Before starting on the Herculean task of destroying the entire cholesterol hypothesis, I thought it would be interesting to look at how, and why, it developed in the first place. And then how it went on to take over the world.
Shockingly, I have found that it was a huge conspiracy between right-wing governments across the world, pursuing a neo-imperialist pro-globalisation agenda, in conjunction with the pharmaceutical industry!
Oh, OK, so it wasn’t. It was more a case of people under huge pressure to come up with answers grasping the wrong end of stick, then seeing exactly what they wanted to see, and ignoring all evidence to the contrary. To quote Bing Crosby: ‘You’ve got to acc-entuate the positive, e-liminate the negative.’ Which, speaking as a ‘negative’, is slightly worrying. Perhaps I will end up as part of the foundations for a huge new statin-manufacturing plant…
To find out how the cholesterol hypothesis actually started, we have to travel back far into the past, to Berlin in the mid-19th century. Let us peer into the laboratory of a brilliant and already famous pathologist, Rudolf Von Virchow. Although it’s late at night young Rudolf is still working, his mind ever active. He is gazing with feverish intent through a powerful new microscope at the arteries of corpses (though they were not necessarily all the victims of heart disease). He has noted that the arteries have thickened ‘plaques’ in them, and he wants to know more.
And tonight he makes a breakthrough discovery that will echo throughout history for the next 150 years. He has found that the plaques in the arteries contain a great deal of cholesterol. And where, he ponders, could this cholesterol have come from? The blood seems the only possible place. In a state of agitation, he jumps up, leaps upon his horse and gallops through the streets of Berlin shouting ‘Eureka’. (Actually, perhaps that was someone else…)
The thing about this (admittedly over-dramatised) story that I am most impressed by is that Virchow was able to recognise cholesterol when he saw it. However, despite Virchow’s findings, very little actually moved forward during his lifetime. His was an era in which medicine was preoccupied with infectious diseases. In 1850 you could still die from a small scratch. Tuberculosis felled millions, as did infection during childbirth. Anyone who managed to avoid an infectious death and ended up clutching their chest from a heart attack was probably considered to have done pretty well. ‘A heart attack, young man, is the sign of a long life, well-lived.’ (Actually, no one would have said this, because no one knew what a heart attack was back then: it was called discombubulitis praecordia, and considered – by learned opinion leaders of the time – to be due to a lack of prompt leech application.)
Thus many years passed without anyone taking much interest in heart disease. Indeed, it would seem to have been at least 50 years before the next significant move forward was made, this time by Dr Nikolai Anitschkov, a Russian researcher. He fed rabbits a high-cholesterol diet; their arteries then thickened and filled up with cholesterol. So, cholesterol in the diet is deadly, and causes heart disease in humans – case proven? Well, Anitschkov certainly thought so.
And how silly of me even to question such research. Let me see. Rabbits are carnivores… check. Rabbits normally eat a high-cholesterol diet… check. And the thickenings that they get in their arteries are exactly the same as those found in humans… check. Ergo, feeding rabbits is an excellent model for heart-disease causation in humans… check.
Perhaps Anitschkov should have fed cats the normal diet of a rabbit, just to see how long they would have lasted. I would give it a week, max. Frankly, trying to prove anything about humans by carrying out dietary experiments on rabbits is nonsense. But when your aim is to push a cholesterol hypothesis, such results look good, and appear superficially convincing. As do many things if you avoid thinking about them too hard.
If you add Anitschkov to Virchow, the cholesterol bandwagon had started to roll. As no one else had any particularly strong opinions on the matter at this time – at least, none that I have come across – the putative diet-heart/cholesterol hypothesis established itself in the number-one position as the cause of heart disease, and has remained at the top of the heap ever since, swatting all pretenders effortlessly into touch.
However, even after Anitschkov, no one was really that interested in heart disease. Was this because it was very rare, or not recognised? Hard to say. The first medical description of a heart attack was not published until 1926 by Dr James B Herrick, in the USA. Even then, I get the impression that this was seen as a medical rarity, not something to get the entire medical community excited.
In reality, it was not until after WWII that doctors started to get really interested in heart disease. After the upheaval of the war was over, people noticed that middle-aged men were dropping like flies. This appeared to be the start of an ‘epidemic’ that had swept in from nowhere, and it began in the USA.
