If you eat too much cholesterol, or saturated
fat, your blood cholesterol will rise to dangerous levels. Excess cholesterol
will then seep through your artery walls causing thickenings (plaques), which
will eventually block blood flow in vital arteries, resulting in heart attacks
Scientific hypotheses don't get much simpler
than this: the cholesterol, or diet-heart, hypothesis, which has broken free
from the ivory towers of academia to impact with massive force on society.
It has driven a widespread change in the type of
food we are told to eat, and consequently the food that lines the supermarket
shelves. Many people view bacon and eggs as a dangerous killer, butter is
shunned, and a multi-billion pound industry has sprung up providing 'healthy'
At the same time, millions of people are
prescribed statins to lower cholesterol levels, and each new set of guidelines
suggests that ever-more lowering of cholesterol is needed. When it comes to
explaining what causes heart disease, the cholesterol hypothesis reigns
But as the US editor and critic HL Mencken put
it, 'For every complicated problem there is a solution that is simple, direct,
understandable and wrong.' This is how we might view the diet-heart hypothesis:
just because it is dominant does not mean it is right, and just because it
looks simple does not mean that it actually is.
development of the cholesterol hypothesis
Rudolf Virchow notes the presence of cholesterol
in atherosclerotic plaques, and suggests that excess cholesterol in the
bloodstream may be the cause.
Ashoff feeds rabbits on fat and cholesterol, and
notes the development of atheroma.
First heart attack described by Herrick.
Epidemic of heart disease hits the USA, and
interest in the area explodes. Many researchers blame the high fat/cholesterol
The Framingham study on heart disease begins. It
is still running today.
Ancel Key's seminal Seven Countries Study is
published, demonstrating clear links between saturated fat intake and heart
Framingham confirms the link between raised
cholesterol levels and heart disease.
The first cholesterol-lowering drugs are developed.
Brown and Goldstein find the gene leading to
extremely high cholesterol levels (Familial Hypercholesterolaemia) and
premature heart disease.
Statins are launched.
The Nobel Prize is awarded to Brown and
Statins trials demonstrate that cholesterol
lowering protects against heart disease.
Presented in this way, it's not difficult to see
how the cholesterol hypothesis became the dominant hypothesis, effortlessly
swatting alternative ideas into touch. Indeed, to question this theory is to
risk being placed on the same shelf as flat-earthers and creationists.
However, all is not what it seems. The
cholesterol hypothesis can be likened to a cathedral built on a bog. Rather
than admit they made a horrible mistake and let it sink, the builders decided
to try and keep the cathedral afloat at all costs. Each time a crack appeared,
a new buttress was built. Then further buttresses were built to support the
Although direct contradictions to the
cholesterol hypothesis repeatedly appear, nobody dares to say 'okay, this isn't
working, time to build again from scratch'. That decision has become just too
painful, especially now that massive industries, Nobel prizes, and glittering
scientific careers, have grown on the back of the cholesterol hypothesis. The
statin market alone is worth more than £20billion each year.
In reality, cracks in the hypothesis appeared
right from the very start. The first of these was the stark observation that
cholesterol in the diet has no effect on cholesterol levels in the bloodstream:
'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 PhD,
professor emeritus at the University of Minnesota 1997.
A bit of a blow to a cholesterol hypothesis, you
might think, to find that dietary cholesterol has no effect on blood
cholesterol levels. However, as everyone was by then fully convinced that
something rich and 'fatty' in the diet was the primary cause of heart disease,
nobody was willing to let go.
So the hypothesis quietly altered, from
cholesterol in the diet to saturated fat in the diet - or a bit of both. As if
cholesterol and saturated fat are similar things. In reality, this could hardly
be further from the truth. Saturated fat and cholesterol have completely
different functions in the body, and they have very different chemical
As chemist Joseph Black warned over 200 years
ago: 'A nice adaptation of conditions will make almost any hypothesis agree
with the phenomena. This will please the imagination, but does not advance our
knowledge.' J Black, Lectures of the elements of Chemistry 1803
Unfortunately, this adaptation did not work. It
is true that Ancel Keys appeared to have proven the link between saturated fat
consumption and heart disease, but when it came to the major interventional
trials, confirmation proved elusive.
