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Essays by Malcolm Kendrick, MD
(originally published in RedFlagsDaily)


The Death Of The Reference

(Ye cannae change the laws of physics, Cap'n)


















How The Medical Profession Will Turn A Symptom Into A Disease  

Feb 17, 2004


An Example From Heart Disease Research And Yet Another Reason Why The Scientific Machine Is Close To Meltdown  

by Malcolm Kendrick MD

References are very much a double edged sword, or perhaps a bazooka.
In the wrong hands they can do far more harm than good. And in the, essentially, unchecked system that we now have, one careless reference can end up taking on a life of its own. It gets stuck in the medical information ‘machine' replicating itself like some malevolent computer virus, gradually infecting all data and turning it into useless mush.


It is often said of statistics that scientists use them like a drunk uses a lamp-post, for support rather than illumination.

I suppose the whole point of a scientific reference is that it is used, primarily, to provide support, so I can't really complain about the lack of illumination. However, I can complain about the fact that the abuse of references has led to the point where I have found that, increasingly, I can't be sure if what I read is true anymore.

As some readers will know I have a particular fascination with heart disease. Some would call it an obsession, but I prefer the word, fascination. It's that old Y chromosome thing. Anyway what I have found, as I have researched away, is that a number of bold statements of fact, even those referenced to the gunnels, when exposed to a bit of scrutiny, crumble to dust.

For example, at one stage I was interested why women, in most Western Countries, suffer a much lower rate of heart disease than men - at least until about sixty five or seventy. Women usually have very similar risk factors to men therefore, according to conventional wisdom, there should be little difference in deaths from heart disease.

I suspect I know what you are thinking. Women are protected against heart disease by their sex hormones. This was what I used to think as well as well. Probably because I had seen this fact stated so many times, in so many papers, that I had been brainwashed into believing that it was true. This belief was reinforced by the ‘knowledge' that female protection seemed to disappear not long after the menopause, so I didn't really think to question it.

Nor, it seemed, did anyone else. Just to quote from one study, which accurately reflected mainstream thinking a few years back:

'A protective effect of estrogen is the most obvious reason for the substantial and consistent favored status of women vs. men with regard to coronary heart disease.' Barrett-Connor E Atherosclerosis Dec 1995

However, I started to find out a number of facts about women and heart disease that made me begin to question things. Firstly, it was clear that if you gave female sex hormones to men, their rate of CHD increased dramatically. Which doesn't prove anything for sure, but it does give pause for thought. After all, there is no reason why a chemical that protects women shouldn't also protect men.

Then I found that there were some populations where younger women suffered the same rate of heart disease as men, such as women in Brazil. In addition to this, the Framingham study showed that, when women developed type II diabetes their relative protection against heart disease disappeared, even at a young age. Diabetes doesn't wipe out sex hormones, so where did the protection go?

As this type of information began to pile up, I started to suspect that women may not be protected by sex hormones after all. And so I was galvanised into action and set out to track down the study, or studies, that had been carried out proving that women are protected by sex hormones. In effect I went on the quest to track down the original source of this hypothesis. Which I knew from previous experience can be very hard work.

Just because it states in a recent scientific paper that female sex hormones are protective, doesn't mean that the authors did a study. They are usually just quoting from another paper, which has quoted from another paper, which quoted from another paper, which quoted from… sometimes it seems ad-infinitum. Trying to track backwards in time to find that very first study from which all other studies sprang is not the work of a single day.

You can, it sometimes seems, find yourself late at night reading manuscripts with illuminated script, penned by Monks in the early fourteenth century. ‘ And it has been rightly noted by the good physics of this borough that the clutching disease of the breast is more common in the male than the female, and that the protection of fair lady folk be due to the most strange substance of eastrogenne found in the most fecund of ye womanne .'

Well, not quite, but I once chased down a reference linking heart disease to impotence and found the source reference from a study in Germany in 1928 (In German).

Other times I have found that there is no source study at all. The whole thing has sprung to life from thin air. On bad days I sometimes think that references are no more than the scientific equivalent of rumour and gossip.

‘Ooooh, you'll never guess what, sex hormones protect against heart disease.'

‘Who told you that.'

‘The Mayo clinic did a study, I think. Or at least that's what Harvard said.'


‘And I read it in the Lancet too.'

‘Oh well, it must be true. I'll have to go off and tell all my students.'

And then they'll go off and tell all their students. Some of whom will write papers starting with the comment. ‘It is known that women are protected against heart disease by their sex hormones.' Then other people will use their papers as references, then…

After a while this rumour reaches the point where it becomes an unquestioned truth because so many people have said it so many times, and it has been written in hundreds of papers. In addition, experts stand up at conferences and re-affirm it. Which means that when you write ‘Sex hormones protect women against CHD,' you are then able to support this with hundreds and hundreds of references from major journals?

But in this case, where was that original study, the source reference? What was it all based on? Well, gentle readers, it was based on nothing at all. Because there never was an original study. Or if there was, it is so damned well hidden that I have never able to find it (he said covering himself from the inevitable pedant who will no doubt triumphantly unfurl the 1936 trial done in Serbia-Montenegro).

All I could find were papers referring to other papers that referred to other papers. Yes, it is true that a number of studies were done which showed that estrogen raised HDL levels and reduced LDL levels and protected the endothelium, and all sorts of other ‘test-tube' effects. But in the end, if you wanted to prove that female sex hormones protect against CHD, there are only two direct ways to do it.

1. Remove sex hormones from younger women, and see if the rate of heart disease goes up

2. Add sex hormones to women who no longer produce them, and see if the rate of heart disease goes down.

Had anyone done this? No.

Actually I lie, the correct answer is yes. In 1963, a study was done in which women who had hysterectomies were matched with women who had hysterectomies with removal of both ovaries (no sex hormones). And the result of this study was…..?

As you might have guessed, the result of this study was that there was no difference in the rate of heart disease between the two groups.

‘We found no difference in the prevalence of Coronary Heart Disease in the oopherectomised (both ovaries removed) and hysterectomised (no ovaries removed) women.' Ritterband et al Gonadal function and the development of CHD. Circulation 1963 (2) pp 237 – 51

Okay, it's only one study, but it was totally negative, and no-one had ever done a study that was positive. Yet, despite a complete lack of evidence, the sex hormones theory had built to the point where millions of women around the world were being prescribed HRT in order to prevent heart disease. All this, resting on a piece of pure speculation that only became ‘fact' through the process of endless repetition and cross-referencing.

And when, finally, researchers decided it was time to see if HRT did actually protect against HRT, what did they find? Well, a few large studies were done, and if I may quote from the New England Journal of Medicine on the matter:

‘Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.' Manson et al NEJM Aug 2003

Now then, at this point, some of you may have picked up on the gentle irony that I am using references to support my argument that references are a load of rubbish. But of course, references used properly, are a good thing. (I mean the way I use them, or course)

However, references are very much a double edged sword, or perhaps a bazooka.

In the wrong hands they can do far more harm than good. And in the, essentially, unchecked system that we now have, one careless reference can end up taking on a life of its own. It gets stuck in the medical information ‘machine' replicating itself like some malevolent computer virus, gradually infecting all data and turning it into useless mush.

I don't know what the answer to this problem is. Wipe the whole database clean and start again? Set up a system to hunt down and check all references, and remove those that are found to be wrong. Then remove all references to those references. The mind boggles at the size of that task.

In the meantime, until someone does something (he said passing the buck), I find that when I want to know what the truth may be, or to get as close to the truth as is possible, the only solution is to go back, get the original paper used as a reference, and read it for myself. Which is an enormous time consuming pain. But I believe that references are now so badly corrupted that it is virtually impossible to trust them, or the papers based on them, anymore. In effect this means that the entire medical research machine is close to meltdown. If it hasn't melted down already.

In the meantime, remember that the truth is out there. It is just extremely difficult to know what it is any more.

 More essays by Malcolm Kendrick


Jan. 25, 2003

(Ye cannae change the laws of physics, Cap'n)

by Malcolm Kendrick MD

The change in internal energy of a system is equal to the heat added to a system minus the work done by the system.'

Please don't get me wrong. I am a great supporter of the Atkins diet. Anything that helps to demolish the myth that eating animal fat, or saturated fat, causes health problems gets my vote every time. And I do believe that many people who try the Atkins diet do lose weight – when no other diet has worked.

But I want to tackle a myth about the Atkins diet which seems to have taken hold of people's minds, causing them to believe in magic. Namely, that you can eat as much protein and fat as you like and still lose weight. It is those terrible carbohydrates that turn to fat and make you fat.

Of course if you eat fat, it doesn't need to turn to fat, because it already is fat. And once you eat it, it is transported straight to the fat stores in your body, where it is stored as….you got it… fat. Quite how fat converted from carbohydrate is worse for you than fat that comes straight from fat escapes me.

Equally, one gram of fat contains twice as much energy as energy as one gram of carbohydrate. So if you eat more fat, by weight, than carbohydrate, you are taking in more energy and should get fatter.

But somehow people seem to fervently believe that there are some processes going on when you eat the Atkins diet that somehow allow the body to dispose of excess energy gained from eating fat – in some way. However, if you eat carbohydrates these will….what? Gather energy from another dimension and convert this excess energy to fat?

The reality is that, when it comes to energy, the body is like any other system. It loses energy by radiating energy to the surrounding environment, or doing work. And the only way that the human body can radiate energy is as heat. We don't produce light, electromagnetism, radioactivity, or very much in the way of sound.

For very good reasons we don't excrete excess energy either. It is true that some food passes straight through without being absorbed, but not much. If you are diabetic, you can lose some sugar through the kidneys, and a few ketones can escape here or there. But the body is a complete miser where energy is concerned. What comes in stays in.

And the only way to increase energy output is to increase work.

So to suggest that you can eat as many calories as you like – in the form of protein and fat – and still lose weight is quite frankly nuts. If the Atkins diet can achieve this, then the single most important law of physics is wrong. If energy can just disappear from the body, then it is departing this Universe and going somewhere else. So, someone in a parallel universe must be getting mightily pissed off that they are eating nothing, and still putting on weight. (I know how they feel).

I like to think that I have an open mind. But even I draw the line somewhere, and in this is case it is here. Energy cannot disappear. Full stop.

Atkins zealots have tried to explain this, the inexplicable, in a variety of increasingly desperate ways. It is claimed that it is much more complicated to turn fat into energy, so it takes more energy to do this than it does to convert sugar into energy.

It's true, converting fat into energy takes several more steps. Which probably does use up more energy. What's the point being made here? That burning fat takes up more energy than burning up sugar, so….. The body uses more energy burning fat. And what would happen to this excess energy? It would be used to heat the body. Jolly good, that's mainly what we use energy for.

Others have said that on the Atkins diet you start to excrete ketones, and as ketones are molecules that contain energy this is one way that the body sheds excess energy on the diet. I have never believed this, but it is possible I suppose.

However, I watched a programme on the Atkins diet a couple of nights ago. On this programme they got identical twins and put one on the Akins diet, and the other a low fat diet. They then stuck them both in sealed rooms where all energy expenditure could be monitored. Oxygen use, loss of ketones in urine and breath. They collected everything, which sounds a bit yucky, but there you go.

The findings were that over a two week period the twin on the Atkins diet lost approximately one extra calorie in ketone bodies. Equivalent to about one grain of sugar. Which is exactly what I expected.

The reality about the Atkins diet is that, firstly, it works for many people. Secondly, it does not cause any health problems, as far as I'm concerned. Thirdly, it can only work because people cut back on their energy intake. Because, to quote Scotty of the Starship Enterprise. ‘You cannae change the laws of physics Captain.' Energy cannot just disappear.  

More essays by Malcolm Kendrick


Dec 3, 2003


When someone sent me a copy of an article in the Washington Post, stating that more and more doctors now think that children as young as four should be put on statins, my fingers started to itch.  

by Malcolm Kendrick MD

Here’s the offending headline:

 ‘Despite Controversy, Pressure Grows to Treat High Cholesterol in Children After Studies Link Elevated Levels to Adult Heart Disease.’
By Elizabeth Agnvall
Special to The Washington Post
Tuesday, December 2, 2003

The first thing that I have to point out here is that, in primary prevention trials, statins have never been found to reduce the risk of death. I don’t care if they have been found to reduce the rate of heart disease. Does it really matter if someone is saved from dying of heart disease, only to die of something else?

By primary prevention trials, I mean trials in people who, whilst they may have risk factors for heart disease, have not been found to have any clinical signs, or symptoms related to heart disease.

Secondary prevention trials are different. These are done on people who have already suffered a heart attack, or have angina, or some other clinical manifestation of CHD.  And it is true that in ‘secondary prevention’ trials, statins have been found to reduce the rate of dying of heart attacks, and also to reduce overall death rates. By a small, but significant, amount.

However, that is not relevant to this discussion. Because, by definition, all children are in the primary prevention category. And this means that there is not one scrap of evidence to suggest that statins will do them any good. The best you might manage is to shift their cause of death from heart disease to something else – usually cancer – about sixty years in the future.

How do I know this? Because the clinical trials tell me so.

If we look at five major primary prevention trials: PROSPER, ALLHAT, WOSCOPS, ASCOT and AFCAPS. (Don’t worry about the acronyms, they are not important, they are just supposed to make the trials memorable). We can pull them apart to look at the figures.

By the way, if you want to check my figures visit The Therapeutics Initiative at The University of British Columbia http://www.ti.ubc.ca/ and look for Therapeutics newsletter number 48. Or, get the data from the trials themselves.

These five trials had, between them, over forty thousand patients enrolled. Most of them lasted at least five years, and they have all been endlessly quoted in the medical literature. In short they are big, important and influential.

So, what was the overall mortality rate in those given statins versus the ‘control’ population?

Morality in those on statins was 6.6%
Mortality in the control population was 6.9%

And what was the percentage of serious adverse events (SAEs)? A serious adverse event is something like developing cancer, or having a non-fatal MI, or a non-fatal stroke. So, pretty damned serious.

In fact, only two of trials reported this, as the majority of statins trials keep quiet about SAEs.

Serious adverse events in the control population was 43.9%
Serious adverse events in those on statins was 44.2%

I suppose you may be thinking, my goodness, there was a 0.3% reduction in overall mortality. It may be small, but it’s still there. True. However, although these five trials are usually presented as purely primary prevention trials, they all included a secondary prevention population, 18% on average. This more than accounts for any difference in overall mortality.

Even if it doesn’t. I must point out that the difference is not large enough to discount the possibility that this was merely a chance finding. These figures do not get anywhere near statistical significance - the holy grail of clinical trials.

In addition to this, the 0.3% reduction, if it really exists, took five years to appear. Which means that, even if you take the best case scenario possible, and ignore the fact that any difference is most likely due to chance, you would have to a take a statin for fifty years to reduce your risk of dying by 3%. At the same time, of course, you would have a 3% greater risk of suffering a serious adverse event, such as a stroke, or developing cancer.

Does this really represent powerful enough evidence to warrant starting a four-year-old child on statins, and keeping them on for the rest of their life?

I don’t think so. Especially not in the case of this Washington Post reporter. For, in her article, she was using the example of a four-year-old girl. And what do the statin trials tell us about the benefits of statins in primary prevention in girls, or women? According to The Therapeutics Initiative group:

‘There were 10,990 women in the primary prevention trials (28% of the total). Only coronary events were reported for women, but when these were pooled they were not reduced by statin therapy. Thus the coronary benefit in primary prevention trials appears to be limited to men.’

