A medical doctor friend two days ago asked me if high cholesterol has anything to do with heart disease and how it really works in blocking the arteries? I have already answered this issue many times in the past.
I knew that neither
cholesterol nor saturated fats was the cause of heart disease in 1964 when I
was a postgraduate student of Professor John Yudkin MA, MD, PhD, FRCP, FRIC,
FIBiol who was the Chair of Nutrition at Queen Elizabeth College, University of
London. See John Yudkin’s biography here:
https://en.wikipedia.org/wiki/John_Yudkin#Career
At that time the prevailing theory
was saturated animal fats that caused elevated blood cholesterol that in turn
caused coronary heart disease. John Yudkin’s greatest rival was Ancel Keys
(1904 – 2004) who advocated saturated animal fats as the cause of coronary
heart disease. Yudkin’s theory of sugar as pure, white and deadly was the root
cause of death from heart disease that rocked the entire world and the medical
community.
Below are two links that I
wrote to two of my other medical specialist colleagues who asked the same,
seeking my opinion about cholesterol and heart disease.
https://scientificlogic.blogspot.com/search?q=cholesterol
The Truth about Cholesterol, HDL
and LDL and Heart Disease here:
Cholesterol per sec is
completely harmless. It is a pale-yellow substance, though waxy, it does not
stick on to anything, let alone onto the coronary arteries of the heart. It is
not soluble in water except in organic nonpolar solvents such as petroleum ether
(pet ether), chloroform, ether, benzene, ethanol and methanol (alcohols). I
have seen and touched very pure analytical grade cholesterol many times before
when we were working in an analytical medical diagnostic laboratory.
Cholesterol is intentionally
produced by the body for numerous biochemical and physiological functions such
as for the brain and nervous system. It is needed to produce hormones,
especially the corticosteroid hormones produced by the adrenal glands.
It is the diet that partially
determines the HDL and LDL cholesterols ratios and total amounts in the blood.
It is the liver that synthesizes cholesterol from acetyl-CoA. We shall go
into this later.
Most dietary cholesterol are
neither HDL or LDL cholesterol except certain foods like eggs, dairy products,
and certain types of meat that contain both HDL and LDL cholesterol. Most
dietary cholesterol is just neutral cholesterol. It is the types and amounts of
fat in the diet that help determine the quantity of triglycerides, the HDL, and
LDL cholesterol ratios in the bloodstream.
Cholesterol-rich foods generally as
already mentioned contain the normal cholesterol with the molecular formula
C27H46O. It is neither called high- or low-density cholesterol. But they
can contribute to the production of both high-density lipoprotein (HDL)
cholesterol and low-density lipoprotein (LDL) cholesterol levels in the body.
Cholesterol is synthesized by the
liver through a complex series of enzymatic reactions, and its production
involves multiple metabolic pathways. The primary pathway for cholesterol
synthesis is known as the mevalonate pathway or the HMG-CoA reductase pathway.
The key steps in cholesterol biosynthesis comes from acetyl-CoA formation.
This process begins with the
conversion of acetyl-CoA, a molecule derived from the breakdown of
carbohydrates, fats, and proteins, into a compound called acetoacetyl-CoA.
Then we have the HMG-CoA
Formation in which two molecules of acetoacetyl-CoA combine to form
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) through the action of the enzyme
thiolase.
Next comes the mevalonate
formation where HMG-CoA is then converted into mevalonate by the enzyme
HMG-CoA reductase. This step is often considered the rate-limiting step in
cholesterol synthesis, and HMG-CoA reductase is the target of statin drugs,
which are commonly prescribed to lower cholesterol levels.
Statin drugs are a class of
medications commonly prescribed to lower LDL (low-density lipoprotein)
cholesterol levels in the blood. LDL cholesterol is often referred to as
"bad" cholesterol because elevated levels can contribute to the
buildup of plaque in arteries, leading to atherosclerosis and an increased risk
of cardiovascular disease.
Statins work by inhibiting an
enzyme called HMG-CoA reductase, which plays a key role in the synthesis of
cholesterol in the liver. By reducing the production of cholesterol,
particularly LDL cholesterol, statins help lower overall cholesterol levels in the
bloodstream.
In addition to lowering LDL
cholesterol, statins may also have other beneficial effects, such as increasing
high-density lipoprotein (HDL) cholesterol often referred to as
"good" cholesterol and reducing inflammation. We shall go into
“good” and “bad” cholesterol a little bit more later.
