Nov 28, 2002
WHY THE CHOLESTEROL-HEART DISEASE THEORY IS WRONG
Find a long-term study showing that a high cholesterol or saturated fat diet has any impact on blood cholesterol levels in a normal healthy population - or any effect whatsoever on the rate of death from coronary heart disease
Cholesterol is a much maligned substance, the ‘cause’ of heart disease. If it is, it must have killed billions of people. Far more than the plague, every war ever fought, and all plane, train and car crashes ever - all added together, then multiplied by three.
But if it does cause heart disease, how does it do it? The simple ‘answer’ is that, if you eat too much cholesterol, the level in your blood rises, the cholesterol then travels through the artery wall causing cholesterol-laden plaques to develop which then rupture and kill you. That’s the initial cholesterol hypothesis. Dead simple, couldn’t be more simple.
First little problem - dietary intake of cholesterol has no impact on the level of cholesterol in your blood. If we look at two major long-term studies, Framingham and Tecumseh, it is clear that those who ate the most cholesterol had exactly the same level of cholesterol in their blood as those who ate the least cholesterol.
Table: Cholesterol intake - The Framingham Heart Study
704 ± 220.9
492 ± 170.0
Table : Cholesterol intake and blood lipids - The Tecumseh Study
Blood Cholesterol in Thirds
This is hardly news. The man, who, more than any other, is responsible for the creation of the diet heart hypothesis fully agrees. To quote Ancel Keys, from a paper in 1956:
‘In the adult man the serum cholesterol level is essentially independent of the cholesterol intake over the whole range of human diets.’
What did Ancel Keys think, more recently, about the connection between cholesterol in the diet, and cholesterol in the blood?
"There's no connection whatsoever between cholesterol in food and cholesterol in blood. And we've known that all along. Cholesterol in the diet doesn't matter at all unless you happen to be a chicken or a rabbit." Ancel Keys, Ph.D., professor emeritus at the University of Minnesota 1997.
Does this come as a surprise?
So, it doesn’t matter one jot how much cholesterol you eat, it has no impact whatsoever on blood cholesterol levels. Which just blows up a fairly important part of the cholesterol hypothesis.
‘But, hold on, that doesn’t matter,’ (the sound of goalposts being desperately moved fills the air) ‘It is not cholesterol in the diet that causes the cholesterol level to rise, it is the consumption of saturated fat?’
Look again at the Tecumseh study.
Table : Fat intake and blood lipids - The Tecumseh Study
Blood Cholesterol in Thirds
Fat - total (g)
Fat Saturated (g)
To explain that table in a little more detail. Basically, it divides people into thirds with high, average or low blood cholesterol levels. The absolute values are not important.
Having done this we can examine the level of saturated fat consumed by these three groups. As can be seen:
1. Those in the lowest third of cholesterol levels consumed 52g/day of saturated fat
2. Those in the mid-range consumed 54g/day of saturated fat
3. Those with the highest levels consumed 54g/day of saturated fat
Which lead to the conclusion, from the authors that:
‘Serum cholesterol and triglyceride values were not positively correlated with selection of dietary constituents.’
I shall translate those weasel words into plain English. ‘You can eat as much saturated fat as you like and it makes no difference whatsoever to your blood cholesterol levels.’
And what of Framingham and saturated fat. Let us quote William Castelli, director of the Framingham study for many years.
"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...we found that the people who ate the most cholesterol, ate the most saturated fat, ate the most calories weighed the least and were the most physically active." Dr William Castelli 1992 (Director of the Framingham study)
Now you may think that I am just quoting studies that support my ideas. However, a special prize to the man, or woman, who can find a long-term study showing that a high cholesterol, or high saturated fat diet, has any impact on blood cholesterol levels (in a normal, healthy population). Or, indeed, has any effect whatsoever on the rate of death from CHD.
Quick, time to move those goalposts again.
It’s not saturated fat in the diet, it’s the ratio of polyunsaturated to saturated fat ratio….. the P/S ratio. Hey, can’t you people just give up and admit that fat, of whatever sort, in the diet and cholesterol levels just are not related?
But how could they be? For, in the next episode I shall make it clear that there is no way you can link fat intake with cholesterol levels in the blood. The two substances are completely unrelated chemically, and only ever meet when they are, coincidentally, rammed together inside a lipoprotein.
