture is the primary mechanism responsible for myocardial infarction and stroke, the top two killers worldwide. Despite being potentially fatal, the ubiquitous prevalence of atherosclerosis amongst the middle aged and elderly renders individual events relatively rare. This makes the accurate prediction of MI and stroke challenging. Advances in imaging techniques now allow detailed assessments of plaque morphology and disease activity.

Both CT and MR can identify certain unstable plaque characteristics thought to be associated with an increased risk of rupture and events. PET imaging allows the activity of distinct pathological processes associated with atherosclerosis to be measured, differentiating patients with inactive and active disease states. Hybrid integration of PET with CT or MR now allows for an accurate assessment of not only plaque burden and morphology but plaque biology too.

In this review, we discuss how these advanced imaging techniques hold promise in redefining our understanding of stable and unstable coronary artery disease beyond symptomatic status, and how they may refine patient risk-prediction and the rationing of expensive novel therapies.’ 9

The key words in that abstract are ‘hold promise.’

My final recommendation is that we should NOT be doing CAC scans, until it can be proved in a well conducted clinical trial, that we can do something positive and beneficial about the findings.

Yes, a ‘negative’ CAC is reassuring. This, however, must be set aside against the psychological damage caused by a ‘positive’ CAC scan. At present we are playing a form of psychological Russian Roulette. Half the population walks away reassured, half the population reels away, scared witless.

Also, often puzzled and disappointed. I have lost count of the number of people who have written to me saying that they: don’t smoke, exercise regularly, are not overweight, have low cholesterol levels, do not have high blood pressure, do not have high blood sugar levels, etc. etc. yet they have a terrifyingly high CAC score. What should they do?

Well, what can they do?

I don’t know. Because I don’t know what the test means. Not for sure. Not enough to provide any advice that I can be certain is right. Some boxes are better left unopened, however tempting it may be to peek inside.

Just because you can do something does not mean that you should.












Another new study

23rd December 2019

Another new study

Question: If a tree falls in the forest, and there’s nobody around to hear, does it make a sound?

This is a philosophical question that has been around for some time. I shall change it slightly to the following: “If a journal publishes a study, and it doesn’t make a noise, can it make a difference?”

A couple of weeks ago the Lancet published a ridiculous study with the snappy title:

‘Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.’

Which created headlines around the world – most of which failed to understand the difference between LDL (‘bad’ cholesterol) and non-HDL cholesterol. Which may, or may not, have been deliberately done.

This study was reported as saying that twenty-five-year olds should get their cholesterol checked, because raised cholesterol is far more damaging, at a young age, than previously thought. All based on, pretty much nothing at all. I critiqued it in my last blog. It was, to use a word I rather like … bilge!

Then another study came out last week to which I was pointed by a reader of this blog… thanks. It had the even snappier title:

‘Association between hyperlipidaemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score matched cohort study and a meta-analysis.’ 1

You know that title really does not scream ‘READ ME!’ What is it about medical journals, and medical writing, which demands all enthusiasm and interest is sucked out, leaving only the driest, of dry, husks. I call it mummified prose.

What I first noticed was that it did not appear to make any headlines, anywhere, at all. Of course, making enough noise to be heard, in today’s jittery, overloaded information world, takes a lot of money and effort. Which is why the Lancet study got blanket coverage. Someone, somewhere, will have been paid a lot of money to ensure that it happened.

The money was paid because there are people who stand to make billions and billions from increased cholesterol testing, including younger people, and suggesting that “raised” cholesterol must be ‘treated’ from an ever-younger age. Perhaps you would like to guess who those people may be.

On the other hand, the study ‘Association between hyperlipidaemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score matched cohort study and a meta-analysis.’ could result in the loss of billions and billions.

Because what they found, was that, after an acute myocardial infarction (AMI), and in people with acute decompensated heart failure (ADHF) – normally caused by a previous MI – the higher the LDL level, the lower the overall mortality. They called a higher LDL level hyperlipidaemia (HLP), but it was a high LDL a.k.a. ‘bad’ cholesterol.

The ‘association’ of which they spoke, is in the exact opposite direction to that in the Lancet study. Just to repeat their main finding. Those with higher LDL levels lived the longest. Full stop, exclamation mark.

They set the study up to consider the following questions – I make no excuses for the jargon here:

‘We postulated that if a diagnosis of HLP [Hyperlipidaemia] decreases the mortality after AMI or HF [Heart Failure], then, it also lessens the magnitude of mortality risks associated with other competing comorbidities.

We tested this hypothesis, separately, in large cohorts of patients hospitalised for incident AMI and acute decompensated HF (ADHF). To compare patients with and with no HLP, we assembled 1:1 balanced groups using propensity score-matching for each study condition.

Our objectives were three-fold:

(1) to estimate the association of HLP with all-cause mortality among patients with AMI or ADHF,

(2) to determine the extent to which the association between other competing comorbidities and mortality is modified by HLP

(3) and to provide risk estimates for mortality associated with HLP after incident AMI or HF through systematic review and meta-analyses of published and current study data to place the current findings in the context of published literature.’

Here were the main results. First for those diagnosed with AMI:

  • In matched patients, mortality was significantly lower among patients with Hyperlipidaemia (HLP) versus those with no Hyperlipidaemia (HLP)
  • Overall mortality 2182 (50.2%) vs 2718 (62.5%)
  • 5.9 vs 8.6 deaths/100 person-years of follow-up, p<0.0001.

Next for those diagnosed with acute decompensated heart failure (ADHF):

  • In matched patients, mortality was significantly lower among patients with HLP versus those with no HLP
  • Overall mortality 1687 (58.6%) vs 1948 (67.7%)
  • 12.4 vs 16.3 deaths/100 person-years of follow-up, p<0.0001.

You may have noted that the mortality rate in these patients was very high. For those with ADHF, and lower cholesterol levels (LDL levels), the mortality rate was 16.3 deaths per 100 person years. That is a sixteen point three per-cent death rate per year. One in six.

This, therefore, is a super, exceptionally high-risk population. It is also a super exceptionally high-risk secondary CV prevention population. The exact group where statins are purported to do the most good – through the specific action of lowering LDL levels.

At this point, a short detour. I know any cardiologist reading this will be thinking – or has been taught to think: “Yes, but low cholesterol is a sign of other serious conditions, such as cancer. Ergo, it is not the low cholesterol that is damaging, it is the other underlying conditions”.

This ‘fact’ been stated for many years – without a single scrap of evidence to support it.

It was Stamler who first came up with this ‘apologia’ for much contradictory evidence about low LDL levels and increased mortality. Like many things in medicine it is universally believed, without any supportive evidence. It is true that in a very few cases, late stage terminal cancer, and late stage liver failure, the LDL levels can drop. Otherwise … nothing.

However, these researchers made sure they adjusted for this, non-existent, factor anyway.

‘Our findings were adjusted for cancer and numerous other Clinical Conditions.’

What were the conclusions of this study? Well, they were exceptionally carefully worded.

‘The findings of this study, if validated, should reinforce the importance of HLP in predicting long-term mortality after index AMI or ADHF and potentially provide guidance for subsequent management. HLP can readily be diagnosed and help recognise AMI and HF patients with lower long-term mortality.

In these patients, clinical care should not focus on certain lipid targets; rather evidence based secondary prevention strategies should be initiated.

Conversely, patients with AMI and ADHF without HLP may be considered to have increased risk for early mortality and potentially alert providers for close monitoring during hospitalisation and after discharge. Both categories of patients would profit from thoughtful tailored programme with distinctive goals of care for existing CCs.’

Let me cut to the key comment in that passage. That is, the comment regarding those patients who had HLP:

Clinical care should not focus on certain lipid targets

Clinical care should not focus on certain lipid targets

Clinical care should not focus on certain lipid targets

I thought it was so good, I should say it thrice, for that makes it true. According to Lewis Carroll anyway.

“Just the place for a Snark!” the Bellman cried,

   As he landed his crew with care;

Supporting each man on the top of the tide

   By a finger entwined in his hair.

“Just the place for a Snark! I have said it twice:

   That alone should encourage the crew.

Just the place for a Snark! I have said it thrice:

   What I tell you three times is true.”

Of course, the comment is couched in such diplomatic language that I am not absolutely sure what is meant by it, although I am pretty sure.

On that basis, I shall wind up the emotion of the language somewhat. ‘These poor people, who are dreadfully ill, who have suffered the agony of a heart attack, or severe heart failure, fare so much better when they have a high LDL level. So, for pity’s sake, I beseech thee in the name of God, do not try to lower their LDL level you mad fools. Aaaaaarrrrrrrrggggghhhhh! Gasp, bonk.’

Maybe a touch too emotive? Oh well – after reading too many clinical papers, the temptation to shout become irresistible. Creeping around in the grey and lifeless world of the passive voice is not really my style. Science should not be a place of hushed diplomacy. Science should be lively and stimulating, nay argumentative. If you’ve got something to say, shout it out. Fight for it and debate it properly.

Anyway, my original question was the following. ‘If a journal publishes a study, and it doesn’t make a noise, can it make a difference?’ The answer is, almost certainly, no. Hopefully, however, I have now made a bit of noise, and maybe this study can make a bit of difference.


The Lancet Study

11th December 2019

Several people have asked me to comment on a recent Lancet paper ‘Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.’ which made headlines around the world. Here – for example – from the BBC website:

What did the researchers find?

People should have their cholesterol level checked from their mid-20s, according to researchers. They say it is possible to use the reading to calculate the lifetime risk of heart disease and stroke.

The study, in The Lancet, is the most comprehensive yet to look at the long-term health risks of having too much “bad” cholesterol for decades. They say the earlier people take action to reduce cholesterol through diet changes and medication, the better.

They analysed data from almost 400,000 people from 19 countries and found a strong link between bad-cholesterol levels and the risk of cardiovascular disease from early adulthood over the next 40 years or more.

They were able to estimate the probability of a heart attack or stroke for people aged 35 and over, according to their gender, bad-cholesterol level, age and risk factors such as smoking, diabetes, height and weight, and blood pressure.

Report co-author, Prof Stefan Blankenberg, from the University Heart Center, Hamburg, said: “The risk scores currently used in the clinic to decide whether a person should have lipid-lowering treatment only assess the risk of cardiovascular disease over 10 years and so may underestimate lifetime risk, particularly in young people.” 1

The Daily Mail in the UK was a bit more excitable in its reporting

‘Adults ‘should have their cholesterol checked at 25’ because slashing it in the mid-30s can drastically reduce the risk of heart attacks and strokes

Researchers predicted huge 30-year risk profiles for heart disease and stroke, they found higher cholesterol in under-45s is more dangerous than in over-60s Even young people with healthy lifestyles ‘may benefit from knowing their risk.’ 2

My first thought, as always, is to look for the conflict of interest statement, just so you know how independent the researchers may be and make an estimate of potential bias.

My second thought was that this study did not look at cholesterol levels, or HDL levels, it looked at non-HDL cholesterol. An interesting thing to study. This is every form of liver derived lipoprotein that is not HDL, otherwise known as ‘good cholesterol’ or simply high-density lipoprotein.

Part of the reason for not looking at LDL, is that LDL is very rarely measured, or reported. Because the only way to measure LDL accurately is through ultracentrifuge, which is time consuming and expensive. Normally, the LDL levels are simply estimated using the Friedwald equation. To quote from the UK GP Notebook

‘… the ultracentrifugal measurement of LDL is time consuming and expensive and requires specialist equipment. For this reason, LDL-cholesterol is most commonly estimated from quantitative measurements of total and HDL-cholesterol and plasma triglycerides (TG) using the empirical relationship of Friedewald et al.(1972).

[LDL-chol] = [Total chol] – [HDL-chol] – ([TG]/2.2) where all concentrations are given in mmol/L (note that if calculated using all concentrations in mg/dL then the equation is [LDL-chol] = [Total chol] – [HDL-chol] – ([TG]/5))3

*TG = triglyceride

This means that the researchers will not have had any data on LDL levels for most people. The difficulty of directly measuring LDL is the reason why the risk calculators used in the UK and US do not even include LDL. These calculators are Qrisk3 and cvriskcalculator

So, it is important to note that this was not a study on LDL levels. Instead, it was a study on non-HDL levels. Which changes it into something completely different than was reported. Obviously, non-HDL levels bear some relationship to LDL, in that a higher LDL level will tend to raise the overall non-HDL cholesterol level.

However, and very importantly, non-HDL also includes the triglyceride (TG) level. Or at least the TG level divided by 2.2. This is important because a high triglyceride (TG) level, divided by 2.2 or not, is a strong indicator of insulin resistance, which leads to type II diabetes. Here is what WebMD has to say on the matter

‘High TG’s signals insulin resistance; that’s when you have excess insulin and blood sugar isn’t responding in normal ways to insulin. This results in higher than normal blood sugar levels. If you have insulin resistance, you’re one step closer to type 2 diabetes.’ 4

Insulin resistance, whether or not it has developed into type II diabetes, greatly increases your risk of both CVD and overall mortality, as outlined in the paper. ‘Triglyceride–to–High-Density-Lipoprotein-Cholesterol Ratio Is an Index of Heart Disease Mortality and of Incidence of Type 2 Diabetes Mellitus in Men.’

‘This study shows that a high TG/HDL-C ratio in men is a predictor of mortality from CHD and CVD. The TG/HDL-C ratio had a significant and higher HR [hazard ratio] for mortality from CHD and CVD than was found for the TyG index [fasting blood sugar]. These 2 measures, TG/HDL-C ratio and TyG index, similarly predicted incidence of type 2 diabetes, but the HR associated with a high TG/HDL-C seems to make the ratio a preferred single parameter of measurement.’ 5

You will get no argument from me that a high triglyceride level is going to indicate the underlying metabolic catastrophe that is insulin resistance. This, in turn, is going to greatly increase the risk of CVD and early death. But this will have nothing to do with the LDL level. So, it has nothing to do with ‘bad’ cholesterol. Instead is to do with triglycerides.

Therefore, this study is like looking at people who smoke, and who eat red meat, then stating that red meat consumption and smoking cause lung cancer. You have arbitrarily rammed two things together without making any effort to decided which causes what. Scientific nonsense.

There also some massive statistical problems with this study. Where, for example is overall mortality? Not mentioned. Not mentioned means it will not have been significant. Also, the use of a very wide and fuzzy ‘combined end-point.’ I have written about this many times, in many different places. It is a game played to claim statistical significance, where none really exists.

To try and explain as quickly as possible. The most powerful end-point is overall mortality i.e. how many people were dead in either group. Or, to be more positive, how many people were alive in either group.

After this come end-points of decreasing importance. For example, how many people died of CVD. This is clearly important, but if more people died of CVD in one group, yet they were less likely to die of cancer, the overall mortality could remain the same in both groups – even if CVD mortality were lower in one.

Group one

  • CVD deaths 150
  • Cancer death 150
  • Total deaths/mortality 300

Group two

  • CVD deaths 180
  • Cancer death 120
  • Total deaths/mortality 300

Net benefit = zero. But such results can often be hailed as a massive success for, say, a drug. For example, the ‘FOURIER’ study on Repatha (injectable LDL lowering agent) was hailed as a great success, despite overall mortality being higher in the Repatha arm. How, you may think, was this possible?

Well, the Fourier study had five end-points. Known as a ‘combined end-point’. [Mortality was not one of them.] The primary end point was the combined total of:

  • Cardiovascular death
  • MI (myocardial infarction)
  • Stroke
  • Hospitalization for unstable angina
  • Coronary revascularization

How can you have five different end-points as a primary end point? Well, you just can… apparently. 6

What you may notice, or maybe not, is that three of these are clinical events: cardiovascular death, MI and stroke. Two of them are clinical decisions. To admit someone to hospital for unstable angina, and to carry out a coronary revascularisation. Revascularisation is, essentially, putting in a stent to keep a coronary artery open.

So, the second two end-points are potentially subject to significant clinical bias. If someone has a low non-HDL cholesterol level, the decision may well be to not admit to hospital for unstable angina, and to not carry out coronary revascularisation. Why, because the physicians think they are protected by their low cholesterol.

[Guess which end-point dragged the FOURIER study into statistical significance.]

You think that clinical decisions are all objective. Then ask yourself why all clinical trials, wherever possible, are double-blinded (neither the patient or the doctor knows who is taking the drug, or the placebo)? This double blinding is considered essential to remove clinical bias. No blinding, bias introduced.

Even if you look at MIs and strokes, this diagnosis is less certain than you might wish. I have had many patients where it is entirely unclear if they have actually had a stroke or a heart attack. With a small stroke it is often, simply a guess. Low cholesterol, I guess not a stroke. High cholesterol, I guess that it is.

Just in case you think I am now talking nonsense, as I was writing this blog, I was sent a BBC report of a clinical trial done on stents in the US, which stated that stents were as safe as bypass surgery, with regard to MIs. However, the researchers decided to use a completely different system for diagnosing MI…

‘The trial called Excel started in 2010 and was sponsored by big US stent maker, Abbott. It was led by eminent US doctor Gregg Stone and aimed to recruit 2,000 patients. Half were given stents and the other half open heart surgery. Success of the treatments was measured by adding together the number of patients that had heart attacks, strokes, or had died.

The research team used an unusual definition of a heart attack, but had said that they would also publish data for the more common “Universal” definition of a heart attack alongside it. There is debate around which is a better measure and the investigators stand by their choice.

In 2016, the results of the trial for patients three years after their treatments were published in the prestigious New England Journal of Medicine. The article concluded stents and heart surgery were equally effective for people with left main coronary artery disease.

But researchers had failed to publish data for the common, “Universal” definition of a heart attack. Newsnight has seen that unpublished data and it shows that under the universal definition, patients in the trial that had received stents had 80% more heart attacks than those who had open heart surgery.

The lead researchers on the trial have told Newsnight that this is “fake information7

When is a heart attack not a heart attack? When it is measured by investigators in the clinical study – who have financial conflicts of interest.

Another problem is that, if you carry out a coronary artery revascularisation, there is a fifty per cent chance of triggering a heart attack. Usually pretty small and not clinically significant – but an MI, nonetheless. So, for each two additional revascularisations, you may get one more MI. Which further skews the statistics. [Not an issue in the FOURIER study where only the first event was counted].

Anyway, I hope you are getting the general message that a quintuple combined endpoint is, primarily, nonsense. Full of potential bias, particularly in an observational study. As the Lancet study was.

Finally, because I have run out of energy to spend another minute looking at this study, there is the issue of Lipoprotein(a). Otherwise known as Lp(a). This too forms part of the non-HDL cholesterol measurement.

Lp(a) and LDL are identical apart from the fact that Lp(a) has an additional protein attached to the side called apolipoprotein(a). This protein has a critical role in blood clotting and therefore Lp(a) can be viewed as a pro-coagulant agent – makes the blood clot bigger and more difficult to break down. Higher levels have long been linked to an increased risk of CVD.

Just to choose one quote from many thousands of studies about Lp(a): ‘Lipoprotein (a) and the risk of cardiovascular disease in the European Population: results from the BiomarCaRE consortium.’

Elevated Lp(a) was robustly associated with an increased risk for MCE (major cardiovascular events) and CVD in particular among individuals with diabetes. 8

Yes, you will have spotted the link with diabetes a.k.a. insulin resistance. So, a higher triglyceride level, added to raised Lp(a), further increases the risk of CVD.

So, with non-HDL cholesterol and Lp(a) we have another massive confounding factors built into the measurement. Again, I absolutely cannot disagree that raised Lp(a) increases the risk of CVD. I have written about it many, many times. Non-HDL cholesterol is a measure that contains Lp(a) within it…. You probably get the drift by now.

The whole paper, in my opinion, is complete nonsense. Assumptions, built on bias, built on a measure that has nothing much to do with LDL, or ‘bad’ cholesterol. Zoe Harcombe did a more forensic dissection of the paper. I like her ending:

‘The researchers assumed that a 50% reduction in non-HDL cholesterol could and would be achieved. The researchers assumed that a mathematical formula for risk reduction could be applied to that assumed 50% reduction in non-HDL cholesterol. The researchers’ assumed formula included the variable “number of years of treatment” and hence the formula produced a higher number, the earlier treatment started. The assumptions made it so.

The final paragraph of the paper stated: “However, since clinical trials investigating the benefit of lipid-lowering therapy in individuals younger than 45 years during a follow up of 30 years are not available, our study provides unique insights into the benefits of a potential early intervention in primary prevention.”

No, it doesn’t.’

Yet, there was no controlled clinical trial data to back this all up. There are only models and assumptions. Yet it made headlines around the world, as such stuff always does. Not only that, it made the wrong headlines.