It's important to note that the use
of statins is typically recommended based on an individual's overall
cardiovascular risk profile, and the judgement to prescribe statins is made by
healthcare professionals. While statins are effective in lowering cholesterol
and reducing the risk of cardiovascular events, they may also have side effects
such as damage to the liver, and their use should be monitored and managed.
Unfortunately, statins have been abused by health care providers through over
prescribing. For instance, statin prescriptions average a total annual
cost of $24.5 billion in the US alone.
Back to the synthesis of body
cholesterol, after the mevalonate formation where HMG-CoA is
converted into mevalonate by the enzyme HMG-CoA reductase, the next step
in the synthesis of cholesterol in the body results in conversion to
Isoprenoids where mevalonate undergoes a series of enzymatic reactions to
form isoprenoids, such as farnesyl pyrophosphate and geranylgeranyl
pyrophosphate and the formation of squalene in which Isoprenoids are
then converted into squalene through a series of reactions. The squalene
undergoes cyclization and modification reactions to form lanosterol, which is
then further converted into cholesterol.
These are the biochemical steps how
the body naturally produces its own cholesterol, and it could do this far more
efficiently than the cholesterol we can eat through food.
The liver is a major site of
endogenous cholesterol production. The amount of cholesterol produced by the
liver varies among individuals. It is influenced by factors such as genetics,
dietary habits, and overall health. On average, the liver synthesizes a
substantial amount of cholesterol each day to meet the body's needs for cell
membrane structure, hormone synthesis, and other essential functions. There are
feedback mechanisms on the amount of dietary cholesterol intake and the
endogenous turnover by the liver to keep the level of cholesterol in the blood
under check and balance.
The impact of dietary cholesterol
intake on blood cholesterol levels can vary from person to person. Even though
dietary cholesterol does contribute to total cholesterol levels, the body's
response to dietary cholesterol is complex. Some individuals are more sensitive
to dietary cholesterol, while others are less affected.
Since cholesterol is not water
soluble as already mentioned, for cholesterol to be transported through the
bloodstream, which is water-based, cholesterol needs to be combined with
proteins in the blood to form lipoproteins. These cholesterol-protein complexes
vary in density, and there are two main types. Let’s talk about them in a bit
more detail.
Low-Density Lipoprotein (LDL):
LDL cholesterol is often referred to as "bad" cholesterol. LDL
particles are denser and smaller. They transport cholesterol from the liver to
the cells. However, if there is an excess of LDL cholesterol or if the LDL
particles are damaged by oxidation such as from free radicals to become gummy
and sticky, and this can contribute to the buildup of plaques on the intima or
inner walls of arteries, leading to atherosclerosis. Foods high in saturated
and trans fats, which are often found in animal products and processed foods,
can raise LDL cholesterol levels to cause this problem, whereas fruits,
vegetables and plant-based foods rich in antioxidants can short-circuit free
radicals into harmless neutral molecules, thus preventing atherosclerotic
plagues formation.
High-Density Lipoprotein (HDL) cholesterol
is often referred to as "good" cholesterol. HDL particles are larger
and less dense. They help remove excess cholesterol from the bloodstream by
transporting it to the liver, where it can be broken down and excreted from the
body. HDL is considered beneficial because it helps prevent the buildup of
cholesterol in the arteries. It is also less prone to become sticky through
oxidation. Foods that are rich in healthy fats, such as certain oils, fatty
fish, nuts, and seeds, can contribute to increased levels of HDL cholesterol.
The terms "low density"
and "high density" refer to the comparative proportion of lipids
(fats) to proteins in these lipoprotein complexes. LDL has a higher ratio of
cholesterol to protein, making it denser, while HDL has a higher ratio of
protein to cholesterol, making it less dense.
It is important to note that the
relationship between dietary cholesterol and blood cholesterol levels is
complex. For many people, dietary cholesterol has less of an impact on blood
cholesterol than the types of fats consumed.
In recent years, research has
indicated that the link between dietary cholesterol and heart disease is not as
straightforward as once thought, and factors such as overall diet, genetics,
and lifestyle play central roles. What is important is to limit the intake of
sugar, saturated and trans fats and focus on consuming healthy fats to support
heart health.