And then I will show why a high blood cholesterol level cannot cause heart disease. Ladies and gentlemen, roll up, roll up and gasp in amazement as the fearsome cholesterol hypothesis disintegrates in front of your very eyes.
Some studies have shown that a high saturated fat intake raises cholesterol levels; others have shown the exact opposite. The longest, most prestigious and widely quoted long-term study on CHD, the Framingham study, clearly shows that those who eat the most saturated fat have the lowest cholesterol levels.
My own belief is that in healthy people, dietary intake, of anything, has no effect on cholesterol levels - beyond a few percentage points of non-significant wobble.
But my belief is not an act of personal faith with no foundation on fact. For the science of fat metabolism confirms that there cannot be any connection whatsoever between saturated fat consumption and cholesterol levels. And I am wondering how best to explain this without getting too technical.
The first point to make is that you do not have a cholesterol level in your blood. Cholesterol is insoluble in blood, and therefore has to be carried around the body inside a small sphere known as a lipoprotein. There are many different types of lipoprotein, ranging from the monster chlyomicron to the teeny, weeny, High Density Lipoprotein (HDL).
Lipoproteins do not just carry cholesterol. They also carry all sorts of other fats, saturated, monounsaturated and polyunsaturated. These fats are all attached to a glycerol molecule, in sets of three, and the resulting substance is therefore called a triglyceride.
Triglyceride = three fats attached to a backbone glycerol molecule. (Just in case you’re wondering, a fat is a fatty acid, and a fatty acid is a fat).
Thus, when you eat cholesterol and saturated fat, they are both absorbed into the intenstinal wall, where the saturated fats are all stuck onto a glycerol molecule, to make triglycerides, the cholesterol remains unchanged. Then, within the intestinal wall both are rammed into a chylomicron before being expelled into the portal circulation system to be moved around the body.
Most chylomicrons go directly to the liver where they are absorbed, broken down, and reconstructed into a smaller type of lipoprotein known as a Very Low Density Lipoprotein VLDL. These VLDLs then go out into the general circulation and gradually lose triglyceride. As they do so, they get smaller, transforming from VLDL to Intermediate Density Lipoproteins (IDLs), then Low Density Lipoproteins (LDLs).
The LDL is either absorbed back into the liver, to be reused to create more VLDLs, or they are absorbed into other tissues where the contents are used by the cell.
So, at what point does saturated fat get turned into cholesterol?
Answer, it doesn’t. You don’t make cholesterol out of saturated fat. Cholesterol, when it is made in the liver, starts out as a substance called Acteyl-co A. This is not a fat; it is nothing like a fat. It has several nitrogen atoms in it, and nitrogen comes from protein.
A SATURATED FAT* CHOLESTEROL
Point one, therefore, is that saturated fat and cholesterol and completely unrelated chemically, and you don’t make cholesterol from fats. So why would eating saturated fat increase cholesterol production in the liver?….. It can’t and it doesn’t.
But of course, the substance we are interested in nowadays is LDL. Which is not the same thing as cholesterol at all. So why do we called a raised LDL level a raised cholesterol level?
In fact, the nomenclature in this whole area is just designed to make things almost impossible to understand. For example, a raised VLDL level is known as hypertriglycerideamia. Why? Goodness only knows. Perhaps if researchers in this area were to use a clear form of nomenclature, the weakness of the diet/heart hypothesis would be more easily exposed.
Time for a little review
1. Cholesterol and saturated fats are unrelated substances and you don’t make cholesterol from saturated fat, or any other type of fat
2. A raised cholesterol level is, in reality, a raised LDL level
3. A raised VLDL level is called hypertriglyceridaemia
4. The only connection between saturated fats and cholesterol is that, because they are insoluble in water, they sit inside lipoproteins in order that they can be carried around the body
5. The liver doesn’t make LDL - LDL is the metabolic residue of VLDL.
Suddenly the whole concept of saturated fat intake raising cholesterol levels doesn’t seem so simple anymore, does it? But, if the substance in the blood that causes CHD is actually LDL, maybe we just need to move the goalposts….again, and ask a different question.
Does a high saturated fat intake increase LDL levels?