As the BBC website stated: ‘The study, in The Lancet, is the most comprehensive yet to look at the long-term health risks of having too much “bad” cholesterol for decades’ Bad cholesterol is the bonkers, unscientific term that is used to describe LDL. This study did not look at ‘bad’ cholesterol… Scientific journalism at is finest.

My analysis. Crumple, throw, bin… forget.









What causes heart disease – part 67 – The Blood Brain Barrier

10th November 2019

The Blood Brain Barrier

Here I am going backwards in time and space to try and explain, from a different angle, a fundamental problem with the LDL/cholesterol hypothesis. In doing so I hope to again make clear why I am certain the entire process of cardiovascular disease (CVD) requires a complete re-think.

In a medical school long, long ago, on a planet far, far, away, I was part of a small group teaching session on cardiology… Aberdeen 1980, actually. I have mentioned this event before, a critical moment in my life. The tutor was Dr Elspeth Smith, who was researching heart disease at the time. Research that, to my chagrin, I knew little about until several years later, when I began more detailed research into cardiovascular disease.

At one point in the tutorial, Dr Smith stated that LDL (low density lipoprotein) cannot get past, or through, the endothelium. At that time, I hadn’t much of a clue what LDL was, and very little idea about the endothelium. However, something about the intensity of her comment created an itch, one that I have spent very nearly forty years scratching.

I say this because, if LDL cannot get past the endothelium, then the widely accepted, and supposedly primary causal mechanism of heart disease, must be wrong!

Just to remind you that the central mechanism underpinning the ‘cholesterol hypothesis’ has always been that LDL leaks out of the blood past, or through, the endothelium, and into the arterial wall behind.

This then stimulates a whole series of downstream processes whereby you end up with thickenings in the artery wall narrowing the artery – known as atherosclerotic plaques. The higher the LDL level, the faster the leakage? I put a question mark there, because I don’t think I have ever seen this stated explicitly – I suppose it is implied as self-evident.

Clearly, however, if LDL cannot pass through the endothelium – the single layer of cells that lines all artery walls – then the ‘cholesterol hypothesis’ is a busted flush. Which is sort of interesting in a ‘hold the front page’ sort of fashion. ‘LDL hypothesis completely wrong – shock horror.’ Dr Elspeth Smith explains that LDL cannot get through the endothelium. Experts around the world, agree, and look for other explanations for heart disease.

This is a headline that I must have missed.

At this point you may be thinking, how do we get from LDL, and the endothelium, to the Blood Brain Barrier (BBB), which is the title of this blog. Well, are you sitting comfortably? Then I shall begin, at the end, with the blood brain barrier itself.

All doctors are taught there is a barrier between the bloodstream and the brain called the Blood Brain Barrier (BBB). Very few know what it actually consists of, other than that there is a barrier, of some kind, that prevents various things from entering the brain at will.

A barrier between the blood and the brain is critical because the brain is a highly delicate organ, which copes very badly with noxious substances, such as bacterial toxins. Which makes the BBB essential for life. However, it can become a problem if you have, for example, a brain tumour and the doctors want to give you chemotherapy. Because most anti-cancer drugs cannot get past the BBB. Some drugs can, most can’t.

However, a certain number of things must enter our brains, or we would almost instantly die. Glucose, for example. If our brain cannot get enough glucose, we go into a coma, then die. We also need amino acids (the building block of proteins), some fats and vitamins and suchlike.

Clearly, therefore, the BBB needs to be a selective barrier. It must block some things, but allow entry – and exit – of those substances that are required for brain function. Ethanol from malt whisky, for example, distilled from glucose. Well it is essential for my life anyway – in moderation obviously … obviously.

At this point you may be thinking, we are getting further and further away from LDL and heart disease, but please bear with me on this, because it does all come together at the end.

Next question, what is the BBB? The answer is that it is comprised of endothelial cells that are tightly bound to each other, and have a strong support structure underneath called the basement membrane. This membrane keeps the endothelial cells wrapped even more closely, further protecting them from any possible disruption.

This ‘tight’ binding of endothelial cells means that anything that wants to get into the brain must first pass through an endothelial cell. As you may imagine, this is an extraordinarily complicated and tightly controlled process. Substances in the blood cannot flow down a concentration gradient and straight through an endothelial cell.

LDL, for example, can only enter a cell, if there is an LDL receptor on the cell wall. The LDL links onto the receptor and then LDL and the receptor (the ‘LDL receptor complex’) is dragged inside the cell in a process known as ‘endocytosis.’

It does not matter what the concentration of LDL in the blood is – without a receptor, LDL is unable to gain entry to a cell. If it cannot get in, it cannot pass through. This is why the concentration of LDL becomes very high in Familial Hypercholesterolaemia (FH).

In this condition there is a lack of LDL receptors on all cells in the body, so LDL cannot easily enter cells, therefore the concentration in the blood rises very high.

Proof, if proof were needed, that LDL cannot ‘escape’ from the bloodstream and find refuge in the artery wall, or any other tissue. No matter what the concentration in the blood. Osmosis and/or diffusion of LDL through any cell is biologically impossible.

Therefore, getting back to the BBB, for substances to move through the BBB they first must be ‘endocytosed’ and then need to be shuttled through the cell via an active transportation system. This is known scientifically as ‘transcytosis.’ Literally, transport through the ‘cytoplasm’ where cytoplasm is the name for the jelly-like substance that fills up cells.

Once the substance has been transcytosed through the cell it must be ejected out through the cell membrane on the opposite side. Another complex process known as exocytosis.

Not everything needs a receptor to enter a cell. However, nothing gets in without the cell controlling the entry and exit. Even individual ions (charged atoms), tiny as they are, must pass through ‘gates’, or channels, to get into a cell. Calcium, sodium, potassium etc.

Their passage is carefully monitored and controlled. If this were not the case, you would instantly die. If a cell loses control of its internal environment it is either dying – or dead. See under, hyponatremic encephalopathy (for those with a scientific bent).

It has been argued that LDL molecules do not need to pass through endothelial cells, they can simply slip through the ‘cracks’ between endothelial cells. I have seen this argument used as to why ‘small dense LDL’ can cause CVD because, in this form, it is small enough to get through the cracks between the endothelial cells.

The problem with this hypothesis is that, first, small dense LDL is almost exactly the same size as normal LDL. Second, and most important, there are no cracks, or gaps, between the endothelial cells in our arteries – or the BBB. Endothelial cells in large arteries are bound together very tightly indeed. They are linked together by zips, buttons, and super-glue, then welded to create what is called a ‘tight junction’.

You can Google ‘tight junctions’ under ‘images’ to see how complex they are. There are over twenty protein bonds, sealing any gap shut. Tight junctions are so tight that they, too, can prevent the entry and exit of single ions. So, there is absolutely no way through for LDL here, either. For a quick size comparison, if a human were the size of an ion, an LDL molecule would proportionately be around the size of a super tanker.

In short, the idea that LDL can simply leak through the endothelium and into the artery wall behind requires that several key mechanisms – required for life – do not exist.

As I hope you can now see, Elspeth Smith was quite correct. LDL cannot pass through the endothelium. At least it cannot pass through a healthy endothelium, and nor can anything else either. Unless, unless the endothelium enables its passage.

Complication number one – yes, there is always a complication.

As blood vessels get smaller and smaller, like the branches on a tree, the endothelium changes dramatically. As arteries shrink down to became arterioles, then capillaries, the endothelium is no longer an impenetrable barrier.

In these very small blood vessels, the endothelium develops holes (fenestrations). Gaps also appear between individual endothelial cells, and the supporting basement membrane becomes loose. What you have is more like a sieve than a castle wall.

This ‘sieve like’ quality allows substances to move in and out of arterioles and capillaries, almost at will. Which, of course, makes perfect sense. There is little point in blood arriving at, say, the kidneys, where various waste products are removed, if it was all stuck behind an impenetrable endothelial barrier. The blood would flow into your kidneys, then flow out again, unchanged. This is not a good recipe for life.

So, yes, in the very small blood vessels, the endothelium allows the free passage of substances. But absolutely not in the larger blood vessels. If the blood simply leaked out as it passed through larger blood vessels, it would never reach the smaller blood vessels, nor get back to the heart again. It would be like having a garden hose that was full of holes along its entire length. Nothing would reach the sprinkler head.

Anyway, bringing some strands together here, the endothelium lining the large arteries has the same impenetrable structure as the endothelium lining the BBB, and therefore represents a barrier. Substances just cannot leak through this – and that includes LDL.

But can things be transcytosed through? More specifically, can LDL transcytose through it? Because, if it can, this would be a possible mechanism in support of the cholesterol hypothesis. Although, once again, you have to ask the question, why would the body have a system for actively transporting LDL through the endothelium and into the artery wall underneath. What would be the purpose of such a system? To cause atherosclerosis?

The mystery of this question is further deepened by the fact that the larger blood vessels in the body are supplied with nutrients via their own, small, blood vessels known as vasa vasorum. Literally, blood vessels of the blood vessels. These are arterioles, and capillaries, that penetrate/permeate the vessel wall.

These very small blood vessels, lying within the artery wall, have fenestrations (holes) and loose junctions that allow the free movement of LDL – in an out of artery walls. So, any LDL in the bloodstream can quite easily enter the artery – and exit the artery (and the veins) – without having to cross any barrier at all.

Which raises a further conundrum for the cholesterol hypothesis. Why would LDL that enters the artery wall, via the vasa vasorum, cause no problems. Whilst the LDL – that is claimed to enter the artery wall by forcing itself past the endothelium – creates atherosclerotic plaques. Same artery wall, same LDL.

Which then raises another question. Why do atherosclerotic plaques only form in artery walls? Why not everywhere else, within every other organ and tissue in the body. If LDL, once it leaves the bloodstream, is so destructive, acting as the focus for plaque development, why doesn’t it cause plaques within the liver, or the kidneys, or the muscles, or the gut. Only, it seems, in artery walls. [Please don’t say xanthelasma, until you have thought very carefully about it]


But to get back on track. I wanted to see if I could answer a final question. We know that LDL cannot simply flow through endothelial cells, nor can it squeeze between non-existent gaps. But can it be actively transported through? Because, if it cannot, then this is the final nail in the cholesterol hypothesis. There is, literally, no way past. Elspeth Smith was quite correct.

[Other than via the vasa vasorum, obviously. However, veins have more vasa vasorum than arteries, so this if this is the route for LDL to enter blood vessel walls, then veins should have more atherosclerosis than arteries, which they do not. In fact, veins never develop atherosclerosis – ever.]

So, deep breath.

I wanted to know if LDL could get past the BBB. If not, then it could not get past the endothelium in the larger arteries either, end game. This is the sort of question to which you would think there should be a straightforward, yes or no answer. It took me a long time to find a definitive answer.

I did know that the brain manufactures its own cholesterol, because cholesterol is absolutely vital for brain function. Neurones are wrapped in myelin/cholesterol sheaths. New synapses have a very high proportion of cholesterol in them, and animal work has shown that – without cholesterol – new synapses cannot be made.

‘Brain cholesterol accounts for a large proportion of the body’s total cholesterol, existing in two pools: the plasma membranes of neurons and glial cells and the myelin membranes  Cholesterol has been recently shown to be important for synaptic transmission, and a link between cholesterol metabolism defects and neurodegenerative disorders is now recognized.’ 1

This ‘brain’ cholesterol is synthesized in support cells, known as glial cells. These cells surround neurones and nourish neurones, and the cholesterol is transported about in its own lipoprotein called Apo E.

So, on initial analysis, it did seem unlikely that the brain would have developed its own, specific, cholesterol manufacturing capability if it could simply absorb it from the bloodstream. As it turns out, and as I eventually discovered, the brain cannot absorb LDL from the bloodstream.

‘… the blood brain barrier (BBB) prevents the uptake of lipoprotein-bound cholesterol from the circulation.’ 1

In quick summary here, the brain requires cholesterol, yet the BBB prevents it from entering the brain. Which means that an intact endothelium can completely block the passage of LDL Which means that LDL cannot get past, or through, the endothelium. Elspeth Smith was quite right.

But what did she think caused CVD, or atherosclerosis, or atherosclerotic plaques – or whatever term is currently in vogue? Well, this is one thing that she wrote about the matter:

‘After many years of neglect, the role of thrombosis in myocardial infarction is being reassessed. It is increasingly clear that all aspects of the haemostatic (blood clotting) system are involved: not only in the acute occlusive event, but also in all stages of atherosclerotic plaque development from the initiation of atherogenesis to the expansion and growth of large plaques.’ 2

She believed, as I have been trying to outline for a few years now, that to start atherosclerosis, you need to damage the endothelium, then a blood clots forms, then we are on the pathway to the final occlusive thrombosis (a blood clot that completely blocks an artery).

She believed, as I believe, that LDL has no part to play in this process. It does not, because it cannot. If you believe in the ‘thrombogenic’ hypothesis, you cannot believe in the LDL hypothesis, and vice-versa.

Which hypothesis is correct?  Well, it is certainly true that the LDL hypothesis is currently in the ascendancy. But science is not, thankfully, a popularity contest like Strictly Come Dancing. Science is built on facts. Well, it is eventually. The fact is that the LDL hypothesis requires a central fact to be true but which can be proven to be wrong.

Elspeth Smith proved it to be wrong over fifty years ago, but no-one was listening. She was a hero, and I intend to do all that I can to ensure that it is her name, not that of Ancel Keys, that will echo through the history of CVD research. Because she was a true scientist. Whereas he….

Next time, why LDL also cannot damage the endothelium.



What causes heart disease – a summary

9th October 2019

But not by me

Following a podcast by Ivor Cummings, where I bored him for an hour and a half on what causes CVD*, a journalist that I know well, Jerome Burne, had a go at summarising the ‘thrombogenic’ hypothesis. I thought this was brave of him. I consider him a friend and an ally.

Of course, this is the Readers Digest version and, by necessity, misses out a great deal of the detail. However, I would be grateful if readers of this blog, go have a look on Jerome’s site and see what you think. Leave comments if you feel the urge.

I told him that I could not really comment on it, because I know this whole are so well that I cannot look at it the way a naïve reader could. Or, to put it another way, does it make any sense to an interested and intelligent reader coming across these ideas for the first time.

The blog can be found here:

*Ivor Cummings/Fat emperor podcast:

Or you can view it on Ivor’s site here

What causes heart disease part 66

5th October 2019

How does lead cause CVD?

Following my last blog, several people asked the question. How does lead cause CVD – or atherosclerotic plaques? What is the mechanism of action? It’s a good question, one that I think I have answered before, at least in part. However, I think there is real value in going over it again.

First, I want to highlight some of the more general thinking about causes of CVD, I believe this is important as well, in order to see how lead fits in, and where my interest in lead came from.

For many, many, years now I have been trying to create a unified hypothesis about cardiovascular disease. A journey I thought I would never finish. Mainly, I now realise, because I kept coming across ever more ‘factors’ that had a role in CVD. This meant that – although I couldn’t quite work out why at first – I was running into the impossible, and unsolvable, problem.

246 factorial

The unsolvable problem is a direct result of the number of possible interactions between all the risk factors that have been identified.

To try and explain this further, I shall start with the latest UK risk factor calculator which is called Qrisk3. The previous one was Qrisk2. Qrisk3 can be found on-line here You can play with it to your heart’s content. Qrisk3 has moved on considerably from Qrisk1 and 2. It now incorporates twenty different factors.  If you strip them out of the algorithm they are, in no particular order:

  • Age
  • Sex
  • Smoking
  • Diabetes
  • Total cholesterol/HDL ratio
  • Raised blood pressure
  • Variation in two blood pressure readings
  • BMI
  • Chronic kidney disease
  • Rheumatoid arthritis
  • Systemic Lupus Erythematosus (SLE)
  • History of migraines
  • Severe mental illness
  • On atypical antipsychotic medication
  • Using steroid tablets
  • Atrial fibrillation
  • Diagnosis of erectile dysfunction
  • Angina, or heart attack in first degree relative under the age of 60
  • Ethnicity
  • Postcode

As a quick side-track, it amuses me that LDL is not in there – yet HDL is.

Now, you may think that this appears to be a relatively short list. At first sight it does not appear a complex task to fit these factors together into a coherent model. A twenty-piece jigsaw puzzle – at most?

Not so. The reality is that, if you view the model of CVD as twenty independent and unconnected risk factors, the number of possible interactions, or pieces, you need to analyse becomes mind-boggling.

Just to give you an idea of the scale of the maths involved here. You have twenty different risk factors, and you do not know how the connections between them work. Every risk factor can, potentially, interact with all the others – independently. This means that the possible combinations you must analyse is twenty factorial.

Calculating factorials is, on one hand, very straightforward. You simply multiply each factor, by all of the other factors, in turn. Thus, twenty factorial = 20 x 19 x 18 x 17 x 16 etc.

The result of multiplying 20 x 19 x 18 x 17 x 16 etc. is you end up with the following number: 432,902,008,176,640,000. Which is the number of different possible combinations between twenty factors. Rounding this figure up slightly, that equates to four hundred and thirty-three quadrillion. Which is a lot. And it gets far worse than that.

As far back as 1981, a paper was published outlining 246 different risk factors involved in CVD 1. Today, there would be far more, several thousand at least. However, even by 1981 the number of possible combinations was already incomprehensibly huge. I say this because 246 factorial is:


Yes, to my amazement, there is a website which will calculate factorials for you. You don’t think I worked that out myself do you? I would have definitely got bored and made several mistakes on the way. Therefore, I have no idea if this figure is right or wrong, but it seems to be in the right sort of ballpark.

There is no way to even describe a number that big, and it would certainly make for some jigsaw puzzle. In truth what we have here represents a figure so huge that you cannot possibly do anything with it. It has fifty-seven zeros before you even get to another number. At least I think it is fifty-seven, I may have lost count.

How long would it take to feed in the data on all these risk factors, run the combinations, and see if you can establish how they all fit together? That would take as close to an infinite amount of time as makes no practicable difference. Even with the latest Google quantum computer.

Thinking about things in this way, I came to realise that unearthing risk factor, after risk factor, after risk factor, was not going to make it easier to work out the cause of CVD. It was making it impossible.

The other word for impossible, I came to realise, is ‘multifactorial’.

Multifactorial = a word commonly used by cardiologists to prevent any discussion as to the real causes of CVD. In conversation on this issue, I silently change the word multifactorial to ‘246-factorial’, just to remind myself what a stupid concept it is to call a disease multifactorial. Then to believe that, by doing so, you have explained anything. ‘So, how do the factors all fit together?’ I mutter, imaging a number so vast that it is beyond comprehension.

Then I may quote Poincaré at them.

Science is built up of facts, as a house is built of stones; but an accumulation of facts is no more a science than a heap of stones is a house.’ Henri Poincaré.

Because multifactorial also effectively = a pile of stones. Well done, you have found thousands of stones, and carefully piled them ever higher, but this gets no nearer to constructing a house. To build a house you need to know how all the stones join up. You need a plan my friend.

Which starts to bring me, in a roundabout way, back to lead.

As regular readers of this blog will know, I ripped up the multifactorial model of CVD and tried to replace it with a process model. The plan of the house, if you like. I was no longer interested in finding endless risk factors, then chucking them on the pile. I wanted to know the process – or processes – involved.

In the end I stripped it down to three main elements. Basement, walls, roof.

  • Endothelial damage (damage to the lining of artery walls)
  • Formation of a blood clot
  • Repair

Or at least I stripped it down to three main processes – going wrong. Because this triad is all quite normal, and healthy. It is only when endothelial damage and clot formation accelerate, or repair is sub-optimal, that CVD/atherosclerosis will develop.

So, the simplest possible model is: rate of damage > rate of repair = CVD

Using the three-process model I began a different search. Starting with things that could damage the endothelium. I cast the net far and wide. Of course, it is more difficult to do the searching this way. Where do I begin? Do you just start thinking of things that might be damaging, and hope for the best? You will find yourself wandering all over the place. At least I did. Although it is quite an interesting journey – for a geek.

Bringing some structure into my search strategy, I decided that heavy metals were something that could not be doing any good to the human body. Mercury, lead, cadmium, and suchlike. Gold? Gold doesn’t seem to do much, one way or another. It was used to treat rheumatoid arthritis at one time. As for the others – not great. Lots of damage to health.

But do they damage the endothelial lining of the artery wall? Well, yes, they do. Looking at lead, here is a passage from the paper: ‘Mechanisms of lead-induced hypertension and cardiovascular disease.’