The MR-FIT trial in the USA was the most
determined effort to prove the case. This was a massive study in which over
350,000 men at high risk of heart disease were recruited. In one set of
participants, cholesterol consumption was cut by 42 percent, saturated fat
consumption by 28 percent and total calories by 21 percent. This should have
made a noticeable dent in heart disease rates.
But nothing happened. The originators of the
MR-FIT trials refer to the results as 'disappointing', and say in their
conclusions: 'The overall results do not show a beneficial effect on Coronary
Heart Disease or total mortality from this multifactor intervention.'
In fact, no clinical trial on reducing saturated
fat intake has ever shown a reduction in heart disease. Some have shown the
exact opposite: 'As multiple interventions against risk factors for coronary
heart disease in middle aged men at only moderate risk seem to have failed to
reduce both morbidity and mortality such interventions become increasingly
difficult to justify. This runs counter to the recommendations of many national
and international advisory bodies which must now take the recent findings from
Finland into consideration. Not to do so may be ethically unacceptable.'
Professor Michael Oliver, British Medical Journal 1991
This quote followed a disturbing trial involving
Finnish businessmen. In a 10-year
follow-up to the original five-year trial, it was found that those men who
continued to follow a low saturated fat diet were twice as likely to die of
heart disease as those who didn't.
It is not as if this was one negative to set
against a whole series of positive trials. In 1998, the Danish doctor Uffe Ravnskov looked
at a broader selection of trials: 'The crucial test is the controlled,
randomised trial. Eight such trials using diet as the only treatment has been
performed but neither the number of fatal or non-fatal heart attacks was
reduced.' As Ravnskov makes clear, no
trial has ever demonstrated benefits from reducing dietary saturated fat. At
this point most people might think it was time to pull the plug.
Far from it: in 1988, the
surgeon general's office in the
USA decided to silence the nay sayers by putting together the definitive report
proving a causal link. Eleven years later the project was abandoned. In a
circulated letter, it was stated that the office 'did not anticipate fully the
magnitude of the additional external expertise and staff resources that would
Bill Harlan, a member of the oversight committee
and associate director of the Office of Disease Prevention at the US National
Institute of Health, says: 'the report was initiated with a preconceived
opinion of the conclusions, but the science behind those opinions was not
holding up. Clearly the thoughts of yesterday were not going to serve us very
The sound of a sinking cathedral fills the air
with a great sucking slurpy noise. But still nobody let go. Instead, more buttresses
were desperately thrown at a rapidly disappearing pile of rocks.
Variations on a theme emerged. It is not
saturated fat per se that causes heart disease. It's the ratio of
polyunsaturated to saturated fat that is critical. Or is it the consumption of
monounsaturated fats, or a lack of omega-3 fatty acids, or an excess of
omega-6? Take your pick. These, and a host of other add-on hypotheses, have
As of today nobody can - or will - tell you
which type of fat, in what proportions, added to what type of anti-oxidant,
vegetable, monounsaturated fat or omega-3 is the true culprit. Hugely
complicated explanations are formulated, but they all fall apart under
This may all seem incredible, such has been the
level of anti-fat propaganda, but it is true. With the exception of the Ancel
Keys' flawed Seven Countries Study (he pre-selected the seven countries for his
study in order to prove his hypothesis); there is not one scrap of direct
But, of course, there are two parts to the
cholesterol hypothesis. The diet part, and the raised cholesterol level part.
Leaving diet behind, surely it has been proven beyond doubt that a raised
cholesterol level is the most important cause of heart disease?
levels and overall mortality
Before looking at the connection between blood
cholesterol levels and heart disease, it is worth highlighting a critically
important - remarkably unheralded - fact: After
the age of 50, the lower your cholesterol level is, the lower your life expectancy.
Perhaps even more important than this is the
fact that a falling cholesterol level sharply increases the risk of dying of
anything, including heart disease.
The dangers of a low cholesterol level were
highlighted by a major long-term study of men living in Honolulu: '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.'
