The Cholesterol Myths
Uffe Ravnskov, M.D., Ph.D.
9. The benefits of high
with high cholesterol live the longest.
This statement seems so incredible that it takes a long
time to clear one´s brainwashed mind to fully understand its importance. Yet
the fact that people with high cholesterol live the longest emerges clearly from
many scientific papers.1 But let us take a look at heart mortality,
the risk of dying from a heart attack if cholesterol is high.
Consider for instance the finding of Dr.
Harlan Krumholz of the Department of Cardiovascular Medicine at Yale University,
who reported that old people with low cholesterol died twice as often from a
heart attack as did old people with a high cholesterol.2 Supporters
of the cholesterol campaign consistently ignore his observation, or consider it
as a rare exception, the result of chance among a huge number of studies finding
But it is not an exception; there are now
a large number of findings that contradict the lipid hypothesis. To be more
specific, most studies of old people have shown that high cholesterol is not a
risk fact for coronary heart disease. This was the result of my search in the
Medline database for studies addressing that question.3 Eleven
studies of old people came up with that result, and a further seven studies
found that high cholesterol did not predict all-cause mortality either, and more
such studies have been published since then.
I have mentioned it before, but it is worth
repeating, that more than 90 percent of those who die from a heart attack or a
stroke have passed the age of 65. You may also recall that high cholesterol is
not a risk factor for women nor for a number of other population groups. Thus,
high cholesterol is only a risk factor for less than five percent of those who
die from a heart attack.
But there is more comfort for those who
have high cholesterol. At least fifteen studies found that total mortality was inversely associated with either total or
LDL-cholesterol, or both. This means that it is actually much better to have
high than to have low cholesterol if you want to live to be very old.
studies have found that low cholesterol in certain respects is worse than high
cholesterol. For instance, in nineteen large studies of more than 68,000 deaths,
reviewed by David R. Jacobs and his co-workers from the Division of Epidemiology
at the University of Minnesota, low cholesterol predicted an increased risk of
dying from gastrointestinal and respiratory diseases.4
Most gastrointestinal and respiratory
diseases have an infectious origin. Therefore, a relevant question is whether it
is the infection that lowers cholesterol or the low cholesterol that predisposes
to infection? You have probably already guessed what the directors of the
cholesterol campaign have said, but is it true?
To answer that question Jacobs and his group,
led this time by Dr. Carlos Iribarren, followed more than 100,000 healthy
individuals in the San Francisco area for fifteen years. At the end of the study
those who had low cholesterol at the start of the study had been admitted more
often to hospital, either because of an infectious disease of the respiratory
system5 or because of another type of infection.6 This
finding cannot be explained away with the argument that the infection had caused
cholesterol to go down, because how could low cholesterol, recorded when these
people had no evidence of infection, be caused by a disease they had not yet
encountered? Isn´t it much more likely that low cholesterol in some way made
them more vulnerable to infection, or that high cholesterol protected those who
did not become infected? Much evidence exists to support that
Young, unmarried men with a previous sexually
transmitted disease or liver disease run a much greater risk of becoming
infected with HIV virus than other people. The Minnesota researchers followed
such individuals for seven or eight years. After having excluded those who
became HIV-positive during the first four years, they ended up with a group of
2446 men. At the end of the study, 140 of these people tested positive for HIV;
those who had low cholesterol at the beginning of the study were twice as likely
to test postitive for HIV compared with those with the highest cholesterol.7
Similar results came from a study of the
MRFIT screenees. Sixteen years later four times more among those with the lowest
cholesterol had died from AIDS compared with those who had the highest.8
disease may lead to a weakening of the heart muscle. A weak heart means that
less blood and therefore less oxygen is delivered to the arteries. To compensate
for the decreased power, the heart beat goes up, but in severe heart failure
this is not sufficient. Such patients become short of breath because too little
oxygen is delivered to the tissues, the pressure in their veins increases
because the heart cannot deliver the blood away from the heart with sufficient
power, and they become edematous, meaning that fluid accumulates in the legs and
in serious cases also in the lungs and other parts of the body. This condition
is called congestive or chronic heart failure.