I admit that it is far too jargon heavy for most people. But I enjoyed it and I reproduced it in full because, what we have here, is the perfect storm. Many mechanisms I have previously mentioned in my long and winding series on what causes heart disease can be found here. Including many I did not mention because they were just too technical. I have put in bold some of the more important mechanisms:

‘Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic illnesses. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension (HTN) and cardiovascular disease. In vivo and in vitro studies have shown that chronic lead exposure causes HTN and cardiovascular disease by promoting oxidative stress, limiting nitric oxide availability, impairing nitric oxide signaling, augmenting adrenergic activity, increasing endothelin production, altering the renin-angiotensin system, raising vasoconstrictor prostaglandins, lowering vasodilator prostaglandins, promoting inflammation, disturbing vascular smooth muscle Ca2+ signaling, diminishing endothelium-dependent vasorelaxation, and modifying the vascular response to vasoactive agonists. Moreover, lead has been shown to cause endothelial injury, impede endothelial repair, inhibit angiogenesis, reduce endothelial cell growth, suppress proteoglycan production, stimulate vascular smooth muscle cell proliferation and phenotypic transformation, reduce tissue plasminogen activator, and raise plasminogen activator inhibitor-1 production.’ 2

So, there you go. Not just one mechanism of action, but twenty-one different processes that lead can cause CVD. Fifteen ways of damaging the endothelium, four that inhibit repair, and two mechanisms for making blood clots more difficult to get rid of, as highlighted in the final passage… reduce tissue plasminogen activator, and raise plasminogen activator inhibitor-1 production.’

Tissue plasminogen activator (TPa) is the enzyme that activates the breakdown of blood clots. TPa converts plasminogen to plasmin, and plasmin then chops fibrin to bits, thus shaving down blood clots. Plasminogen activator inhibitor-1 is a substance that inhibits the action of tissue plasminogen activator (TPa = the clot buster, often given to patients after a heart attack or stroke).

Clearly, if you reduce TPa, and increase TPa inhibition, you end up with a blood clot that is very difficult to get rid of and is thus more damaging.

So, when people ask, have you got a mechanism of action to explain how lead causes CVD I say (rather smugly), no, I have got twenty-one. In truth, I have found quite a few more, but twenty-one is probably enough to be getting on with. One thing I have found is that once you start looking at all the potential processes, there seems almost no end to this stuff. It stretches in all directions.

Big fleas have little fleas upon their backs to bite ’em,

And little fleas have lesser fleas, and so, ad infinitum.

And the great fleas, themselves, in turn, have greater fleas to go on;

While these again have greater still, and greater still, and so on

Anyway, getting back on track, I started to look for factors, causal agents, whatever is the best name for them, that can impact on one of three processes:

  • Endothelial damage (damage to the lining of artery walls)
  • Formation of a blood clot
  • Repair

This is how I got to lead, only to discover that there was a huge body of research linking lead to CVD… that I had been completely unaware of. My analogy was that of a round the world sailor bumping into Australia and wondering why no-one had bothered to tell him it was there. ‘It’s pretty big, you know.’

Looking at things, by starting with one of the three processes, is also how I came across the evidence on sickle cell disease (SCD). I reasoned that sharp pointy red blood cells (sickled cells) hammering through the blood vessels would create serious damage to endothelial cells.

When I started looking, I found that, in some studies, SCD increases the (relative risk) of CVD by fifty thousand per cent. Yes, you did read that right. Fifty thousand per cent. With none of the other ‘established’ risk factors present.

Which makes SCD a ‘sufficient’ cause of CVD. In fact, it is the only sufficient cause I have ever found – in that it can lead to atherosclerosis in the blood vessels in the lungs, where the blood pressure is pretty low.

Which means that, with SCD, you don’t even need a high blood pressure. SCD can cause CVD all by itself. If you can find any other factor that can do that – let me know. For a more in-depth discussion on causation, and the concept of ‘sufficient’ see this article:

Then, I thought, what else causes damage to the endothelium. I ended up looking at a group of diseases known as ‘vasculitis’. Itis means, inflammation, as in tonsillitis, appendicitis. So, vasculitis means inflammation of the vascular system, by which I mean inflammation of the lining of the blood vessels. By which I mean, damage (and repair) to the lining of the blood vessels. Remember, inflammation = repair.

There are many different forms of vasculitis, most of which are not really thought of as being ‘vasculitis.’ For example, Rheumatoid arthritis, and Systemic Lupus Erythematosus. These conditions cause inflammation in many different places, but they also cause vasculitis. You may have noticed that both also appear on the Qrisk3 calculator.

Other forms of vasculitis, or diseases where vasculitis is an important part of the spectrum of abnormalities include:

  • Scleroderma
  • Sjogren’s
  • Erythema nodosum
  • Takayasu’s arteritis
  • Kawasaki’s disease

I think they all have great, evocative names:

All these forms of vasculitis are associated with a greatly increased risk of CVD. You can look this up yourself, if you want. In fact, children who suffer Kawasaki’s can die of myocardial infarctions (MIs), aged five. They have a brief, super-accelerated, form of endothelial damage that lasts a few weeks. Some can then end up with large aneurysms (balloon-like swellings) in their coronary arteries. These can burst, causing a MI.

So, not an entirely conventional MI. Nor conventional atherosclerosis. However, if you think of an aneurysm as a late stage abnormality in atherosclerosis [which most are] then in Kawasaki’s we can get from endothelial damage, to an aneurysm, in a month. Something that normally takes about sixty years to develop.

Three stones to make a wall

Lead, sickle cell disease, vasculitis.

In one sense it could be said that I have been discussing three completely unrelated things here. Lead, sickle cell disease, vasculitis. In another sense I hope you can see that these three ‘factors’ are related to CVD. Not by what they are, but by what they do. The damage they cause… the process.

They all fit very neatly into the walls of the house that are called ‘endothelial damage’. How else can you explain how three such disparate things can possibly cause exactly the same disease.

I must admit that this breakthrough in my thinking, from causes to process, was not mine. It was entirely due to one man. Professor Paul Rosch. We were discussing stress (strain) and CVD and he was critiquing a presentation I had given.

I shall paraphrase his comment. ‘Very good, you have given us the what, but not the how.’ Yes, very simple, when you think of it that way. What he was really asking was, what is the process? Since then, I have often wondered why have others not gone down this route?

I then realised that the problem, the great problem in all research into CVD, is that very early on it was decreed that LDL/cholesterol causes CVD. Therefore, all thinking, and any hypothesis on CVD required that LDL sat at the centre.

To my mind this is like opening a two-thousand-piece jigsaw puzzle and deciding, straight away, that one big piece – LDL/cholesterol – sits at the centre, and the other pieces must be made to fit around it.

Well, perhaps it does have a (small role) to play in CVD, but it most certainly does not sit and the centre. But if you keep it there, you distort the entire puzzle and make it impossible to complete. The pieces must be forced into place. Hammered down, or twisted into extreme shapes.

This, though, is where CVD research currently sits. Thousands of pieces are lying about the board. A few of them have been fitted together, here and there. As for the whole puzzle, it is doomed to failure, because the wrong piece is taking up the key position. Unfortunately, if you are a ‘serious’ CVD researcher, who wants to get grants for research, you can’t move it.

What I found if that you chuck that piece away, and start again, then everything becomes clear. The puzzle can be made to fit into one of these three processes:

  • Endothelial damage (damage to the lining of artery walls)
  • Formation of a blood clot
  • Repair

Lead, for example. Lead makes no sense as a significant risk factor using conventional thinking. It doesn’t raise BP, it doesn’t raise LDL, it doesn’t cause diabetes, it simply does not fit. So, it has become, essentially, ignored. But how can you ignore something that may be responsible for four hundred thousand deaths per year, in the US alone? Most of them CVD deaths?

The answer is that you cannot.



What causes heart disease part 65 – Lead again

23 September 2019

Lead again

I am returning to lead, the heavy metal. Not the verb to lead, or a noun – such as a dog lead. Yes, English is complicated, with the same word meaning several different things, which can lead to confusion.

I am indebted to Leon Vd Berg for bringing my attention to another paper about lead that I had missed. Which is slightly surprising as I tend to look for such papers. However, such is the daily avalanche of medical publications that it is literally, impossible to keep up.

There are several things about the paper that I found fascinating. However, the first thing that I noticed was that…. it hadn’t been noticed. It slipped by in a virtual media blackout. It was published in 2018, and I heard nothing.

This is in direct contrast to almost anything published about diet. We are literally bombarded with stories about red meat causing cancer and sausages causing cancer and heart disease, and veganism being protective against heart disease and cancer, and on and on. Dietary articles often end up on the front page on national newspapers.

Here is one such headline from the Daily Mail 7th August 2019

‘Eating chicken instead of steak, lamb or sausages ‘slashes a woman’s risk of developing breast cancer by 28%’

Mind you, here is another headline from the Daily Mail 8th Sept 2019

Chicken ’causes cancer’: Oxford University scientists say people who eat poultry are at increased risk of developing deadly disease.’

Tricky thing eating chicken. It can cause and prevent cancer simultaneously. You read it here first.

However, the point I wish to make is not so much the utter nonsense and constant contradictions of dietary studies. Nor is it the fact that the increased, and decreased risk in such studies, is minute. Sitting well within the boundaries of reasonable chance. Which is why you keep getting contradictory studies.

Researcher one:      ‘I just threw a head – all throws of a coin must be heads.’

Researcher two:       ‘No, sorry, I just threw two tails – most throws of a coin end up tails

Researcher one:      ‘Hold on, forget your tails, I just go four more heads – in a row – most throws end up heads, not tails.’

The correct term for this is idiot research, and those who do it are – primarily – idiots. However, none of this nonsense is really important. The point I am trying to make here is that this type of dietary research hogs the limelight.

It seems that whatever else Ancel Keys did not achieve – scientific truth and accuracy, for starters – he most certainly did manage to convince almost everyone in the World that diet is the single most critical important factor for health.

In years gone by, people ate food because they enjoyed eating it. This still happens in France. Imagine that. Nowadays every meal comes with implied fearmongering, and high-level criticism. Are you destroying the world or not – you evil scum.

‘Hold on, it’s only a bacon sandwich. With a fried egg and a bit of cheese grated on top…. Yes, I suppose you’re right, I am personally responsible for the destruction of the Amazonian rain forest. Forgive me father, for I have sinned.’

Destruction of the planet is only one aspect of eating, it’s also destruction of your health – with added moral judgement. If you go to Slimming World, you can eat various tasteless stuff, but you are allowed ‘sins.’ A sin would be something you really like eating, but it is so deadly, that it is a sin to eat it. Chocolate, for example. Get thee behind me Satan.

I don’t understand how anyone manages to eat anything nowadays. I have almost given up eating salads because someone will always remark ‘Oooooh, that’s healthy.’

My reply used to be. ‘I am not eating it because it is healthy, I am eating it, because I enjoy it.’ Nowadays I just grunt in a vaguely non-threatening way. I do not say. ‘No, a healthy meal would be a full English breakfast with bacon, eggs, sausages, fried bread. a few more sausages and a bit of lard melted on top.

I do not say this because, in truth, almost all diets are perfectly healthy. Vegetarian, paleo, keto, vegan (with a few essentially nutrients thrown in, so you don’t die), HFLC, etc. In fact, the only non-healthy diet would be the one recommended by all the experts around the world.

Namely, High carb, low fat (HCLF). The ‘eat well plate’, ‘the food pyramid’ – whatever it is now called. Stay away from that, and you will be fine.

Rule one of diet.       Everything the ‘experts’ recommend, is wrong.

Rule two:                   Eat food you enjoy – and enjoy eating

Rule three:                Eat food that looks like food

Rule four:                   Cook your own meals – when possible

Rule five:                   Try fasting from time to time

Rule six:                     That’s it

Where was I? Oh yes, lead. The heavy metal. The thing that, unlike diet, makes no headlines whatsoever, the thing that everyone ignores. Here is one top-line fact from that study on lead, that I missed:

‘Our findings suggest that, of 2·3 million deaths every year in the USA, about 400 000 are attributable to lead exposure, an estimate that is about ten times larger than the current one. 1

Yes, according to this study, one in six deaths is due to lead exposure. I shall repeat that. One in six. Eighteen per cent to be exact, which is nearer a fifth really.

Of course, this study is observational, with all the usual caveats associated with such studies. Indeed, many people commenting on this blog have stated that correlation [found in such studies] does not mean causation. I think you will find that this does not include me – although I may have said it by mistake. It is true that correlation does not mean causation, up to a point. However, once that point has been reached, causation can be considered proven.

For example, in observational studies, smokers were found to have fifteen times the risk of lung cancer. That is a powerful enough correlation to prove causation – beyond any reasonable doubt. There is no point in setting up a controlled clinical trial to prove this. In fact, any such trial would be completely unethical.

The question is, at what level of increased risk/correlation can causality be accepted. There is no absolute clear-cut answer to this Life ain’t black and white. However, most epidemiologists will tell you that unless the odds ratio (OR) is above two, you cannot attempt to claim causality. Too much noise, too many possible confounders.

Which means (deep breath, waiting for statisticians to attack this mercilessly) you need to find that a ‘factor’ is associated with at least a doubling of risk, before you do not simply crumple up the published paper and throw it in the bin.

Most dietary studies get absolutely nowhere near two. We have risks such as one point one (1.10), or one point three. One point three (1.3) is a thirty per-cent increase in risk. Here for instance is a review of red meat and colo-rectal cancer

‘As a summary, it seems that red and processed meats significantly but moderately increase CRC risk by 20-30% according to these meta-analyses.’  2

Figures like this, from an observational study, mean only one thing. Crumple, throw, bin. Remember also, they are only looking at one form of disease colo-rectal cancer (CRC).  The impact on overall mortality (the risk of dying of anything) would be minuscule, if it could even be found to exist at all. Of course, overall mortality is not mentioned in that CRC paper. Negative findings never are.

So, on one side, we have papers (that make headlines around the world) shouting about the risk of red meat and cancer. Yet the association is observational, tiny, and would almost certainly disappear in a randomised controlled trial, and thus mean nothing.

On the other we have a substance that could be responsible for one sixth of all deaths, the vast majority of those CVD deaths. The odds ratio, highest vs lowest lead exposure, by the way, depending on age and other factors, was a maximum of 5.30 [unadjusted].

Another study in the US found the following

‘Cumulative lead exposure, as reflected by bone lead, and cardiovascular events have been studied in the Veterans’ Normative Aging Study, a longitudinal study among community-based male veterans in the greater Boston area enrolled in 1963. Patients had a single measurement of tibial and patellar bone lead between 1991 and 1999. The HR for ischemic heart disease mortality comparing patellar lead >35 to <22 μg/g was 8.37 (95% CI: 1.29 to 54.4).’ 3

HR = Hazard Ratio, which is similar, if not the same to OR = Odds Ratio. A Hazard Ratio of 8.37, means (essentially) a 737% increase in risk (Relative Risk).

Anyway, I shall repeat that finding a bit more loudly. A higher level of lead in the body leads to a seven hundred and thirty-seven per cent increase in death from heart disease. This is, in my opinion, correlation proving causation.

Looking at this from another angle, it is true that smoking causes a much greater risk of lung cancer (and a lesser but significant increase in CVD), but not everyone smokes. Therefore, the overall damage to health from smoking is far less than the damage caused by lead toxicity.

Yet no-one seems remotely interested. Which is, in itself, very interesting.

It is true that most Governments have made efforts to reduce lead exposure. Levels of lead in the children dropped five-fold between the mid-sixties and the late nineties. 4 Indeed, once the oil industry stopped blowing six hundred thousand tons of lead into the atmosphere from vehicle exhausts things further improved. Lead has also been removed from water pipes, paint, and suchlike.

However, it takes a long old time from lead to be removed from the human body. It usually lingers for a lifetime. Equally, trying to get rid of lead is not easy, that’s for sure. Having said this, chelation therapy has been tried, and does seem to work.

‘On November 4, 2012, the TACT (Trial to Assess Chelation Therapy) investigators reported publicly the first large, randomized, placebo-controlled trial evidence that edetate disodium (disodium ethylenediaminetetraacetic acid) chelation therapy significantly reduced cardiac events in stable post–myocardial infarction (MI) patients. These results were so unexpected that many in the cardiology community greeted the report initially with either skepticism (it is probably wrong) or outright disbelief (it is definitely wrong).3

Cardiologists, it seems from the above quotes, know almost nothing about the subject in which they claim to be experts. Just try mentioning glycocalyx to them… ‘the what?

Apart from a few brave souls battling to remove lead from the body, widely derided and dismissed by the mainstream world of cardiology, nothing else is done. Nothing at all. We spend trillions on cholesterol lowering, and trillions on blood pressure lowering, and more trillions on diet. On the other hand, we do nothing active to try and change a risk factor that kicks all the others – in terms of numbers killed – into touch.

Funny old world. Is it not?

Next time, back to diet, because everyone knows how important diet is…. Only joking.





Review of statins needed

7th September 2019

In the UK, it has been decided that high intensity statins can now be sold over the counter to people – no prescription required. The European Society of Cardiology has decreed that there is no normal level for cholesterol, the lower the better. It goes on, and on.

However, there are some glimmers of light, occasionally. Aseem Malhotra, and I, wrote a letter to Sir Norman Lamb MP. Chairman of the Science and Technology Select Committee – at his request – asking for a review of statins, and safety issues.

It was reported in the few news outlets that had any space left after Brexit. You can see the video on Sky with Aseem, here

(or here is the link to YouTube…

The letter is below.

Sir Normal Lamb MP

Chairman, Science and Technology Select Committee

Dear Norman,

Re: The need for an independent reappraisal of the effects of statins

Statins are the most widely prescribed class of drugs in the UK.[1] They were designed to lower the blood cholesterol (LDL) level and therefore prevent cardiovascular disease.

Publications based on clinical trials have reported reductions in cardiovascular disease in people at high and low risk, and also a very low rate of side effects (drug-related adverse events).

It has been widely claimed that statins have therefore been responsible for the considerable reduction in the cardiovascular disease seen over the past 30 years both in the UK  and the rest of the Western World,[2] but there is evidence that refutes this claim. An ecological study using national databases of dispensed medicines and mortality rates, published in 2015, concluded: ‘Among the Western European countries studied, the large increase in statin utilisation between 2000 and 2012 was not associated with CHD mortality, nor with its rate of change over the years.[3] In the UK, despite far greater statin prescribing, the rate of cardiovascular disease has been rising for the past four years.[4]

In the absence of an analysis of the clinical trial data carried out by an independent group with full access to the raw data in the form of “clinical study reports”, there is good reason to believe that the benefits of statins have been ‘overhyped’ especially in those at low risk of cardiovascular disease, and the potential harms downplayed, unpublished, or uncollected.

Positive spin on the benefits of statins

It is well recognised that ‘positive spin’ is used to ‘hype’ the results from clinical trials. This should not happen but is widespread. According to one review: ‘Clinical researchers are obligated to present results objectively and accurately to ensure readers are not misled. In studies in which primary end points are not statistically significant, placing a spin, defined as the manipulation of language to potentially mislead readers from the likely truth of the results, can distract the reader and lead to misinterpretation and misapplication of the findings.’[5]

The authors continued: ‘This study suggests that in reports of cardiovascular RCTs with statistically nonsignificant primary outcomes, investigators often manipulate the language of the report to detract from the neutral primary outcomes. To best apply evidence to patient care, consumers of cardiovascular research should be aware that peer review does not always preclude the use of misleading language in scientific articles.’ [5]

As one example of such positive spin in relation to statins, the lead author of the JUPITER trial, Paul Ridker, writing in a commentary in the journal Circulation, summarised apparently statistically significant benefits between statin and placebo:

 The JUPITER trial was stopped early at the recommendation of its Independent Data and Safety Monitoring Board after a median follow-up of 1.9 years (maximum follow-up 5 years) because of a 44% reduction in the trial primary end point of all vascular events (P<0.00001), a 54% reduction in myocardial infarction (P=0.0002), a 48% reduction in stroke (P=0.002), a 46% reduction in need for arterial revascularization (P<0.001), and a 20% reduction in all cause mortality (P=0.02).’ [6]

Picking up on these figures, another well-known cardiologist wrote in equally positive terms: ‘Data from the 2008 JUPITER Trial suggest a 54 percent heart attack risk reduction and a 48 percent stroke risk reduction in people at risk for heart disease who used statins as preventive medicine. I don’t think anyone doubts statins save lives.’[7]

In fact in the JUPITER trial there was no statistically significant difference in deaths from cardiovascular disease among those taking rosuvastatin compared with placebo. There were 12 deaths from stroke and myocardial infarction in both groups among those receiving placebo, exactly the same number as in the rosuvastatin arm.[8] So the results of this clinical trial do not support claims that statins save lives from cardiovascular disease. This dissonance between the actual results of statin trials and the way they are reported is widespread.[9]

Other studies, looking at whether statins increase in life expectancy have found that, in high risk patients, they may extend life by approximately four days, after five years of treatment.[10] Doubts have also been raised about the claims of benefit in otherwise healthy people aged over 75, in whom statins are now being actively promoted.[11]

An overview of systematic reviews that examined the benefits of statins using only data from patients at low risk of cardiovascular disease found that those taking statins had fewer events than those not taking statins. However, when the results were stratified by the patients’ baseline risk, there was no statistically significant benefit for the majority of outcomes.[12] In conclusion, the absolute benefits in people at low risk are relatively small. If the 2016 guidelines are implemented in full, large numbers of otherwise healthy people will be offered statins, it has been estimated that 400 will need to take statins for five years to prevent one person from suffering a cardiovascular event.[13]

This information is not routinely given to patients, or indeed doctors who prescribe statins, and both doctors and patients therefore tend to have false expectations of the benefits of statins. Clinical guidelines call for shared decision making, including informing patients of the actual likelihood of benefits and risks, but this rarely occurs. There are also obvious questions in relation to value-for-money and the efficient use of finite healthcare budgets.