Or did it? One thing that I have discovered during my trawls back through the history of heart disease is how much of the information is less than reliable. For example, it wasn’t until a few years after WWII that the World Health Organization (WHO) got its act together and created an International Classification of Diseases (ICD). Prior to this, different countries had different ways of classifying disease. Some countries had diseases that didn’t exist in others, and vice versa. Heart disease was a big mess, and it is almost impossible to work out who was classifying what, as what, or why. France, for example, did not move to using full ICD classification until 1968. And the French had no term for a myocardial infarction until this time.
So, it is fully possible that heart disease, or coronary heart disease (CHD), was wiping out millions in the 1930s, but that no one really noticed. I have to admit that this sounds unlikely, but the ability of doctors to ignore diseases that they haven’t been trained to recognise is a recurrent pattern in medicine. ‘It’s not in a textbook, so it doesn’t exist. Now, pray be silent on the matter.’
My own view – which, admittedly, I cannot fully support – is that heart disease (of the sort this book is interested in) was at quite a high level in the USA in the 1920s and 1930s, but went unnoticed. The upheaval of WWII obscured a further rise in the 1940s, and the true extent of heart disease only really came to light after this.
Fig. 16 USA death rates for major cardiovascular diseases 1900–1997 (Exhibit A)
In support of my argument, I produce exhibit A (Fig 16). This is a graph of death rates for major cardiovascular diseases in the USA from 1900 to 1997. May I draw your attention to a number of features in particular:
1: CHD did not exist until 1948, when the WHO decided that it did. So there are no deaths from CHD before that, but plenty afterwards.
2: There is a rapid rise in CHD from 1948 until about 1965, or thereabouts, then a fall for the next 30 years. However, this is completely out of synch with the level of ‘heart disease’, which peaked in about 1948 and has fallen ever since.
3: The total number of cardiovascular deaths (CVD) – which is the combination of all heart disease and strokes – also peaked in about 1948, then fell.
4: From about 1940 to 1965, the rate of death from ‘heart disease’ remained relatively constant, although the rate of CHD rose sharply during this period.
5: From about 1965, the rate of death from CVD, ‘heart disease’ and CHD run almost parallel, in contrast to the previous 20 years.
I think that there is only one possible interpretation of these figures, which is that it took around 20 years for many doctors to start using the new ‘disease’ classification of coronary heart disease (CHD) properly. Until 1965, therefore, a number of deaths from CHD were being misclassified under the generic term ‘heart disease’.
What this almost certainly means is that the peak of deaths from CHD in the USA occurred before 1965, possibly in 1948 itself. You won’t read that in any textbook, but it’s probably true. Therefore, if you can assume – as I think you can – that many people who died of ‘heart disease’ prior to 1948 were really dying from CHD, then it would appear likely that CHD was actually killing people in large numbers in the 1920s and 1930s.
Is this important? It may be, for reasons that I hope to explain a bit later on. But I think this example mainly highlights the fact that you have to be extremely careful in interpreting medical data, and not take it too literally. If you did, you could end up making a statement such as the following: ‘CHD did not exist in the USA until 1948. At which point it suddenly started killing millions of people. It rose to a peak in 1965, and has fallen since.’ That is, literally, what the previous graph indicates. But it clearly doesn’t represent the true picture. What can be said about CHD in the USA, I believe, is that it (probably) rose rapidly during the 1920s and 1930s, peaked some time between 1948 and 1965, and has fallen ever since.
Over the next 50 years, a number of different populations have taken over the USA’s mantle as holder of the ‘top death rate from heart disease’.
Heart disease – the top six
1950s – USA
1960s – Finland
1970s – Scotland
1980s – Poland
1990s – Rest of eastern Europe
2000s – Emigrant Asian Indians/Aboriginals in Australia and North America
More about these populations later. However, in this particular historical trawl I was most interested to establish the point when the diet-heart hypothesis became the number-one hypothesis. That said, spotting the point at which an idea achieves dominance is tricky. Often ideas seem to have been around forever, and it is surprising to find how recent they are.