What the statin trials tell us about women is that, in primary prevention, statins can’t even manage to prevent heart disease, let alone anything else!

Has the world gone completely mad? Are we really suggesting that we should start a healthy four-year-old girl on a medicine, and continue this medicine for the rest of her life? Something that could turn her into one of the ‘worried well’, and even if it doesn’t, will most likely cause side-effects.

Can we really be contemplating this, when all of the evidence that exists points to the fact that STATINS WILL DO HER ABSOLUTELY NO GOOD AT ALL!

Apparently, we are. ‘Anyone for tea?’ Asked the Mad Hatter.

More essays by Malcolm Kendrick

Nov 22, 2003


I was idly watching a programme on the Atkins diet last night which, to my surprise, was reasonably balanced. Yes folks, the Atkins diet has crossed the pond to reach the United Kingdom. Although, in reality, all it is doing is returning. After all we invented it nearly one hundred and fifty years ago.  

by Malcolm Kendrick MD

A man called Banting promoted a diet pretty much indistinguishable from that of Atkins in 1863. In fact, the verb to ‘bant' is used in Sweden as a term for going on a diet

To find out more about the Banting diet (now known as the Atkins diet) go here

Anyway, reasonably balanced or not, on this programme there was still an unquestioned view that, even if the Atkins diet did help with weight loss, it was still damaging to health. It would cause kidney disease, and osteoporosis and heart disease. Various professors of nutrition were wheeled out to condemn the Atkins diet as dangerous nonsense.

Ignoring the kidney disease and the osteoporosis for now, the nutritional professors made the usual statements. For example, ‘It is known that saturated fat increases the level of blood cholesterol and causes CHD.' They didn't quote any evidence for this. As far as they were concerned it is just a known fact.

Well, what is the evidence that a diet high in saturated fat raises your cholesterol level? Where does it come from? The Framingham Study? That world famous study that is quoted by medical experts around the world.

"In Framingham, Massachusetts, the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower people's serum cholesterol...” Dr William Castelli 1992 (Director of the Framingham study)

So the evidence obviously didn't come from Framingham. What about studies in children?  These poor vulnerable imps, where the damage is first being done? Just to get a bit of genetic diversity into the equation, let's look at Chinese children first.

‘Children in the intervention group were fed with low-cholesterol and low-saturated fatty acid diet, and the control group with normal diet. The duration of intervention was three months. Compared with the control group, serum cholesterol levels of children under intervention were not significantly changed. Total cholesterol: 4.64 (186dg/ml) vs 4.68 (188dg/ml) mmol/L LDL: 2.66 (107dg/ml) vs 2.62 (106dg/ml).' Zhu WL et al Zhonghua Liu Xing Bing Xue Za Zhi. 2003 Sep

Then children in the UK:

‘Unexpectedly, significant inverse associations were found between the dietary content of saturated fatty acids on the one hand and the serum concentrations of cholesterol… on the other.' Samuelson G et al Br J Nutr Mar 2001

The reality is that, in many different studies, it has been shown that the more saturated fat you eat, the lower your cholesterol - although the difference is not that great. Of potentially greater importance is that a high fat diet has a more significant effect on raising HDL and lowering VLDL. Which is supposed to be very healthy indeed.

Consider this extract from the University of Pennsylvania:

‘The Atkins Diet limits carbohydrates but permits unrestricted amounts of protein and fat. Compared to a conventional, high-carbohydrate, low-calorie approach… at one year, the Atkins dieters had significantly greater increases in good cholesterol (HDL) and greater decreases in triglycerides (VLDL).'

I'm sorry that I can't present you with anything much from PubMed (the bible of mainstream medical research) about this. But as others may have discovered, any paper that supports the Atkins diet has no abstract attached in PubMed – you just get blanks. Did someone use the word censorship? Not me your honour. I would never dream of saying such a thing.

Now, anyone who has read my scribbles before will realise that I don't think the level of any lipid in your blood makes the slightest difference to the rate of CHD. But most other people do, so I think it is worth explaining why a high fat diet will automatically raise HDL and lower triglycerides.

A fact, by the way, that seems to have created stunned surprise amongst many researchers when results from the Atkins diet were published. Which just shows that they need to go back and read their textbooks again.

In order to understand why a high fat diet should, and does, raise HDL levels and lower VLDL levels (and may also lower LDL levels), you need to understand a bit about fat and sugar metabolism and the role of lipoproteins in your blood. Starting here.

When you eat fat it is absorbed by the gut and stuffed into very large lipoprotein known as a chylomicron. The fat in a chylomicron is almost all stored in the form of three fat molecules attached to a glycerol molecule, a structure known as a triglyceride. Three fats and a glycerol = tri-glyceride. By the way, cholesterol also sits in chylomicrons as a co-passenger. (Anything insoluble in water/blood, such as cholesterol, has to be carried around in a lipoprotein)

Chylomicrons are then released into the bloodstream and travel through the body losing chunks of triglyceride all the while as they pass fat cells. (Fat cells attack chylomicrons with a ‘lipase' enzyme, chopping bits off). As this happens chylomicrons shrink, turning into Very Low Density Lipoproteins (VLDLs), which are otherwise known as… ‘triglycerides.' How confusing is that?

In fact, the nomenclature in this area must be the most confusing in all of medicine.

  • LDL is known as ‘bad' cholesterol
  • HDL is called ‘good' cholesterol
  • VLDLs are named triglycerides…

It's little wonder that most people haven't the faintest idea what anyone is talking about in lipid metabolism. Chylomicrons, VLDL, HDL and LDL are all lipoproteins. I wish that people would stop calling them things like ‘cholesterol' and ‘triglycerides', and ‘good' cholesterol and ‘bad' cholesterol. It really doesn't aid understanding.

Anyway, moving on. Apart from chylomicrons, the gut also sends out VLDLs de-novo, and the VLDLs do pretty much the same thing as chylomicrons, dropping off triglycerides here and there (mainly into fat cells) and shrinking. Quite what the difference is between a shrunk down chylomicron and a VLDL is, I don't know. (By the way, just in case you're wondering, VLDLs also contain cholesterol as a co-passenger. All lipoproteins have cholesterol in them)

Not all chylomicrons and VLDLs travel round dropping off triglycerides. Some go straight to the liver where they are absorbed, broken down, and unpacked. And their contents are used to make other things the body needs.

However, wherever they go, all of the ‘fat containing' chylomicrons and VLDLs produced by the gut drop off their fat load, shrink, are then absorbed and completely disappear. So a few hours after a meal they are gone. And if you were to measure VLDL levels a few hours after a high fat meal they would have returned to ‘normal'. Whatever normal may be.

Thus, if you eat a high fat meal, almost all sign of it will have disappeared in a relatively short space of time. And there will be no change in any lipid level. Or at least not any lipid level that anyone can be bothered measuring.

However, if you eat a high carbohydrate meal, the metabolism acts in a very different way. Carbohydrates are absorbed and transformed into sugars in the gut, from whence they go straight into the bloodstream, same as fat. But because sugars are soluble in water they don't need to be carried in a lipoprotein, so there is no immediate effect on lipid levels from a high carb meal. You just get a sharp rise in blood sugar level.

A certain amount of the sugar will be absorbed into fat and muscle cells, and then stored as glycogen. But if you eat a big carbohydrate meal, the fat and muscle storage cannot cope, and the excess sugar has to be absorbed by the liver to prevent the sugar level getting too high.

However, the liver cannot store that much sugar, so it starts to convert it into fats, in the form of triglyceride. At which point, the liver then packs this excess triglyceride into a VLDL and sends it out into the bloodstream - along with some cholesterol. (Unlike with sharks, the liver in humans is not an energy storage organ)

So you get a kind of delayed VLDL rise after eating carbohydrates. But there is a key difference between the VLDL made by the guts, and the VLDL made by the Liver. The VLDL made by the liver, unlike that made in the gut, shrinks into a low density lipoprotein (LDL). The dreaded heart disease causing lipoprotein – the one they call co-lest-erol.

Why does this happen to ‘liver manufactured VLDL', when it doesn't happen to the VLDL made in the gut? Well, as liver manufactured VLDL leaves the liver, it interacts with an HDL molecule which transfers it's proteins to the VLDL molecule. One of the proteins transferred is apolipoprotein B-100. And the apo B-100 molecule is the unique LDL ‘identifier.'

On the other hand, VLDL made in the gut has apolipoprotein B-48 attached to it and this VLDL doesn't become an LDL molecule as it shrinks.

Now, if you are not already completely confused, I will explain what this means.

Rewind. If you eat fat, it is absorbed from the gut, packed into chylomicrons and ‘VLDL B-48s,' and transported around the body and then got rid of. Gone. So immediately after a high fat meal you will have a very high triglyceride level, made up of VLDL B-48, but this will fall relatively rapidly. Importantly, there can, and will be no effect on HDL or LDL levels. And so if you measure the lipid levels in the fasting state (which is when such things are measured) you will find nothing at all after a high fat meal.

On the other hand, if you eat a high carbohydrate meal, the level of VLDL B-48 will not rise. But some time later, the liver will start converting excess sugar into fat and sending this out in VLDL B-100 molecules. And this process can go on for many hours after a meal. So the VLDL level may still be high when you measure it.

In addition to finding a high VLDL you should also find a low HDL. Because, for each VLDL the liver makes, an HDL hands over its proteins and disappears. So the more VLDL the liver makes, the less HDL you will have. Cause and effect.

Also, as you may have noted. If the VLDL B-100 all ends up as LDL, the more VLDL the liver makes, the higher the LDL level is likely to be.

Therefore, if someone is on a high carbohydrate diet, they should automatically have a raised VLDL level, a reduced HDL level and quite possibly a raised LDL level.

Golly gee whiz. A high fat diet reduces VLDL, raises HDL and may even lower LDL. And a high carbohydrate diet does the exact opposite. In short, the metabolism does exactly what you would expect it to.

So you see. Atkins was right all along. Even if he didn't appear to know why.

 More essays by Malcolm Kendrick



“ The concept that HDL could remove cholesterol from a plaque is such a stupid idea that I cannot believe it still exists. Once you understand the science, the whole thing is patently ridiculous.”

by Malcolm Kendrick MD

Synthetic 'Good' Cholesterol Helps Clear Arteries. Small Study Indicates the Possibility That Drug Therapy Could Reverse Heart Disease. Rob Stein Nov 5th 2003

‘A synthetic form of "good" cholesterol has been shown to quickly shrink blockages clogging coronary arteries, offering for the first time the possibility of a drug that could actually rapidly reverse heart disease, researchers reported yesterday….'

I'm writing a book at the moment called Cholesterolmania. That plus a job, plus children and home, an attempt at a social life and columns at redflagsdaily.com. That's a tad busy, and I thought I'd take a short break from column writing, but…I couldn't let the above story from the Washington Post go without comment.

Here is my immediate response. Aaaaaarrrrrrggggghhhhh! Thud.

It's almost impossible to know where to start without ranting. Firstly, just to clear something up, HDL is not cholesterol ‘good' or otherwise. HDL, stands for High Density Lipoprotein. It is a lipoprotein that is manufactured in the guts and the liver, and it contains a small amount of cholesterol.

HDL appears to have two basic functions in the body. Firstly, it transfers proteins, known as apolipoproteins, to VLDL, allowing the VLDL to be recognised by receptors around the body. Secondly, it removes cholesterol that is floating about and takes it back to the liver.

When cells do break down in body, which is happening all the time, the cholesterol from cell walls is released into the surrounding extra cellular fluid. The HDL lurking in the vicinity ‘mops up' this excess cholesterol and transfers it back to the liver. This scavanged cholesterol is then used in the manufacture of Very Low Density Lipoproteins VLDLs. VLDLs contain two basic ingredients, fats (in the form of triglyderides) and cholesterol.

VLDLs are then sent back out into the bloodstream. As VLDLs lose triglycerides they shrink in size, becoming Low Density Lipoproteins LDLs (otherwise known as ‘bad' cholesterol – for some stupid reason). LDLs are then absorbed by cells that need cholesterol, and the cholesterol is unpacked and used to build various structures within the cell, including the cell wall.

Which means that HDLs are part of a re-cycling mechanism for cholesterol. At the risk of repeating myself, the liver manufactures cholesterol and sends it out within VLDLs. As VLDLs lose triglyceride – which provides energy for cells around the body - they shrink into LDLs, and LDLs are then absorbed into cells where the cholesterol is unpacked.

When a cell then dies, it releases cholesterol, which is mopped up by HDL and transferred back to the liver. This is not immensely complex, but for some reason, mainstream researchers have decided that HDL can, in some way, protect against the build up of atherosclerosis.

There are two reasons for this, I think. Firstly, because a low HDL level seems to be an important risk factor for CHD, even more so than a raised LDL level (So surely it must be doing something…Duh!) Secondly, because it has been noted that, as HDL does indeed transfer cholesterol from around cells and back to the liver, it is thought that this reverse cholesterol transport might, in some way, be able to suck cholesterol out of atherosclerotic plaques.

In answer to the first piece of stupidity. If VLDL levels go up HDL automatically goes down, it's all to do with the transfer of apolipoproteins from HDL to VLDL. The raised VLDL itself is caused by underlying insulin resistance – one of the basic causes of heart disease. So a low HDL is merely a ‘marker' for raised VLDL, which itself is a marker for insulin resistance. A low HDL by itself causes nothing and prevents nothing.

With regard to the reverse cholesterol transport nonsense. HDL cannot, I repeat cannot, remove cholesterol from atherosclerotic plaques. It is impossible for this to happen. The cholesterol in a plaque is not ‘floating free' in the extra cellular fluid. It is trapped in a solid atherosclerotic lump. HDL is completely and utterly incapable of getting at it, and even if it could, it could not separate it out from the surrounding plaque structure. HDL is a passive inanimate chemical. It cannot carry out complex tasks.

The concept that HDL could remove cholesterol from a plaque is such a stupid idea that I cannot believe it still exists. Once you understand the science, the whole thing is patently ridiculous.

If synthetic HDL can reduce the size of plaques then I will eat my hat. What these researchers are seeing, probably, is what all researchers see. Most plaques, if left alone, do gradually reduce in size – a bit. Alternatively, they have been looking at their findings with eyes of faith. Let's just see if anyone else can verify these results.

P.S. In the Heart Protection Study (HPS), a major study in which the rate of deaths was reduced in patients taking a statin (simvastatin), at post-mortem, the people who had been taking the statin had bigger and more complex plaques than those who had not. In reality, the size of the plaque does not actually have anything to do with how dangerous it is.

More essays by Malcolm Kendrick

Sept. 17, 2003  


The first step in teleoanalysis, as demonstrated in a paper just published in the British Medical Journal, apparently, is to condemn all clinical trials that fail to show you what you want…. And it appears that this method of analysis provides the answers to questions that would be obtained from studies that have not been done or cannot be done….This way you can always get the results you want….When I read this I thought it must be a joke….But it was not a joke….  

by Malcolm Kendrick MD

After reading a paper in the British Medical Journal which appeared a few days ago, I didn’t know whether to laugh or cry, or stand at the edge of a cliff and scream. Instead I thought I would write a column, so that you may share my sense that the world has finally gone completely bonkers.

The paper was called:

Teleoanalysis — combining data from different types of study’

Which sounds pretty unremarkable, and contains seemingly sensible remarks, such as: ‘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.’

My, how reasonable this seems. Yes, of course, carry on — carry on. This is mathematics isn’t it, or something of the sort? So, what comes next?