Side effects/adverse effects underplayed

There has been a heated debate about the adverse effects of statins. On one side, it is claimed that the rate of adverse effects is extremely low, affecting fewer than one in a thousand people.[14] Other studies have suggested adverse events are common, with up to 45% of people reporting problems.[15]

Attempts to resolve this important controversy have been hampered by the fact that  the data on adverse effects reported in the clinical trials are not available for scrutiny by independent researchers. The data from the major trials of statins are held by the Cholesterol Treatment Triallists Collaboration (CTT) in Oxford and they have agreed amongst themselves not to allow access by anyone else.[16] Many groups, have called for access to these data, but so far, this has not been granted.[17]

It is not even clear whether the CTT themselves have all the adverse effect data, since the relevant Cochrane Review Group does not seem to have had access to them. According to Professor Harriet Rosenberg of the Health and Society Program at York University: “It’s not clear if the AE (adverse events) data was withheld from the Cochrane reviewers (by CTT) or were not collected in the original trials.”[18]

When asked the lead author of the Cochrane review, Dr Shah Ebrahim, the CTT did not have the data. “Full disclosure of all the adverse events by type and allocation from the RCTs is now really needed, as the CTT does not seem to have these data.”[18]

Release of the data would undoubtedly help answer the question on how and whether the trials collected data on the most common side effects of muscle pain, weakness or cramps.


Rather than mass prescription based on incomplete and selective information, patients and the public deserve an objective account so that individuals can make their own informed decisions.

We believe there is now an urgent need for a full independent parliamentary investigation into statins:

  • a class of drug prescribed to millions in the UK and tens of millions across the world.
  • which, based on the publications available, have had their benefits subjected to significant positive spin, especially among people at low risk of cardiovascular disease, and their potential adverse effects downplayed
  • where independence would mean review of the complete trial data by experts with no ties to industry and who have not previously undertaken or meta-analysed clinical trials of statins.

Among the signatories to this letter, there are a range of views: some of us are deeply sceptical of the benefits of statins, others are neutral or agnostic. But all are strongly of the view that such confusion, doubt and lack of transparency about the effects of a class of drug that is so widely prescribed is truly shocking and must be a matter of major public concern.

Yours Sincerely,

Dr Aseem Malhotra, NHS Consultant Cardiologist and Visiting Professor of Evidence Based Medicine, Bahiana School of Medicine and Public Health, Salvador, Brazil.

Dr John Abramson, Lecturer, Department of Healthcare Policy, Harvard Medical School

Dr JS Bamrah CBE, Chairman, British Association of Physicians of Indian Origin.

Dr Kailash Chand OBE, Honorary Vice President of the British Medical Association  (signing in a personal capacity)

Professor Luis Correia, Cardiologist, Director of the Centre of Evidence Based Medicine, Bahiana School of Medicine and Public Health, Salvador Brazil. Editor in Chief, The Journal of Evidence Based Healthcare

Dr Michel De-Lorgeril, Cardiologist, TIMC-IMAG, School of Medicine, University of Grenoble-Alpes, Grenoble, France.

Dr David Diamond, Cardiovascular Research Scientist, Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA

Dr Jason Fung, Nephrologist and Chief of the Department of Medicine, The Scarborough Hospital, Toronto, Canada and Editor in Chief of the Journal of Insulin Resistance.

Dr Fiona Godlee, Editor in Chief, The BMJ

Dr Malcolm Kendrick, General Practitioner

Dr Campbell Murdoch, General Practitioner, NHS England Sustainable Improvement Team, Clinical Adviser

Professor Rita Redberg, Cardiologist, University of California, San-Francisco.

Professor Sherif Sultan, President, International Vascular Society

Sir Richard Thompson, Past President, The Royal College of Physicians

Professor Shahriar Zehtabchi, Editor in Chief,, and Professor and Vice Chairman for Scientific Affairs Research, SUNY Downstate Health Science University, Brooklyn, New York











  1. Armitage J, Baigent C, Barnes E, Betteridge DJ, Blackwell L, Blazing M, et al. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. The Lancet. 2019;393(10170):407-15.
  2. Byrne P, Cullinan J, Smith A, Smith SM. Statins for the primary prevention of cardiovascular disease: an overview of systematic reviews. BMJ Open. 2019; 9(4):[e023085 p.]. Available from:
  3. Byrne P, Cullinan J, Gillespie P, Perera R, Smith SM. Statins for primary prevention of cardiovascular disease: modelling guidelines and patient preferences based on an Irish cohort. Br J Gen Pract. 2019. Available from:







Will this have any impact, on anything. We must keep bashing away, until the nonsense about cholesterol – has gone.

What causes heart disease part 64 – Not changing your mind

22 August 2019

‘A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.’ Max Plank.

Perhaps the greatest challenge facing anyone who has a new idea is the sheer difficulty of getting anyone to change their mind. About anything. This difficulty is compounded if a committee, or any group of people, has to change their minds. Not only do they have to change their mind, they must make a public admission that they were wrong.

Many years ago, I was in contact with a geologist Thomas Gold. Yes, don’t worry, you have never heard of him. Neither had I. It was simply an honour that having read some of my ramblings he chose to reach out for a few on-line chats. Sadly, he is now dead.

He was a maverick. In the nineteen fifties he had been repeatedly thrown out of the American Geological Society for being a vigorous promoter of the tectonic plate hypothesis. Namely, that the Earth’s surface is make up of vast plates that glide about above the mantle. Not so much gliding as grinding very slowly.

Of course, this is now universally accepted as being true. Not so sixty years ago, when anyone mentioning tectonic plates was considered a dangerous fool, who understood nothing about geology, or science. Oh yes, indeed.

However, Thomas Gold did not stop with tectonic plates, he also promoted the abiotic theory of oil generation. I think he also came up with the idea of neutron stars as well. Anyway, getting back to abiotic oil generation, he did not believe that oil was created when trees – or other organic matter – died, rotted, went underground and was, gradually converted to oil.

He believed that oil was generated spontaneously within the Earth’s core. To quote:

‘Gold’s theory of oil formation, which he expounded in a book entitled The Deep Hot Biosphere, is that hydrogen and carbon, under high temperatures and pressures found in the mantle during the formation of the Earth, form hydrocarbon molecules which have gradually leaked up to the surface through cracks in rocks. The organic materials which are found in petroleum deposits are easily explained by the metabolism of bacteria which have been found in extreme environments similar to Earth’s mantle. These hyperthermophiles, or bacteria which thrive in extreme environments, have been found in hydrothermal vents, at the bottom of volcanoes, and in places where scientists formerly believed life was not possible. Gold argues that the mantle contains vast numbers of these bacteria.

The abiogenic origin of petroleum deposits would explain some phenomena that are not currently understood, such as why petroleum deposits almost always contain biologically inert helium. Based on his theory, Gold persuaded the Swedish State Power Board to drill for oil in a rock that had been fractured by an ancient meteorite. It was a good test of his theory because the rock was not sedimentary and would not contain remains of plant or marine life. The drilling was successful, although not enough oil was found to make the field commercially viable. The abiotic theory, if true, could affect estimates of how much oil remains in the Earth’s crust.’ 1

There you go. You have never heard of this before – ever. I think I can pretty much guarantee this. Neither had I. But I loved it. It was utterly and completely different to everything I had been told. Is it right, or is it wrong? No idea. I ain’t no geologist. Worth exploring as an idea though, surely.

What I do know, from speaking to Thomas is that almost all of his peers instantly rejected his ideas out of hand. Why? Because it didn’t fit with the knowledge they had been brought up with. Custom is king …

For many years it was taught that bacteria could not live in the human stomach. It was too hostile, too acidic. So, when it was proposed that a bacterium (H. Pylori), living in the stomach, could be an important cause of stomach ulcers, the idea was pretty much dismissed out of hand.

Warren and Marshall eventually proved that the scientific consensus on this matter was utter nonsense. This despite being attacked viciously from all sides. They eventually won the Nobel prize for their work where they were specifically praised for battling on in the face of implacable hostility. It is clear that had Warren not been a cussed swine, they could easily have given up, worn down by the opposition.

Had Max Plank not decided to publish some wild and whacky papers in his journal ‘Physics’, from a patent clerk, it is perfectly possible we may never have heard of a certain Albert Einstein.

When people ask me why do you think people cling onto the cholesterol hypothesis with such tenacity, is this vast conspiracy driven by the pharmaceutical industry? I expect most of them think I will say yes. I mean, obviously, there is a vast conspiracy going on to protect profits from cholesterol lowering.

However, the main reason why people cling to ideas is the natural human response – which is to reject new ideas out of hand.

“The mind likes a strange idea as little as the body likes a strange protein and resists it with similar energy. It would not perhaps be too fanciful to say that a new idea is the most quickly acting antigen known to science.”  Wilfred Trotter

Ooh, I do like Wilfred Trotter. Here is another one of his:

‘The truly scientific mind is altogether unafraid of the new, and while having no mercy for ideas which have served their turn or shown their uselessness, it will not grudge to any unfamiliar conception its moment of full and friendly attention, hoping to expand rather than to minimize what small core of usefulness it may happen to contain.’

What has this to do with heart disease, you could ask? The answer is: almost everything.


A second look at vaccination – answers that cannot be questioned

29th July 2019

 ‘No man can be forced to be healthful, whether he will or not. In a free society, individuals must judge for themselves what information they choose to heed and what they ignore.’ John Locke. ‘A letter concerning Toleration’

Here, I am going have another look at vaccination, before scurrying away from the subject for a bit, and getting back to the safe ground of cardiovascular disease. Much to the relief of some of the regular readers of this blog, no doubt.

I have to say that I thought long and hard about blogging on vaccination. It is the most brutal area for discussion that I have ever seen, and a reputation shredder. If you even dare to hint that there may just be the slightest issue with any vaccine, people come down upon you like a ton of bricks.

I also know that by daring to write on this subject, there will inevitably be people moving behind the scenes to have my blog taken down. I cannot imagine WordPress management going to the wire to protect my right to free speech. A little flick of a switch, and I will be gone from the airwaves.

However, as we move towards a world where it seems that all Governments around the world are going to pass laws mandating vaccination for everyone, and people are fined, or lose their jobs, for speaking out, or refusing to be vaccinated, then I feel that some attempt to discuss the area is essential.

Because, once something becomes mandatory, and any research into possible harms moves strictly off limits, we really need to be absolutely one hundred per-cent certain that there is no possibility that we may be doing harm. Or, that we are reducing any potential harm to the lowest level possible.

Can vaccines do harm?

‘Prof Martin Gore, 67, one of the UK’s leading cancer scientists, has died, the Royal Marsden NHS foundation trust has said. His death was following a yellow fever vaccination.’ 1

A tragedy for a brilliant medical researcher and his family. It was brought to my attention by my wife, who knew him quite well.

However, even here, we can see any criticism of vaccines being toned down and deflected. The words ‘caused by’ were carefully avoided. It was reported that he died following a yellow fever vaccination – which could mean he was vaccinated, then got hit by a bus. In fact, if you read a little more deeply, it becomes inarguable that the yellow fever vaccine was the direct cause of his death.

Yes, such an event is rare, but such events do occur. People can die following vaccinations, as a direct cause of that vaccination, although the information can be very difficult to find. In Germany, the Paul-Erlich Institute [PEI] is the organisation responsible for the reporting of vaccine security/safety.

‘Between 1978 and 1993 approximately 13,500 cases of undesired effects resulting from medications for vaccinations was reported to the Paul Erlich Institute (PEI) which is the institute which is responsible for vaccine security; the majority was reported by the pharmaceutical industry. In 40% of cases the complications were severe, 10% pertained to fatalities on account of the effects.’ 2

Yes, the numbers are relatively small – although by no means vanishingly small. In a fifteen-year period that is 1,350 deaths. If the Germans are preventing tens of thousands of deaths a year through vaccination, then a thousand severe complications and a hundred deaths or so, per year, may be a price worth paying? Discuss.

Primum non nocere

My own view is that you should never compel people to undergo a medical procedure that could result in severe damage – or death. But my philosophy is very much on the radical libertarian end of the spectrum. Others feel that personal liberties should be restricted for the overall good of society. A central philosophical divide, I suppose.

One of the other interesting facts from the Paul-Erlich Institute is that ‘severe cases’ of vaccine damage, that occur, that must be reported, include:

  • Encephalopathia: Encephalopathia is frequently overlooked as it does not always entail severe symptoms. However, there can later be developmental retardation. Encephalopathia can also trigger cri encéphalique
  • Seizures
  • Epilepsy
  • Autism
  • Sleeping sickness 2

These are not my words; these are the words of the PEI.

This list obviously raises the issue of potential brain damage following vaccination. Something that was seen with Pandemrix, used to protect against Swine Flu (HIN1).

‘An increased risk of narcolepsy was found following vaccination with Pandemrix, a monovalent 2009 HIN1 influenza vaccine that was used in several European countries during the HIN1 influenza pandemic. Narcolepsy is a chronic neurological caused by the brain’s inability to regulate the sleep-wake cycles normally. This risk was initially found in Finland, and then some other European countries also detected an association. Most recently, scientists at the United Kingdom’s Health Protection Agency (HPA) have found evidence of an association between Pandemrix and narcolepsy in children in England. The findings are consistent with studies from Finland and other countries.’ 2

[A finding not seen in any safety testing carried out prior to the launch of Pandemrix]

Thus, not only can vaccines cause severe reactions up to, and including, death. They can also lead to neurological damage such as narcolepsy. Is this all specifically to do with the vaccine itself, or the preservative it is carried in, or something else? Who knows?

Yet, and yet, despite the apparently indisputable evidence that vaccines can, and do, cause neurological damage we can find articles such as this below. Chosen pretty much at random, but it sums up the current mainstream thinking.

The “urban myth” of the association between neurological disorders and vaccinations

‘In modern society, a potentially serious adverse event attributed to a vaccination is likely to be snapped up by the media, particularly newspapers and television, as it appeals to the emotions of the public. The widespread news of the alleged adverse events of vaccination has helped to create the “urban myth” that vaccines cause serious neurological disorders and has boosted antivaccination associations. This speculation is linked to the fact that the true causes of many neurological diseases are largely unknown. The relationship between vaccinations and the onset of serious neuropsychiatric diseases is certainly one of coincidence rather than causality. This claim results from controlled studies that have excluded the association between vaccines and severe neurological diseases, therefore it can be said, with little risk of error, that the association between modern vaccinations and serious neurological disorders is a true “urban myth”. 3

What is being stated here, very forcefully indeed, is that there is no causal relationship between vaccination and neurological damage. It is simply a myth. I find the two bodies of evidence here impossible to reconcile.

Just to give two examples, the Paul Erlich Institute records encephalopathia, seizures, epilepsy, deaths and suchlike, following vaccination. The Pandemrix vaccine, in turn, has been proven to cause narcolepsy. Even the manufacturers, GSK, admitted that it did.

‘The 2009 H1N1 influenza pandemic left a troubling legacy in Europe: More than 1300 people who received a vaccine to prevent the flu developed narcolepsy, an incurable, debilitating condition that causes overpowering daytime sleepiness, sometimes accompanied by a sudden muscle weakness in response to strong emotions such as laughter or anger. The manufacturer, GlaxoSmithKline (GSK), has acknowledged the link, and some patients and their families have already been awarded compensation. But how the vaccine might have triggered the condition has been unclear.4

This is… I am not sure what it is. The evidence clearly says one thing, yet we are told we must believe that this evidence is simply an ‘urban myth.’ I feel as though I have been transported to Wonderland, or some scary totalitarian state, where the truth cannot be spoken.

Even when it comes to the most contentious area of all, vaccines and autism, it appears to have been accepted – at least in one case in the US – that vaccination lead to autism, with a girl called Hannah Polling.

‘Officials at the US Department of Health and Human Services investigating Hannah’s medical history said that vaccine had ‘significantly aggravated an underlying mitochondrial disorder, which predisposed her to deficits in energy metabolism’, causing damage ‘with features of autism spectrum disorder’. 2

The final part of the statement was very difficult to understand. ‘The officials said that the vaccine didn’t cause her autism, but ‘resulted’ in it.’ The vaccine resulted in her autism. Or, her autism resulted in her vaccination?

I have tried that statement a few different ways around, and I have no idea what that means. A lead to B, but A did not cause B. Because B resulted in A…

“Then you should say what you mean,” the March Hare went on.

I do, “ Alice hastily replied; “at least I mean what I say, that’s the same thing, you know.”

“Not the same thing a bit!” said the Hatter. “Why, you might just as well say that “I see what I eat” is the same thing as “I eat what I see!”  Alice in Wonderland.

However, the Polling case does raise a further potentially important issue. Namely, that it seems possible that some people have underlying ‘mitochondrial dysfunction,’ and that vaccination may aggravate this problem, with potentially serious consequences.

Narcolepsy, for example, is believed by some researchers to be a problem with energy production in the mitochondria. Others feel that ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) could be the result of a mitochondrial dysfunction triggered by various viral infections and, therefore, possibly vaccination?

All of which means that the possibility exists that vaccination could trigger, or exacerbate, significant mitochondrial dysfunction in susceptible individuals. This may or may not be true, but it must surely be an area for research?

To my mind it would be extremely important to establish if mitochondrial dysfunction represents a ‘risk’ for vaccination. We could then identify, using some genetic/epigenetic test, those individuals who are more likely to be damaged by vaccination. At which point we could look at ways to prevent the risk of damage – however small that risk may – be in a susceptible population.

For example, it could be possible to space out the vaccines, or only give separate vaccinations to these individuals. Maybe we could avoid vaccinating against relatively mild conditions e.g. chicken pox, or rubella (in boys) in these individuals. To me, these things seem eminently sensible areas for study.

However, it seems that we are trapped within a paradigm where it is impossible to suggest that any vaccine, for any disease, may be associated with/cause any degree of harm. In such an environment, objective scientific research becomes impossible. ‘As vaccine can harm no-one, we cannot try to find out who may be harmed. Thank you, comrade.’

As you can probably tell, I find this all very worrying and deeply, deeply, disturbing. If science has any purpose it is to seek the truth – however much that upsets the current status quo. When I see, what I believe to be important and valid questioning being crushed, I find it almost physically painful.

If that questioning results in the finding that vaccines truly do not cause any adverse effects, then that is fine. I would be more than happy with that outcome, although it currently seems inarguable that vaccines do cause adverse effects. However, as I see it, we currently have a situation whereby:

  • Pharmaceutical companies do their own safety testing on vaccines (somewhat like Boeing did on the 737 Max 8). The regulatory authorities have been, effectively, side-lined.
  • Many safety studies have only lasted days, with little or no research on any long-term effects. In fact, as far as I can establish, there has been no long-term safety research [see under Pandemrix]
  • Some vaccines have been proven to cause neurological damage
  • The preservatives and adjuvants in vaccines have not been studied for safety
  • There has never been a randomised controlled clinical study on the efficacy of any vaccine – beyond looking for a raised level of antibodies
  • Some/many people can suffer from the diseases they have been vaccinated against – and this is not monitored in any way.

Any of these things should be a very large red flag.