Somewhat ironically, the danger of a falling
cholesterol level was first discovered in the Framingham study: 'There is a direct
association between falling
cholesterol levels over the first 14 years [of the study] and mortality over
the following 18 years.'
It seems almost unbelievable that warnings about
the dangers of a high cholesterol level rain down every day, when the reality
is that a low cholesterol level is much more dangerous than a high level. Given this,
why would anyone want to
lower the cholesterol level? On the face of it, it would make more sense to
take cholesterol-raising drugs. Especially after the age of 50.
levels and heart disease
The reason why everyone is so keen to lower
cholesterol levels is that supporters of the hypothesis have decreed the
- A high level of cholesterol causes premature
- A low level of cholesterol is caused by an
underlying disease. It is the underlying disease that kills you, not the low
Ergo, if you lower the blood cholesterol level,
you will reduce the risk of heart disease, and you will not increase the risk
of dying of any other disease. This could be true, but it is worth reviewing
some of the evidence that linked raised cholesterol levels to heart disease in
the first place. Let's begin with women.
Perhaps the largest single analysis of
cholesterol levels, and death from cardiovascular disease (and other diseases),
was published in 1992. This review included over 100,000 women, aggregated from
a number of different studies and countries.
To quote from the study: 'The pooled estimated
risk for total cardiovascular death in women showed no trend across TC (total
cholesterol) levels.' In short, for more than 50 percent of the world's
population - women - raised cholesterol is not a risk factor for heart disease.
Moving to men, it is true that under the age of
50 there does seem to be an association between raised cholesterol levels and
heart disease. But after the age of 50, when more than 90 percent of heart
attacks happen, the association disappears.
In addition, those populations in the world with
the highest rates of heart disease in younger men, including Emigrant Asian
Indians, Eastern Europeans, Native Americans and Australian Aboriginals, tend
to have significantly lower cholesterol levels than the surrounding
Perhaps the single most directly contradictory
fact is that, in young Japanese men, the average cholesterol level has risen
over the past 20 years, yet the rate of heart disease has fallen. But as with
many facts in this area, if they don't fit the cholesterol hypothesis, they are
cholesterol levels with drugs
Surely, despite everything written up to this
point, all previous arguments are refuted by the knowledge that lowering
cholesterol levels with statins protects against heart disease? As all good
scientists know, 'reversibility of effect' provides the most powerful
supportive evidence for a hypothesis.
However, the flipside to this argument is as
follows. How can lowering cholesterol levels prevent heart disease in people
who do not have a high level? The most often quoted clinical trial in the past
few years is the UK-based Heart Protection Study (HPS): a veritable triumph for
statins, demonstrating protection in almost every group studied.
What is most intriguing, however, is that
protection was apparent if the starting cholesterol level was high, average or
low. How can this be explained?
At this point we enter Alice in Wonderland
territory. A rational person would accept that a normal cholesterol level
cannot be a risk factor for heart disease (or anything else for that matter).
Therefore, people with normal cholesterol levels can gain no benefit from
having their levels lowered. Therefore, if statins do protect those with
normal, or low, cholesterol levels - which they clearly do - they must be doing
this through some other mechanism of action, unrelated to cholesterol lowering.
In fact, there is a growing body of evidence to
support the idea that statins have a whole series of different protective
actions. However, accepting that statins
work 'in another way' would demolish the final buttress keeping the cholesterol
And so the latest argument is that nobody in modern society has a normal
cholesterol level. [Also acknowledge
this would promote use of over the counter drugs such as high dose aspirin,
CiQ10, estradiol, and others, which reduce the immune response like statins to
damage LDL, the cause of cardiovascular disease--jk].
An article in the Journal of the American
College of Cardiology best sums up this line of thinking. Under the heading
'Why average is not normal', O'Keefe, the lead author, makes the claim that:
'Atherosclerosis is endemic in our population, in part because the average LDL
("bad" cholesterol) level is approximately twice the normal
physiologic level.' In short, according
to O'Keefe, our cholesterol level should be about 2.5mmol/l, not 5.2mmol/l.
This argument, if true, does neatly demolish the
question 'How can people with normal, or low, cholesterol levels be protected
against heart disease?'. O'Keefe and
others would argue that we all have a high cholesterol level. Everyone is ill,
and all shall have statins.