In short, and simply put in simple
language, LDL cholesterol often referred to as "bad" cholesterol and
high-density lipoprotein cholesterol or HDL cholesterol often referred to
as "good" cholesterol may not be technically correct so to speak. LDL
cholesterol may not be “bad” after all if a diet has a high content of
antioxidants to deal with oxidative stress of the cells and on the intima of
coronary and other blood vessels by damaging free radicals.
HDL merely picks up excess
cholesterol in the blood and returns them to the liver where it's broken down
and removed from the body. It is also less prone to oxidation and oxidative
stress. That’s why they term HDL cholesterol as “good cholesterol”. It is the
diet that partially determines the HDL and LDL cholesterols ratios and total
amounts in the blood. It is the liver that synthesizes cholesterol
from acetyl-CoA as already described in some details.
In summary, I have found no
relationship between blood cholesterol and heart disease when our medical
technicians analysed tens of thousands of blood samples at the Institute for
Medical Research where I once worked as a Senior Medical Research Officer, and
what clinicians wrote there in their requests for cholesterol analysis. The
blood samples were taken from hundreds of government hospitals in East and West
Malaysia. I have gone through these analytical data and have signed tens of
thousands of these analytical and diagnostic reports for doctors in hospitals.
But I found no relationship between
serum cholesterol and heart disease and heart attacks. Their requests were sent
to us for support and confirmatory diagnosis.
But I could not do anything to tell them because the prevailing theory at that
time was saturated animal fats and cholesterol that caused coronary heart
disease. So, I signed all their doctors' and government hospitals' requests and
sent them back to the hospitals and let them do what they like that pleased
them.
There was nothing I could do
to change the mindset of doctors who insisted that high cholesterol was the
culprit, and should be treated with statins when sugars, smoking, stress, free
radicals were the wrongdoers.
I was the only lone voice in
the wilderness in Malaysia at that time, but numerous scientists and eminent
physicians in the UK who were my mentors would have supported me.
It is only now that multiple voices
from the scientific and medical communities are revealing the myth about
cholesterol and coronary heart disease.
Here are just a few publications
since 1998 with their scientific voices in support of my silent thoughts in the
mid 1960’s
Do I need to say more?
How this myth about cholesterol and
heart diseases first started is here:
Cover Story | The Heart Study Heard
Around the World: Origins of Framingham and its Continued Legacy
The Framingham Heart Study and the
Epidemiology of Cardiovascular Diseases: A Historical Perspective
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159698/
Dietary Cholesterol and the Lack of
Evidence in Cardiovascular Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024687/
7 Myths About Cholesterol, Debunked
https://time.com/6287926/cholesterol-myths-debunked/
Cholesterol does not cause coronary
heart disease in contrast to stress here:
https://www.tandfonline.com/doi/full/10.1080/14017430801993701
“The real truth about diet and
cholesterol came out in a 1992 Archives of Internal Medicine article
stating that, “in Framingham, Mass, the more saturated fat one ate, the more
cholesterol one ate, the more calories one ate, the lower the person's serum
cholesterol”. The author who said this was William Castelli who was the
Director of the Framingham study at that time.
Lack of an association or an
inverse association between low-density-lipoprotein cholesterol and mortality
in the elderly: a systematic review here:
https://bmjopen.bmj.com/content/6/6/e010401
From Framingham to Hunt 2: 60 Years
Blaming the Wrong Culprit?
https://medcraveonline.com/JCCR/from-framingham-to-hunt-2-60-years-blaming-the-wrong-culprit.html
The US Government
finally officially removed Cholesterol from Naughty List here:
Think this over and thank you for
reading.
Lim ju boo
1 comment:
Thank you, Dr Lim for your splendid article and explanation on why cholesterol is not the main cause of heart disease as all along we all thought even among doctors, that cholesterol is the cause of heart disease, resulting in untold profits from statin drugs being prescribed unnecessary as you correctly said. I don’t encourage the use of statins myself as a doctor.
Frankly I find your biochemical equations on the synthesis of cholesterol in the body difficult to follow. I wonder if other readers understand.
You also mentioned Professor Dr John Yudkin who was your mentor at London University that sugar was the primary cause of coronary heart disease rather than saturated fats or cholesterol. I have heard and read about Professor John Yudkin who was very famous. His findings on why sugar is deadly rocked the world and medical and scientific professions are now reviving very strongly among the medical communities.
But how does that work since fruits also contain a lot of sugar? As a doctor, as with everyone else, I would have thought fruits are good for health and may also be heart protective as they are rich in antioxidants. How would you explain that?
Dr Mary Lee
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