There are many indications that bacteria
or other microorganisms play an important role in chronic heart failure. For
instance, patients with severe chronic heart failure have high levels of
endotoxin and various types of cytokines in their blood. Endotoxin, also named
lipopolysaccharide, is the most toxic substance produced by Gram-negative
bacteria. Cytokines are hormones secreted by white blood cells in their battle
against pathogenic microorganisms; high levels of cytokines in the blood
indicate that inflammatory processes are going on somewhere in the body.
The role of infections in chronic heart
failure has been studied by Dr. Mathias Rauchhaus and his team at the Medical
Department, Martin-Luther-University in Halle, Germany. They found that the
strongest predictor of death for patients with chronic heart failure was the
concentration of cytokines in the blood, in particular in patients with heart
failure due to coronary heart disease. To explain their finding they suggested
that bacteria from the gut may more easily penetrate into the tissues when the
pressure in the abdominal veins is increased because of heart failure. In
accordance with this theory, they found more endotoxin in the blood of patients
with congestive heart failure and edema than in patients with non-congestive
heart failure without edema, and endotoxin concentrations decreased
significantly when the heart’s function was improved by medical treatment.9
A simple way to test the functional state
of the immune system is to inject antigens from microorganisms under the skin.
If the immune system is normal, an induration (hard spot) will appear about 48
hours later at the place of the injection. If the induration is very small, with
a diameter of less than a few millimeters, this indicates the presence of "anergy,"
a reduction in or failure of response to recognize antigens. In accordance,
anergy has been found associated with an increased risk of infection and
mortality in healthy elderly individuals, in surgical patients and in heart
Dr. Donna Vredevoe and her group from the
School of Nursery and the School of Medicine, University of California at Los
Angeles tested more than 200 patients with severe heart failure with five
different antigens and followed them for twelve months. The cause of heart
failure was coronary heart disease in half of them and other types of heart
disease in the rest. Almost half of the patients were anergic, and those who
were anergic and had coronary heart disease had a much higher mortality than the
Now to the salient point: to their
surprise the researchers found that mortality was higher, not only in the
patients with anergy, but also in the patients with the lowest lipid values in
The latter finding was confirmed by Dr.
Rauchhaus, this time in co-operation with researchers at several German and
British university hospitals. They found that the risk of dying for patients
with chronic heart failure was strongly and inversely associated with total
cholesterol, LDL-cholesterol and also triglycerides; those with high lipid
values lived much longer than those with low values.12
Other researchers have made similar
observations. The largest study has been performed at the UCLA Department of
Medicine and Cardiomyopathy Center in Los Angeles. It included more than a thousand patients with severe heart
failure. After five years 62 percent of the patients with cholesterol below 129
had died, but only half as many of the patients with cholesterol above 223.13
When proponents of the cholesterol
hypothesis are confronted with findings showing a bad outcome associated with
low cholesterol--and there are many such observations--they usually argue that
severely ill patients are often malnourished, and malnourishment is therefore
said to cause low cholesterol. However, the mortality of the patients in this
study was independent of their degree of nourishment; low cholesterol predicted
early mortality whether the patients were malnourished or not.
Children born with very high cholesterol,
so-called familial hypercholesterolemia, are protected against infection. But if
inborn high cholesterol protects against infections, inborn low cholesterol
should have the opposite effect. Indeed, this seems to be true.
Children with the Smith-Lemli-Opitz syndrome have very low cholesterol
because the enzyme that is necessary for the last step in the body’s synthesis
of cholesterol does not function properly. Most children with this syndrome are
either stillborn or they die early because of serious malformations of the brain.
Those who survive are imbecile, they have extremely low cholesterol, and they
suffer from frequent and severe infections. However, if their diet is
supplemented with pure cholesterol or extra eggs, their cholesterol goes up and
their bouts of infection become less serious and less frequent.14
Laboratory studies are crucial for learning
more about the mechanisms by which the lipids exert their protective function.