Just to review some of the facts. The liver doesn’t make LDL, it makes VLDL, and when VLDL loses triglyceride it turns into LDL.
So, if you eat more saturated fat (or any other kind of fat), the liver will churn our more VLDL. NOT because there is more cholesterol around, but because there are more triglycerides around to deal with.
Therefore, presumably, after all the VLDLs have shrunk in size, there will be more LDLs left. Which means that a high fat consumption could lead to a higher level of LDL, via VLDL metabolism - although we have to abandon the whole cholesterol argument at this point, as cholesterol has nothing whatsoever to do with this process, it just gets carried around as an innocent bystander.
But even if you move the discussion onto LDLs rather than cholesterol, there is a further huge and insurmountable problem here. After a meal VLDL levels go up, as you would expect, but the LDL level remains absolutely constant. Absolutely constant….(and there is no delayed response either).
So, the amount of VLDL in the blood is totally unrelated to the level of LDL in the blood. Despite the fact that you ‘make’ one from the other.
What this proves, beyond any doubt, is that the metabolic system tightly controls the level of LDL in the blood. It doesn’t matter how many VLDLs are converted to LDL, the system takes the excess LDL out of play - instantly. It pulls excess LDLs into the liver where it recycles them.
So, although fat intake can increase VLDL production, it has no effect on the level of LDL. Which means that, not only does saturated fat have no effect on cholesterol production in the liver, it also has no effect on LDL levels. In reality, it has no effect at all. And why should it? If you eat too much protein, your blood protein level doesn’t rise. If you eat too much sugar your ‘fasting’ blood sugar level doesn’t rise. Why should fat or cholesterol be any different?
You will not read this type of information anywhere, but here. However, every single fact I have used has been demonstrated many, many times. These are facts beyond dispute. It’s just that no-one chooses to highlight what all of these facts, when brought together, actually mean.
Fact one: The liver does not use fats, saturated or otherwise to make cholesterol
Fact two: The liver does not make LDL, it makes VLDL
Fact three: VLDL is converted into LDL through triglyceride loss
Fact four: VLDL levels and LDL levels are totally unrelated - totally
Which means that: Saturated fat intake has no impact on LDL levels
A Raised LDL Level Has No Impact On Heart Disease
Having previously demonstrated that neither cholesterol, nor saturated fat consumption, can have any impact on LDL levels. I now intend to make it clear that a raised LDL level has no impact on heart disease (CHD).
As most of you probably know, current thinking in CHD is that when the level of Low Density Lipoprotein (LDL) is raised, LDLs travel through the artery wall and form a big lumpy cholesterol deposit (‘plaques’) that narrow the arteries. Cholesterol is found in plaques because LDL contains lots of cholesterol.
As these plaques get bigger they narrow the artery so much that blood flow is obstructed - causing symptoms such as angina. Finally a plaque may burst, causing a blood clot to form over the ruptured area. This blocks the artery completely. A myocardial infarction results, which may or may not kill you.
I agree with this basic mechanism underlying CHD, but there are about eight million problems with the idea that a raised LDL is the cause. Let’s just concentrate on three:
1: People with normal and even low LDL levels develop plaques and die of CHD.
Which means that we have a disease process on our hands that can occur when the LDL is level is high, average or low. The first ever example in medical history whereby a normal level of a normal (and vital) substance in the blood can cause a disease.
Yes, LDL is so terrible that any level at all can kill you. The only good LDL is a dead LDL - or words to that effect. This concept, that a normal level of substance in the blood can cause disease, is absolutely nuts and runs contrary to all of biological science, or any other type of science. ‘My goodness you have a NORMAL LDL level, it must be lowered.’
Leaving that aside, for the moment, let’s move to problem number two.
2: LDL can’t get through the lining of the artery wall
The endothelium - single cell lining of the artery wall - is impermeable to LDL - unless you get the level to about three times normal, which is 15mmol/l, rather than 5.0mmol/l. So how does LDL get through in the first place? Considering that 99% of the population has an LDL level below 10.
Answer, you can’t get it through. And even if it could, you run into problem number three:
3: Plaque distribution
Plaques are discreet ‘lesions’ in the artery wall, they are not present everywhere in all artery walls. So, if LDL ‘leaks’ through the arteries when the concentration is raised, then it should leak through all artery walls everywhere, and what we should see, therefore, is thickened artery walls full of LDL everywhere, which is exactly what we don’t see.