It may also be necessary to quantify the individual effects that relate to separate steps in a causal pathway–that is, the effect of factor A on disease C is determined from the estimate of the effect of A on an intermediate factor B and the estimate of the effect of B on C, rather than by directly measuring the effect of A on C. The exercise is like putting together the pieces in a jigsaw puzzle.’

I see, so A causes B, and B causes C. So it can be deduced that A causes C. Bravo…. Well done. How simply splendid.

Therefore, we can use the following reasoning.

A high saturated fat intake (A) causes an increase in cholesterol levels (B) (A causes B), a raised cholesterol level (B) causes heart disease (C) (B causes C). Ergo, we know that a high saturated fat intake causes heart disease (A causes C).

You may not think that there is anything much wrong with this. It sounds utterly logical — doesn’t it. So, why is anyone bothering to write this article?

Well, you see there is a problem with the ‘saturated fat caused heart disease’ hypothesis. Namely, that no interventional trial has ever shown that reduced saturated fat intake has any impact whatsoever on heart disease rates. (An interventional trial is one where you ‘intervene’ and change something, such as dietary fat intake — these are normally considered ‘gold standard’ clinical trials). As admitted by the authors:

‘A meta-analysis of randomised trials suggested that a low dietary fat intake had little effect on the risk of ischaemic heart disease.’

So we have a problem. We ‘know’ that saturated fat raises cholesterol levels, and we ‘know’ that raised cholesterol levels cause CHD. We just can’t seem to show that if you lower the saturated fat intake you have a reduction in the rate of CHD. Which would kind of suggest to most people that A doesn’t cause B, and B doesn’t cause C.

But no, this cannot be true, this is wrong! Therefore, any results contradicting this must be wrong. So there! It’s always reassuring when a scientist just ‘knows’ that something is true. It avoids all those tedious clinical trials that are sometimes needed for proof.

Anyway, in order to prove that the interventional trials are wrong we use teleoanalysis. The first step in teleoanalysis, apparently, is to condemn all the trials that fail to show what you want, using statements such as: ‘But the effect of a significant reduction in dietary fat can easily be underestimated, even when it is based on the results of randomised trials.’

Then we use the second step in teleoanalysis, which is that we to look at the studies we want (A causes B, and B causes C — carefully ignoring all studies that showed the complete opposite), and from that extrapolate the answer to studies that have not been done, but had they been done, would have shown exactly what we already know to be true. You think I am joking?

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.’

It is so much better, I find, to rely on answers from studies THAT HAVE NOT BEEN DONE, and COULD NEVER BE DONE. In this way you can always get the results that you want, and you never ever need to carry out any more studies that might contradict the things you already know to be true because for ethical and financial reasons these trials never can be done.

Truly… I mean. Gasp….thud. When I read this, I thought it must be a joke. But this was written by one of the authors of the infamous Polypill article, suggesting a one-trick multiple pill could prevent heart disease. The man who also wrote the ‘time-lag hypothesis,’ explaining that the French don’t have much CHD because they haven’t been eating as much saturated fat as people in the UK and USA, at least not before 1970.

Are there any limits to the double-speak that can be used to prop up the diet-heart hypothesis? Apparently not. Perhaps I will wake up and find this is all a dream, for right now I do feel as if I have fallen down the rabbit hole.

P.S. If you think I have made this up as a joke, I refer you to the BMJ article.

More essays by Malcolm Kendrick


Sept 12, 2003  


"I wanted to make it clear that the attacks on Atkins are not scientific, not rational. Atkins, may he rest in peace, is being attacked because his diet threatens the mainstream. He and his supporters are being subjected to the secular equivalent of the Spanish Inquisition…."  

by Malcolm Kendrick MD

I am a great fan of the science philosopher Karl Popper, that is whenever I can manage to understand what it is that he is saying. I get through one paragraph at a time, very slowly, then I have to go and lie down until my brain stops hurting.

Popper has much to say on the theme of science, scientific progress and the like. He was highly pro-science and the proper use of the scientific method. But he was also acutely aware of the danger that science, and scientists, could become so entranced by a hypothesis that it became the answer, the truth, a belief. And those who dared to question such a fundamental belief were metaphorically burned at the stake.

In fact, if you were to share my interest in the development of scientific thought, it is clear that the big breakthroughs, the things that we all now accept as true e.g. the theory of evolution, were generally forced through against the might of the prevailing scientific orthodoxy. And, in general, the famous scientists that you have heard of e.g. Darwin, usually followed a few others who were crushed so effectively that there names have vanished from the record.

Darwin was far from the first to propose the theory of evolution. However those, like Chambers, who promoted the idea before Darwin were cut down and humiliated by the leading scientists of the time who believed that a species could not change into another species — for some unfathomable reason or another. Darwin bided his time, and let a few others line his path to glory with their broken reputations.

This happened about one hundred and fifty years ago. However, with regard to unquestioned dogma, things are much the same today. As I write this, there are new hypotheses that cannot be questioned. For example, the hypothesis that mankind is causing global warming by burning fossil fuels. Or, that we are creating a massive hole in the Ozone layer by use of CFCs. The hole in the Ozone layer closed up last year by the way — but you probably never heard much about that.

Anyway, dare to question those two orthodoxies and you will receive hysterical abuse. Everybody just knows that the world is warming up, and we are ripping a great hole in the Ozone layer. This may or may not be true, but neither belief is based on rational thought. They are driven by rather deeper, emotional beliefs. As an aside, when you find yourself really wanting to believe that something is true — then it usually isn’t.

However, over to Atkins. Current scientific orthodoxy has decreed that a high fat diet, especially saturated fat, is bad for health. It raises cholesterol, kills us from heart disease, and causes breast cancer and all sorts of other nasty things. For many, and especially those at the heart of the medical community, this is a Truth that cannot be questioned. And a huge scientific and financial structure has grown up around this Truth.

But in the last few years Dr Atkins and his diet have begun to make significant inroads. Now, I know that people generally use the Atkins diet for weight loss, and not any other health promoting reasons. But the Atkins diet was virtually heresy. Here was a man saying that if you ate saturated fat you would lose weight and be healthier. People taking the Atkins diet even had the cheek to find that their cholesterol levels dropped. Shock horror.

At first the scientific community used the first of the immunizing tactics that scientists use to defend sacred beliefs, as defined by Popper:

Immunizing tactics

1: Ignore the refutation
2: Deny that the refutation is a refutation
3: Develop ad-hoc hypothesis to explain contradictory results

So at first Atkins was ignored, but he would not go away. The mainstream medical church then said that the Atkins diet was not actually high in fat, or at least not the really damaging sort of fat. But it was, so that didn’t work. They then said that there was a huge bulk of evidence to support the hypothesis that saturated fat raised cholesterol levels, and that Atkins was wrong. But he wasn’t, and the trials set up to show that the Atkins diet was dangerous were hopeless failures, in that these trials confirmed what Akins had said all along. People on the Atkins diet achieved a reduction in cholesterol levels (not that I believe this matters a tin of beans).

Where next to support the diet/heart hypothesis. The ‘hypothesis that is the truth,’ as revealed to us by Ancel Keys. Where next indeed? After failing to show terrible dangerous levels of raised blood cholesterol, or any other nasty things, came the personal attacks. Atkins is a dangerous man promoting a highly dangerous diet. Atkins is not a scientist, how can he know anything. Aktins cannot prove the benefits of his diet, he hasn’t done the required research (mostly true, by the way).

Next came the terror tactics: the Atkins diet is dangerous and damages your kidneys; makes your blood acidic; it upsets your metabolism; and, in fact, people are dying on the diet.

This is all complete rubbish. Whilst it is true that a diet high in fat and protein will result in greater production of acidic residues, ketone bodies and the like, and your blood and urine will become slightly more acidic, there is not the slightest, remotest, teeny weeniest piece of evidence to support the claim that this is in any way damaging. Not a single clinical end-point has ever been demonstrated to be affected.

And if you read anything that does claim the Atkins diet is damaging, please take the time to read the small print — if you can find it. What you will normally discover is that the level of some substance in the blood is found to be raised which may (note the word may), lead to kidney damage. But by the time this reaches the newspapers it has been converted into ‘Atkins diet kills thirteen year old girl by destroying her kidneys.’

Perhaps those leading the Atkins attacks would care to raise their gaze up to the Innuit in Canada and the frozen north. In years gone by they rarely ate a vegetable, any fruit or a carbohydrate molecule. They existed almost entirely on fat and protein. When they were studied (before their lifestyle changed), they were found to be in exceptional health. Without, it must be added, any sign of heart disease or renal failure.

But my point, the point of this column, is not to discuss whether or not the Atkins diet works. I wanted to make it clear that the attacks on Atkins are not scientific, not rational. Atkins, may he rest in peace, is being attacked because his diet threatens the mainstream. He, and his supporters, are being subjected to the secular equivalent of the Spanish Inquisition. ‘Admit that you are wrong, or I shall destroy your reputation.’ None of the attacks on Atkins are scientific, none of them are correct. They are an attempt by the ‘herd’ to protect the sacred diet/heart hypothesis. The sort of attacks that Popper would have recognised for what they are.

Atkins must be destroyed to protect the mighty diet-heart hypothesis. And all of the recent articles that just seem to be springing out of nowhere about the terrible dangers of the Atkins diet are designed to do just this.

 More essays by Malcolm Kendrick



One thing that has seriously hampered research in this area is the factor that I call "terminological inexactitude"  

by Malcolm Kendrick MD

When you have spent twenty years of your life studying something, you can become somewhat of a bore on the subject. But please bear with me, because I am going to reveal to you the true cause of Coronary Heart Disease (CHD). A bold claim indeed, but I think I can sustain it.

The first thing to state, however, is that there is no single cause, no one factor. If there was, it would have been discovered by now. I sometimes think that the obsession with finding the cause of a disease has seriously hampered research into this, and many other areas. There is always a sense, within science, that the answer, when you find it, should be simple, and that therefore the simplest explanation is usually correct: E = MC2 and all that. Occam’s razor, terribly seductive, but not always true.

Another thing that has seriously hampered heart disease research is the factor that I call "terminological inexactitude." In CHD research, the words heart disease, CHD, CAD, CV disease are all whirled about almost interchangeably. Equally, various papers talk about atherosclerosis. But the term doesn’t actually mean anything.

If you describe atherosclerosis as thickening and hardening of the arteries, then almost all populations throughout the world suffer from the same rate of atherosclerosis. Yet, the rate of CHD between populations can vary more than fifteen-fold. Which means that atherosclerosis isn’t the underlying cause of CHD, at least not if you define atherosclerosis as anything that isn’t a perfect, springy, smooth artery.

In order to understand CHD (another horribly inexact term), you must be a bit more precise about what it is that you are actually talking about. And what I am talking about are discrete, or focal, areas of arterial damage. Some people refer to them as plaques, and so that is the term I will use.

Plaques are the little beauties that can narrow an artery, causing things like angina. They can also ‘rupture’ causing a blood clot, and then complete obstruction to blood flow within an artery, leading to myocardial infarction, or a stroke (or problems elsewhere). You can have as much thickening, or hardening, or atherosclerosis of the arteries as you like. But if you haven’t got a plaque or two, you will not die of CDH.

So, what causes plaques to develop?

There are two basic processes that do this

  • Endothelial damage (the endothelium is a single layer of cells lining the artery wall)
  • Formation of a blood clot (thrombus)

The two processes are highly interconnected. For example, damage to the endothelium stops it from acting as an anti-coagulant surface, making it more likely for a thrombus to form over the damaged area.

When a blood clot, or thrombus, forms over an area of artery wall, this is the start of plaque formation. Repeated thrombus formation over the same spot causes the plaque to grow, and eventually it can completely block the artery.

Therefore, any ‘factor’ that causes either endothelial damage or increased blood coagulability will increase the risk of dying of CHD.

Factors that have been shown to damage the endothelium include:

  • High blood sugar levels
  • High levels of insulin
  • Smoking
  • High levels of cortisol (and other stress hormones)
  • High levels of triglyceride
  • High levels of homocysteine
  • A lack of certain vitamins e.g. vitamin C, or B

Factors that make the blood more prone to clotting include

  • High blood sugar levels
  • Smoking
  • Insulin resistance — Metabolic syndrome
  • High levels of triglycerides
  • High levels of stress hormones

These lists are not exclusive, but they highlight the main factors. You will have noticed a great deal of overlap, which is not surprising.

Why some things protect against heart disease

If you look at those lists, it becomes clear that things that protect the endothelium and/or reduce blood clotting should reduce the risk of heart disease. So, what things do protect against CHD, and how.  








Anti-coagulant and endothelial protection



Omega-3 fatty acids



Endothelial protection (Nitric oxide synthesis


stress hormones Anti-coagulant and endothelial protection

Vitamin(s) B

Endothelial protection due to _homocysteine


Equally, what factors cause plaques to develop?

Some of them are the usual suspects:


This leads to insulin resistance and raised blood sugar levels


This causes increased blood coagulability and endothelial damage

Lack of exercise:

This leads to increased levels of stress hormones in the blood

Whether or not a raised blood pressure can cause plaques to form is a moot point. One can see that a high blood pressure may cause endothelial damage, but the evidence from blood pressure lowering trials shows zero impact on the rate of death from CHD So, I think the jury is out on this one.

There are other factors that are relatively rare that directly cause CHD. Such as:

Nephrotic syndrome:

This leads to increased clotting factors and also all sorts of other things that damage the endothelium


This can be a genetic condition. Homocysteine, in high levels damages the artery wall, and increased blood coagulation

The single most important cause of CHD, however, is metabolic syndrome. This syndrome can be caused by a number of different factors:

  • Depression
  • Anxiety
  • Stress
  • Use of certain drugs, e.g. steroids
  • Use of Protease Inhibitors (for AIDS patients). Where metabolic syndrome is known as HIV-lipodystrophy


Whatever the cause, metabolic syndrome develops because of abnormal cortisol levels. The abnormal cortisol levels, in turn, cause insulin resistance (cortisol is a powerful insulin antagonist). This then leads to a spectrum of metabolic abnormalities:

  • Raised triglycerdies
  • Raised sugar levels
  • Reduced HDL levels
  • Abdominal obesity
  • Raised fibrinogen levels (a clotting factor)
  • Raised PAI-1 levels (a clotting factor)
  • Raised lipoprotein (a) levels (a clotting factor) 

As previously described, these factors then lead to plaque formation.

It is likely that the most common cause of metabolic syndrome is chronic stress, which creates HPA-axis abnormalities (the HPA-axis is the system that controls the reaction to stress) and then abnormal cortisol secretion. Populations most likely to suffer from chronic stress are those suffering social dislocation, emigration, forced relocation, etc.

For this reason migrants will generally have high rates of CHD. Also populations who have been disrupted by other populations moving in on top of them, e.g. Australian aboriginals, Native Americans, Maoris in New Zealand, etc. In addition, populations undergoing rapid social change will suffer from CHD. This is currently true of Eastern Europe where the rate of CHD has exploded since the breakdown of the Soviet Union.

In support of this general hypothesis, the population group with the highest levels of heart disease, currently, are ‘Asian Immigrants,’ i.e. those who have emigrated from countries such as India, Bangladesh, Pakistan. Wherever Asian immigrants move to, they suffer very high rates of heart disease. Additionally, they have a very high rate of metabolic syndrome, and high levels of cortisol secretion. And just to treat you to one quote on this:

The cardiovascular risk factors which comprise the metabolic syndrome are associated with increased hypothalamic adrenal axis (HPAA) activity in some Caucasian populations. South Asians have high rates of cardiovascular disease and its risk factors. We investigated the relationships between HPAA activity, adiposity and the metabolic syndrome…..