Looking specifically at efficacy, on that list, it is usually stated that vaccines are rigorously tested for efficacy. Here is what the University of Oxford has to say in its site ‘Vaccine Knowledge Project.’

‘Phase III trials gather statistically significant data on the vaccine’s safety and efficacy (how well it works). This means looking at whether the vaccine generates a level of immunity that would prevent disease, and provides evidence that the vaccine can actually reduce the number of cases.5

However, this does not actually test whether a vaccine really does reduce the number of cases of a disease. As I wrote in the previous blog, even in population with a 98% vaccination rate against measles, a school population still suffered a measles outbreak, and many of those previously vaccinated suffered from measles.

Which means that the statement from the Vaccine Knowledge Project…. and provides evidence that the vaccine can actually reduce the number of cases’ needs to be read very carefully. It could be taken to mean ‘provides all the evidence needed.’ Which is what it has been crafted to imply. However, it actually means ‘provides evidence regarding a ‘surrogate end-point’ which suggests that vaccines may reduce the number of cases.

If you want to know if a vaccine really works, vaccinate a hundred thousand people against a disease. Do not vaccinate another hundred thousand people (matched and randomised) – and then see what happens. Then you will know how well your vaccine works.

This is a requirement of all other forms of medical intervention (with provisos), but it is not a requirement for vaccines. A true efficacy study does not simply look at a ‘surrogate’ marker. It needs to study hard endpoints e.g. how many people are truly protected against the disease. Also, what the rate of adverse events may be.

Of course, there are those who think that such a trial would be ridiculous and unethical. Here, I quote from a website KevinMD:

‘….as some have actually demanded, we must have a randomized controlled trial (RCT), the gold standard of clinical research. RCTs use random assignment of subjects to one group or the other, in this case vaccine or a placebo (fake vaccine), and ensure both the subjects and evaluation team be blinded to who got what.

Think about this for a minute. They are demanding parents agree to subject their child to a trial in which they have a 50/50 chance of getting a fake vaccine. All this to satisfy the concerns of vaccine deniers.

It would be incredibly unethical to do such a study, and no institutional review board (aka human studies committee) would ever approve such a thing. For such trials, there must be reasonable uncertainty about which group is getting the better treatment, and in this case, there is none. The bottom line is any vaccine skeptic who demands proof like this is being massively disingenuous. It’s akin to demanding a randomized controlled trial of parachutes.’ 6

What is being said here is that there is no uncertainty that vaccines work, so there is no need for a randomised controlled trial. The counter argument to this is simply to turn the argument inside out. Without an RCT, how do you know that vaccines work? Where is your evidence? Or does ‘just knowing that it works’, count?

Medicine is littered with examples of interventions that were considered so inarguably beneficial that no trials were ever done. Strict bed rest following an MI, the radical mastectomy, x-ray screening for lung cancer, PCI in the non-acute setting.

Bernard Lown was a man who dared challenge the ‘unquestionable’ benefits of coronary artery bypass surgery. He had a long and arduous battle to publish his evidence that CABG may cause more harm than benefit. His blog on this, ‘A Maverick’s Lonely Path in Cardiology (Essay 28)’, is well worth a read. As he concludes:

‘A new treatment, whether involving drugs or procedures, is improper without indubitable supporting evidence of benefit. The patients’ well-being must not be compromised by imagined good when countervailing interests are at the same time being served. Our forty-year struggle essentially concerned medicine’s first and inviolate principle, primum non nocere. “First do no harm” is the litmus test sanctioning the privilege to practice medicine.’ 7

Bernard Lown is one hundred per cent correct, and I find it difficult to conceive that anyone who has the slightest understanding of science could write the words ‘The bottom line is any vaccine skeptic who demands proof like this [an RCT] is being massively disingenuous.’

Disingenuous… Personally, I demand proof like this for all medical interventions, wherever possible, and so should everyone else. The reason why, is because evidence from controlled clinical trials (with all their inherent flaws) is the only tool that we possess to properly assess benefit vs. harm. Without such evidence we are simply hoping and praying that benefits truly outweigh any downsides.

For example, with the Pandemrix vaccine. Had an RCT been done, it is possible, even probable, that the adverse impact on Narcolepsy would have been picked up. Therefore, it would not have been used, therefore many thousands of people would not have been harmed – above and beyond narcolepsy. Some of the key issues around Pandemrix were discussed in the BMJ article ‘Pandermix vaccine: why was the public not told of early warning signs?’

‘Eight years after the pandemic influenza outbreak, a lawsuit alleging that GlaxoSmithKline’s Pandemrix vaccine caused narcolepsy has unearthed internal reports suggesting problems with the vaccine’s safety.

‘…the raw numbers of adverse events were not small. Although it is often said that perhaps only up to 10% of adverse events are reported to national reporting systems, by late November, GSK had received 1138 serious adverse event reports for Pandemrix—a rate of 76 per million doses administered. By mid-December, there had been 3280 serious adverse event reports (68/million doses). The last report seen by the BMJ, dated 31 March 2010, shows 5069 serious adverse events for Pandemrix (72/million doses).8

As the article goes on to say:

“What is the purpose of pharmacovigilance if nobody is acting on the information? This information took eight years to come to light through academic work and litigation. Is this acceptable? If the information at our disposal is partial, that is the direct consequence of secrecy, which should not surround any public health intervention.”

Pandemrix and Arepanrix were designed for a pandemic and were removed from global markets after the pandemic. Whatever adverse events they may have caused, they are vaccines of the past. But the events of 2009-10 raise fundamental questions about the transparency of information. When do public health officials have a duty to warn the public over possible harms of vaccines detected through pharmacovigilance? How much detail should the public be provided with, who should provide it, and should the provision of such information be proactive or passive?’

All good questions.

Had Pandemrix not caused narcolepsy in large numbers, litigation against GSK would not have taken place – in Ireland. Had this not happened, data about the high rate of other adverse effect would never have seen the light of day. It seems that the European Medicines Agency had little interest in the matter.

‘What EMA knew—or could have known—about the comparative safety of GSK’s pandemic vaccines is hard to discern. It told The BMJ that “EMA does not perform comparative benefit and risk evaluations between products approved in the EU, or between EU products and products approved or used outside the EU.”

So, if monitoring product safety is not of interest to them, what exactly do the EMA do? Central here, however, is the fact that we had a vaccine causing a high number of serious adverse events and no-one did, or said, anything. Had there not been a lawsuit, we would still have been unaware of any problems. At least that is my understanding of what happened here.

Does anyone care? Well, in many countries you cannot even sue the manufacturer if a vaccine damages you – as also mentioned in the BMJ article.

‘Another element, adopted by countries such as Canada, the US, UK, France, and Germany, was to provide vaccine manufacturers indemnity from liability for wrongdoing, thereby reducing the risk of a lawsuit stemming from vaccine related injury.’ Quite extraordinary. In my view, beyond extraordinary.

A manufacturer makes a product that you believe may have damaged or killed a loved one, and you cannot do anything about it. Or, those who made the product cannot be sued. In banking they have a phrase for this. They call it moral hazard.

‘lack of incentive to guard against risk where one is protected from its consequences, e.g. by insurance.’ In this case no insurance is required. Governments have given pharmaceutical companies a free pass. Depending on your belief in the inherent ethical standards of pharmaceutical companies you may – or may not – find this reassuring.

Personally, I find it extremely worrying that people, and the entire medical profession, appear willing to accept that all vaccines, for all conditions, are entirely effective and have no adverse effects…. Even when it has been demonstrated, beyond doubt, that they do.

Anyway, I feel I should probably stop here. Others have gone much further than me, others have been braver. But there should be nothing ‘brave’ about asking legitimate scientific questions. As Richard Feynman said. ‘I would rather have questions that can’t be answered than answers that can’t be questioned.’



2: Doctoring Data pp 228 – 9 ISBN 978-1-907797-46-0







My feelings about the vaccine debate

9th July 2019

As readers of this blog will know, my primary area of interest is cardiovascular disease, which a big and complex subject, where anyone questioning the ‘conventional’ ideas gets ruthlessly attacked. However, in comparison to the area of vaccination, the battles in cardiovascular disease pale into insignificance. Mere squabbles in the nursery.

I am a member of an on-line doctors’ community in the UK called Doctors Net. Not open to the public. Whenever any story about vaccination emerges, the vitriol, anger and naked rage is quite scary to observe.

Whenever the issue of MMR raises its head on Doctors Net, doctors have stated that Andrew Wakefield should be thrown in jail, and never allowed to earn any money ever again, that he is a crook and a criminal – and those are the nicer comments.

It is clear that, in the medical profession, there is an unquestioned faith in vaccination. That is, all vaccinations, for all diseases, everywhere – for everyone. Anyone who dares to hint that, ahem, there could be some negative issues associated with vaccination is subjected to withering contempt. ‘You will be responsible for killing millions of children.’ You don’t understand science.’ And suchlike.

When it comes to the science, it does amuse me that vaccination began before anyone understood any of the science – of anything to do with microbes and the immune system. It all began, so it is recorded, with the observation that milkmaids were much less likely to get smallpox.

This led to the idea that you should deliberately infect people with a bit of cowpox, to prevent them getting smallpox. Bold.

‘The terms vaccine and vaccination are derived from Variolae vaccinae (smallpox of the cow), the term devised by Jenner to denote cowpox. He used it in 1796 in the long title of his Inquiry into the Variolae vaccinae known as the Cow Pox, in which he described the protective effect of cowpox against smallpox.’ [from the website that cannot be named… Wikipedia actually]

This was suggested at a time when all doctors thought infections were spread by Miasma. Basically, a nasty smell. No-one had the faintest idea that there were bacteria, or viruses. Somewhat ironically, vaccination – giving a small amount of a substance to cure/prevent a nasty disease – became the underlying principle of homeopathy – which most doctors now angrily dismiss as ‘woo woo medicine.’

Clearly, vaccination did not start as science. It basically started as a hunch, based on no comprehension of the science at all. Of course, that doesn’t make it wrong, but you can hardly suggest it was founded on a thorough understanding of the human immune system. Edward Jenner did not know that such a thing existed, and nor did anyone else. It was just a good guess.

The science of vaccination then became, what I call, backwards rationalisation. ‘It works, now let us work out how the hell it actually works.’ Again, nothing wrong with this. The best science often starts with observation, not a hypothesis. Graphene is a recent example. Two scientists larking about in the lab with Sellotape and pencils.

Just in case you are wondering. Yes, I do believe that vaccination works. Or, to be more accurate I believe that some vaccination works. Most vaccination, all vaccinations?

However, I do speak as one who has had seven hepatitis B inoculations and, once, just about managed to provide a blood test to show that I had made enough antibodies – to allow me to work as a doctor. A friend, who worked as a surgeon, had twenty-two hep B inoculations, and never managed to raise an antibody. He did explain to me how he continued to work as a surgeon, but I have forgotten how he managed.

Which means that I have personal – and slightly painful – experience that vaccination is not equally effective for everyone. Why not? Does anyone care about such things? It seems not. Just close your eyes and vaccinate away. No-one can question anything. Such as, why do inoculations produce antibodies in some people, and not others? Kind of interesting you would think – but no. Question not, the mighty vaccination.

This is strange, because it has been clearly established that vaccination does not work in many people:

‘An outbreak of measles occurred in a high school with a documented vaccination level of 98 per cent. Nineteen (70 per cent) of the cases were students who had histories of measles vaccination at 12 months of age or older and are therefore considered vaccine failures. Persons who were unimmunized or immunized at less than 12 months of age had substantially higher attack rates compared to those immunized on or after 12 months of age.

Vaccine failures among apparently adequately vaccinated individuals were sources of infection for at least 48 per cent of the cases in the outbreak. There was no evidence to suggest that waning immunity was a contributing factor among the vaccine failures. Close contact with cases of measles in the high school, source or provider of vaccine, sharing common activities or classes with cases, and verification of the vaccination history were not significant risk factors in the outbreak.

The outbreak subsided spontaneously after four generations of illness in the school and demonstrates that when measles is introduced in a highly vaccinated population, vaccine failures may play some role in transmission but that such transmission is not usually sustained.’1  

We are told that if you reach a measles vaccination rate of 95%, in a population, you cannot get an outbreak. Seems that is wrong. You can get an outbreak in a 98% vaccinated population. Wouldn’t it be nice to know why?

It does seem weird that measles is the chosen battleground for the vaccine furies. I am not entirely sure why. You would think the highly vocal pro-vaccinators would point to smallpox, or polio – or suchlike. Although, to be frank, I look at smallpox and wonder. I wonder how the hell we managed to eradicate this disease so quickly and simply. The entire world successfully vaccinated in a few years – with a perfect 100% record. No vaccine failures, all populations in the entire world vaccinated? Quite some feat.

An alternative explanation is that some diseases naturally come and go. Measles, for example, was an absolute killer three hundred years ago. Captain Cook introduced it to South Seas islands. The mortality rate was enormously high in native populations that had never been exposed to it before. Gradually the death rate attenuated. In most of the Western World measles was becoming a ‘relatively’ benign disease by the time vaccination came along.

If we look back in history, the black death wiped out half the population of Europe. What was it? It was almost certainly not the plague, although many people claim that it was. From the descriptions of those who died from it, it seems it was possibly a form of Ebola (haemorrhagic fever).

‘The Black Death of the 1300s was probably not the modern disease known as bubonic plague, according to a team of anthropologists studying these 14th century epidemics. “The symptoms of the Black Death included high fevers, fetid breath, coughing, vomiting of blood and foul body odor,” says Rebecca Ferrell, graduate student in anthropology. “Other symptoms were red bruising or hemorrhaging of skin and swollen lymph nodes. Many of these symptoms do appear in bubonic plague, but they can appear in many other diseases as well.”

Modern bubonic plague typically needs to reach a high frequency in the rat population before it spills over into the human community via the flea vector. Historically, epidemics of bubonic plague have been associated with enormous die-offs of rats. “There are no reports of dead rats in the streets in the 1300s of the sort common in more recent epidemics when we know bubonic plague was the causative agent,” says Wood.’ 2

Of course, we cannot be sure what the Black Death was. We do know that it came, it killed, it went. It also appeared to leave a legacy of people with CCR5 Delta32 mutations. People with this mutation cannot, it seems, be infected by the Ebola virus (or, indeed HIV). Ebola and HIV both gain entry to cells using the CCR5 protein, and if it is missing, the virus cannot get in. [Yes, you can cure HIV by giving bone marrow transplant from a donor with the CCR5 Delta 32 mutation – little known fact].

Why would we have this mutation far more commonly in areas of Europe than, in say, Africa – where the Black Death did not occur? Unless it provided a survival advantage at some point, against a virus that was (or was very like), Ebola.

Looking back at smallpox, did vaccination get rid of it? Or did vaccination simply apply the final push to see off a weakened opponent?

The plague itself – where has it gone?

Yes, I do look at the official history of vaccination with a jaundiced eye. The greatest successes… Well, it seems inarguable that vaccination has created enormous health benefits. Polio and smallpox – gone. But has this been entirely due to vaccination – possibly? I am yet to be convinced.

In truth, I find the entire area of vaccination quite fascinating. But the problem, the great problem, is that even by writing this blog I will have said several things that cannot be said.

  • Vaccination does not always work – burn the unbeliever.
  • Vaccination may not have been entirely responsible for ridding the world of smallpox – burn the unbeliever.
  • Measles is not the killer disease that it once was – burn the unbeliever.
  • You can have measles vaccination and still get measles – burn the unbeliever.

To me, these are just facts, and to state them is simply part of valid scientific questioning. For some reason, I am not entirely sure why, to question any ‘fact’ about vaccination is to be flung into the outer darkness. People get very, very, angry. They close their minds and they get polarised. Parts of this blog will almost certainly be taken out of context and used to attack me.

I don’t really know how to open the debate out into something sensible. Something scientific, something questioning and positive. Screeching at people that they simply don’t understand ‘science’ is not a good approach. In addition, yelling that they are ‘killing thousands of children’ is not a way to conduct a debate.

I feel that I do understand ‘science’, whatever that means exactly. Or at least I understand the scientific method. Which primarily consists of questioning everything – and feeling free do to so. One thing I do know is that anyone who states that the science is settled, and inarguable, and all the experts agree, and must therefore be right – clearly does not understand anything about science. At all.



Writer’s block

June 4th 2019

Several people have asked after my welfare as I have not updated this blog for some time. The answer is that I am okay. Thanks for your concern. There have been a few things going on, one of which I will be able to speak about – at some point in the future – that have been taking up inordinate amounts of my time.

I am also writing, but for some reason, every time I sit down to write a new blog my mind goes completely blank. A very difficult thing to explain. It is as if a million thoughts all gather and just mangle each other up. Things seem very clear when I am walking about, but the moment I try to get started – glomp.

I am not sure if this is what is called writer’s block. It cannot really be, because I am writing other things – such as another book. However, it is very frustrating. I did fear maybe that I have run out of things to say – but in truth each day sees a newspaper headline, or a medical research paper, that has me itching for the keyboard. How can there be so much nonsense written in the world?

So, instead I am writing this rambling nonsense, that is of very little interest to anyone I suspect, but it may get me started again. Re-set my brain into super-blog mode – if there is such a thing.

Because I still believe there is a need for voices to question the misleading rubbish   being churned out by people who claim to be scientists. Especially medical scientists, such as my great friends in Oxford who can write the most outrageous gibberish and get it published.

I have always liked to believe that science is a self-correcting system. Researchers can head of in the wrong direction for many years, decades even, but in the end the scientific truth will always catch up with them, tap them on the shoulder and make it very clear they are just being silly.

The days when there were special devices for blowing smoke up the rectum have faded from memory:

When an “apparently dead from drowning” person was pulled from the Thames [river running through London], it was thought that two things needed to happen to successfully resuscitate them: warming of the body and stimulation. Tobacco was becoming popular in Europe thanks to its exportation from the Americas, and a well known stimulant thanks to the alkaloid nicotine. The nearly dead drowning victim can’t smoke themselves, and certainly can’t swallow anything. And since hypodermic needles weren’t to be fully-invented for another hundred years, the only logical way to administer tobacco was rectally. Plus, the warm smoke would warm the individual from the inside. Win-Win. Thus, the tobacco smoke enema was born, and devices placed all along the Thames river.’ 1

From here came the mocking expression ‘Blowing smoke up your arse.’ Yes, doctors have always been keen on such activities. The first Chinese Emperor was advised by his doctors to inhale vaporised mercury – which was a magical substance so incredibly healthy that everyone should be ingesting it.

Inevitably he went mad through mercury poisoning, and started running around the forests naked before being overthrown and murdered. Still he did leave a nice tomb with terracotta soldiers and even, so it is said, an underground lake of mercury – to keep him healthy in the afterlife.

My how we laugh now at such silly ideas. But medicine has continuously felt the need to do something, anything, for the patient – even if they have not the faintest idea what will happen. Good, or bad. Bernard Shaw wrote about this over a hundred years ago in Doctors Dilemmas.

‘When your child is ill or your wife dying,” when you are confronted by “the spectacle of a fellow creature in pain or peril, what you want is comfort, reassurance, something to clutch at, were it but a straw. This the doctor brings you. You have a wildly urgent feeling that something must be done; and the doctor does something. Sometimes what he does kills the patient.”

Leeches, other forms of bloodletting, trepanning, full frontal lobotomies, removal of the toxic colon, the radical mastectomy, strict bed rest following a heart attack – all these things and many more. The ‘sometimes’ that kill the patient.

These things have all gone – mostly. Evidence, science, got rid of them. Stupidity cannot run forever. At least this was once true. Today, I am not so sure. The need to do something, anything, still runs deep in the psyche of all doctors. The concept of ‘sorry, I can’t really do anything about that’ has never been front of mind.

My personal motto is ‘Don’t just do something, stand there.’ I call it masterful inactivity; others may call it laziness.

Anyway, to return to the main issue here, which is that medical science may now be incapable of self-correction. Erroneous ideas will be compounded, built on, and can never be overturned. Because of a thing called non-reproducibility.

In most areas of science, there is nothing to stop a researcher going back over old research and trying to replicate it. The correct term is reproducibility. In every branch of science there is currently an acknowledged crisis with reproducibility.

‘Reproducibility is a hot topic in science at the moment, but is there a crisis? Nature asked 1,576 scientists this question as part of an online survey. Most agree that there is a crisis and over 70% said they’d tried and failed to reproduce another group’s experiments.’ 2

This is not good, but in medical research this issue is magnified many times. Because there is another in-built problem. You cannot reproduce research that has been positive. Take clinical trials into statins. You start with middle aged men, split them into two groups, give one a statin and one a placebo. At the end of your five-year trial, you claim that statins had a benefit – stopped heart attacks and strokes and suchlike.