To use an analogy, if you lie in the sun for too long, all of your body will become sunburned, not just a few bits here and there. But we are expected to believe that, if you bathe the artery wall in a high level of LDL, it will only leak through in a few discreet areas. Hmmmmm? Again, quite frankly, bonkers.
I know what you are thinking at this point, I think. Aha, you are thinking, obviously you need to damage the artery wall, in discreet areas, to get LDL through…… Exactly. And this could hardly be more obvious. So, the underlying process that starts a plaque is damage to the endothelium. Of course it is; there is no other possible explanation.
But, to admit this, is to admit that LDL has nothing whatsoever to do with causing atherosclerotic plaques, because LDL doesn’t damage the endothelium.
Faced with this major, and I would say insurmountable problem, what has the cholesterol/LDL brotherhood chosen to do? Discard the diet-heart/cholesterol/LDL (whatever it is now called) hypothesis. Or keep trying to find ways to explain the causal role of LDL in plaque formation.
No surprise to find that no-one was remotely willing to discard the hypothesis. This square peg of orthodoxy had to be rammed into the circular hole of CHD causation at all costs. Otherwise the entire diet-heart/cholesterol/LDL hypothesis collapses into a little heap of dust.
So where are we now? How exactly does LDL cause CHD?
Because it is oxidised.
You may faintly detect the sound of me beating my head against a wall in the distance, somewhere just south of Manchester UK.
Because, dear reader, LDL is oxidised! You have probably heard of anti-oxidants, and their magical protection against CHD. But how are they thought to provide this protection? Mainly because oxidised LDL can be absorbed by the endothelium, as there are receptors for oxidised LDL on endothelial cells (called Lox-1 receptors, if you are interested).
So, the thinking goes, once oxidised, the LDL binds to the Lox-I receptor it is then transported into - then through - the endothelium and into the artery wall behind. At which point, white blood cells, designed to get rid of all nasty substances in the body, attack, engulf and try to clear away all of the oxidised LDL molecules.
But these white cells have no means to tell them to stop engulfing oxidised LDL, allegedly, so they just get bigger and bigger until they explode, releasing a horrible goo of dead white blood cells, bits of LDL, cholesterol and triglyerides etc. into the artery wall. Once you have enough exploding white blood cells, the lump of goo becomes big enough to start an atherosclerotic plaque. And that is why oxidised LDL is such a bad thing, and why anti-oxidants are protective.
There are so many problems with this proposed mechanism of action that it is almost impossible to know where to start. Perhaps the best place to start is with a previous example.
If there are receptors for oxidised LDL on endothelial cells, then oxidised LDL will be absorbed through all artery walls everywhere, and therefore we would not see discrete plaques forming, just general thickening of all artery wall as they fill up with the residual goo from exploding white blood cells. But we do see discreet plaques, and therefore? Therefore the hypothesis is wrong as it does not match the observed disease process.
The other problem is just as serious, although a little more difficult to explain.
If plaques are created by oxidised LDL, then the ‘cause’ of CHD must be excess oxidisation of LDL in the bloodstream. If this is true, then the level of LDL is completely irrelevant, it is only the amount of oxidised LDL that counts. Therefore, if you believe in this hypothesis, then the ‘raised LDL causes CHD’ hypothesis has to be discarded.
In essence, you can’t have this argument both ways. You can claim a raised LDL causes CHD - in which case how can people with a low level get CHD? Or you can claim that excess oxidised LDL causes CHD. In which case CHD has nothing to do with LDL levels.
Ironically, the oxidised LDL hypothesis - which was supposed to protect the LDL hypothesis - actually destroys the LDL hypothesis. But by throwing up so much jargon and incomprehensible mechanisms of actions into the air, it appears that you are keeping both hypotheses going. But you can’t, it’s one or the other, you can’t have both.
And by the way, in the Heart Protection Study (HPS), which lasted five years, ten thousand patients received the anti-oxidants and ten thousand patients did not. And the results?
‘’’There was no evidence of any benefit at all’ from antioxidant vitamins. On the other hand, there was no evidence of any harm.’’’ Dr Rory Collins BMJ Nov 2001
So, bang goes the anti-oxidant hypothesis. Please spare me the claim that they used the ‘wrong’ anti-oxidants.