One of the first to study this phenomenon was Dr Sucharit Bhakdi from the
Institute of Medical Microbiology, University of Giessen, Germany along with his
team of researchers from various institutions in Germany and Denmark.15
Staphylococcus aureus α-toxin is the most toxic substance
produced by strains of the disease-promoting bacteria called staphylococci. It
is able to destroy a wide variety of human cells, including red blood cells. For
instance, if minute amounts of the toxin are added to a test tube with red blood
cells dissolved in a saline solution, the blood is hemolyzed, that is the
membranes of the red blood cells burst and hemoglobin from the interior of the
red blood cells leaks out into the solvent. Dr. Bhakdi and his team mixed
purified α-toxin with human serum (the fluid in which the blood cells
reside) and saw that 90 percent of its hemolyzing effect disappeared. By various
complicated methods they identified the protective substance as LDL, the carrier
of the so-called bad cholesterol. In accordance, no hemolysis occurred when they
mixed α-toxin with purified human LDL, whereas HDL or other plasma
constituents were ineffective in this respect.
Dr. Willy Flegel and his co-workers at the
University of Ulm, and the Institute of Immunology and Genetics at the German
Cancer Research Center in Heidelberg, Germany studied endotoxin in another way.16
As mentioned, one of the effects of endotoxin is that white blood cells are
stimulated to produce cytokines. The German researchers found that the
cytokine-stimulating effect of endotoxin on the white blood cells disappeared
almost completely if the endotoxin was mixed with human serum for 24 hours
before they added the white blood cells to the test tubes. In a subsequent study17
they found that purified LDL from patients with familial hypercholesterolemia
had the same inhibitory effect as the serum.
immune systems in various mammals including human beings have many similarities.
Therefore, it is interesting to see what experiments with rats and mice can tell
us. Professor Kenneth Feingold at the Department of Medicine, University of
California, San Francisco, and his group have published several interesting
results from such research. In one of them they lowered LDL-cholesterol in rats.
After that, injection of endotoxin was followed by a much higher mortality in
the low-cholesterol rats compared with normal rats. The high mortality was not
due to the cholesterol-lowering drugs because, if the drug-treated animals were
injected with lipoprotein just before the injection of endotoxin, their
mortality was reduced to normal.18
Dr. Mihai Netea and his team from the
University Hospital in Nijmegen, The Netherlands, injected purified endotoxin
into normal mice, and into mice with familial hypercholesterolemia that had
LDL-cholesterol four times higher than normal. Whereas all normal mice died,
they had to inject eight times as much endotoxin to kill the mice with familial
hypercholesterolemia. In another experiment they injected live bacteria and
found that twice as many mice with familial hypercholesterolemia survived
compared with normal mice.19
Several researchers have found that children
with allergic symptoms, including asthma, have lower cholesterol than healthy
children. As allergic diseases have been more common and as their frequency is
still increasing in the Western world it is tempting to suggest that the cause
is the increasing consumption of the polyunsaturated vegetable oils. But there
is room for another explanation.
At the Department of Dermatology, Skin and
Allergy Hospital in Helsinki, Finland Dr.Maria Pesonen and her coworkers
followed 200 children from their birth to their 20 year anniversary.20
They found that the children with allergic disorders had lower total and LDL
cholesterol than the others. The difference was significant already at age 2
months at a time where all 200 children were breastfed. Thus, the difference
could not be explained by different dietary habits. The researchers had no
explanation to their findings, but as the lipoproteins are able to bind
microbial products, it seems not too farfetched to assume that they can bind
other molecules as well, for instance allergens, those that starts the allergic
There is no contradictory observation that can´t be
explained away by the believers. One of the most striking aberrations appeared
in two recent studies from the US.
The first one came from the medical department
at the University of California in LA.21 A total of 137,000 patients
from 541 hospitals in the US had been admitted because of an acute heart attack.
In all of them, their cholesterol was analysed within the first 24 hours of
hospital admission. To their surprise, the authors found that their cholesterol
was lower than normal when compared with the average. To be precise, their mean
total cholesterol was 174 (4.46 mmol/l) and the ‘bad’ LDL cholesterol was
also much lower than normal.