For example: tectonic plate movement. First proposed in 1912 by Alfred Wegener, immediately followed by harsh ridicule. Dr Rollin T Chamberlin of the University of Chicago commented, ‘Wegener’s hypothesis in general is of the footloose type, in that it takes considerable liberty with our globe, and is less bound by restrictions or tied down by awkward, ugly facts than most of its rival theories.’ The concept of tectonic plate movement was stomped on with pitiless hostility for the next 50 years or so, then accepted as self-evident truth in about 1965, or thereabouts. Rather more recently than you thought, I would guess.
And with heart disease, despite Virchow and Anitshkof and Herrick and others, it is clear that the diet-heart hypothesis was not remotely dominant until well after WWII. Below is a passage describing a seminal meeting in the 1950s that demonstrates this fact nicely. It was written by Henry Blackburn, a friend and supporter of Ancel Keys. Here he discusses his view on the motivation of Ancel Keys to carry out his huge dietary studies:
In 1954, the fledgling World Health Organization called its first Expert Committee on the Pathogenesis of Atherosclerosis to consider the burgeoning epidemic of coronary disease and heart attacks. Several medical leaders of the time were assembled in Geneva: Paul Dudley White of Boston, Gunnar Björk of Stockholm, Noboru Kimura of Japan, George Pickering of Oxford, Ancel Keys of Minnesota, and others. As reported by Pickering the discussion was lively, tending to tangents and tirades.
Ancel Keys was in good form – outspoken, quick, typically blunt. When at this critical conference, he posed with such assurance his dietary hypothesis of coronary heart disease, he was ill prepared for the indignant reaction of some.
George Pickering, recently named Knight of the Realm by Queen Elizabeth, interrupted Keys’ peroration. He put it something along these lines: ‘Tell us, Professor Keys, if you would be so kind, what is the single best piece of evidence you can cite in support of your thesis about diet and coronary heart disease?
Keys, ordinarily quick on the draw, was taken aback. Rarely, of course, is there ever a ‘single best piece of evidence’ supporting any theory. Theory is developed from a body of evidence and varied sources. This is particularly true in regard to the many facts of lifestyle that relate to disease. It is the totality and congruity of evidence that leads to a theory – and to inference of causation.
Keys fell headlong into the trap. He proceeded to cite a piece of evidence. Sir George and the assembled peers were easily able to diminish this single piece of evidence, and did so. And by then it was too late to recover – for Keys to summon the total evidence in a constructive, convincing argument.
My theory is that Keys was so stung by this event that he left the Geneva meeting intent on gathering the definitive evidence to establish or refute the Diet-Heart theory. Out of this single, moving, personal experience – so my theory goes – came the challenge, the motivation, and eventually, the implementation of the Seven Countries Study.
So there you have it. As a result, Ancel Keys stormed off, put together a huge research budget, hired a staff of thousands, did his study and was then able – in objective ‘scientific speak’, of course – to go ‘I told you so, I told you so. Nyah, nyah, nyah!’
However, Keys’s supporter Henry Blackburn, claimed, ‘Oh, the study has been criticised for the method in which populations were selected.’
Before getting pulled too far off track, let me summarise my main points:
1: It was not until some time in the early 1950s that coronary heart disease (CHD) was seen as a massive health problem. Recognition first occurred in the USA, almost certainly because the USA did have by far the highest rate of heart disease at that time…
2:At this point panic ensued. Stung into action, the medical profession needed some answers – fast. Mainly the answers to two rather important questions.
Suddenly the earlier work of Virchow and Anitschkov became relevant. A Russian researcher called Kritchevsky carried out experiments on rabbits, published his work and was hailed as a hero. Cometh the hour, cometh the research study.
But the main man was Ancel Keys, and his famous Seven Countries Study. Keys looked at saturated-fat consumption in seven countries and found a straight-line relationship between heart disease, cholesterol levels and saturated-fat intake. The seven countries were:
• Italy
• Greece
• Former Yugoslavia
• Netherlands
• Finland
• USA
• Japan
Why these particular seven countries? He could have chosen another seven and demonstrated the exact opposite. Here are my seven countries:
• Finland
• Israel
• Netherlands
• Germany
• Switzerland
• France
• Sweden
What do you mean I can’t choose my own countries? That’s not fair. Keys did.