Once again, as with almost every part of the diet-heart/cholesterol hypothesis, when you start to examine the facts objectively, the whole thing starts to disintegrate in front of your very eyes. There is no way that LDL, oxidised or otherwise, can ‘cause’ CHD, and here are a few more facts to back this up.
There is a direct association between falling cholesterol levels over the first 14 years and mortality over the following 18 years (11% overall and 14% CVD death rate increase per 1 mg/dL per year drop in cholesterol levels).Anderson KM JAMA 1987
In Framingham therefore, as LDL/cholesterol levels fell, CHD rates went up.
‘Our data accord with previous findings of increased mortality in elderly people with low serum cholesterol, and show that long-term persistence of low cholesterol concentration actually increases the risk of death. Thus, the earlier that patients start to have lower cholesterol concentrations, the greater the risk of death.’ Lancet Aug 2001
In Honolulu, the lower the LDL/cholesterol, the greater the risk of dying - of everything, including CHD.
The main author of the report on this study was Shestov, of the Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg. And the main conclusion of this study was as follows:
‘The results disclose a sizeable subset of hypocholesterolemics in this population at increased risk of cardiac death associated with lifestyle characteristics.’ Russian Lipid Research Clinics Prevalence Follow-up Study Shestov
In Russian, a greater risk of death from heart disease in those with low blood LDL/cholesterol levels
Between 1980 and 1989, age-adjusted total serum cholesterol levels increased from 4.84 to 5.22 for men and from 4.91 to 5.24 mmol/l for women. Prevalence of age-adjusted hypercholesterolaemia of > or = 5.68 mmol/l increased from 15.8% to 29.4% for men and from 18.4% to 30.6% for women…. Considerable increases in total serum cholesterol levels do not offer an explanation of the recent decline in mortality from coronary heart disease in Japan.’ Okayama A, Marmot MG Int J Epidemiol Dec 1993
In Japan, as cholesterol/LDL levels went up, death rates from CHD went down.
How much more evidence would you like? Perhaps another study from the USA?
‘Kummerow and colleagues from the UI and Carle Foundation Hospital in Urbana, Ill., studied 1,200 patients who were cardiac-catheterized. Sixty-three percent had at least 70 percent of their arteries blocked -- enough to warrant bypass surgery. Of the 506 men who had a bypass, only 71 (14 percent) had plasma cholesterol levels above 240 (6.2mmol/l); 50 percent had levels below 200 (5.2mmol/l). Thirty-two percent of the 244 women who had bypass surgery had levels above 240 (6.2mmol/l); 34 percent were below 200 (5.2mmol/l)…
… a 3-to-1 ratio of LDL (bad cholesterol) to HDL (good cholesterol) is a low heart-disease risk? with a total cholesterol of less than 200 (5.2mmol/l) being the most desirable. However, in this study, Kummerow noted, 51 percent of the catheterized men had levels below 200 (5.2mmol/l) but needed a bypass.’ Paper by Kummerow Atherosclerosis March 2001
In this study, the majority of men who needed a bypass had cholesterol levels below 5.2mmol/l.
These were not, I will add, small studies, with surrogate end-points. These were great big studies done on thousands and thousands of people, and they measured death rates and blockages in coronary arteries, which are ‘hard’ end-points. They include Framingham - the study that is used to set the CHD prevention guidelines! And they all demonstrate very clearly that the rate of CHD has nothing whatever to do with the level of LDL/cholesterol in your bloodstream.
These studies were also published in journals as prestigious as the Lancet, Atherosclerosis and JAMA. This is not wacky, fringe research, carried out by people with a distrust of mainstream medicine. This is as mainstream and conventional as it gets, and all of this research utterly and completely contradicts the current cholesterol/LDL theory of CHD. And I will bet that you have never, ever, come across these facts before. For some strange reasons this research doesn’t get a lot of publicity.
Ah but, you might say, statins reduce LDL levels and protect against CHD. Surely that proves - despite your clever arguments, and all of the evidence - that a raised LDL truly is the cause of CHD, even if it is biologically impossible.
Well, for those of you who are interested, I can easily prove that the LDL lowering effects of statins have nothing whatsoever to do with their impact on CHD.