It is not possible to explain away the result by
using the argument that it was a result of chance, considering that this is the
largest study of the cholesterol levels of heart patients, which has ever been
published.The researchers were of course surprised. One explanation could be the
well-known fact that cholesterol goes down in patients with an acute myocardial
infarction, but they rejected it, because this happens first after two-three
days and the reduction is only fifteen percent at most.22
Did the authors, three of whom were supported by
up to eight drug companies, realize that they had stumbled upon something
important? That high cholesterol may not be the cause of heart disease?
Of course not. What they concluded was that cholesterol
must be reduced even further.
A few months later a research group from Henry
Ford Heart and Vascular Institute in Detroit came up with a similar result.23
Again, LDLcholesterol measured within the first 24 hours of admission was lower than normal, not higher. To be precise, in half of the
500 patients LDLcholesterol was lower than 105 (2.69 mmol/l).
They thought that something had gone wrong and
were convinced that those whose LDL was below 105 had a much better chance to
survive than those whose LDL was higher, because this is what all of us have
been told by the American Heart Association and the drug companies repeatedly.
Three years later it appeared that among
those with low LDL twenty-six patients had died, but only twelve among those
with high LDL. The authors considered their finding very salient. They warned
their readers against feeling a false sense of security in patients with low LDL.
Although more of those with low LDL were on statin
treatment, they wrote , ”these patients may in fact need more aggressive risk
- Kozarevic D et al. Serum
cholesterol and mortality: the Yugoslavia Cardiovascular Disease Study. Am J Epidemiol. 1981 Jul;114(1):21-8.
Rudman D al. Antecedents
of death in the men of a Veterans Administration nursing home. J Am
Geriatr Soc. 1987 Jun;35(6):496-502.
Forette B et al.. Cholesterol
as risk factor for mortality in elderly women. Lancet.
1989 Apr 22;1(8643):868-70.
Staessen J, et al.
Is a high serum cholesterol level associated with longer survival in elderly
Hypertens. 1990 Aug;8(8):755-61.
Harris Tet al. The
low cholesterol-mortality association in a national cohort. J Clin
Epidemiol. 1992 Jun;45(6):595-601.a
Casiglia E et al. Predictors
of mortality in very old subjects aged 80 years or over.
Eur J Epidemiol. 1993 Nov;9(6):577-86.
Krumholz HM et al.Lack
of association between cholesterol and coronary heart disease mortality and
morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994 Nov
vs low-density lipoprotein cholesterol as the risk factor for coronary
artery disease and stroke in old age. Arch
Intern Med. 2003;163(13):1549-54.
Weverling-Rijnsburger AW et al.
Jonsson A, Sigvaldason H, Sigfusson N. Total cholesterol and mortality after
age 80 years. Lancet. 1997 Dec 13;350(9093):1778-9
of serum lipids, lipoproteins, and apolipoproteins on vascular and
nonvascular mortality in the elderly. Arterioscler
Thromb Vasc Biol. 1997 Jul;17(7):1224-32.
Räihä I, Marniemi J, Puukka P, Toikka T, Ehnholm C, Sourander L.
total cholesterol is associated with high total mortality in patients with
coronary heart disease. The
Bezafibrate Infarction Prevention (BIP) Study Group. Eur Heart J. 1997
Behar S et al.
factors for 5-year mortality in older adults: the Cardiovascular Health
Study. JAMA. 1998 Feb
Fried LP et al.
cholesterol concentrations and all-cause mortality in older people. Age Ageing. 2000 Jan;29(1):69-74.
Chyou PH, Eaker ED.
Schatz IJ et al-. Cholesterol
and all-cause mortality in elderly people from the Honolulu Heart Program: a
cohort study. Lancet.
2001 Aug 4;358(9279):351-5.
vs low-density lipoprotein cholesterol as the risk factor for coronary
artery disease and stroke in old age. Arch
Intern Med. 2003;163(13):1549-54.
Weverling-Rijnsburger AW et al..
Onder G et al.. Serum
cholesterol levels and in-hospital mortality in the elderly. Am J Med. 2003;115(4):265-71.