One regularly quoted fact, which superficially
seems supportive of O'Keefe's hypothesis, is that peasant farmers in China have
very low cholesterol levels and a very low rate of heart disease (although
their average cholesterol levels are actually about four, not two-and-a-half).
But when you study the figures with more care,
they reveal something else. As usual, those with low cholesterol levels have by
far the highest mortality rates. Liver failure and liver cancer are common
causes of death. However, there is a simple explanation for this association.
Many Chinese peasant farmers have chronic hepatitis, which creates low
cholesterol levels, and also leads to liver failure and liver cancer. This is
why people with low cholesterol levels die young.
Does this mean that a low cholesterol level
protects against heart disease? No: what the Chinese data tell us is that those
with higher cholesterol levels are not chronic hepatitis carriers, so they live
longer and have more chance of developing heart disease in old age. On the
other hand, those with low cholesterol levels cannot die of heart disease,
because they are already dead.
Without chasing too many mad arguments around,
the simple fact is that everyone in the West does not have a raised cholesterol
level. Repeated studies have shown that a perfectly normal, or healthy, cholesterol
level lies between about four and six, and lowering it cannot protect against
heart disease, otherwise we will have introduced a new concept into medical
science: normal is unhealthy and must be treated.
People are grasping at straws in their attempts
to explain why statins protect against heart disease in those with normal
cholesterol levels, and in women and the elderly - where a raised cholesterol
level is not even a risk factor. The only possible explanation for the results
of the statin trials is that statins do not work by lowering cholesterol
The cholesterol hypothesis is a complicated mess
The cholesterol hypothesis has always exuded the
siren song of simplicity. However, once you start to examine it in any detail,
the simplicity rapidly mutates into complexity.
Even at the very start, people should have known
that cholesterol in the diet was never capable of appearing, unchanged, in the
bloodstream. Cholesterol is not soluble in water (thus blood) which means that
after absorption, cells lining the gut pack cholesterol into a small
protein/lipid sphere, known as a lipoprotein, before releasing it into the
Thus, you do not have any cholesterol floating
about in the blood - it is all contained within lipoproteins. You do not
actually have a cholesterol level. Instead, you have a level of different
lipoproteins, with the low-density lipoprotein (LDL) or 'bad' cholesterol being
the so-called dangerous one.
Next question, what raises the LDL level? Eating
too much fat, or cholesterol? The first problem here is that the cells lining
the gut do not make, or release, LDL - they make other forms of lipoprotein. So,
no matter what you eat, it can have no
direct effect on LDL levels.
So where does LDL come from? LDL is,
effectively, the shrunken form of a very low-density lipoprotein (VLDL). VLDLs are
made in the liver and used to
transport fat and cholesterol from the liver to other cells around the body. As
VLDLs lose fat they shrink, transforming into LDL.
Therefore, in order to find out what makes LDL
levels rise, we must surely find out, firstly, what makes VLDL levels go up;
and what makes VLDL levels go up,
primarily, is eating excess carbohydrates. What makes them go down is eating
Recognising this, and a host of other problems,
the supporters of the cholesterol hypothesis have twisted and turned. As of
today (and this will certainly change), the original - dietary - cholesterol
hypothesis has become the following: If you eat too much saturated fat, the
body will reduce the number of LDL receptors (things that remove LDL from the
bloodstream), forcing the LDL up. A more tenuous, and unproven, link could
hardly be imagined, but that is what is left of the originally super-simple
cholesterol hypothesis. The diet part anyway.