….This study demonstrated that fasting 09.00h cortisol concentration is strongly associated with cardiovascular risk factors in a South Asian population.’ Ward A.W et al: Clinical Endocrinology (2003) 58,500-505.

Another important cause of heart disease is eating food under stress. If you eat whilst under physical or mental stress, you will be producing stress hormones: cortisol, adrenaline (epinephrine), glucagon and growth hormone. These are all powerful insulin antagonists.

The antagonism from these hormones during a meal will lead to spikes of blood sugar, insulin and triglyceride (to name but three factors) as insulin, the anabolic hormone, battles against the catabolic stress hormones.

Which is why a country such as France — which has the same level of ‘classical’ risk factors as the USA — has a low rate of death from heart disease. The French spend a long time eating their meals, so they give their metabolism a chance to absorb and digest food properly, rather than set up a metabolic battleground with stress hormones.

So, there you have it, now you know what causes heart disease. And if you want to protect yourself against heart disease, do the following things:

  • Don’t smoke
  • Take exercise
  • Lose weight
  • Relax when you eat, and eat slowly
  • If you feel ‘trapped’ in your life, change it
  • Don’t disrupt your social network — or create a good social network

  P.S. What about high cholesterol levels? Well, what about high cholesterol levels? This red-herring has thrown researchers off the scent for the last sixty years. Only when it is abandoned as a risk factor will mainstream researchers be able to make sense of heart disease.

More essays by Malcolm Kendrick


July 10, 2003  


An analysis that will make it easier for you to hack your way through the misinformation that spews forth from the great medical research machine  

by Malcolm Kendrick MD

I have only just recovered from the idea that everyone in the whole world over the age of fifty-five should spend the rest of their lives on six different medications, all stuck together in one great big pill. You may have seen the non-story about the non-existent polypill peddled in the British Medical Journal (BMJ). I was stimulated to look again at the concept of risk.

The authors of the madcap polypill article in the BMJ made the claim that taking their polypill would reduce the risk of dying of coronary heart disease (CHD) by 80%. Whether or not you believe their figures — and I don’t — I sense that this figure of 80% would be taken by most people to mean that eighty out of one hundred people would be saved from death.

Yet, that is not what it means at all, for this figure is a relative risk reduction figure. And a relative risk reduction means nothing, by itself. However, because everyone’s eyes glaze over whenever you start talking about statistics, most researchers manage to get away with using relative risk reduction figures when, in reality, they should be shot for doing so.

Now, here’s a challenge. The challenge to make an article about statistics interesting….. Okay, that’s not possible. But maybe a little bit interesting?

When you talk about a risk, you need to know the absolute risk of a thing happening. For example, the risk of getting struck by lightening. I don’t actually know what that risk is, but I would imagine it is about one in five million. But again, that figure means nothing unless you put a time scale on it. Is this a one in five million risk over a hundred years, or one year?

If you don’t put a time scale in, you can claim anything you like. For example ‘The Earth will be hit by a big Asteroid. This is one hundred percent certain — shock claim from Astronomer.’ Read all about it. And of course, this is true. The Earth will be hit by a big Asteroid, sometime in the next three billion years or so. The odds ratio for this event is 1 = 100% certain. I am even willing to take a bet on it.

So, I must define risk in two ways, the possibility of the thing happening, and the time period during which that thing will happen. With lightening strikes, this is about a one in five million risk, over a five year period. Not high.

However, people don’t tend to bend statistics by ignoring the time factor that often. Unless they want money to fund their Asteroid defence system. A snip at five trillion dollars, plus VAT. What generally happens is that people inflate the risk in the following way. For example, the chances of dying of lung cancer, for a non-smoker, are about 0.1%, lifetime risk. If, however, you live with a heavy smoker, your chances will increase to about 0.15%. (These figures are for illustration only).

Now you can report this in two ways. You can state that passive smoking can increase the risk of lung cancer by 0.05% - one in two thousand. Or, you can state that passive smoking increases the risk of lung cancer by fifty per cent. Both figures are correct. If you are an anti-smoking zealot, then I would imagine you would prefer to highlight the second figure. The relative risk figure.

And when it comes to reducing cardiovascular risk, exactly the same procedure is used (in reverse). Let’s say that the chance of dying of CHD over five years, in a healthy fifty-five year-old, is 1%. By reducing this risk to 0.2%, you will have reduced the relative risk of dying of CHD by 80%. In this way a 0.8% absolute risk reduction is hyped up as an 80% reduced risk of dying of CHD. Mangling statistics is easy when you know how. It’s even fun.

Anyway, now you know the difference between a relative risk and an absolute risk, and I hope this makes it easier for you to hack your way through the misinformation that spews forth from the great medical research machine.

More essays by Malcolm Kendrick


May 13, 2003


Everyone is quite happy to accept that there is a placebo effect, without ever bothering to measure it in any meaningful way. It just happens, it’s there, and we all believe in it. We’ve all seen it, for goodness sake! Or have we?

by Malcolm Kendrick MD

Not that long ago, a number of people were put under general anaesthetic and had holes drilled into their skulls. These procedures carried all the risks of major surgery, yet the doctors who carried out the operations knew that they would provide no benefit. Surely, you might think, this flies in the face of the primary imperative of the medical profession ‘First, do no harm.’

Why was this done? It was done to satisfy the demands of the great placebo God. A strange creature that lives in a metaphysical world. A creature of belief without substance, a wraith like thing that constantly changes its shape and appears in a different guise to everyone who sees it.

But surely, everyone knows that there is a placebo effect; it really exists. Give someone a white pill with no active ingredients and it will have an impact of some sort — usually a positive impact. Everyone believes this to be true. So strong is this belief that almost all major clinical trials, wherever possible, are split in two, with one group being given an active substance, and the other group a placebo.

If you didn’t do this, you would not know if any improvement that you saw from the drug was, in fact, due to the ‘placebo’ effect. So we are told.

Ah, the placebo effect. It is funny how, in science, there is normally some attempt to define the impact of an ‘effect’ (e.g. the gravitational effect). It would be difficult to imagine NASA sending up the space shuttle without having made some effort to establish the escape velocity required to break free of the Earth’s gravitational attraction.

Yet, everyone is quite happy to accept that there is a placebo effect, without ever bothering to measure it in any meaningful way. It just happens, it’s there, we all believe in it. We’ve all seen it, for goodness sake! Or have we?

Well, let’s assume that I gave you a white sugar pill and said. ‘I am giving you this pill, it is completely inactive, but you are supposed to think it is going to do you some good. Do you understand… it won’t work, it is completely ineffective.’

Do you think that this would make the placebo effect more or less powerful?

Has anyone ever bothered to measure this… ah, well…. No. Never. Never ever.

Most people assume that the placebo only works if the patient thinks they are taking a real drug. Has this ever been tested, or measured? Ah, well… no. And, of course, the placebo has no ‘effect.’ A sugar pill cannot do anything. It is only the belief in the pill that works. Or is it? Do we know?

And if there is a real placebo effect, should we not use it to treat diseases? Actually, we can’t. Why not? Because the placebo effect doesn’t really exist. Or, at least, it only exists if the patient really believes that they are taking a real drug. Or does it? Most mainstream doctors believe that alternative medicine works purely through the placebo effect. Is this true… who knows?

But if it were true, what’s wrong with that. Just don’t look down, otherwise you will be like one of those cartoon characters, suspended in air, until they look below them and realise that there is nothing holding them up. At which point…..aaaaaahhhhh!

All that we really know about the placebo effect is that, in some areas, such as pain relief, patients who take a placebo report reduced pain, an effect as powerful in some people as that achieved by strong painkillers. We have no idea if there is any placebo effect in many other ‘objectively’ measurable areas, such as in cancer regression, wound healing, and progression of coronary artery disease.

Equally, no study has ever been done comparing active drug, placebo and ‘doing nothing at all’, to find out if doing nothing at all is equivalent to placebo. No-one, in fact, really knows if a placebo arm is ever required in any clinical trial. It is just an article of faith.

And to look at this another way: If clinical trials are supposed to reflect what may happen in real clinical practice, no-one is ever prescribed a placebo in clinical practice, they either get the drug, or they don’t. So surely, it is important to establish the difference between taking a drug, and taking nothing — as this will reveal the absolute benefit of taking the drug in real life — even if that did include some placebo effect. So the placebo arm offers no value, other than some data of purely academic interest.

Yet, to return to the start of this article, I was reading a recent trial on a treatment for Parkinson’s disease which required implanting a major electrical device in the patient’s brain. The placebo arm was required to have surgery with holes drilled in their skulls, so that they could not know that they did not have the device implanted…..

Has anyone ever established the maximum possible placebo effect in the treatment of Parkinson’s disease? I think you may be able to guess at the answer to this by now. In fact, some studies have clearly shown that there are conditions with no placebo effect at all (whatever a placebo effect might actually be), e.g. impact on major stroke. If Parkinson’s disease were one of them, then a whole lot of people had holes drilled in their skulls for no reason whatsoever.

All this, in reality, because a placebo can reduce pain. Big deal. It is hardly surprising that the perception of pain can be altered enormously by telling someone that ‘this white pill’ will reduce pain. I have never taken morphine, or heroin. But I have spoken to those who have (for pain relief). They have stated that they still knew the pain was there, but that it didn’t bother them. Soldiers shot in combat often say that they feel no pain at all.

If you cut off someone’s leg, they can suffer huge phantom pain from the leg, with no leg present. The brain can create pain out of nothing, and also shut it off completely.

So it is not exactly surprising that an inactive white pill presented as a painkiller can reduce the perception of pain, or the recollection of it, or the reporting of the recollection of it. However, from this completely subjective and unscientific observation has sprung the assumption that there is always a placebo effect — in all conditions. And so we drill holes into people’s skulls, when we don’t know whether we need to or not, and no-one questions the need.

Beware the dreaded placebo effect, my son.

Twas brillig, and the slithy toves
Did gyre and gimble in the wabe;
All mimsy were the borogoves,
And the mome raths outgrabe.

"Beware the Jabberwock, my son!
The jaws that bite, the claws that catch!
Beware the Jubjub bird, and shun
The frumious Bandersnatch!"

He took his vorpal sword in hand:
Long time the manxome foe he sought–
So rested he by the Tumtum tree,
And stood awhile in thought.

And as in uffish thought he stood,
The Jabberwock, with eyes of flame,
Came whiffling through the tulgey wood,
And burbled as it came!

One, two! One, two! And through and through
The vorpal blade went snicker-snack!
He left it dead, and with its head
He went galumphing back.

"And hast thou slain the Jabberwock?
Come to my arms, my beamish boy!
O frabjous day! Callooh! Callay!"
He chortled in his joy.

Twas brillig, and the slithy toves
Did gyre and gimble in the wabe;
All mimsy were the borogoves,
And the mome raths outgrabe


 More essays by Malcolm Kendrick

April 15, 2003


That’s because it’s merely a blood sugar measurement. A sign. An effect. Not a disease, or a cause. We have become mesmerized by blood sugar levels — we fight to get them down — we are happy when the level is lowered. Doctors claim when the blood sugar level falls below an arbitrary figure that the Type ll Diabetes has been treated, even cured. But what exactly have we cured?  

by Malcolm Kendrick MD

What is a disease? Here are a few definitions, culled from three dictionaries:

  • a condition of the living animal or plant body or of one of its parts that impairs normal functioning
  • illness of people, animals, plants, etc., caused by infection or a failure of health rather than by an accident
  • unhealthy condition of organism or part of organism. 2 (specific) disorder or illness.


Okay, so that counts as pretty unhelpful. A disease is: an illness, an unhealthy condition, a failure of health, an impairment of normal functioning. I can sense a circular discussion arriving.

There was a time when I thought I knew what a disease was. Then I started thinking about it, and realized that the concept of disease is horribly difficult to get a handle on. Superficially, it seems relatively simple to define disease, and this is probably most true when it comes to an infectious ‘disease’. For here we have an agent, and a set of symptoms and signs caused by that infection. But even in the case of an infection, what is the disease? Where is it?

If you get infected with the tuberculin bacillus you may develop TB. But TB can affect the lungs, the gut, the lymph nodes, bone. The infective agent is the same in each case, but the disease state can vary enormously. Having TB in the lungs can lead to coughing up blood, breathlessness — death. TB in the gut can just sit there dormant, unnoticed. Is TB, therefore, always the same disease, or several different diseases caused by the same agent?

Extending this thought slightly, if we couldn’t find the infective agent in TB, would we think that lesions in the gut were the same disease as lesions in the lungs? I suspect not. We would call TB in the lungs, consumption, and TB in the guts, bowel nodularity — or something of the sort.

What becomes clearer, when you start thinking about things more deeply, is that, in general, the process of defining disease starts when doctors find an abnormality. At this point they usually define the abnormality as the disease, unless, or until, they find a deeper underlying cause for that abnormality. Thus high blood pressure of unknown cause becomes essential hypertension, and hypertension is considered by most doctors to be a disease. Even though there must be a deeper problem that causes the blood pressure to be high in the first place.

Equally, if you find a number of interconnected abnormalities clustered together, these are quite often named as a disease after the doctor who first noticed the connections, for example: Parkinson’s disease, Addison’s disease, Graves disease, Cushing’s disease, Hodgkin’s Lymphoma, Fallot’s tetralogy, etc.

None of these doctors had the faintest idea what the underlying cause might be. They just said that they had seen patients with this set of abnormalities. I hereby name this set of symptoms and signs… Kendrick’s’ disease. Well, it has a ring to it. The most recent example I know of is Gerry Reaven of Stanford University who noticed a number of interconnected metabolic abnormalities in patients at high risk of CHD. This was called Reaven’s syndrome. A syndrome, not a disease — discuss.

So you might ask where has all this has got us.The point I am trying to make here is that our definition of a disease is actually totally arbitrary. I am sure that almost everyone believes that they know what a disease is, and what it is not. But when you try to get a grip on it, you will find the concept slips away like mercury.

Does it matter at all? Is this not just playing with words, asking ‘how many Angels can dance on the head of a pin?’ Actually it does matter, rather a lot. Primarily when we try to treat diseases when we do not know, or haven’t bothered to define, what it is that we are really trying to treat — symptom or disease; cause or effect. Which, in a roundabout way, is how we get back to diabetes.

Everyone I speak to is certain that diabetes is a disease. But what is diabetes? The Greek root of "diabetes" means "siphon," and the Latin root, "mellitus," means "honey," referring to the copious voiding of sweet-tasting urine by the diabetes sufferer. From the first century a.d. onward, other emotional descriptions of this killer disease included "sugar sickness," "pissing evile," and "melting down of flesh and limbs into urine."

Actually, that almost certainly wasn’t type II diabetes they were talking about. These were descriptions of type I diabetes. What’s the difference? Type I diabetes happens when the insulin producing cells in the pancreas are destroyed by an auto-immune process — of unknown origin. With no insulin, the blood sugar rockets up and sugar starts to leak into the urine. Amongst other things.

Type II diabetes is primarily caused by resistance to the effects of insulin, or insulin resistance. Usually, there is enough insulin kicking around, but it doesn’t work so well, so the blood sugar level rises. The different types of diabetes have gone through a number of different naming protocols. Type I used to be called juvenile diabetes, as it tended to start at an early age. Type II was called adult diabetes, for obvious reasons.