Once this claim has been made, in this group, it becomes unethical/impossible to replicate this study, in this group – ever again. The ethics committee would tell you that statins have been proven to have a benefit, you cannot withhold a drug with a ‘proven’ benefit from patients. Therefore, you cannot have a placebo arm in your trial. Therefore, you cannot attempt to replicate the findings. Ever.

Thus, if a trial was flawed/biased/corrupt or simply done badly. That’s it. You are going to have to believe the results, and you can never, ever, have another go. Ergo, medicine cannot self-correct through non-reproducibility. Stupidity can now last for ever. In fact, it is built in.

We face a rather dismal eternity of blowing smoke up our arses.



Diet and heart disease – again!

April 25th 2019

Thank you to those of you enquiring after my health. I have had a horrible cough and cold and proper ‘man flu’ for the last couple of weeks, now settling. Before that, skiing, before that lecturing. But enough about me.

Over the last few weeks I have watched a flurry of activity from all directions, as the attacks on red meat and saturated fat intensify. Walter Willett must be writing up a new research paper every five minutes, such is the wealth of material he has cascaded down upon a grateful world in recent weeks (I suspect others may be doing much of the heavy lifting on his behalf).

It also seems that the Lancet has given up any pretence of being an objective seeker of the truth. Instead, the Lancet appears to have become a mouthpiece for the vegan movement. Here is what the Lancet has to say about their new EAT-Lancet project.

‘Food systems have the potential to nurture human health and support environmental sustainability; however, they are currently threatening both. Providing a growing global population with healthy diets from sustainable food systems is an immediate challenge. Although global food production of calories has kept pace with population growth, more than 820 million people have insufficient food and many more consume low-quality diets that cause micronutrient deficiencies and contribute to a substantial rise in the incidence of diet-related obesity and diet-related non-communicable diseases, including coronary heart disease, stroke, and diabetes. Unhealthy diets pose a greater risk to morbidity and mortality than does unsafe sex, and alcohol, drug, and tobacco use combined. Because much of the world’s population is inadequately nourished and many environmental systems and processes are pushed beyond safe boundaries by food production, a global transformation of the food system is urgently needed.’1

Many out there probably agree with much of this statement, especially the parts about environmental sustainability and insufficient food to feed many people. However, even if you do, you have to ask what an investigative medical journal is doing in this space. There is no longer even an attempt to be mildly objective. The Lancet has simply taken sides. Which is the exact opposite of what any scientific journal should ever, ever, do. You may notice that Professor Walter Willett was the lead author of the article quoted above

Here is one statement that I would like to further highlight. Unhealthy diets pose a greater risk to morbidity and mortality than does unsafe sex, and alcohol, drug, and tobacco use combined.’

At this point I completely part company with Walter Willett. For it is the most complete and absolute nonsense. For a start, how did he calculate the figures? For example, sexually transmitted disease – and death. How many people die of this? How many people suffer, and by how much? Do we have any idea?

Well, we know that many children die from congenital syphilis. How many around the world? I checked the WHO publications on this, and there are only estimates to be had. HIV? Gonorrhoea? Hundreds of millions that are infected, and affected, but how many millions? How many deaths? Unknown really.

We can perhaps be a little clearer on the other things such as cigarette smoking. Just looking at one country, the US:

‘Cigarette smoking is responsible for more than 480,000 deaths per year in the United States, including more than 41,000 deaths resulting from secondhand smoke exposure. This is about one in five deaths annually, or 1,300 deaths every day.’ 2

The US population is around three hundred million. The population of the world around seven billion. If 480,000 deaths a year occur in the US, this would equate to eleven million deaths a year around the world.


Around the world, about 1 in 5 adults were estimated to drink heavily in any given 30-day period. The burden of ill health for alcohol was less than for tobacco, but still substantial: 85.0 million DALYs [Disability adjusted life years]. Alcohol-related illness was estimated to cause 33.0 deaths per 100,000 people worldwide.3

Thirty-three deaths per 100,000 people worldwide is two point three million deaths each year from alcohol, worldwide. As for ‘illegal’ drug deaths.

‘Globally, UNODC estimates that there were 190,900 (range: 115,900 to 230,100) drug-related deaths in 2015, or 39.6 (range: 24.0 to 47.7) deaths per million people aged 15-64 years. This is based on the reporting of drug-related deaths by 86 countries.’4

This figure seems low, based on the CDC review of drugs deaths in the US

‘70,237 drug overdose deaths occurred in the United States in 2017. The age-adjusted rate of overdose deaths increased significantly by 9.6% from 2016 (19.8 per 100,000) to 2017 (21.7 per 100,000). Opioids—mainly synthetic opioids (other than methadone)—are currently the main driver of drug overdose deaths. Opioids were involved in 47,600 overdose deaths in 2017 (67.8% of all drug overdose deaths).’ 5

70,237 in the US would extrapolate up to 1.623 million deaths a year worldwide. Maybe other countries don’t hand out opiods like sweeties to everyone. Although, in the UK, we are certainly following suit.

So, we have some figures to go on. Somewhere in the fifteen to twenty million per year killed by unsafe sex, alcohol, drug and tobacco use each year. Who knows what the morbidity might be?

This is a gigantic figure, and we are supposed to believe that unhealthy diets are worse than this? I would challenge Walter Willett to find a single randomised controlled clinical study demonstrating that any dietary substance has significantly increased the risk of death in anyone, ever.

By unhealthy, of course, what the authors mean is animal fats/saturated fat, red meat, bacon, sausages and suchlike. Essentially, anything that is not vegan.

What of saturated fat? The last time it was possible to get an accurate assessment of saturated fat and deaths from CHD in individual countries was in 2008. After that, the figures mysteriously disappeared. Luckily Zoe Harcombe kept a copy and sent it to me.6

From these figures, I present you with a graph. Sorry, it is a bit complicated. So, please take a little time to study it, because it has two axes. The percentage of energy from saturated fat in the diet is the top axis, going from 0% up to 18%. As you can see from this, saturated fat intake is highest in France at 15.5%, and lowest in Georgia at 5.7%. Second lowest Azerbaijan, then Ukraine, then Russia.

The other axis looks at deaths from CHD. With the highest being Russia, then Georgia, then Azerbaijan, then the Ukraine.

The fact that stands out is that the countries with the lowest saturated fat intake had, on average, six times the rate of death from CHD, in comparison to the four countries with the highest saturated fat intake. I like to wave this graph at people who tell me that saturated fat in the diet is the single most important risk factor for CVD. I also like teasing vegans with it. Although they rarely respond well to teasing – as you may imagine.

I would also like to enquire of Walter Willett what he makes of data like this? I presume he would just ignore it, or point to the vegetarians of La Loma California, or suchlike. But, as any scientists know, you cannot just pick and choose populations you like and ignore those that you don’t. Nor would I dream of saying that, from this graph, we can prove that saturated fat intake protects against CVD. However tempting that may be.

But I know that this is what the EAT-Lancet are likely to do, along with all other researchers who simply ignore things they don’t like. In fact, the games played to prove that saturated fat is bad for you, twist the fabric of logic well beyond breaking point.

Which takes to me to favourite paper of all time. ‘Teleoanalysis: combining data from different types of study.’ Published in the BMJ more than fifteen years ago. 7

The paper makes this statement:

‘A meta-analysis of randomised trials suggested that a low dietary fat intake had little effect on the risk of ischaemic heart disease.’ Good, I like that. It seems astonishingly accurate. Randomised trials on dietary fat have had no effect. Which is the point where this paper should really have fallen silent.

But no, the authors decided that we should ignore these pesky studies a.k.a. evidence. Instead we should use teleolanalysis. I shall now quote directly, and heavily from the papers itself.

‘Once a causal link has been established between a risk factor and a disease it is often difficult, and sometimes impossible, to determine directly the dose-response relation. For example, although we know that saturated fat intake increases the risk of ischaemic heart disease, the exact size of the effect cannot be established experimentally because long term trials of major dietary changes are impractical. One way to overcome the problem is to produce a summary estimate of the size of the relation by combining data from different types of study using an underused method that we call teleoanalysis. This summary estimate can be used to determine the extent to which the disease can be prevented and thus the most effective means of prevention. We describe the basis of teleoanalysis, suggest a simple one-step approach, and validate the results with a worked example.

What is teleoanalysis?

Teleoanalysis can be defined as the synthesis of different categories of evidence to obtain a quantitative general summary of (a) the relation between a cause of a disease and the risk of the disease and (b) the extent to which the disease can be prevented. Teleoanalysis is different from meta-analysis because it relies on combining data from different classes of evidence rather than one type of study.

In contrast to meta-analysis, which increases the precision of summary estimates of an effect within a category of study, teleoanalysis combines different categories of study to quantify the relation between a causative factor and the risk of disease. This is helpful in determining medical practice and public health policy. Put simply, meta-analysis is the analysis of many studies that have already been done; teleoanalysis provides the answer to questions that would be obtained from studies that have not been done and often, for ethical and financial reasons, could never be done.

In so doing we can prove that saturated fat causes heart disease. ‘I say, Bravo. Bravo, sir. You are truly a genius.’

It is upon such foundations as this that the EAT-Lancet authors can say – in all seriousness – Unhealthy diets pose a greater risk to morbidity and mortality than does unsafe sex, and alcohol, drug, and tobacco use combined.’

Keep saying it and people will end up believing you. Even if you have not a scrap of evidence to support it. A phenomenon first noted by Lewis Carroll in his magical poem the Hunting of the Snark…

“Just the place for a Snark!” the Bellman cried,

   As he landed his crew with care;

Supporting each man on the top of the tide

   By a finger entwined in his hair.


“Just the place for a Snark! I have said it twice:

   That alone should encourage the crew.

Just the place for a Snark! I have said it thrice:

   What I tell you three times is true.”

Unfortunately for the EAT-Lancet crew, repeating nonsense as many times as you like cannot magically transform it from nonsense to truth. The biggest recent study on the impact of diet and heart health was the PURE study. Which was reported thus, last year:

‘Findings from this large, epidemiological cohort study involving 135,335 individuals aged 35 to 70 years from 18 low-, middle- and high-income countries (across North America, Europe, South America, the Middle East, South Asia, China, South East Asia and Africa) suggest that high carbohydrate intake increases total mortality, while high fat intake is associated with a lower risk of total mortality and has no association with the risk of myocardial infarction or cardiovascular disease-related mortality.

Furthermore, a higher saturated fat intake appeared to be associated with a 21% lower risk of stroke. Why might these results be in such contrast with current dietary advice? “The conclusion that low fat intake is protective is based on a few very old studies with questionable methodology,” explains Professor Salim Yusuf (McMaster University, Hamilton, Ontario, Canada), senior investigator for the PURE study. “The problem is that poorly designed studies performed 25–30 years ago were accepted and championed by various health organisations when, in fact, there are several recent studies using better methods, which show that a higher fat intake has a neutral effect,” he continues, citing the example of the Women’s Health Initiative trial conducted by the National Institutes of Health in 49,000 women that showed no benefit of a low-fat diet on heart disease, stroke or cardiovascular disease.’ 8

Anyway, I know that facts are pretty much useless against the diet-heart behemoth. It eats facts, turns them through one hundred and eighty degrees and spits them out again. I just felt the need to let people know that IT IS ALL COMPLETE AND UTTER RUBBISH. Gasp. Thud. I feel my man flu returning.



2: ‘




6: European cardiovascular disease statistics 2008 edition. Steven Allendar et al: Health Economics Research Centre, Dept of Public Health, University of Oxford.



What causes heart disease – Part 63

17th March 2019

[Is stress the most important cause of cardiovascular disease?]

Forgetting for a moment attacks by various people, and newspapers, that shalI remain nameless [Mail on Sunday UK], I thought I would return to the more interesting topic of what actually does cause cardiovascular disease and. As I have done several times before, I am looking at stress/strain.

I know that, deep down, most people feel that stress can lead to illness. ‘Oh, I was terribly stressed, then I went down with the flu.’ Or ‘He has been under a lot of stress and had a heart attack.’ If we go back over a hundred years William Osler, a famous physician, described a man suffering from angina as ” … robust, the vigorous in mind and body, the keen and ambitious man, the indicator of whose engines are always at ‘full speed ahead’ “.

The idea that hard driving Type A personalities were more likely to die of heart attacks gained great popularity at one time. But you don’t hear so much about this anymore. It is all diet, and cholesterol, and blood pressure and diabetes and tablet after tablet. Measure this, monitor that, lower this and that.

I believe that the side-lining of stress to be a monumental mistake. Because it remains true that stress is the single most important cause of heart disease, and I intend to try and explain exactly how this can be. Once more into the breach dear friend.

I shall start this little journey by explaining that stress is the wrong word to use. In fact, the use of the word stress has often been more of a barrier than an aid understanding. This is because, when we talk about stress, we really mean strain.

Stress or strain

It was Hans Seyle who coined the term ‘stress’ to cover the concept of negative psychological events leading to diseases, specifically heart disease. Of course, this is a terrible oversimplification, but it will do for now. Seyle later admitted that, had English been his first language (he was born in Slovakia) he would have used the term strain, not stress.

This is because stress is the external force placed on an object, or a human being. Strain is the resulting deformation or damage that can occur. Therefore, it is the resultant strain that is the driver of ill health.

For example, being told you are a useless idiot by one or another parent would be considered a significant external negative ‘stressor.’ The resultant anxiety and upset then represents the strain. However, the two things do not necessarily match up very well.

If you are highly resilient, or perhaps deaf, being told you are a useless idiot may have absolutely no effect on you whatsoever. You will continue to whistle a happy tune, whilst skipping along the pavement.

If, on the other hand, you are a rather more sensitive soul, or perhaps being told you are a useless idiot is a daily occurrence, then the resultant strain/deformation may be quite severe. In this case, the same external stressor can result in completely different levels of internal strain – depending on the resilience of the individual.

To give another example, some people enjoy giving public talks, they look forward to it. Others would rather chew their own arm off rather than stand up and talk in public. Once again, we have the same external stressor, resulting in completely different levels of internal strain.

The death of a close relative, such as a husband, is a major negative stressor which, for most people would cause a significant burden of strain. However, if the husband was an abusive bully, who regularly beat his wife, the death may be a blessed relief and the levels of strain will be reduced greatly. Then again, the conflicting feelings of guilt, relief, happiness and grief can lead to immense strain.

In short, there is no point in saying that an individual is under a great deal of stress. That may or may not be true, but it is very difficult to define, or measure. What matters is their response to negative stressors – real or perceived. The internal strain.

Of course, this does not mean that you can discount external stressors. These can be very important on both an individual, and a population wide basis. So, before looking at strain in more detail, I am going to review external ‘population-wide stress(ors)’.

Population-wide stressors

Whilst this is a fascinating area, the terminology used is more than a little variable, and confusing. One of the problems is that the terminology swirls around, and people write about the same thing using different words or use the same words to describe different things. A bit like using IHD, CHD, CAD and CVD to describe much the same thing, I suppose.

To keep this simple, and stripping terminology down things down to basics, the concept I am trying to capture, and the word that I am going to use, here to describe the factor that can affect entire populations is ‘psychosocial stress’. By which I mean an environment where there is breakdown of community and support structures, often poverty, with physical threats and suchlike. A place where you would not really want to walk down the road unaccompanied.

This can be a zip code in the US, known as postcode in the UK. It can be a bigger physical area than that, such as a county, a town, or whole community – which could be split across different parts of a country. Such as native Americans living in areas that are called reservations.

On the largest scale it is fully possible for many countries to suffer from major psychosocial stress at the same time. This happened very dramatically after the breakup of the Soviet Union, which started in some countries earlier than others e.g. Poland. But the main event was the fall of the Berlin wall, and the collapse of communism across most of Eastern Europe. It was studied quite closely by a number of researchers. Here is one paper:

‘The mortality crisis in transition economies. Social disruption, acute psychosocial stress, and excessive alcohol consumption raise mortality rates during transition to a market economy.’ 1

As the paper states:

‘Acute psychosocial stress was one of the main drivers of the sharp mortality increase experienced by the former communist countries of Europe. In central Europe, the post-communist mortality crisis was quickly solved, while in much of the former USSR, life expectancy at birth did not return to 1989 levels until 2013.’

The splintering of the Soviet Union is something to be, generally, celebrated. However, it caused a massive surge in premature deaths, mainly from cardiovascular disease (CVD).

Below is a graph which tracks at CVD deaths in men under 65s in four former Soviet countries: Russia, Kazakhstan, Ukraine and Belarus. The graph starts in the year 1980 and goes on to 2015 2.

CVD was similar in all four countries and was pretty steady, perhaps gently falling. Then, Berlin wall fell in 1989, with major disruption hitting Russia by 1991 when Gorbachev was ousted by Yeltsin. At which point CVD took off in all country.

It may be easier to see a clear pattern if we look at a single country in the Soviet Union, Lithuania. This is a graph that I have used several times before. Figures are from Euro Heart Statistics.

In Lithuania CVD was gently dropping until 1989 then – Bam! Virtually a doubling of the rate in a five-year period. Then it dropped straight back down again.

If you want a comparator country in Europe, here is the UK during the same time period. A steady uninterrupted fall (completley undisturbed by the launch of statins in 1987) Every other country in Western Europe, the USA, Canada, Australia etc. show the same pattern as the UK – a steady fall.

Getting back to the Soviet Union, it is it interesting that the main increase in those who died was seen in men, mainly middle aged men. To quote from the social disruption paper again:

‘Looking back, it could have been expected that the European mortality crisis would primarily have affected children, pregnant women, the elderly, and the disabled. Yet, as shown.. men were much more affected than women in every transition country. The fastest relative upswing in mortality was recorded for 20−39 year olds, who experienced a marked rise in violent deaths, while the fastest absolute rise occurred among 40−59 year olds, who were mainly affected by a rise in cardiovascular deaths.’

It seems inarguable that extreme psychosocial stress, as experienced in ex-Soviet Union countries after 1989, drove a massive spike in CVD deaths, which is only now beginning to settle down in many of the countries.

As an important aside, you may notice that, in Russia, the rate of CVD rose quickly from 1990 until about 1995, then dropped. Then it jumped up again in 1998. You may ask, what happened in 1998? Well, this was the year of the collapse of the Ruble – known as the Ruble crisis. It resulted in massive financial chaos, and levels of poverty exploded.

‘Mobs trying to get their savings were barred from entering the banks, executives flew to London to get suitcases full of dollars and coup plans were discussed in the newspapers. The value of the stock market dropped to 10 percent of its value of the previous year, the value of Ruble tumbled by 75 percent, and 18 of Russia’s 20 major banks effectively collapsed under massive debts. Foreign investors, some of them calling Russia “Indonesia with nukes,” fled the country.

Some have said the damage to the economy was greater than that unleashed by Hitler’s armies in World War II. By the time of the 1998 Ruble crash ran its course the poverty level had increased from 2 percent of the population in the Soviet era to 40 percent.’  3

Moving away from the Soviet Union to the population that has undergone the single greatest and most extreme form of social breakdown and disruption, social stress and dislocation known. This is the Australian aboriginals. A group of people that has been subjected to an immense burden of negative stressors.

Here are a few bullet points from a study carried out by the Australian Government:

  • Stress is a significant factor of the lives of Aboriginal young people.
  • High levels of self-harming intent and behaviour. Feelings connected to loss of hope – high levels of anxiety and depression
  • Rapid social change in Aboriginal communities.
  • Interpersonal violence, accidents and poisoning, stress, alcohol and norms of violence as in male to male fighting.
  • Domestic violence and child abuse, as well as sexual assault, are further stressors and sources of mental ill health.
  • These behavioural outcomes reflect the impact of historical factors, colonisation and disadvantage.

What impact has this had, specifically on cardiovascular disease rates? A research study was done, called the Perth Aboriginal Atherosclerosis Risk Study (PAARS) population. The investigators looked at CHD (coronary heart disease), not CVD (cardiovascular disease) – which would also include strokes. Sorry for jumping about in the terminology, but everyone does. Indeed, it is hard to find two studies that use the same terminology, or end points.

Sticking to CHD, which basically means deaths from heart attacks, researchers found that the CHD rate in Austrailian Aboriginals was 14.9 per 1000/year versus 2.4 for the general population. This is 1,490 per 100,000 per year [this is metric most commonly used] and represents the highest rate I have ever seen in any population, in any country, at any time – ever. Although Belarus came pretty close at one point.