But the difficulties of trying to establish a
dietary link to heart disease actually pale into insignificance when you start
trying to work out how the raised LDL level itself may cause heart disease. If it were simply a case of
excess LDL seeping through the artery wall when the level gets too high, then
why doesn't this happen in all artery walls, everywhere? If I lie
too long in the sun I expect to get
sunburned on every bit of
skin exposed. I do not expect to get discrete patches of sunburn. Yet we do see little
atherosclerosis. Some people die of heart disease and are found to have
perfectly clean arteries, apart from a single killer plaque (thickening). So
why did the LDL seep through at only one place? What protected the rest of the
do veins never develop atherosclerotic plaques? They
are exposed to exactly the same LDL level as the arteries. They are thinner
than arteries, but their general structure is identical. I should add that if
you use a vein as a coronary artery bypass graft (effectively turning it into
an artery), it will develop atherosclerosis.
questions represent only the tip of a huge iceberg. In an
attempt to answer some of them, the cholesterol hypothesis has turned itself
into the following, complicated mess:
when it is oxidised, travels through the lining of the
artery wall (endothelium) into the middle part of the artery. (How oxidised LDL passes
straight through an
endothelial cell into the artery wall behind is unexplained.)
this oxidised state it attracts white blood cells from the
bloodstream. They, in turn, migrate into the artery wall and start to 'digest'
the oxidised LDL in order to remove it. (This bit is plausible.
white blood cells, once they have started to digest
oxidised LDL cannot stop. They get bigger and bigger until they burst. This, in
turn, attracts more white blood cells to the area which then burst. (White
blood cells that just burst? This makes
no sense whatsoever. Why on earth would the body develop a scavenger system
that automatically self-destructs?)
burst white blood cells, in turn, release substances that
trigger a whole cascade of inflammatory reactions in the arterial wall. After a
period of time you have a mass of dead white blood cells, cholesterol, oxidised
LDL remnants, and a whole series of other inflammatory agents all focused in
one area, trapped in the artery wall. (Well, this is what is found in a plaque,
among many other things.)
is allegedly how a plaque starts and grows. I have kept that
explanation as simple as humanly possible, but it seems absurdly unlikely.
Oxidised LDL - what happened to normal LDL? Well, there's no way anyone can see
of getting that through an arterial wall. Exploding white blood cells....
truth, the current ideas on plaque formation used to keep the
cholesterol hypothesis afloat are complex nonsense. But the entire area is now
protected by a ring-fence of scientific jargon that frightens off all but the
most dedicated seeker after truth.
those who have studied the hypothesis with a critical eye, it
seems unbelievable that it can possibly still be standing. Dr George Mann pronounced
it dead in an editorial in the New England
Journal of Medicine in 1977, referring to it as the 'Greatest scam in the
history of medicine'. Yet this hypothesis has never had more followers than
I think, that it was consigned to the dustbin of history. It
is not simple, direct, or understandable - the only certain thing about it is
that it is wrong.
Malcolm Kendrick is a medical doctor who has spent many
years researching the causes of heart disease. He has been critical of the
'cholesterol hypothesis' for many years, and more of his writing on the area
can be found on the website of the International Network of Cholesterol
Skeptics. This is an edited version of a chapter in Panic Nation? Unpicking the
myths we're told about food and health, edited by Stanley Feldman and Vincent
Marks (buy this book from Amazon (UK) or Amazon (USA))
holds that statins studies when grouped as a whole (rather than cherry picking)
fail to demonstrate a reduction in total mortality, or of death from CHF
(coronary heart failure), In
the 4 studies examined in Braunwald’s cardiology textbook, 1999 edition, 3 out
of 4 of seminal studies failed to show a reduction in deaths from coronary
events. Secondly JK holds that the
protocol for the study and the published results are worked for marketing goal
of the pharmaceutical company that funded the study and owns its results.
How this is done is rarely made public;
although in the rare case the Jupiter study used the pretrial technique, where
participants are given the drug, and then called back to see how they
respond. Fully one third at this
were dropped, then the study began.
Another widely used technique (not revealed in the journal article) is
last point carried forward. All
who drop out, their outcome at that point is carried forwards as though they
had no side effects (the likely cause for their dropping out) o other adverse
event such as MI, death, stroke, etc.
Enter here the fact that certain types of virus and bacterial live in the
artery walls and cause atheroma. In
study of those who died from an MI, 22 out of 24 had had pathogens in the
artery wall at the point where the plaque leaked. This doesn’t mitigate the oxidation process
for carbon monoxide from tobacco at a pack a day long-term doubles death from
MI. High serum glucose level is
diabetics also doubles the rate. It
has yet to be worked out.