Type I and type II diabetes have also been designated insulin dependent and non insulin dependent, and type A and type B. There is another terminology kicking around called Latent Autoimmune Diabetes of Adults (LADA), which describes adults who end up with auto-immune destruction of insulin producing cells. There is even another type of diabetes entirely, called diabetes insipidus. And computer people think it’s difficult to keep up with the speed of change — pah!

In this discussion, however, something is already happening that you won’t even have noticed. Something critical. Something that you could stare at for the rest of your life and never even realize that there was anything wrong at all.

An underlying assumption is now forming in your mind, actually it has already formed, and it is this. Diabetes is a disease where the blood sugar level rises too high. (I am restricting the discussion here to type II diabetes by the way). Of course that is true. Diabetes is a disease where the blood sugar level rises too high. But what is the disease? The high blood sugar level? Or the underlying problem that causes the sugar to get high in the first place.

Tracking backwards in time for a moment. When all that doctors were able see was the passing of ‘too much sweet sugar in the urine,’ diabetes was called diabetes mellitus ‘passing too much sugary urine.’ We know that passing too much sugar in the urine was a symptom, not a disease, yet we got stuck with a name that merely described a symptom. We’ve still got it.

Next, it was discovered that in diabetes, the sugar level in the blood was also very high. So diabetes came to mean a high blood sugar level. It still does. When Banting Best and Mcleod isolated insulin from the pancreas of cows and injected it into people with type I diabetes, their blood sugar level went down, and they recovered. Until the insulin ran out, of course.

But it was never the high blood sugar levels that killed a type I diabetic patient. In diabetes, you die because insulin is required to switch on the production of sugar receptors from within cells all around the body - other than in the brain. With no insulin, no sugar receptors are produced, and no sugar can be absorbed from the blood.

With no sugar to use for energy, the cells start to metabolise fat, and protein. One of the residues of fat and protein metabolism are ketone bodies, and these are acidic. After a while this ‘acidity’ cannot be compensated for, the diabetic falls into an acidic coma and dies.

So when Banting and Best gave patients insulin they weren’t saving life because they lowered blood sugar levels, even though they thought they were. By giving insulin they were allowing cells to manufacture sugar receptors, absorb and metabolise sugar and clear out the acidity from the blood. The ‘disease’ they were treating was not a high blood sugar level — it was a lack of insulin.

But because the disease, in diabetes, was a raised blood sugar level, it was just assumed that it was the lowering of the sugar that was critically important. And even though everyone now knows that type I diabetics die of diabetic ketoacidosis, the historical baggage that comes with diabetes has proven impossible to shift.

So we still define diabetes, the disease, as a high blood sugar level. The current goal of treatment in type II diabetes is to lower the blood sugar level. But a raised blood sugar level is always a sign of an underlying ‘disease, whatever that disease may actually be. Can lowering a metabolic sign really prevent mortality and morbidity? Are we treating a disease when we lower blood sugar levels? No, we are not. We are lowering blood sugar levels which is an effect, not a cause.

Does this mean that lowering blood sugar levels is a waste of time…. I didn’t say that, although the evidence that keeping blood sugar levels under control provides benefit (in type II diabetes) is proving somewhat elusive. In fact, some studies appear to show that tight blood sugar control may actually result in increased mortality. This would be surprising if we were actually treating a disease. But it is less surprising once you recognize that you are treating a metabolic sign.

I will try to finish where I started with the statement that type II diabetes is not a disease. It can’t be because type II diabetes is merely a blood sugar measurement. A sign, an effect. Not a disease, or a cause. We have become mesmerized by blood sugar levels — we fight to get them down — we are happy when the level is lowered. Doctors claim, when the blood sugar level falls below an arbitrary figure, that the type II diabetes has been treated, even cured. But what, exactly, have we cured? An annoyingly high figure on a piece of paper that comes back from the laboratory — or a disease?

More essays by Malcolm Kendrick

March 21, 2003  


If you want to understand coronary heart disease, you cannot ignore the role of the humble blood clot.

by Malcolm Kendrick MD

Up to now I have resisted writing about this area, as blood clotting is a mind-boggling and complicated area of human physiology. In the end, however, if you want to understand coronary heart disease (CHD), you cannot ignore the role of the humble blood clot.

For it is now accepted by everyone involved in CHD research that the final event, the thing that kills you with CHD, is the formation of a blood clot on top of an atherosclerotic plaque. If the blood clot is big enough to completely block a critical artery, in a critical area, you will die.

In the last few years medics have become increasingly expert at trying to clear these potentially fatal clots. Aspirin is the first line of defence, then the clot busters streptokinase, or tissue plasminogen activator (tPA) are used.

Increasingly, cardiologists get to work with thin wires and balloons, and stents, to remove the clot, prize the artery apart, and stick a metal framework to keep the artery open after unblocking it. New drugs have been developed to keep the artery patent. This is all great stuff, and many thousands of people who used to die are now being saved.

So there is no argument from anyone about the final event in CHD. It’s a blood clot. It is also recognised that blood clots develop over atherosclerotic plaques on quite a regular basis without causing any symptoms at all, presumably because they are not big enough to fully block the artery.

However, in these silent episodes, once the blood clot stabilises it adds to the plaque size, and can lead to greater narrowing of the artery. In this way, repeated blood clots forming over an area of existing plaque cause atherosclerotic plaques to ‘grow’. And if you look at plaques closely, you can — in many plaques — clearly see bands, with each band indicating an episode of plaque growth.

This is all agreed upon by almost everyone. And if you were a simple soul, like me, you might argue that if plaques grow, and eventually kill you due to clots forming on the artery wall, could this not be how they start in the first place? Are atherosclerotic plaques not, in fact, just the remnants of repeated blood clots, which are ‘drawn in’ to the artery wall, in time turning into a form of scar tissue?

If you did think this, you wouldn’t be the first. This hypothesis was initially proposed by Karl Von Rokitansky in 1852. Although supporters of Rudolf Virchow may argue that he said it first. Unfortunately, therefore, I can hardly claim that this idea is either new, or mine.

Can it really be that simple? Surely there must be something wrong with the hypothesis that atherosclerotic plaques are the remnants of repeated blood clots? Where does this idea break down? I could say, don’t ask me, I happen to believe it’s true. But I will attempt to be a little more objective than this.

The key point of objection is that, whilst you can see how blood clots can form over a ‘damaged’ artery wall, it is very difficult to see how they form over a healthy artery wall. After all, a critical function, perhaps the critical function of the lining of the artery (the endothelium) is to prevent blood clots from forming. So how can this process actually start? A good point from my learned friend.

But I put it to you, members of the jury, that every ‘factor’ that has been identified as increasing the risk of CHD, has clearly identifiable pro-coagulant activity. Equally, every factor that has been identified as reducing the risk of CHD has clearly identifiable anti-coagulant activity. Which, I would vouchsafe, is pretty heavyweight proof.

Is this really true?

Well, yes. But you have to understand that there are three interconnected factors at play here that can cause a clot to form over the artery wall. Factor one, is ‘damage’ to the endothelium. Once damaged, the endothelium stops acting as a non-stick anti-coagulant surface. Indeed, if the endothelium is stripped away, it exposes the middle layer of the artery, the media, to the blood, and the media releases the most powerful pro-clotting factor known to man: Factor VII, the ‘extrinsic’ factor.

The second factor is how pro-coagulant the blood is itself. There are a multitude of clotting factors in the blood. Some of which you may have heard of, such as factor XIII - the one that is missing in haemophiliacs; some of which you probably haven’t heard of e.g. Von Willibrand factor. Increase a pro-coagulant factor, and you increase the chance of clots forming.

The third factor is the structure of the blood clot itself. Some clots are wobbly and weak; others are very tough, and difficult to break up. For example, incorporated into all blood clots is a substance called plasminogen. This is an enzyme which, when activated, chops the clot into pieces. (Which is why tPA — tissue plasminogen activator - is given to people having a heart attack) However, if you have a high level of Plasminogen activator inhibitor — 1 (PAI — 1) in the blood, plasminogen is less effective at breaking the clot up.

So, you have to look at three basic factors:

  • The anti-coagulant status of the endothelium
  • The pro-coagulant state of the blood
  • The relative ‘toughness’ of the blood-clot once it is formed

Bearing this in mind, I think it is interesting to run through a few factors known to alter the risk of CHD, and see how they fit:


Smoking creates free-radicals in the blood, these reduce nitric oxide (NO) synthesis in the endothelium, and NO is the single most powerful anti-coagulant factor in the body. Smoking also has pro-coagulant effects in the blood; it raises fibrinogen levels. It also has endothelium damaging effects. So, if you want to avoid CHD… STOP SMOKING!


Ethanol, in moderate doses, reduces free-radical synthesis, reduces clotting factors, such as fibrinogen, and reduces the blood clot toughness. However, excess alcohol consumption creates rebound platelet stickiness (platelets are hugely important in blood-clotting). Moderate drinking protects against CHD, heavy drinking is a risk factor.


A high blood sugar level leads to increased free-radical synthesis, see above. A high blood sugar, independent of its effects on NO synthesis, also causes endothelial ‘damage.’


Not surprisingly, haemophilia reduces blood coagulability. Haemophilia also reduces the absolute risk of CHD by 80%.


Statins have strong anti-coagulant effects, they stabilise plaques and increase NO synthesis.


Aspirin reduces the stickiness of platelets (see alcohol). Platelet aggregation is the first step in blood clotting.

Omega-3 fatty acids

Omega-3 fatty acids have strong anti-coagulant effects in the blood


Physical, or psychological stress causes the release of the stress hormones: cortisol, adrenaline, growth hormone and glucagon. These hormones all increase blood coagulabiltiy, raise the blood sugar level (see above), and ‘damage’ the endothelium.

Raised blood pressure

  I am a little ambivalent about this risk factor. I am unconvinced that a raised blood pressure really is a ‘cause’ of plaque development. However, it is possible to see how high pressure, and turbulent blood flow, could strip away a layer of endothelium, exposing the blood to the media, and thus factor VII, thus stimulating a blood clot to form. It is certainly true that plaques don’t form in low pressure blood vessels (e.g. veins).

However, the clinical trials on blood pressure lowering are very unconvincing when it comes to a correlation between the degree of blood pressure lowering and the prevention of CHD.


HDL has strong anti-coagulant effects

LDL (Oxidised LDL)

  This is a complex pathway. When platelets start to stick together, they release free radicals. Free radicals oxidise LDL. Oxidised LDL is a powerful blood clotting factor. LDL is also incorporated into the blood clot as it forms, and provides a ‘lipid’ surface (along with VLDL) for the construction of fibrin. Fibrin is the hugely strong protein strand that binds a clot together and makes it ‘tough.’

Frankly, I think that’s enough. If you wish to, it is possible to link every single factor known to have an impact on CHD rates to one of three effects: endothelial damage, blood coagulation, or toughness of the clot. If you don’t affect any of these three things, then you have no effect on CHD rates. If you manage to impact all three, then it’s time to increase the life insurance. (On a positive note you won’t need a big pension fund).

So, if it’s that simple, then why have you never heard of this before? Now that is another story altogether. But if enough people think I am making all of this up, then I will provide a series of references from prestigious journals to support every single fact that I have presented.

To my mind, the answer as to the underlying cause(s) of CHD is not only ‘out there,’ it has been staring everyone in the face for the past fifty years. Perhaps it is too obvious for anyone to see it.

To quote a riddle that my son came home with the other day:

 What is greater than God
More evil than the devil
The poor have it
The rich need it
If you eat it you will die

Once you know the answer you cannot believe that you couldn’t see it straightaway.

More essays by Malcolm Kendrick

March 14, 2003


The pro and anti-fat battle seems to be raging in the colonies, with people hurling data of mass destruction at each other with great vigour. As usual, I find that "truth is the first victim in any war."  


by Malcolm Kendrick MD

A number of people have written, asking me to comment on the Gary Taubes-Michael Fumento battle. What do I think, what is true?

Over on this side of the pond, most people have never heard of Taubes or Fumento, or Dr Aktins. But the pro and anti-fat battle seems to be raging in the colonies, with people hurling data of mass destruction at each other with great vigour. As usual, I find that ‘truth is the first victim in any war.’

So what is the truth? Who is right, the pro or anti-fat lobby? The question, in the case of Taubes vs. Fumento appears to split in two. Does eating fat or carbohydrates make you fat? Secondly, does eating fat or carbohydrate give you heart disease? For the sake of brevity, I’m not going to deal with the second question here.

Unfortunately, any discussion of food and eating carries a huge emotional baggage. It becomes wrapped up with issues such as vegetarianism, greed, guilt, sin, pleasure. You name it and Freud would have had a field day. After sex, food has probably screwed up more ids, egos and superegos than anything else.

So, the context is not exactly ideal for any rational discussions. In this area, people tend to believe the facts that they like, and discount the facts that they do not. And when you study diet and health, you can find hundreds of studies to support almost any position that you care to take.

Anyway, with regard to eating fat and getting fat: Where to start? Perhaps with some facts that are accepted as absolutely true by almost everyone. I should warn you that there are not too many of these, and you will probably disagree with at least one of them.

Fact one, fat contains twice as many calories as carbohydrates, weight for weight. So if you ate one hundred grams of fat you will be eating twice as many calories as if you ate one hundred grams of carbohydrates.

Fact two, the body has two ways of getting rid of energy. Physical work and heat generation. We cannot, as far as I am aware, radiate energy through electromagnatism, light, microwaves, or any other high intensity radiation. Nor does the body have any way of shedding excess fat through excretion by the kidneys, bile, faeces, sweat or saliva. In short, once you have stored energy as fat it has only two ways of being used up.

Fact three, whenever anyone has studied this area closely, i.e. putting people into a closed environment and accurately measuring calorific input and output, the two match. Big surprise?

Fact four, there is no such thing as a ‘naturally’ high or low metabolic rate. Thin people eat less than fat people — with three provisos. The first proviso is that exercise burns calories. I read that in the Tour de France cycle race, the competitors use about twelve thousand calories a day. And people who walk across the South Pole use about six to eight thousand calories a day. So, exercise can keep you thin.

The second proviso is that a seven-foot tall male will naturally burn up more calories than a five-foot woman. So size and sex have an impact on the number of calories needed for energy equilibrium. The third proviso is that some diseases can affect the metabolism, such as thyroid disease.

What else is known for sure….. well, nothing very much. Does the weight of evidence support the hypothesis that eating fat makes you fat? No. Does the weight of evidence support the hypothesis that eating carbohydrates makes you fat? No. What of Dr Atkins and his marvellous diet? Does it work? I’m sure it does. Any calorie restricted diet works, so long as you stick to it. Does it work in the long term? I’m sure it does if you stick to it in the long term.

Gosh, how boring. If you want to lose weight, eat less or exercise more. What did you want to hear? That fat has some magical, weight losing, second law of thermodynamic altering properties. Those things could possibly happen in another Universe, but not this one. A calorie is a calorie is a calorie. They don’t just disappear — unless you use liposuction.

End of discussion? Perhaps. But there is a more interesting question lurking in the depths, which I shall call the satiety question. Does eating too many carbohydrates create a metabolic situation that results in people eating more than they would if they ate something else, such as fat?

The hypothesis underlying this question is fairly simple and it goes something like this: If you eat sugar, this will be absorbed very rapidly, causing a sudden ‘kick’ in blood sugar levels. This triggers insulin release and within a short period of time all the sugar will have ‘gone’ from the bloodstream.