What also stands out is that the rate of heart attacks in Aborignal Australians was six fold higher than the surrounding population. However, if we separate the figures from men and woman, we can see something even more astonishing.

For Aboriginal men the rate of CHD was 15.0 versus 3.8 per 1000 per year. A four hundred per cent increase on men in the surrounding population. For aboriginal women the CHD was almost exactly the same as for the men, 15.0 per 1000 per year – which is highly unusual in itself – as men normally have a much higher rate than women.

The astonishing fact is that Australian Aboriginal women had a rate of CHD that was ten times the rate of the surrounding female population. Or, to put it another way. One thousand per cent higher. 4

A similar picture, though less extreme, can be seen in Native Americans. As outlined in this 2005 paper. ‘Stress, Trauma, and Coronary Heart Disease Among Native Americans.5

‘This study quantified exposure to trauma among American Indians, adding to the existing evidence that this population experiences a disproportional amount of trauma. We were intrigued by the statement “It may be that high rates of trauma exposure contribute to the increasing prevalence of cardiovascular disease among American Indian men and women, the leading cause of death among this population” and wanted to lend support to this assertion. Indeed, American Indians now have the highest rates of cardiovascular disease in the United States.

In a study similar to the AI-SUPERPFP study (American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP) Team). Koss et al. documented adverse childhood exposures among 7 Native American tribes and compared these exposures to levels observed in the Adverse Childhood Experiences (ACE) Study conducted by Kaiser Permanente and the Centers for Disease Control and Prevention in a health maintenance organization population. Compared with participants in the ACE study, not only did the American Indians have a significantly higher rate of exposure to any trauma (86% vs 52%), but they also had a more than 5-fold risk of having been exposed to 4 or more categories of adverse childhood experiences (33% vs 6.2%).’

Wherever you look, you can see that populations that have been exposed to significant social dislocation, and major psychosocial stressors, have extremely high rate of coronary heart disease/cardiovascular disease.

This can be supported if we look at the twenty countries in the world that have the highest rates of CVD – both men and women. Figures from WHO 2017 6.  Ex-soviet countries in bold

  • Turkmenistan
  • Ukraine
  • Kyrgyzstan
  • Belarus
  • Uzbekistan
  • Moldova
  • Yemen
  • Azerbaijan
  • Russia
  • Tajikistan
  • Afghanistan
  • Syria
  • Pakistan
  • Mongolia
  • Lithuania
  • Georgia
  • Sudan
  • Egypt
  • Iraq
  • Lebanon

I feel that some of these figures may not be entirely accurate. Such as the CVD rate in Syria, or Iraq in the last few years. As for the rest. I would not like to comment on the social and political situations in all of these countries in too much detail. However, we are not looking at peaceful and mature democracies here. Mainly dictatorships and countries riven by internal conflict.

Winding this back to the US, there is a pattern of CHD showing that certain counties suffer much higher rates than others. Figures taken from the CDC. On this graph darker means a higher rate of heart disease, lighter means less heart disease. These are deaths per 100,000 per year. You may discern a pattern.

The UK shows precisely the same sort of picture with inner cities and more deprived areas, having much higer rates than affluent suburbs.

Wherever and however you look it becomes apparent that higher levels of psychosocial stress are strongly associated with CVD/CHD. In some cases, very strongly indeed.

But how can psychosocial stress and factors such as childhood trauma, as seen in the Australian Aboriginals, or Native Americans, lead to a build up of atherosclerotic plaques in the arteries,the main cause of CVD?

Or to put it another way, how does a negative external stressor, lead to the internal physiological strain, that causes CVD? For that we need to turn to Sapolski, Bjortorp and Marmot. Which comes next!






Cholesterol Games

3rd March 2019

Mahatma Gandhi. ‘First they ignore you, then they laugh at you, then they fight you, then you win.’

A few days ago, the health editor of the Daily Mail wrote to me [and Zoe Harcombe and Aseem Malhotra]. I was informed that the Mail on Sunday was gong to attack us for daring to question the cholesterol hypothesis and the benefits of statins.

Below is the e-mail I received.

From: Barney Calman
Sent: 28 February 2019 16:53
To: malcolmken
Subject: MOS/Right to reply

Dear Dr Kendrick – The Mail on Sunday plans to publish an article this weekend on growing concerns about claims you and a number of other individuals have publicly made about statins, the role of cholesterol in heart disease, and the allegations that researchers into the drugs are financially conflicted due to payments made to the organisations they work for, and so the evidence they provide about the effectiveness of these medications, and their side effects, are in some way untrustworthy.

Over the past 30 years, more than 200,000 patients have been put through the most rigorous forms of clinical trials to produce definitive proof the tablets lower heart attack risk by up to 50 per cent, and a stroke by 30 per cent, and reduce the risk of death – from any cause.

In January, the editors-in-chief of all 30 major heart health medical journals – each a leading cardiologist – signed a joint open letter, warning: ‘Lives are at stake [due to the] wanton spread of medical misinformation. It is high time that this stopped.’

A 2016 analysis from the London School of Hygiene and Tropical Medicine, which tracks outbreaks and public health concerns, found fake news about statins may have prompted 200,000 patients in Britain alone to quit the drug over a single six-month period following an article you wrote for the BMJ which claimed, incorrectly, that 20 per cent of statins patients quit the drug because of side effects.

They estimate that up for 2,000 heart attack and strokes could be a result of this. We would like to offer you the opportunity to respond to this and the following:

*In your latest book, A Statin Nation, you state: ‘People are being conned. The way to avoid heart disease… has nothing to do with lowering cholesterol.’ This is despite clinical trial evidence to the contrary, and despite no evidence that there is a con, which would imply that those who claim that lowering cholesterol can help lower the risk of heart disease know this is untrue and are deliberately misleading the public.

*It has been alleged that the potential consequences of claims you have made about statins and cholesterol, far outweigh that of the infamous MMR vaccine scandal with one researcher saying: ‘In terms of death and disability that could have been prevented, this could be far worse.’

*In our article, one leading cardiologist states that the facts you and others often cite about cholesterol and statins sound convincing but that in reality ‘they contain a grain of truth, mixed with speculation and opinion, which makes is very difficult for the public to know who to trust.’

*You often quote observational studies as proof of your claims about statins and cholesterol in articles and in media appearances which contradict findings of authoritative clinical trials, which you do not mention. This is misleading.

*In a recent blog you wrote: ‘Professor Sir Rory Collins and Professor Colin Baigent made a pact with the dev… sorry … they made a pact with the pharmaceutical industry to take hold of all the data on statins. They will not let anyone else see the data they hold. Including all the data on side-effects. It is kept completely secret.’ Also: ‘A fact that needs to be emphasised is that the CTT will not let anyone else see the data they hold. Including all the data on adverse events [side-effects] and serious adverse events.’ It is a version of similar claims you have made numerous times over the years. However, the CTT have stated numerous times that they did not originally request the data on all adverse events so did not have it. They also point out that the said data must be requested from the individual research organisation which carries out the trials, and is not in their gift to provide. They say you know this, as they have told you this, so to repeat the claim amounts to a lie.

*Your stance on statins and the link between cholesterol and heart disease amounts to misinformation.

*There is no evidence you work in NHS practice, or as a GP in private practice.

If you wish for any comments to be included in our article please send them to us by midday this Friday.

Many thanks,

Barney Calman
Health & Lifestyle Content Director
Mail on Sunday


I wondered whether or not I should bother to reply, as I knew that the article would already have been written, and very little was going to be altered – no matter what I wrote. Indeed, I thought long and hard about responding to the allegation that there is no evidence you work in NHS practice, or as a GP in private practice.

This would have been a complete lie, so I wondered about letting them print it, then suing their backsides off afterwards. Then I thought I will spend the next ten years having people write that I am not a doctor at all – on the basis of a lie printed in the Daily Mail. So, I disavowed them of printing this direct lie. Maybe I should just have let them get on with it.

They were also going to write this…

A 2016 analysis from the London School of Hygiene and Tropical Medicine, which tracks outbreaks and public health concerns, found fake news about statins may have prompted 200,000 patients in Britain alone to quit the drug over a single six-month period following an article you wrote for the BMJ which claimed, incorrectly, that 20 per cent of statins patients quit the drug because of side effects.

Frankly, I wish I had written that paper, but I did not. It was written by Aseem Malhotra. This, I trust, gives you some idea of the high level of fact checking going on at the Daily Mail. In the end I did write back to the Daily Mail, and this is what I said. Amazingly, there were very few swear words.

Dear Barney Calman,

Thank you for your e-mail. This is all very familiar ground to me. I am not entirely sure how you would like me to respond to each of your points.

First, I do work for the NHS as a GP, and if anyone wishes to claim that I do not – then that would be direct libel. I am employed by two NHS trusts East Cheshire and CCICP (Central Cheshire Integrated Care Partnership). Feel free to check with either trust, or look me up on the GMC website. But if anyone states that I am not employed in the NHS then I will most certainly sue. And I will win, so I would recommend caution on this point.

As for other specific points.

*You often quote observational studies as proof of your claims about statins and cholesterol in articles and in media appearances which contradict findings of authoritative clinical trials, which you do not mention. This is misleading.

Do I not mention that the studies I quote are observational, or that I do not mention the findings of authoritative clinical trials? Which of these is a problem, and why?

I would add that the proof of the link between smoking and lung cancer was based on observational studies. Does this mean that smoking does not cause lung cancer? Or is that not their argument. Whilst observational studies are not generally considered as robust as randomised clinical trials, they have value. Equally, most epidemiologists would agree that, whilst observational studies (demonstrating association) cannot prove causality (unless the hazard ratios are very high) a lack of association does disprove causation. So, it can be fully valid to rely on observational studies where there is no association, or the observation is in direct contradiction to the hypothesis.

*It has been alleged that the potential consequences of claims you have made about statins and cholesterol, far outweigh that of the infamous MMR vaccine scandal with one researcher saying: ‘In terms of death and disability that could have been prevented, this could be far worse.’

If I am wrong, then this statement could, perhaps be true, although it does represent a form of reprehensible bullying – accusing someone of causing many thousands of deaths. This is an accusation that Rory Collins has repeatedly made. He attacked the BMJ for publishing an article suggesting statins may have a high incidence of adverse effects. You may wish to see the e-mail exchange between Rory Collins and Fiona Godlee on this site

I would also like to point you to a study published in the BMJ open Kristensen ML, et al. BMJ Open 2015;5:e007118. doi:10.1136/bmjopen-2014-007118

The main findings of this study – not refuted by anyone were…

6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively.

What this study found was that if you took a statin for five years, the increase in life expectancy would be (on average) 3.5 days. That is around 0.75 days per year of statin treatment. That is the important outcome. The figures quoted by Collins and Baigent and the Oxford CTT group are relative risk reductions, and these figures are entirely meaningless unless you know the absolute risk. Equally, to state lives can be saved is meaningless. No-one’s life can be saved. The best we can achieve is to increase life expectancy. That is what matters. I covered much of this in my book Doctoring Data, which I would recommend you read, as it outlines the ways that data are presented to look as beneficial as possible.

*In our article, one leading cardiologist states that the facts you and others often cite about cholesterol and statins sound convincing but that in reality ‘they contain a grain of truth, mixed with speculation and opinion, which makes is very difficult for the public to know who to trust.’

I cannot answer this, what does a grain of truth mean? What is a grain of truth mixed with speculation and opinion? Specific and concrete examples would be required before I could provide any meaningful answer.

*In your latest book, A Statin Nation, you state: ‘People are being conned. The way to avoid heart disease… has nothing to do with lowering cholesterol.’ This is despite clinical trial evidence to the contrary, and despite no evidence that there is a con, which would imply that those who claim that lowering cholesterol can help lower the risk of heart disease know this is untrue, and are deliberately misleading the public.

Yes, I believe that people are being conned, and I believe the public are being deliberately misled. That is why I called my first book The Great Cholesterol Con. I would point out that there has been one major placebo controlled double blind statin study done. ALLHAT-LLT, which was funded by the National Institutes of Health in the US. The conclusions of the study, published in 2002, were that:


Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C.

All of the industry funded studies were positive. This is either a remarkable coincidence – or something else. A con perhaps?

In a recent blog you wrote: ‘Professor Sir Rory Collins and Professor Colin Baigent made a pact with the dev… sorry … they made a pact with the pharmaceutical industry to take hold of all the data on statins. They will not let anyone else see the data they hold. Including all the data on side-effects. It is kept completely secret.’ Also: ‘A fact that needs to be emphasised is that the CTT will not let anyone else see the data they hold. Including all the data on adverse events [side-effects] and serious adverse events.’ It is a version of similar claims you have made numerous times over the years. However, the CTT have stated numerous times that they did not originally request the data on all adverse events so did not have it. They also point out that the said data must be requested from the individual research organisation which carries out the trials, and is not in their gift to provide. They say you know this, as they have told you this, so to repeat the claim amounts to a lie.

You could perhaps ask them to point you to any letter or any other form of communication that the CTT have had with me. I will let you know the answer, they have never communicated directly with me, at any time. So, for them to say that they have told me anything is, to be fully accurate, a lie. They claim do not hold the data, yet they have managed to publish major papers on statin adverse effects? For instance, this one. Interpretation of the evidence for the efficacy and safety of statin therapy.

Which contains sections such as these

‘The only serious adverse events that have been shown to be caused by long-term statin therapy—i.e., adverse effects of the statin—are myopathy (defined as muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50–100 new cases of diabetes, and 5–10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50–100 patients (ie, 0·5–1·0% absolute harm) per 10 000 treated for 5 years.’

So, they have written a paper outlining all the issues of adverse effects and serious adverse effects – and yet they do not have the data. So, how did they manage that?

*Your stance on statins and the link between cholesterol and heart disease amounts to misinformation.

Perhaps you would like to read this paper (which I co-authored) ‘LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature.’  Which was THE most downloaded paper published by Taylor and Francis in the last year.

Or this paper ‘Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review.’ Published in the BMJ open in 2016

‘High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Which was the most read paper in the journal for five months in a row.

All I see from your e-mail are ad-hominem attacks on me. I see no facts at all.  I hope that I have given you sufficient information

Yours Truly

Dr.Malcolm Kendrick


I followed up with a section of the battle that Prof Sir Rory Collins had with Fiona Godlee over the publication of the Aseem Malhotra paper where Rory Collins demanded an apology and a retraction of the paper. The BMJ took this so seriously they held an independent review.

I wrote a second e-mail to Barney Calman

I would also point you to this paragraph

A 2016 analysis from the London School of Hygiene and Tropical Medicine, which tracks outbreaks and public health concerns, found fake news about statins may have prompted 200,000 patients in Britain alone to quit the drug over a single six-month period following an article you wrote for the BMJ which claimed, incorrectly, that 20 per cent of statins patients quit the drug because of side effects.

I did not write that article. I suggest you check your facts a little more closely before putting any article out there.

Listen, we all know where this attack is coming from. The CTT and Professor Rory Collins and Baigent et al. They attacked Aseem Malhotra and Professor Abramson, then the BMJ, for publishing articles by Aseem and Abramson suggesting statins caused adverse effects in around 20% of people. Collins attacks were severe, and the BMJ was require to hold an investigation, in which Collins attacks on these papers were judged to be unfounded. The entire review can be seen here.

I would strongly suggest that you read it in full. It is, in a restrained manner, damning of Rory Collins and the CTT.

Here are a couple of sections from that report

All-cause mortality —A recent editorial by Vinay Prasad in Annals of Internal Medicine illustrates a fundamental problem that has consistently concerned the panel. Prasad compared two meta-analyses of statins in primary prevention that differed in their statistical conclusions by less than half a percentage point and yet reached opposite conclusions—namely that that “statins reduce . . . total mortality” or conversely that “data. .. showed no reduction in mortality associated with treatment with statins.” Unfortunately, patients and clinicians have to make decisions in the grey area between these two diametrically opposed conclusions. The panel supports Prasad’s contention that “The Cholesterol Treatment Trialists’ study has a robust set of de-identified individual-patient data, which can improve our understanding, and those data should be made widely available.

The conclusions of the BMJ report, which are carefully written are worth considering

The panel was unanimous in its decision that the two articles do not meet any of the criteria for retraction. The error did not compromise the principal arguments being made in either of the articles. These arguments involve interpretations of available evidence and were deemed to be within the range of reasonable opinion among those who are debating the appropriate use of statins. In making this assessment, the panel is not expressing an opinion about the merits of these arguments, as that work was beyond the scope of the panel.

The panel did have one final comment. It became clear to the panel that the fact that the trial data upon which this controversy is based are held by the investigators and not available for independent assessment by others may contribute to some of the uncertainty about risks and benefits. Different investigators may come to different conclusions with the same data. In fact, a particularly germane example occurred recently in which two experienced Cochrane groups were charged with evaluating a particular intervention and, despite being given the same instructions, data, and resources, did not arrive at identical results or conclusions. The panel strongly believes that the current debates on the appropriate use of statins would be elevated and usefully informed by making available the individual patient level data that underpin the relevant studies

Yours truly

Dr Malcolm Kendrick

P.S. employed to work in the NHS as a doctor – which is a fact.


In other words, the attacks on Aseem Malhotra were completely unfounded, as were the attacks on the BMJ. The whole issue of all-cause mortality is complex and there is a need for debate. Rory Collins and his team hold the robust set of de-identified data and those data should be made widely available. That would be the data they claim not to have?

How can it possibly be allowed that one group of researchers hold all the data from the statin trial (not, apparently the adverse effects data – although they have written detailed papers on this issue) and refuse to share it with anyone else?

Anyway, this is probably enough for now. I just wanted to give you some idea of the attacks and battles that are gong on and to shine a little light on what happens. The Mail on Sunday have published a very long article attacking ‘statin deniers’ with pictures of me Zoe and Aseem at the front. I think I look quite dashing. Not as dashing as Aseem who is a very handsome swine, and also young, and intelligent – and brave. Yes, I hate him.

Nor am I as attractive as Zoe Harcombe. But hey, at least I got my picture in the national press. I wasn’t very keen on the bit where they called me self-pitying. But I was quite pleased that they included some of the stuff that I sent.

Until next time, best wishes from the mass-murdering, statin denying, self-pitying Dr Kendrick.

Adherence to statins saves lives

17th February 2019

[Adherence to placebo saves lives]

To an extent I am cursing myself for doing what I am about to do. I have been dragged, yet again, into reviewing a paper that has made headlines round the world which proved, yes proved, that adherence to statins saves lives. I am doing this review because a lot of people have asked for my opinion on the paper.

I do feel like saying. ‘Look, I wrote the book Doctoring Data so that you could read papers like this and work out why they are complete nonsense for yourselves’. Clearly, not enough people have read my book, and I would therefore heartily encourage another million or so people to do so. [Conflict of Interest statement – I will get lots of money if this happens, which I think of as “win, win”].

The paper, in this case was called ‘Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease.’ It was published in the New England Journal of Medicine (NEJM) a couple of days ago.

The main finding was:

‘Using a national sample of Veterans Affairs patients with ASCVD (atherosclerotic cardiovascular disease), we found that a low adherence to statin therapy was associated with a greater risk of dying. Women, minorities, younger adults, and older adults were less likely to adhere to statins. Our findings underscore the importance of finding methods to improve adherence.’ 1

First thing to say is that this was an observational study. So, it cannot be used to prove causality, especially as the improvement in outcomes that they observed was an increased mortality risk of 1.3 (HR) in those who were least adherent – compared to those who were most adherent.

As many people know… sorry I shall rephrase that… as many geeks like myself know, if the hazard ratio is less than two, in an observational study, the best thing to do with said paper is to crumple it up and throw it in the bin. Because it is almost certainly meaningless. To quote Sir Richard Doll and Richard Peto, two of the fathers of medical research and epidemiology:

“when relative risk lies between 1 and 2 … problems of interpretation may become acute, and it may be extremely difficult to disentangle the various contributions of biased information, confounding of two or more factors, and cause and effect.”2

Observational studies with relative risks between one and two, are the type of studies which find that drinking five cups of coffee protect against CVD – or would that be increase the risk of dying of CVD.  Or maybe it is tea, not coffee? [I apologise for mixing up odds ratios, hazard ratios and relative risk. For ease of understanding, think of them as the same thing].

For example, I was looking at this paper:

‘Tea and coffee consumption and cardiovascular morbidity and mortality’.