Despite the crippling flaws of his study. Most people believed that Keys had proven the diet-heart hypothesis beyond doubt. At which point the evidence seemed to flood in from all over the place. In 1948 – a good year for heart disease – a study had been set up in the town of Framingham, near Boston. The whole population was screened for ‘factors’ that might be involved in causing heart disease, and then studied for years and years. In fact, the study continues today – which, for some reason, I find a bit creepy.
One of the first findings to emerge from the Framingham Study during the 1950s was that the level of cholesterol in the blood was the best predictor of the chance of dying of CHD. So another piece of the jigsaw slipped into place. It wasn’t just rabbits who died of high blood-cholesterol levels. Humans did too.
Other researchers looking further back in time noted that rationing was introduced during WWII in Norway and the UK, and in both countries the rate of heart disease fell. (Although the rate of having bombs fall on your head rose rapidly, which could have had something to do with a rapid alteration in the causes of death.)
It was then found that there were some people with a genetic condition known as familial hypercholesterolaemia (FH) – basically, an inherited condition of high levels of blood cholesterol (LDL). Children inheriting the condition from both parents could die as young as five from heart disease. By golly, it was all beginning to look like an open-and-shut case.
Leaping ahead in time somewhat; in the 1970s Brown and Goldstein identified that people with FH had a problem with their production of LDL receptors. With fewer LDL receptors the LDL level skyrocketed and this was the basic ‘fault’ in FH – which, as you will now recognise, should actually be called ‘hyper low density lipoproteinemia.’ It was at this time that the concept of a raised blood cholesterol started to fragment into a constellation of different lipoproteins, and LDL was fingered as ‘bad’ cholesterol.
And so it seemed – although I am leaping about a bit in time and space – that all the pieces of the jigsaw puzzle were falling into place and the diet-heart hypothesis was really flying. As early as 1956 the American Heart Association (AHA), somewhat jumping the gun in my opinion, had launched the concept of the ‘prudent diet’. A prudent diet consisted of replacing butter with margarine, beef with skinless chicken, bacon and eggs with cold cereal, warm baths with cold showers and chocolate by a smack on the back of the neck with a cold kipper.
In the 1960s and 1970s, huge trials on dietary modification were set up. The biggest was probably the MR-FIT trial, involving hundreds of thousands of people. What were the results of this trial? I think it would spoil things to let you know that at this point – all will be revealed later on.
Anyway, despite the odd hiccough on the way, by the latter half of the 20th century most people were utterly convinced that fat in the diet, saturated or otherwise, caused blood-cholesterol/LDL levels to rise. And the subsequent rise in cholesterol was overwhelmingly regarded as the primary cause of heart disease.
But it wasn’t until the arrival of the statins that the cholesterol hypothesis fully conquered the world. Once it was proved that statins both lowered LDL and prevented heart disease, any remaining doubters were silenced. After all, we now had the following evidence:
• Countries with a high saturated-fat consumption have higher cholesterol levels and high deaths rates from heart disease. (See: Ancel Keys)
• People with high levels of cholesterol in the blood have high rates of heart disease. (See: Framingham Study and familial hypercholesterolaemia)
• Rationing in WWII was followed by a fall in heart-disease rates. (See: UK & Norway)
• Plaques in the arteries are full of cholesterol. (See: Virchow, Anitschkov and hundreds of other studies)
• Feed rabbits a high-cholesterol diet and they rapidly develop a high-cholesterol level and atherosclerosis. (See: Ashoff and Kritchevsky and others)
• Lowering blood cholesterol levels with statins reduces the rate of heart disease. (See: many, many clinical trials)
Sorry about bouncing around between cholesterol and LDL, but this is kind of forced on me by the fact that studies, papers and researchers keep doing the same thing. I think, though, that you get the picture. Faced with the evidence above, the case seemed open and shut. A few negative studies here and there were easily explained away. For almost everyone it was clear that the ‘totality of the evidence’, to use Henry Blackburn’s phrase, pointed only one way. The diet-heart/cholesterol hypothesis had to be correct. Only a flat-Earth, creationist lunatic could possible argue against it.
Crikey, they must mean me. So, argue against it I shall.