However, with the insulin still high, your blood sugar level drops, causing a sense of hunger and a need to eat again, very quickly. So you enter a vicious cycle of hunger, carb intake, blood sugar spike, insulin release, blood sugar fall, hunger. Or something of the sort.

On the other hand, if you ate the same amount of calories as fat, this would take much longer to absorb, it would not cause the sudden surge in insulin, and ‘food’ would hang around for longer in the bloodstream. You would not get ‘rebound’ hypoglycaemia and rapid return of hunger.

A reasonable hypothesis, therefore, is that carbohydrates may create a ‘hunger’ cycle, and cause people to eat much more, thus getting fatter. But although this is a reasonable hypothesis, I don’t think there is strong proof to support it. My own difficulty with this hypothesis is that most people don’t seem to eat because they are hungry.

In fact, there seems an almost perfect dislocation between true hunger and eating, in our rich Western societies. I’m never hungry on a plane, but a member of the cabin crew inevitably slaps food in front of me, and I end up eating some of it. Eating, and the reasons why people eat, is much more complex than ‘I eat when I am hungry, and I don’t eat when I am not hungry.’ If people did act like this, I suspect that obesity would never have been heard of. People would travel miles to see ‘The amazing man who stores fat around his waist…. Gasp.’

But we have managed to completely screw ourselves up when it comes to food. When we are young, for example, we are praised for clearing our plate. I don’t recall any parent stating, ‘Thank Goodness you stopped eating when you were full, and did not keep stuffing it down just to please me.’

Instead, I have memories such as the one where I watched a fellow inmate at my school being forced to finish food by a terrible, unbending schoolmaster, unaware that another boy had spat in it — or maybe he was aware. Most unpleasant. Oh yes, over the years we have managed to turn food into a battleground.

Anorexia, bulimina, diets, guilt, anger, fear, praise, ridicule, pain, sickness….. Amongst all of this horrible mess how the hell do you think you are going to prove anything? I just finished reading Gary Taubes reply to Michael Fumento. (See other articles in this debate section) And the best quote came from Ruby Liebel of Columbia discussing research on weight gain and weight loss:

When I interviewed Leibel, who is now at Columbia University, he capped our conversation this way: "if you do feel you understand this," he said, "it will probably indicate that you've lost your mind."’

It partly boils down to this, I think. Whilst having a big brain carries certain advantages for us humans, it also creates great difficulties. For our brains are immensely powerful, and they release powerful hormones into the system. When our brains get upset, they screw up the entire metabolic system by firing off all sorts of neurohormonal messages.

With this huge brainpower at our disposal, we can easily over-ride hunger, or a sense of being full. We can eat for social reasons, the need to be liked, the fear of criticism. We don’t eat if we fear being fat, losing control, being laughed at. We eat when we are stressed to calm ourselves, even though every hormone in the body is screaming at us to stop. When we diet we don’t really feel hunger, we just resent being denied things we want. We eat to bring pleasure to our brains, and the hell with what our body wants to do.

So you want some simple answer? Eating fat makes you thin? Eating fat makes you fat? Not a hope. There are a few too many variables here that, as yet, are not measurable by medical science. To quote Albert Einstein ‘Not everything that matters can be measured, and not everything that can be measured matters.’

So, does eating fat make you fat? I don’t think so. I think that driving a car rather than walking a hundred yards makes you fat. I think that the easy availability of food, especially fast food, makes you fat. I think that connecting food and eating with concepts of good and bad, pleasure and guilt, makes you fat. I think that disconnecting our minds from the messages that our bodies are desperately trying to send us makes us fat.

Finally, I also think that nature quite likes us humans to store fat in times of plenty, so that we don’t starve to death if the food supply dries up. Some animals are designed to get fat, others are not. We are. If we weren’t, we wouldn’t. Try fattening up a chicken some time — not possible.

But never mind, someone somewhere is going to invent a pill that makes us all thin.

More essays by Malcolm Kendrick


Feb 4, 2003


I can’t imagine why anyone ever thought that saturated fat in the diet had an impact on cholesterol levels  


by Malcolm Kendrick MD

I received an overwhelming response to my little primer on lipoproteins, so I thought I should explain a little more about fats. Excuse my diagrams, I got them all from the internet, so they have no overall design template, but I hope that I can keep things clear.

A fat has the basic structure shown below (Fig 1).


(Fig 1) My nameless fat

All fats are, basically, a chain of carbon atoms of varying length, where the carbon atoms are attached exclusively to hydrogen atoms, apart from the group at the end — COOH - called a carboxyl group. The carboxyl group is what defines fats as an acid, or fatty acid. So a fatty acid and a fat are actually the same thing. The terms are interchanged at will. That one caused me endless confusion.

You may have noticed that my nameless fat has a gap at the bottom, where no hydrogen (H) atoms are attached. And there is a double bond between the carbons with the missing hydrogens. This means that the carbon atoms at either end of the double bond are not ‘saturated’ with hydrogen. So this fat is ‘unsaturated.’

The other thing about my nameless fat is that there is only one double bond, so this fat would be referred to as a mono-unsaturated fat. Monounsaturated = one double bond, or two hydrogens missing. If there is more than one double bond, the fat is referred to as poly-unsaturated.

Clearly, therefore, a saturated fat is one with no double bonds, and no hydrogens missing. It is fully saturated with hydrogen. You can see how this nomenclature works in Fig 2.

In real-life you can tell if a fat is saturated primarily because it is solid at room temperature. Monounsaturated fats and polyunsaturated fats are usually liquid are room temperature. Unless you live in Siberia, of course.


Fig 2

So, how come you can spread margarine, it being polyunsaturated and all? Because in the 1930s a very clever chemist learned how to nail extra hydrogens to unsaturated fats using a process known as ‘hydrogenation,’ and thus was born margarine — hoorah. Artificially hydrogenated fats are often called trans-fats, or trans fatty-acids. These types are fat are not really found in nature at all.

As a slight aside, forget GM foods, margarine is as alien as it gets. Even if you call it Flora and paint pictures of lovely flowers around the tub, and get highly paid athletes to promote its health giving wonders. ‘Flora….’ (is this just a UK name?). Sorry, start again with my strap-line (fade-in Beethoven’s pastoral symphony). ‘Flora, as natural as platinum catalysed hydrocarbon cracking itself.’ That, by the way, is what we in the UK call a joke. Just in case the Flora lawyers try to sue me.

So, now you know the difference between a saturated and unsaturated fat. And pretty unexciting it is too. How come it seems so difficult? Because people start using terms like alpha-linoleic, and stearic and Omega-3, and cis-bonds and uncle Tom Cobbly and all.

All of this is really just a form of nomenclature used by chemists (to confuse us poor laypeople). However, to keep it simple, if the double bond in a fat is three along from the ‘Omega’ end of the fat, which is the opposite end from the carboxyl group, the fat is then called an Omega 3 fatty acid. If the double bond is six along, it is an Omega 6. And that’s the difference between an Omega 3 and an Omega 6 fatty acid. Wow — hold onto your seat — is this exciting or what.

Where do the other names come from e.g. stearic, and linoleic, and palmatic etc? Generally, these names are taken from the source of the fat. So palmatic acid comes from Palm oil/fat. Linoleic comes from linoleum (only joking — it’s vice-versa). These types of fat/oil are defined primarily by the length of the carbon chain. Linoleic acid, for example, has eighteen carbon atoms.

Thus, fats are named according to a few different variables. Where they come from, palmatic, coconut (and this also defines the number of carbon atoms), whether they are saturated, or unsaturated, and where the double bond, or bonds, sit. The other significant bit of nomenclature is whether or not the double bond is cis, or trans. To explain.

Usually, in natural fats, the hydrogen atoms sit on the same side of the double bond, causing a ‘kink’ in the chain. See diagram 3. when you get this ‘same-side’ hydrogen structure, the bond is known as a cis bond. If the hydrogens are spread either side it is known as trans.

Because cis bonds have both the hydrogen on the same side, they tend to kink, causing the chain to bend. This bendyness allows the fat to wiggle around more, and so the fat is fluid. A saturated fat has no kinks, no bendiness, and thus remains solid. Trans bonds are also less wiggly than cis bonds, so the fat is more solid, but no too solid. Which is why margarine can spread ‘straight from the fridge,’ or in my case, straight into the dustbin.

Diagram 3

And that’s about all you need to know about fats — or fatty acids. There are other ‘naming’ protocols, but they don’t really have much relevance to non-specialist audiences.

But please keep one thing in mind - within the context of heart disease. The only real connection between fats and cholesterol is that, as they are insoluble in water, they have to be transported around inside lipoproteins. You don’t make cholesterol from saturated fats, or any other sort of fat, or vice-versa.

So, why do people keep telling you that excess saturated fat consumption raises your Cholesterol level? Because this has become an article of faith. It is not susceptible to reason, logic or facts. Metabolically speaking, there is no connection between these two substances at all. They just happen to sit in the same lipoproteins. (And it’s the lipoprotein level you’re interested anyway — you don’t actually have a cholesterol level)

Equally, why do unsaturated fats lower your cholesterol level? They don’t. How could they? Fats, saturated or otherwise, ARE NOT CONNECTED TO CHOLESTEROL METABOLISM. You might as well argue that eating excess protein will raise your blood sugar level. For a graphical illustration of the differences between fats and cholesterol. See diagram 4.








So now you know what a saturated fat is, and what an Omega 3 fatty acid is, and what cholesterol is. I hope you will now find what I found. Once you understand this stuff a bit better, you can’t imagine why anyone ever thought that saturated fat in the diet had an impact on cholesterol levels in the first place. There is just no connection.

More essays by Malcolm Kendrick

Jan 30, 2003


You must have heard this term a million times. Even so, there is an enormous level of confusion about the whole area of cholesterol, lipids, lipoproteins, fats….Can we get real and make the whole debate about cholesterol easier?  


by Malcolm Kendrick MD

I have written a few columns on heart disease for Red Flags and the response has been very positive. However, there is a major problem that emerges quite clearly from e-mails that I get back. The problem is that there is an enormous level of confusion about the whole area of cholesterol, lipids, lipoproteins, fats etc. So I thought I should provide a simple primer on this area, as it makes debate and discussion a lot easier.

Before getting into the area, I must admit that I have a great deal of sympathy with the confusion. When I first started looking at the diet-heart/cholesterol hypothesis I found the science to be almost totally incomprehensible, and much of this is due to, what I refer to, as terminological inexactitude.

To provide a couple of simple examples. A high level of low density lipoprotein (LDL) in the blood is usually referred to as a high cholesterol level. A high level of very low density lipoprotein (VLDL) in the blood is usually referred to as a high triglyceride level. Frankly this is nuts, as LDL and VLDL contain both triglycerides and cholesterol - and neither triglycerides or cholesterol float free in the blood.

Let’s try another example. An LDL with a protein attached to it called apolipoprotein b-100 is called LDL. LDL with a protein attached to it called apolipoprotein (a) is called Lipoprotein (a). Or Lp(a)…. I sense confusion arising.

So, let’s start at the very beginning, it’s a very good place to start. Point number one. cholesterol is not a fat; it is called many different things, even an alcohol, but one thing it is not, is a fat, or a fatty acid. (Fats and fatty acids are the same thing, by the way). Nor can you make cholesterol from fats.

Cholesterol starts life as a chemical called Acetyl coenzyme a. A relatively ubiquitous building block that is used to make all sorts of things that the body needs. The vast majority of cholesterol in your body is synthesised by the liver from Acetyl coenzyme a. You only get about a quarter of your cholesterol from dietary sources.

Point number two: Triglycerides are three fat molecules stuck to a Glycerol molecule - which is where the tri and the glyceride come from. Although the fat part seems to have gone missing in the nomenclature. Most fats are transported around the body and stored as triglycerides.

When you eat cholesterol and/or fat, they are absorbed by the gut. But neither fat/triglyceride, nor cholesterol can be dissolved in blood - they are insoluble in water. So, they have to be wrapped up in a sphere known as a lipoprotein in order to transport them out of the gut.

Point three: Lipoproteins come in many sizes. The biggest is a chylomicron and the smallest is a high density lipoprotein (HDL). If a chylomicron were the size of a football (soccer ball), a VLDL would be the size of a baseball, an LDL would be the size of a golf ball, and an HDL the size of a pea, perhaps even a petit pois.

All lipoproteins contain cholesterol and triglyceride - in varying proportions. The basic function of a lipoprotein is to carry triglycerides from the gut, or the liver, to fat cells, where the triglyceride is then stored and used for energy when needed - in situations such as pressing the remote control for the television, or chewing a hamburger.

Lipoproteins also transport cholesterol and triglycerides to the liver. When a chylomicron reaches the liver, from the gut, it is grabbed, absorbed, and then smashed to pieces. The liver then reconstructs the component parts into VLDLs and sends them out into the bloodstream with an apolipoprotein b-100 protein stuck to the side.

As a VLDL travels around the body, fat cells snatch at it, chop bits off and it gets smaller and smaller, turning first into an intermediate density lipoprotein (IDL), then a low density lipoprotein (LDL). Once the lipoprotein has reached LDL size, it is either re-absorbed by the liver and re-used, or it is absorbed by other cells around the body that are in need of cholesterol.

The reason why LDL can be absorbed is all to do with the apolipoprotein b-100. This is the protein ‘key’ that the cells recognise. It is the key that fits exactly into the LDL receptor on the cell wall. Once the b-100 molecule locks to the receptor, the receptor closes around the LDL, draws it into the cell where the LDL is broken down into its component parts.

And what of High Density Lipoprotein (HDL)? HDL is not part of the same metabolic ‘loop’ as the other forms of lipoproteins. It is made separately, and appears to act as a cholesterol mop, scavenging loose cholesterol from broken down cells and suchlike, and transporting it back to the liver. Which is why it is often called ‘good’ cholesterol. It is called this even though HDL isn’t cholesterol, and cannot possibly have any effect on removing cholesterol deposits from arterial walls. In short, it is neither cholesterol, nor good. Apart from that it is a magnificently accurate form of nomenclature.

Anyway. In short, lipoproteins are the ‘taxis’ that are used to transport insoluble cholesterol and triglyercides around the body. Apart from HDL, lipoproteins start big, as chylomicrons, and gradually get smaller as they lose triglyceride. The VLDLs, produced by the liver get smaller and smaller until they become LDLs. At which point they are reabsorbed into the liver, or other cells.

What then, is the cholesterol level?

Well, it should be obvious by now that the cholesterol level doesn’t actually exist. For there is no cholesterol free in your bloodstream. You can have a level of LDL, or VLDL, or chylomicrons, but you can’t have a level of cholesterol. And so all measurements of ‘cholesterol’ are actually measurement of lipoproteins - which is where most of the terminological confusion arises.

Thus, when someone uses the term ‘total’ cholesterol, what they mean is the level of LDL, plus HDL, plus a few other lipoproteins e.g. Lipoprotein (a) and/or some intermediate density lipoproteins that aren’t quite LDLs, but get mixed up in the process.

When the term LDL/cholesterol, or ‘bad’ cholesterol level is used, this refers only to the level of LDL. This is usually about two thirds the level of ‘total’ cholesterol. Other laboratories will tell you both the LDL and HDL (good cholesterol) level, and give you the proportion of LDL to HDL. With a ratio greater than three seen as ‘bad’ and a ratio less than three as ‘good.’ This can be presented as LDL:HDL 3.2:1, or whatever.

Some people think the level of VLDL is important, and they will give you this measurement as well. But they will call it the level of triglyceride.