Where they found that drinking between three and six cups of coffee reduced CV mortality by 45%:

 ‘A U-shaped association between tea and CHD mortality was observed, with an HR of 0.55 for 3.1 to 6.0 cups per day.’3

That is a far better result than adhering to statins. After all it is a 45% reduction vs. 30% reduction. My advice therefore would be to stop the statins and have nice cup of tea instead. Life would be so much better, and you would live longer as well. Sorry, but I don’t know what sort of tea. English breakfast, Earl Grey, Darjeeling… So many questions. So many stupid studies to read. So much crumpling. So many bins to empty.

Leaving behind the nonsenses they are – the observational studies with a minute difference in hazard ratio – let us move on to the major confounder of this latest crumple, bin, paper. Which is that people who adhere to medications do far better than those who do not – even if that medication is a placebo.

This was first noted, with regard to cholesterol lowering medications, nearly forty years ago in another paper, coincidentally published in the NEJM. It was called:

Influence of adherence to treatment and response of cholesterol on mortality in the coronary drug project.

I have copied the abstract in full. In part because it is written in something akin to understandable English. Most unusual in any medical journal. In this study the researchers were looking at drugs used to lower cholesterol levels, prior to the invasion of the statins.

‘The Coronary Drug Project was carried out to evaluate the efficacy and safety of several lipid-influencing drugs in the long-term treatment of coronary heart disease.  Good adherers to clofibrate, i.e., patients who took 80 per cent or more of the protocol prescription during the five-year follow-up period, had a substantially lower five-year mortality than did poor adherers to clofibrate (15.0 vs. 24.6 per cent; P = 0.00011).

However, similar findings were noted in the placebo group, i.e., 15.1 per cent mortality for good adherers and 28.3 per cent for poor adherers (P = 4.7×10-16). These findings and various other analyses of mortality in the clofibrate and placebo groups of the project show the serious difficulty, if not impossibility, of evaluating treatment efficacy in subgroups determined by patient responses (e.g., adherence or cholesterol change) to the treatment protocol after randomization.’ 4

I think it is worth highlighting the main findings again.

Those who adhered to taking clofibrate               =          15% mortality

Those who had poor adherence to clofibrate     =          24.6% mortality

Those who adhered to taking placebo                 =          15.1% mortality

Those who had poor adherence to placebo        =          28.3% mortality

From this is can be established that it was worse for you to not take placebo regularly than it was to not take clofibrate regularly.

If we move forward in time, others have looked at adherence to taking statins. The first thing they noted was people who take their medication regularly are different in many, many, ways to those who have poor adherence.

The paper is called: ‘Statin adherence and risk of accidents, a cautionary tale.’ Published in the American Heart Association journal Circulation.

As they say in the introduction:

‘Bias in studies of preventive medications can occur when healthier patients are more likely to initiate and adhere to therapy than less healthy patients. We sought evidence of this bias by examining associations between statin exposure and various outcomes that should not be causally affected by statin exposure, such as workplace and motor vehicle accidents.’

As they conclude:

‘Our study contributes compelling evidence that patients who adhere to statins are systematically more health seeking than comparable patients who do not remain adherent. Caution is warranted when interpreting analyses that attribute surprising protective effects to preventive medications.’ 5

This takes us back to Hill and Peto:

“when relative risk lies between 1 and 2 … problems of interpretation may become acute, and it may be extremely difficult to disentangle the various contributions of biased information, confounding of two or more factors, and cause and effect”

In the case of this latest ‘nonsense’ paper on statins, it is not actually difficult to disentangle the various contributions of biased information.

We already know that people who take tablets regularly, and placebo regularly, are more health seeking than those who do not. We already know that if you take a placebo regularly, this almost halves your (absolute) mortality rate. These are both enormous confounders in the latest NEJM study.

In fact, the confounder effect unearthed in previous studies is far larger than the effect they found. Which, if you are going to be ruthlessly logical, would suggest you would be far better off regularly taking a placebo than regularly taking a statin. If you choose to do so, you could entitle their paper “Proof that statins have no beneficial effect”.

You sure as hell cannot use such data to suggest that adhering to statins is beneficial. Yet, the authors of this study have done so. I give their paper a mark of D-Fail, please try again.

Or else, I would say, please inform yourselves of the previous research done in this area before writing a paper. This will avoid wasting everyone’s precious time.


2: Richard Doll & Richard Peto, The Causes of Cancer 1219 (Oxford Univ. Press 1981).




Response to the Lancet paper

3rd February 2019

A number of people have asked for my views on the Lancet Paper ‘Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomized controlled trials.’

It was reported in various major newspapers.

The Times reported the study thus: “Everyone over the age of 75 should be considered for cholesterol-lowering statins, experts have urged, after an analysis found up to 8,000 lives a year could be saved.”1  

The Telegraph had this to say. “Researchers said up to 8,000 deaths a year could be prevented if GPs simply prescribed drugs costing pennies a day.”

This comes hot on the heels of a concerted effort to silence statin critics around the world by a coalition of ‘experts. I suspect the coordinated timing is more than a coincidence.

‘The editors of more than two dozen cardiology-related scientific journals around the world published an editorial Monday to “sound the alarm that human lives are at stake” because of medical misinformation.

These physicians describe regularly encountering patients hesitant to take potentially lifesaving medications or adhere to other prescribed treatments because of something they read online. Or heard from friends. Or saw on television.

“There is a flood of bad information on the internet and social media that is hurting human beings,” said Dr. Joseph Hill, the architect of the essay and editor-in-chief of the American Heart Association journal Circulation. “It’s not just an annoyance, this actually puts people in harm’s way.”

The primary example illustrated in the editorial is the use of statins, a cholesterol-lowering medicine that can reduce heart attack and stroke risk in certain people. But doctors say too many of their patients shun taking statins because of bad information they picked up – often from politicians, celebrities and others who lack medical expertise.’2

Essentially, they feel that certain issues, such as prescribing statins, are so vitally important that critics should be silenced. Perhaps all these editors should try reading this:

‘Congress shall make no law respecting an establishment of religion or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.

Yes, the US founding fathers knew the first thing tyrannies always wish to do is remove freedom of speech. From that, all else follows. If they don’t get that message, they should all be forced to read 1984 by George Orwell.

“Freedom is the freedom to say that two plus two make four. If that is granted, all else follows.”

Getting back to the Lancet paper. What do I think of it? The first thing to note is ‘who done it.’ Well, of course, it was the Cholesterol Treatment Triallists Collaboration (CTT) from Oxford. Run by Professor Sir Rory Collins and Professor Colin Baigent. They do almost all these meta-analyses on statins, because they hold all the data. So, no-one else can really do them.

The CTT is in this hallowed position because they made a pact with the dev… sorry … they made a pact with the pharmaceutical industry to take hold of all the data on statins from all the pharmaceutical companies that manufacture statins and collate the data.

The CTT are very closely associated with the Oxford Clinical Trials Service Unit (CTSU) which is run by, and has employed, most of those in the CTT. Collins and Baigent etc. The CTSU is a clinical trials unit which, last time I looked, had obtained nearly £300 million in funding from the pharmaceutical industry for running clinical trials on various cholesterol lowering medications.

A fact that needs to be emphasised is that the CTT will not let anyone else see the data they hold. Including all the data on adverse events [side-effects] and serious adverse events. It is kept completely secret. I have the e-mail exchange between an Australian journalist and Professor Colin Baigent where the journalist attempts to find out if it is true that the CTT will not let anyone else see the safety data.

It starts quite well and the tone is amiable. Eventually Professor Colin Baigent clams up and refuses to answer any further questions. I have promised said journalist to keep this exchange under wraps, but almost every day I am tempted to publish it. It is toe-squirming.

Anyway, my point here is that the CTT is a horribly conflicted organisation, and has been paid, directly, or indirectly, a great deal of money by the pharmaceutical industry. Here are the conflicts of interest of those involved in writing the Lancet paper:

Conflicts of interest of statement from the Lancet paper: Commercial organisations in bold.

RO’C, EB, IF, CW, and JS have nothing to disclose. JF reports personal fees from Amgen, Bayer, Pfizer, Boehringer Ingelheim, Sanofi, and AstraZeneca, outside the submitted work; and non-financial support from Amgen, Bayer, and Pfizer, outside the submitted work. BM reports grants from the Medical Research Council, British Heart Foundation, and the National Institute for Health Research Oxford Biomedical Research Centre during the conduct of the study, and grants from Merck outside the submitted work. CR report grants from the Medical Research Council and British Heart Foundation during the conduct of the study; and grants from Merck, outside the submitted work. JE reports grants from the Medical Research Council and the British Heart Foundation during the conduct of the study, and a grant from Boehringer Ingelheim outside the submitted work. LB reports grants from the Medical Research Council and the British Heart Foundation during the conduct of the study. MK is an employee of a company that has received study grants and consulting fees from manufacturers of PCSK9 inhibitors and treatments for lipid disorders, outside the submitted work. AT reports personal fees from Amgen and Sanofi, outside the submitted work. PR reports a research grant from AstraZeneca during the conduct of the study; and research grants from Novartis, Pfizer, and Kowa, outside the submitted work. CP reports a grant from Merck, outside the submitted work; and personal fees from Merck, Pfizer, Sanofi, Amgen, and Daiichi-Sankyo, outside the submitted work. EL reports grants from AstraZeneca, Bayer, Boehringer Ingelheim, Amgen, and Merck, outside the submitted work; and personal fees from Bayer, Amgen, Novartis, and Sanofi, outside the submitted work. WK reports grants and non-financial support from Roche, Beckmann, Singulex, and Abbott, outside the submitted work; and personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, GlaxoSmithKline, Dalcor, Sanofi, Berlin-Chemie, Kowa, and Amgen, outside the submitted work. AG reports personal fees from Aegerion Pharmaceuticals, Arisaph Pharmaceuticals, DuPont, Esperion Therapeutics, Kowa, Merck, Roche, Vatera Capital, ISIS Pharmaceuticals, Weill Cornell Medicine, and Amgen, outside the submitted work. SY reports a grant from AstraZeneca, outside the submitted work. RC reports support from the Nuffield Department of Population Health, during the conduct of the study; grants from the British Heart Foundation, Cancer Research UK, Medical Research Council, Merck, National Institute for Health Research, and the Wellcome Trust, outside the submitted work; personal fees from the British Heart Foundation and UK Biobank, outside the submitted work; other support from Pfizer to the Nuffield Department of Population Health (prize for independent research); and a patent for a statin-related myopathy genetic test licensed to University of Oxford from Boston Heart Diagnostics (RC has waived any personal reward). CB reports grants from the Medical Research Council and British Heart Foundation, during the conduct of the study; and grants from Pfizer, Merck, Novartis, and Boehringer Ingelheim, outside the submitted work. AK reports grants from Abbott and Mylan, outside the submitted work; and personal fees from Abbott, Amgen, AstraZeneca, Mylan, and Pfizer, outside the submitted work. LB reports grants from UK Medical Research Council and the British Heart Foundation during the conduct of the study.

As to the study itself. I wrote this as a ‘rapid response’ to an article Colin Baigent wrote in the BMJ about the study. It may be published, it may not be.

I would like to ask Colin Baigent one question on this study – at this time.  He claims that the Lancet study was a meta-analysis of twenty-eight RCTs. The study was called. ‘Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials.’

However, in the Appendix to the Lancet paper it is made clear that five of the studies are a comparison of high dose vs. low dose statins. PROVE-IT, A to Z, TNT, IDEAL and SEARCH. They cannot be used to test the hypothesis that statins are beneficial in the over 75s vs. placebo, as they were not done to answer this question.

Also, in nine of the RCTs used in the meta-analysis there were 0% participants over the age of 75 at the start of the study. These were 4S, WOSCOPS, CARE, Post CABG, AFCAPS/TexCaps, ALERT, LIPID, ASPEN and MEGA.

Which means that five of the studies could not address the question of statins vs placebo in the over 75s, and nine of the studies had no participants over the age of 75, which leaves fourteen studies that would be relevant to the issue of prescribing statins in the over 75s.

My question is, why did you call this study ‘Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials.

Yes, they claimed to have done a meta-analysis of twenty-eight studies, yet they could only use data from fourteen to make their claims. The largest of which was the Heart Protection Study (HPS), carried out by, guess who, Rory Collins from the CTSU and CTT.

As for the actual data, it is the usual obfuscation, skirting as close to the direct lie as possible without crossing that line. I am just going to look at one issue. The main claim was that “statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77–0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol.”

A 21% reduction in major vascular events. That sounds terribly impressive. However, if you have read my book Doctoring Data you will know that what is most important here is not what is said, it is what is not said.

Do you see any mention of overall mortality here? No, you don’t. Which means that it did not change. Also, you may note this wording ‘reduction in major vascular events.’ What is a major vascular event? Well, it is mainly a non-fatal heart attack or a non-fatal stroke. There are other CV events, but they are much less common.

Note again, no mention of fatal CV events. If there had been a reduction here, it would have been trumpeted from the rooftops. Which means that we have no reduction in mortality and no reduction in fatal CV events. Of course, it is worth preventing non-fatal heart attacks and strokes, as these can be extremely damaging and harmful things.

However, there is something worth mentioning here that I have not really covered before. There are heart attacks and heart attacks, and strokes and strokes. A heart attack (MI) can be a crushing near-death event, leaving the heart severely weakened and liable to trigger into a fatal heart arrythmia at any time. The patient can be left a cardiac cripple.

Alternatively, a heart attack can be diagnosed by a marginal rise in cardiac enzymes with no symptoms at all, and no residual problems. Yet, both of these events, so completely different in their impact, will be listed as a non-fatal heart attack, with precisely the same weighting.

Equally, a stroke can leave the person virtually paralysed down one side, incontinent, unable to speak, eat, or move. Or, it can be a half hour strange sensation with slight facial weakness that fully resolves. Again, both these events will be listed with precisely the same weighting.

That is a problem in itself, in that these trials list events of completely different severity as being equivalent. It also leads into another problem, who is going to make the diagnosis of a mild heart attack or stroke – and on what grounds?

It will most likely be a doctor, and that doctor will have prior knowledge of whether or not the patient was on a statin – or placebo. Yes, I know, clinical trials are supposed to be double-blinded, which means that neither the participant, nor the investigator, should know who is taking the drug, or the placebo.

However, in reality, they both know full well.

I was at a meeting a while back where one of the investigators for the PCKS-9 drug Repatha was talking about the study. At one point he mentioned that a trial participant had told him that he knew he was not taking the cholesterol lowering agent. When questioned how he knew this, the participant said – because my cholesterol level is the same as it always was.

He still wanted to continue on the trial, because he thought we was doing a ‘good’ thing and helping to move medicine forward – and suchlike. I feel it may be considered churlish to point out that the only thing he was helping to move forward was the profit margins for Amgen.

The reality is that when you have a medication that has a significant effect, e.g. lowering cholesterol by 40%, this is a very difficult to thing to hide from the patient, or the doctor. They can see the figures on a computer screen in front of them. And when you are on a clinical trial, and you enter hospital, the doctors have to be told you are in a clinical trial, and what it is.

So, these double blinded studies on statins are not effectively, or even remotely, double-blinded. Which means that bias in clinical decision making is now an option. Was it a heart attack, or not? Well, they are on a statin – so probably not. Or, they are taking a placebo, so it probably is. Bias, the very thing you are trying to remove has crept straight back in the side door.

Another issue with an event is that there are many different sorts of clinical event. Death would be one – obviously. Breaking your leg another. Kidney failure would also count as one, as would a severe rash, or emergency admission to a hospital for almost any reason.

So, when a study states, as this one does ‘reduction in major vascular events.’ My mind, as it is now trained to do, thinks to itself: “ What about other events, what happened to them? Were they also reduced, did they say the same, or did they go up?”

Because if you reduce major vascular events, but other serious events go up, then you have achieved exactly and precisely nothing. This is a variation on pushing people off cliffs to stop them dying of heart attacks.

Results: ‘Pushing one hundred people prevented all trial participants from suffering a fatal heart attack. We therefore recommend pushing everyone off a cliff to reduce the incidence of heart attacks in the general population.’ A.N. Idiot et al.

Statins reduce major vascular events. [A major non-fatal vascular event could also be called as Serious Adverse Event (SAE)]. But do they reduce all serious adverse events (SEAs). If not, you are simply replacing a major vascular event with something equally nasty.

Which leads on to the next question, do we know from the statin trials if statins do reduce SAEs in total? The answer is that we do not know this, for sure, because the CTT has these data, and refuses to let anyone else see them. However, some data has not been censored by big brother. The Cochrane collaboration (before they started the sad slide to bias and corruption) looked at this issue – way back in 2003.

They got as much data as they could from the five major primary prevention statin trials at the time. Here was their conclusion on Serious Adverse Events:

‘In the two trials where serious adverse events are reported, the 1.8% absolute reduction in myocardial infarction and stroke should be reflected by a similar absolute reduction in total serious adverse events; myocardial infarction and stroke are, by definition, serious adverse events. However, this is not the case; serious adverse events are similar in the statin group, 44.2%, and the control group, 43.9%.

This is consistent with the possibility that unrecognized serious adverse events are increased by statin therapy and that the magnitude of the increase is similar to the magnitude of the reduction in cardiovascular serious adverse events in these populations. This hypothesis needs to be tested by analysis of total serious adverse event data in both past and future statin trials. Serious adverse event data is available to trial authors, drug companies and drug regulators. The other measure of overall impact, total mortality, is available in all five trials and is not reduced by statin therapy.’ 3

What does this mean in reality? Well, gathering it all together. Statins (in the over 75s) do not reduce mortality. They do not prevent fatal Mis and strokes. Whilst they reduce serious cardiac events, previously published results demonstrate they do not reduce total serious adverse events.

Which means that they are, wait for it, absolutely and completely useless.

Two plus two does equal four. Always bear that fact in mind.





What causes heart disease part 62

19th January 2019

I suppose it is gratifying to see things I write very strongly supported a few days later. After telling everyone that a high cholesterol level is not a risk for stroke, out comes a study almost straight away, demonstrating that a low cholesterol level increases mortality in patients who have already had a stroke.

This was in a population – and I would highlight this fact – in a population who have high grade carotid artery stenosis. Which mean a high degree of atherosclerosis on the carotid arteries (supplying blood to the brain). The paper is called:

‘Lower cholesterol tied to increased mortality in ischaemic stroke patients with carotid artery stenosis.


In patients with acute, first-ever ischaemic stroke with high-grade internal carotid artery (ICA) stenosis and post-stroke functional dependence, lower total cholesterol level was associated with increased risk for 5-year mortality.

Why this matters:

Recent treatment guidelines of hyperlipidaemia suggest more aggressive treatment for reducing risk for atherosclerotic cardiovascular diseases and ischaemic stroke.

However, these findings suggest a careful consideration of aggressive treatment of hyperlipidaemia in patients with acute, first-ever ischaemic stroke with high-grade ICA stenosis and post-stroke functional dependence.

Study design:

Study prospectively evaluated 196 patients with acute ischaemic stroke with high-grade ICA stenosis and modified Rankin Scale score ≥3.

Patients were divided into 2 groups based on total cholesterol level at admission: ≥200 or <200 mg/dL.

Patients were followed-up for 5 years after initial assessment.

Key results:

After adjusting for established clinical predictors of adverse outcomes, lower total cholesterol level (aHR, 1.88; 95% CI, 1.09-3.23; P=.023) was a significant risk factor for 5-year all-cause mortality.

The prevalence of diabetes mellitus (P=.013) was significantly higher and that of atrial fibrillation (P=.011) was significantly lower in patients with high vs low total cholesterol level.

Patients with lower cholesterol level had significantly lower value of haemoglobin (P=.001), whereas glycohaemoglobin was significantly higher in patients with higher total cholesterol level (P=.001).

Funding: None.

Four most annoying words in the English language. ‘I told you so.’

Of course, this study will be dismissed out of hand. “We should still be prescribing statins to people who have had ischaemic strokes” we will be told. “Studies like this are purely observational” we will be told. “A high cholesterol level still needs to be lowered” we will be told. Nothing to see here, please move along!

I do become increasingly weary of finding evidence that directly and absolutely contradicts the cholesterol hypothesis. It never makes the slightest difference – to anything. Hopefully a few people are out there listening, whose minds are not made of reinforced concrete.


Lung YJ, Weng WC, Wu CL, Huang WY. Association Between Total Cholesterol and 5 year Mortality in Patients with Carotid Artery Stenosis and Poststroke Functional D ependence. J Stroke Cerebrovasc Dis. 2019 Jan 11 [Epub ahead of print]. doi: 10.1016/j.jstrokecerebrovasdis.2018.12.030. PMID: 30642665