Casiglia E et al- . Total
cholesterol and mortality in the elderly. J
Intern Med. 2003 Oct;254(4):353-62.
Psaty BM et al. The
association between lipid levels and the risks of incident myocardial
infarction, stroke, and total mortality: The Cardiovascular Health Study. J Am Geriatr Soc. 2004
Ulmer H et al.Why
Eve is not Adam: prospective follow-up in 149650 women and men of
cholesterol and other risk factors related to cardiovascular and all-cause
mortality.J Womens Health 2004 Jan-Feb;13(1):41-53.
Schupf N et al. Costa R, Luchsinger J, Tang MX, Lee JH, Mayeux R.
Relationship between plasma lipids and all-cause mortality in nondemented
elderly. J Am
Geriatr Soc. 2005 Feb;53(2):219-26.
Akerblom JL et al. Relation
of plasma lipids to all-cause mortality inC aucasian, African-American and
Hispanic elders. Age Ageing. 2008;37:207-13.
Newson RS et al. Association
between serum cholesterol and noncardiovascular mortality in older age. J
Am Geriatr Soc. 2011;59:1779-85.
Bathum L et al, Depont
Christensen R, Engers Pedersen L, Lyngsie Pedersen P, Larsen J, Nexøe J. Association
of lipoprotein levels with mortality in subjects aged 50 + without previous
diabetes or cardiovascular disease: A population-based register study.
Scand J Prim Health Care. 2013;31:172-80
- Krumholz HM and others. JAMA. 272, 1335-40, 1994.
- Ravnskov U. QJM 96, 927-934, 2003.
- Jacobs D and others. Circulation 86,
C and others. Int J Epidemiol 26, 1191–202, 1997
C and others. Epidemiol Infect 121, 335–47, 1998.
AJ and others. J Acquir Immune Defic Syndr Hum Retrovirol 17, 51–7,
- Neaton JD, Wentworth DN. 11,
M and others.
Lancet 356, 930–3, 2000.
J and others.
Lancet 353, 1838-1842, 1999.
DL and others.
Am J Cardiol 82, 323-8, 1998.
M and others.
J Am Coll Cardiol 42, 1933-40, 2003.
K and others.
J Am Coll Cardiol 43, 1439-44, 2004.
ER and others.
Am J Med Genet 68, 305-10, 1997.
- Bhakdi S and others.
J Biol Chem 258, 5899-904, 1983.
WA and others.
Infect Immun 57, 2237-45, 1989.
- Flegel WA and others.
Infect Immun 61, 5140-6, 1993.
Feingold KR and others. Infect Immun 63, 2041–6, 1995.
- Netea MG and others. J Clin Invest 97, 1366–72, 1996.
- Pesonen M and others. Clin Exp
Allergy 2007 Epub ahead of print
Sachdeva A and others. Am
Heart J 2009;157:111-7.
- Gore JM. Am J Cardiol
- Sewdarsen M and others. Postgrad Med J 1988;64;352-6.
- Al-Mallah MH. Cardiol J
Some of my scientific papers about this and
questionable role of saturated and polyunsaturated fatty acids in
cardiovascular disease. J Clin Epidemiol 1998;51:443-460.
Read also a dissent to the paper: Golomb BA. Dietary fats and heart
disease-dogma challenged? and my answer; same journal and same issue.
This paper won the Skrabanek award 1999
A hypothesis out-of-date: The diet-heart idea. Published in Journal
of Clinical Epidemiology (2002 Nov;55:1057-63. Same issue: Dissent
W.S.Weintraub, and Reply
U. Ravnskov An evaluation of our discussion is available
atherosclerosis caused by high cholesterol? published in Quarterly
Journal of Medicine (2002; 95:397–403)
cholesterol may protect against infections and atherosclerosis published
in Quarterly Journal of Medicine (2003;96:927-34).
Should medical science ignore the past? BMJ 2008;337:a1681
popular-scientific books, where you can read much more:
and updated version of
my first book
The Cholesterol Myths
||Here you can read
how scientists and editors
of scientific journals have
deceived a whole world,
unintentionally or on purpose.
Also available as a