I think that is enough for one article. I hope that you find it a helpful dash through the nomenclature used in this area. If I get some positive feedback I could explain the difference between saturated fats and unsaturated fats, and what the terms Omega 3 and Omega 6 actually mean, and a few other things as well.

 More essays by Malcolm Kendrick


Jan 9, 2003



by Malcolm Kendrick MD

Let’s suppose that one day you went to the doctor and she decided to take your temperature, just to see what it was. To your surprise it was two degrees higher than normal. As we all know, a high temperature is associated with a higher than normal level of mortality, so the doctor decided to use a drug to get your temperature down, along with advice to wear less clothes and take cold baths.

Time passes and you have been on this drug for five years. The baths and chilly walks are getting to be a bit of a pain. On the bright side, at least the temperature is back to normal.

I think you would agree that such a scenario is, quite frankly, nuts.

Yet, every day, thousands of people are found to have high blood pressure, and put on blood pressure lowering drugs on pretty much the same basis. The logic, after all, is the same.

1.      People with high blood pressure are more likely to die from CHD

2.      Therefore a high blood pressure causes CHD

3.      Therefore if you lower the blood pressure you will reduce the rate of CHD

4.      So, take a blood pressure lowering drug for the rest of your life

I suppose that most people believe that it must have been proven by now that blood pressure lowering does reduce the rate of CHD, rendering the example of a high temperature somewhat pointless. Well, I am going to quote you quite a long passage from the European Heart Journal, issue 20, October 2000. Please read it carefully, for it is actually quite stunning.

‘It is widely believed that randomised trials have proved that lowering blood pressure is beneficial. Actually, that is not true. All antihypertensive drugs have profound effects on the cardiovascular system, aside from their haemodynamic (blood pressure lowering) effect. How much, if any, of the observed risk reduction can be ascribed to the reduction in pressure and how much to the direct action of the drug on the cardiovascular system? Motivated by the belief in the linear relationship of risk to pressure, many automatically attribute the risk reduction to the pressure reduction, ignoring the direct action of the drugs on the target outcomes. But results of a multitude of clinical trials make it clear that such a simplistic view cannot be true. In fact, evidence is mounting (especially from the newer trials) that it is the direct effects that are producing most, if not all, or the benefit and that the accompanying blood pressure reduction may be just an inconsequential side effect.’ Port S et al.

In short, there is no evidence whatsoever that lowering blood pressure has any effect on CHD. As they authors of the paper further state:

‘ALLHAT (A major blood pressure lowering trial) showed a dramatic difference between alpha blockers and diuretics, with essentially no difference in blood pressure between the treatment and control groups.’

Quelle surprise? Not really, after all, the underlying hypothesis that blood pressure causes CHD was always nonsense. After all, how could a high blood pressure make atherosclerotic plaques form? Well, you can create a convoluted argument involving endothelial damage, but you would struggle to create a clear cut case.

On the other hand, it is very much more simple to see how an atherosclerotic plaque, by narrowing an artery supplying blood to a vital organ, can trigger the heart to pump harder, thus overcoming the narrowing in the artery by increasing the blood pressure.

Perhaps it is time for a rewind. What is a high blood pressure, and what could cause it? In about ten per cent of cases there is a clearly established cause for high blood pressure. Conditions such as renal artery stenosis, or hyperthyroidism, or kidney problems. If these are treated, the blood pressure drops back to normal.

However, in about ninety per cent of cases when the blood pressure is raised, no cause can be found. At which point the medical profession, rather than using the somewhat pathetic sounding term ‘Raised blood pressure of no known cause,’ decided to rename the condition Essential Hypertension. You’ve got to admit, this sounds a great deal more scientific and ‘disease like.’ In fact it sounds so impressive that Essential Hypertension has managed the transformation from ‘symptomless medical sign’ to a real disease, one that needs to be treated.

Let’s examine the logic in use here. One day, for no known reason, your body decides that the blood pressure needs to be raised. So your heart pumps harder, or your arteries decide to contract, or both. This has the desired effect of raising the blood pressure to a point where it can cause damage. It can lead to strokes, heart failure, kidney failure, etc.

Undeterred by the damage that this raised blood pressure is causing, the body continues for day after day, month after month, year after year, to keep the pressure up. Eventually your heart can’t carry on any more, so it starts to pack in, you develop heart failure, and within about five years you are dead.

There is just one teensy little thing missing from this model. A cause. Why does the pressure suddenly rise? One thing is for sure, the body does nothing without a cause, especially if the effect is to damage health. So we need to ask a deeper level question. What could cause the blood pressure to rise?

In order to understand this, you need only to the grasp the exceedingly simple concept that the pressure of liquid flowing through a pipe is a function of two variables. The first variable is the rate of flow of the liquid; the second is the diameter of the pipe. If you want to increase the pressure you must pump more fluid, or narrow the pipe.

Therefore, if your blood pressure goes up, for no known reason, one of two basic things is happening.

1.      The heart is pumping harder

2.      The diameter of the arteries has narrowed (causing the heart to pump harder to keep the blood flow the same)

Things that make your heart pump harder would include: anxiety, exercise, stimulants e.g. coffee. Things that narrow your arteries would be……? Dum de dum, let me think. Oh yes. An atherosclerotic plaque (the underlying cause of CHD) would narrow an artery. Therefore, a probable cause of high blood pressure is the presence of CHD.

Thus, ergo etc. a high blood pressure is not a cause of CHD. Instead CHD is a cause of high blood pressure. So yet again gentle reader, as with raised cholesterol levels and CHD, we see another rather grisly example of the medical profession grasping the wrong end of the stick and desperately trying to cure a disease (CHD) by sweeping a symptom of that disease (high blood pressure) under the carpet. No big surprise, it doesn’t actually work.

Does this all seem incredibly basic? It should, because it is. So, whilst blood pressure lowering may have some effect on preventing strokes, heart failure and other pressure related problems, it has no effect on reducing death from heart attacks. After all, how could it?


Some of you may have seen research reported in the New Scientist magazine which established quite clearly that most scientific researchers don’t bother to read the full papers that they use for references. In fact, most of them just copy and paste the list of references used in other papers.

This may seem a somewhat arcane issue, removed at two steps from real life. I can sense a collective ‘so what?’ resonating round the world on this issue. But please pay attention, because this fact is VITALLY IMPORTANT! And it explains much about the treatment paradigm for high blood pressure.

In medical science, many measurements are imprecise. A blood pressure taken at ten in the morning may have changed five minutes later. The doctor may have put the blood pressure cuff on in a slightly different way, whatever. So, when you start drawing a graph of blood pressure measurements taken over time vs. the rate of death, in different groups of people, it does not have precise cut-off points. It may look more like someone has fired blunderbuss at a piece of graph paper.


However, if you are really clever and understand mathematics and calculus, and suchlike, you can draw a perfect line through that mass of dots. This can be called a ‘linear logistic model.’ (My line is just a random guess by the way)


However, to quote the European Heart Journal: ‘Before one can have confidence that the linearity correctly reflects the behaviour of the data, and is not just an artefact of the model, it is necessary to carefully examine the data in relation to the proposed model.’ In plain English, stop guessing. Although guessing does look a lot more impressive when you use terms such as Cox model and double-tailed chi-squared, etc. which no one understands.

So, what does this all have to do with the price of beans?

I have two strands to my discussion so far. Strand one: most researchers never bother to read the papers they quote; at most they manage to read the abstract. Stand two: statistical models used to look at blood pressure vs. mortality are all based on the supposition that ‘the relation of blood pressure to risk of death is continuous graded and strong, and there is no evidence of a threshold.’

Now, where did this supposition first come from? Our old friend Framingham, the world’s longest and most detailed study of the relationship between various ‘risk factors’ and death from heart disease. Researchers looking at the Framingham data started the ‘linear and continuous’ ball rolling, and, ever since, everyone has decided to use the same methodology. A statistical methodology which implies that the lower the blood pressure the better, and there is no lower limit.

No one questions this methodology; in fact it has been quoted in so many papers over the years that it would appear to have been proven beyond the shadow of a doubt. But of course, the reason why it is now quoted so often is that paper after paper has quoted from other papers that have all shown this linear regressive model to be true. A process of error reinforcing error.

To give a more concrete example of how this happens. I write a paper which states that ‘the relation of blood pressure to risk of death is continuous graded and strong.’ Someone else comes along and quotes that paper, without bothering to look at the methodology or results. So now I have two papers making the same statement.

Then, along comes researcher B, who is looking for papers on blood pressure and mortality. He sees two papers with the same self-reinforcing statement on it, and quotes them. Now I have three papers making the same statement. How long before there are one hundred, two hundred, a thousand papers?

You think this number may be an exaggeration, but Simkin and Roychowdury (who looked at the issue of misreporting) found that mis-citations can occur many thousands of times. To quote the New Scientist article again:

‘To find out how common this (misreporting) is, Simkin and Roychowdhury looked at citation data for a famous 1973 paper on the structure of two-dimensional crystals. They found it had been cited in other papers 4300 times.’

And the errors this leads to are not specific to two-dimensional crystals:

‘The problem is not specific to this paper, the researchers say. Similar patterns of errors cropped up in a dozen other high-profile papers they studied. The trouble is that researchers trust other scientists to repeat the key message of a paper correctly. This means that when misconceptions take root, they spread like weeds.’

It should be clear by now, where I am heading.

Someone, somewhere, decided that there is a continuous linear relationship between death and blood pressure. They used a statistical method to establish this, and ever since everyone has used the same model. So there are now thousands and thousands of papers out there ‘proving’ this paradigm to be true. In fact, if you wrote a paper on the treatment of high blood pressure using another model it would almost certainly be rejected on the basis that the linear relationship model was the established, and correct, model, so yours must be wrong.

There is just one teensy, weensy, little problem here. When you actually decide to look at the data - it disproves the model.

‘Shockingly we have found that the Framingham data in no way supported the current paradigm to which they gave birth. In fact, these data actually statistically reject the linear model. This fact has major consequences. Statistical theory now tells us that the paradigm MUST be false..’ EHJ 2000 21, 1635 - 1638

I didn’t add the italics or capital letters. The Authors put them in - the paradigm MUST be false. Normally, in clinical papers, people state things very calmly, e.g. ‘the data suggests an association between.’ So to see a statement such as the paradigm MUST be false is very strong stuff.

So what is really being stated here that is so important?

I will use an analogy to try to make the point. If you chose to live in the Himalayas you may find yourself twelve thousand feet above sea level. Most people can cope with this height, and it has very little impact on your health or life expectancy. Go up a few thousand feet and everyone dies. The exact ‘death zone’ height varies from person to person.

The fact that you die at sixteen thousand feet, however, does not mean that any altitude above sea level is harmful. What it means is that, at a certain level, your body cannot cope any more and the systems start to break down.

Yet, with blood pressure, any rise represents a risk - according to the linear model. There is no ‘death zone’ no cut-off point. According to this logic, even if you have a ‘normal’ blood pressure, it would be better if you could get it lower. And believe me, papers have been written stating this.

But, anyone with half a brain can see that a model with a ‘cut point’ is much more likely to be correct. Is it really likely that a 5-15mmHg rise in blood pressure will cause problems? According to the linear model, the answer is yes. But, as we have seen, the data doesn’t actually support a linear model, and logic would also dictate that at a certain point - which has, in reality, never been defined - a raised blood pressure creates problems. Below that point it may be a bit high, but frankly it’s nothing to worry about.

What is that point…. I don’t know. But I would guess it is something like a systolic of 160 - 180. However, the medical profession, with its ever present desire to squeeze all patients into a little box called ‘normal’ is inexorably bringing down the level at which treatment is needed. I have seen calls to get everyone to a level of 120/70 (the level considered ‘normal’). The WHO has set the limit at 130/85. Already in diabetes the recommended level is 120/85.

Why are they trying to achieve this? On the basis of a model made up years ago which, due to sloppy research, has become accepted fact. On the basis of a model which, if you examine it properly, MUST be wrong. Try explaining this to your local, friendly doctor, you will get the same reaction that I always do. ‘Don’t talk rubbish, it has been proved that you should lower the blood pressure as much as possible.’

More essays by Malcolm Kendrick


Feb 17, 2003


For those of us who enjoy the use of weasel words and non-scientific rubbish dressed up as fact, this is indeed a grand territory to explore….  


by Malcolm Kendrick MD

I have written about hypertension a couple of times. So I thought that I should throw my hat into the ring about the controversy surrounding the ALLHAT trial. A trial which wins my official tortuous acronym award? ALLHAT stands for the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial.

Actually, my favourite acronym is the CARPORT trial. This stands for, wait for it: the Coronary Artery Restenosis Prevention On Repeated Thomboxane A2-receptor blockade. There are others, the TIBET, ALIVE, LIFE, LIMIT. Rule number one, your clinical trial must have a memorable acronym otherwise, self-evidently, no-one will remember it.

Anyway, what is the ALLHAT trial, and what has it shown? The first thing to note is that it is a big trial, with more than 40,000 patients in it. And it is also a long trial; the followup was designed to last at least 6 years. So the results carry a little more weight than the old ‘five patient, twenty eight day study in Tibetan Yak herders.’

The trial had two parts, an antihypertensive part and a lipid lowering part. The purpose of the trial was to assess the incidence of fatal coronary heart disease and nonfatal MI in patients treated with chlorthalidone (a diuretic), amlodipine (a calcium channel blocker), lisonpril (an ACE inhibitor) or doxazosin (an alpha blocker). In the lipid lowering population the plan was to assess the all-cause mortality in those treated with either pravastatin or ‘usual care.’ The lipid lowering study had half the patients in it.

In the hypertensive study, the doctor could start treatment with any of the four antihypertensive drugs. If that didn’t lower the blood pressure enough they could increase the dose, then, if that didn’t work, add in the other agents. One thing of note in this trial is that 55% of patients had to be black, and 45% women. Mainly because most clinical trials had been done in white Caucasian males, and there are racial and sex differences in treatment effects.

So what were the investigators trying to find out?

Two main things. Firstly, is any form of antihypertensive agent better than any other at preventing fatal CHD and non-fatal MI?

Secondly, does lipid lowering with a statin have any effect on all-cause mortality. That is, dying of anything.

A couple of questions immediately arise. Why did they use the terminology ‘fatal CHD and non-fatal MI’ in the hypertensive part of the trial? If fatal CHD is not fatal MI, then what is it? Also, why did they choose to look at different end-points for the statin, namely all-cause mortality? Why didn’t they choose to look at all cause mortality in the hypertensives?

Trials are always much more interesting, in my opinion, for the questions they choose not to ask, than for the questions they actually ask.

And, generally, the questions that the trial didn’t ask form the first point of attack on any trial — that doesn’t provide the results that people agree with. ‘Oh, well, what do you expect from ALLHAT, they didn’t look at fatal MI. Which is really important. Frankly, therefore the entire trial is a complete waste of time….. Pass the port old boy.’ In reality no trial can ever look at all end points. It’s just not logistically possible. And if the nit-pickers decide to get to work, any trial can be pulled to bits. This is exactly what is happening to the ALLHAT trial.

Why is it being pulled to bits?

Because it quite clearly did not show what people wanted it to show.

Firstly, it showed that any form of blood pressure lowering tablet had pretty much the same effect as any other. (This trial did NOT measure the effect of placebo, so all results are one tablet verses another). In short, a diuretic was just as good as a calcium channel blocker, or an ACE-inhibitor. (Alpha blockers got pulled out of the trial early on as they showed an alarming increase in death rates).

So what, you might think. No surprise there. Why the attack?

Well, if I were tell you that diuretics are very cheap, have been around for years and years, and no pharmaceutical company makes any money from selling them; whereas ACE inhibitors and calcium channel blockers are much more expensive, and sell billions of dollars worth ever year….. Then you might, just might, feel that the answer could be found in this area.

Personally, I always ask the question: Is the person attacking the ALLHAT study making money from companies that make ACE-inhibitors or calcium channel blockers? If not, I take the comments very seriously. However, I have yet to identify anyone attacking the hypertensive arm of the ALLHAT study who has zero financial connections — although they can sometimes appear very tenuous.

And what of the lipid lowering part of the trial? What did that show?

Well, slightly to my surprise…not. The impact of pravastatin on overall mortality was absolutely zero. Actually, it wasn’t exactly zero; the overall mortality was slightly higher in the pravastatin group than the group taking placebo.

How is this being explained?

"Both the pravastatin and usual care groups had substantial cholesterol reductions," said Whelton. "This is probably because many of those in the usual care group received a cholesterol-lowering drug. The magnitude of the trend toward increasing use of cholesterol-lowering drugs in usual care during the 8 years of the trial reflects the impact on clinical practice of the many positive statin trials that have taken place in those years. This trend was not fully anticipated when ALLHAT began in 1994. Thus, no difference was found between the groups in deaths and only a modest difference in the rates of heart attack and stroke."

That quote taken from NIH website http://www.nih.gov/news/pr/dec2002/nhlbi-17.htm


For those of us who enjoy the use of weasel words and non-scientific rubbish dressed up as fact, that is a paragraph to savour. Examine the sentence that begins… ‘This is probably because….’ A perfect statement. Not based on any facts, or data, just a guess. The paragraph then goes on to state that if this guess is correct, then it explains why statins didn’t prevent a single death. (Despite the fact, of course, that LDL levels were lowered much more in the Pravastatin group).

So, all the results of a major clinical trial can be demolished by an unproven supposition based on no facts whatsoever. Yes folks, it’s science at its very best. ‘Ignore the results from the ALLHAT trial, it’s rubbish. Things that we never bothered to measure probably caused the negative results.’

Can you imagine what would happen if I said that I just ‘guessed’ that in other lipid lowering trials, people probably stopped smoking in the statin group and not in the placebo group, which explains any beneficial effects seen. Of course I didn’t bother measuring this, I just kind of guessed that it must be so. How else could you explain the benefits of statins?

I must stop now before my blood pressure gets too high and I have to start taking an ACE-inhibitor. I also seem to have got dragged off blood pressure and onto statins. I must be obsessed.

More essays by Malcolm Kendrick


March 10, 2003



"A" equals "B,"and "B" equals "C," yer "C" is greater than "A"  


by Malcolm Kendrick MD

Yes, I know, the title looks a bit like one of those horrible mathematical proofs that only the class swot used to know. Everyone else doodled on the side of the page and waited for the class bell to ring in time for them to make their escape.

But please don’t run and hide, I intend to use no mathematics in this article. What I want to highlight is the fact that a great deal of research directly contradicts the conventional and yet no-one in the medical community appears even slightly concerned.

Instead, what happens is that, when fact A contradicts fact B, those who like fact A will quote it as a reference to support their work. Whereas, those who prefer fact B will quote that instead.

In order to help clarify an issue that may seem rather abstract, I will provide a concrete example. Last year two researchers called Law and Wald wrote a paper in the British Medical Journal which suggested that there is no level of cholesterol that should not be lowered further. The lower the better, there is no lower limit, and no age limit.

I objected to such obvious nonsense in a letter to the BMJ. Even if you do believe that a high cholesterol level causes coronary heart disease (CHD), you surely cannot also believe that a low cholesterol level causes CHD. If that’s true then:

In the middle of the night
In broad daylight
Two young men got up to fight
Back to back
They faced each other
Drew their swords
And shot one another.

Anyway, I quoted a major study done in Honolulu demonstrating quite clearly that, in the elderly, a low cholesterol level was the single most important risk factor for all cause mortality, and death from CHD. On this basis how could Law and Wald support lowering cholesterol in the elderly population?

On that specific point Law and Wald stated that it had been ‘proved’ that a low cholesterol level was the sign of an underlying disease, and it was the underlying disease that killed people, not the low cholesterol level. They quoted a paper by Iribarren in support of this concept.

However, the paper itself was just a hypothesis paper, unsupported by any data. Despite this, the hypothesis is widely accepted to be true. Indeed, the Honolulu researchers were acutely aware of that hypothesis paper, and had chosen to analyse this issue closely. In the end, they could find no sign whatsoever that low cholesterol was caused by any underlying disease.

To quote from that paper, which can be found in the Aug 2001 issue of the Lancet:

Iribarren and colleagues suggested that a decline in serum cholesterol might occur over a decade before diagnosis of disease, and such long-term morbidity could be attributable to chronic subclinical infections with hepatitis B, or to chronic respiratory disease resulting in repeated respiratory infections. These disorders could increase concentration of pro-inflammatory cytokines that cause hypocholsterolaemia. Our present analysis suggest that this hypothesis is implausible and is unlikely to account for the adverse effects of low cholesterol over twenty years.’

Which is the language that one set of researchers use to tell another set of researchers that they are talking bollocks.

As far as Law and Wald are concerned, however, I’m sure they still firmly believe that a low cholesterol is caused by an underlying condition, and that a low cholesterol level is still a good thing. They have no proof of this; they just like it as a hypothesis. But either this is right or it is wrong. And it is also an extremely important point. Shouldn’t someone be trying to establish the truth one way or another?

All of this highlights the fact that utterly contradictory papers can co-exist in the medical research universe, and no-one ever challenges them to fight it out mano a mano. Everyone just carries on ploughing their own little furrows, never daring to peek over the edge.

Which, in a very roundabout way, brings me back to hypertension.

Here are three facts that currently co-exist in the world of medical research. Starting in the early nineteen eighties when the Medical Research Council (MRC) UK carried out the first ever long-term study into the effect of blood pressure lowering on mortality and morbidity. The drugs used were a diuretic and a beta-blocker.

Up to this point, you may be surprised to hear, this issue had never been studied. It was sort of assumed that a high blood pressure caused CHD, so if you lowered the blood pressure, you would prevent CHD. The trial was set up to provide glorious vindication of this hypothesis

Unfortunately "glorious," and "vindication," are not quite the words that we should use for this trial. For the primary finding of the MRC trial was that blood pressure lowering had no impact on the rate of death from CHD. (There was some reduction in stroke and renal failure.)

Jumping to the present day, the ALLHAT study recently showed that there was no difference in CHD prevention between diuretics, beta-blockers, ACE-inhibitors and Calcium Channel blockers.

However, a recent meta-analysis in the NEJM shows that ACE inhibitors do provide protection against CHD.

This provides an interesting sequence of statements:

Placebo = Beta-blockers and diuretics (in preventing CHD. MRC trial)

Beta-blockers and diuretics = ACE-inhibitors and calcium channel blockers (ALLHAT)

ACE-inhibitors are > placebo (NEJM)

Put more simplistically

a: A = B
b: B = C
c: C > A

Now, it almost goes without saying that it is impossible for all three statements to be true. One of them must be false. The question is, which one? Surely this is of high importance? I believe it is, yet the medical research community seems perfectly willing to accept all three statements and carry on regardless.

In my view, if no-one is willing to debate these issues out in the open and make some kind of decision, then the whole area is a complete mess. And this is typical of the whole area of research into heart disease. And how can the public know what to believe when we have data out there that is utterly contradictory?

This is the reason why you get headline after headline stating that, for example ‘Coffee protects against heart disease,’ followed by ‘Coffee causes heart disease,’ followed by ‘Coffee protects against heart disease…. Ad infinitum. Well, either coffee does, or does not cause heart disease.

Surely the editors of medical journals should try to create some kind of consensus on such matters. But they don’t, and so we all sail onto into more and more confused waters. Perhaps I should try to start a new journal. The Journal of Medical Logic and Argument — or something of the sort. Where researchers are forced to debate all areas where there is directly contradictory evidence. Some hope.

Just to sign off. If you want to know my opinion on which statement is false it’s C > A. You see I’m a democrat, and statements A and B support each other, whereas statement C contradicts the others. So we have a two to one majority against C.

More essays by Malcolm Kendrick


May 21, 2003


Now we are all to be officially ill  


by Malcolm Kendrick MD

I write this before I have read all the details on the new Heart Lung and Blood Institute guidelines on raised blood pressure. But there has been enough information flying around to know what they are saying. Frankly, I knew what these guidelines were going to say before the committee met for the first time. Before, in fact, the members of the committee even knew they were going to be on the committee.

But I claim no powers of clairvoyance or insider dealing. Nor do I claim that the ability to predict the future of hypertension guidelines represents any great intellectual feat. For guidelines in all disease states are wearily predictable. The level of anything that is considered to be abnormal rapidly closes in on the average level, whilst simultaneously the level considered average drops. A two-pronged attack ensuring that more and more people slip from the category of healthy into unhealthy.

For example, twenty years ago, a cholesterol level of 7.5mmol/l was considered high. This figure gradually moved down to 6.5mmol/l, then 6.2mmol/l, then 5.2mmol/l. Researchers in the UK are now claiming that, as the average cholesterol level in rural China is something like 2.5mmol/l, that this actually represents the ‘perfect’ level; therefore everyone in the West should be aiming for 2.5mmol/l.

I think that this must mean everyone in the whole Western world other than James McSprokitt who lives alone in a hut in the Western Isles of Scotland, and eats nothing other than prawns and gruel. The Western World’s only healthy man.

With blood pressure, there was a time when 160/90 was the cut-point for the diagnosis of hypertension. It too has moved down and down, and down. Now we have the following statement from on of the authors of the guidelines:

Recent scientific studies show that risk of heart disease actually begins rising once blood pressure creeps above 115 over 75,’ said guideline co-author Ed Roccella, a hypertension specialist.

I have no idea what the exact figures are, but I suspect, for example, that 95% of the adult male population of the USA has a blood pressure that is above 115/75. So we are now in the situation whereby everyone in the Western World either has a high blood cholesterol level, or a high blood pressure level, and the vast majority has both.

To quote inaccurately from the Red Queen in Alice in Wonderland. ‘Everyone has won, and all shall have prizes.’ Now we have reached the point where ‘Everyone is ill, and all shall be treated.’ Of course no-one is suggesting that we treat a blood pressure of 115/75 — yet. We should just be mildly uneasy and dissatisfied with our health.

Where does this all end? Well, I have never seen guidelines go into reverse, by which I mean guidelines that widen the accepted boundaries of normal. Guidelines only ever tighten, like some huge inexorable ratchet. Whether you like it or not, we are now closing in on the point whereby, if your cholesterol level is above 2.5mmo/l, and your blood pressure is above 115/75, you will be persuaded by your doctor to lower them. And if exercise and diet and weight loss don’t work — which they never do…Then guess what? It’s time for drugs.

There will always be mavericks who will refuse medication, but for the vast majority of us…..I look into the future and I see something very bleak. I remember reading something in an updated version of disease classification where all disease states were outlined, and when it came to people who were healthy, the definition of this happy state was…wait for it: ‘temporarily able.’

So remember folks, however healthy you may feel, you probably have a high blood pressure. You definitely also have a high cholesterol level. And always bear in mind that you are always, in reality, only temporarily able. A life of drug-taking disability stretches before us all.

I shall sign off with two quotes from my current favorite article from the European Heart Journal Issue 20, October 2000.

No randomized trial has ever demonstrated any reduction of the risk of either overall or cardiovascular death by reducing systolic blood pressure from our thresholds to below 140mmHg.’

‘Most importantly, the current paradigm considerably over-estimates the risk in the mid-range of pressure (roughly 125 — 180mmHg). This has major consequences. The vast majority of the population falls into that mid-range and the cut-point of 140mmHg lies towards its lower end. Consequently, a large proportion of the population considered at increased risk with the current cut-point are in fact at no increased risk.’

Is there anybody out there listening…… Helloooooo! Ref: Winnie the Poo, ‘Poo’s really big adventure’ 1898, Penguin books pp 63-64’

More essays by Malcolm Kendrick

Nov 21, 2002



How The Medical Profession Will Turn A Symptom Into A Disease  


by Malcolm Kendrick MD

You may have heard a bit about a substance in the blood called C-reactive protein (CRP). It is released in ‘inflammatory’ conditions in the body: infections, rheumatoid arthritis and also heart attacks. CRP has been around, and known about, for years. However, CRP is about to suffer the same fate of other innocent substances in the blood that have the misfortune to rise in people who have heart disease. It is going to be accused of causing heart disease.

It is a dispiriting fact that, when faced with diseases of unknown cause, the medical profession unerringly manages to get cause and effect completely the wrong way round. In the world of heart disease this has happened with blood pressure, LDL, visceral obesity, insulin resistance and HDL - to name but five. Now it is going to happen to CRP.

When you find an abnormality of some sort that is associated with a disease, you can make a number of different conjectures:

1.      The abnormality is caused by the disease

2.      An underlying problem causes both the abnormality and the ‘disease’

3.      The disease is caused by the abnormality

4.      It’s a coincidence (one in twenty chance)

5.      You haven’t measured things properly

You would think it wouldn’t be that difficult to sort things out, but if you get things the wrong way round to start with, it can takes years, decades - forever? Take high blood pressure. In some cases there is a clear underlying cause e.g. renal artery stenosis. But in the vast majority of cases there is no (clearly) definable cause.

At this point, rather than say ‘you have high blood pressure of unknown cause,’ the medical profession decided to use a bit of jargon, and so the term ‘essential hypertension’ was born. It means exactly the same thing, but it sounds more scientific and impressive.

Twas but a small step from here to suggest that essential hypertension wasn’t just a sign of some underlying abnormality; it was, in fact, a disease. A disease that needed to be treated. And because essential hypertension was found to be associated with heart disease, it was further decided that if you ‘treat’ hypertension, then you would ‘cure’ heart disease.

Despite this, many of you probably still think that treating essential hypertension does reduce the risk of heart disease. But, of course, it doesn’t. A fact so carefully hidden behind all sorts of barriers that it can take months to work it out. Finally, you realise that when you read ‘reduction in CV events’ this doesn’t mean reduced rate of death from Coronary Heart Disease (CHD). It primarily means reduced rate of death from stroke.

Hey guys, I can see how a high blood pressure might burst the arteries in your brain. But I can’t see how high blood pressure causes the build up of plaques in the arteries. On the other hand I can see how narrowing an artery with a plaque might reduce blood flow, and trigger a response by the body to raise the blood pressure to keep the blood flow up. Cause that’s simple fluid dynamics. In short, CHD (or atherosclerotic plaques) causes a high blood pressure - AND NOT THE OTHER WAY ROUND.

The example of high blood pressure serves as a lesson in how to turn an ‘associated symptom’ into a disease, and how to get cause and effect hopelessly mixed up. With CRP, we are going to see exactly the same thing. History is in the making, right now, in front of your very eyes.

As a raised CRP is now a recognised risk factor for heart disease, t’will be a very small step to suggest that by lowering it, you will prevent heart disease. I can already see the CRP lowering agents being lined up by the pharmaceutical companies. Watch for the buzz words IL-6 and hyper(c)-proteinaemia. You read it here first.

A word of warning. Whisper it quietly ‘c-reactive protein reducing agents won’t work.’

 More essays by Malcolm Kendrick