The Straight Dope on Cholesterol: 10 Things You Need to Know
Mark’s Daily Apple
To put this
summary post and, more importantly, this 10-part series in perspective,
let’s examine one of the most pervasive pieces of dietary advice
given to people worldwide:
foods that contain any cholesterol above 0 mg is unhealthy.”
- T. Colin
Campbell, PhD, author of The China Study.
of this length can begin to fully address a topic as comprehensive
as cholesterol metabolism and the pathogenesis of atherosclerosis.
In fact, those of us who challenge conventional wisdom often find
ourselves needing to do exactly what Frederic Bastiat suggested:
admit that our opponents in this argument have a marked advantage
over us. They need only a few words to set forth a half-truth; whereas,
in order to show that it is a half-truth, we have to resort to long
and arid dissertations.”
So, at the
risk of trying to minimize the “long and arid” part of this process,
below are the 10 things you need to know to be the judge –
for yourself – if the conventional advice about cholesterol
1. The sine
qua non of atherosclerosis is the presence of a sterol in an
artery wall. How it gets there is the only thing we should be worrying
popular belief, atherosclerosis is not caused by many of things
we think of, such as smoking, high blood pressure, diabetes, high
LDL (the so-called “bad” cholesterol), or low HDL (the so-called
“good” cholesterol). Some of these are certainly markers of risk
– low HDL, for example – while others accelerate the
process – smoking, for example – but none of these are
the direct cause of atherosclerosis.
qua non of atherosclerosis is the presence of sterols (cholesterol
or phytosterol) in arterial wall macrophages. Sterols are delivered
to the arterial wall by the penetration of the endothelium
by an apoB-containing lipoprotein, which transport the sterols.
In other words, unless an apoB-containing lipoprotein particle violates
the border created by an endothelium cell and the layer it protects,
the media layer, there is no way atherogenesis occurs. If this is
a bit confusing, don’t worry. It’s all made clear below.
is vital for life; no cholesterol = no life.
is a 27-carbon molecule shown in the figure below. Each line in
this figure represents a bond between two carbon atoms. That’s it.
All this talk
about “cholesterol” and most people don’t actually know
what it is. So, there you have it. Cholesterol is “just” another
organic molecule in our body.
I need to make
one distinction that will be very important later. Cholesterol,
a steroid alcohol, can be “free” or “unesterified” (“UC”
as we say, which stands for unesterified cholesterol) which
is its active form, or it can exist in its “esterified” or storage
form which we call a cholesterol ester (“CE”).
The diagram below shows a free (i.e., UC) molecule of cholesterol.
An esterified variant (i.e., CE) would have an “attachment”
where the arrow is pointing to the hydroxyl group on carbon #3,
aptly named the “esterification site.”
of the biggest misconceptions is that cholesterol is “bad.”
This could not be further from the truth. Cholesterol
is very good! In fact, there are (fortunately rare) genetic disorders
in which people cannot properly synthesize cholesterol. One such
disease is Smith-Lemli-Opitz
syndrome (also called “SLOS,” or 7-dehydrocholesterol reductase
deficiency) which is a metabolic and congenital disorder leading
to a number of problems including autism, mental retardation, lack
of muscle, and many others.
is absolutely vital for our existence. Every cell in our
body is surrounded by a membrane.
These membranes are largely responsible for fluidity and permeability,
which essentially control how a cell moves, how it interacts with
other cells, and how it transports “important” things in and out.
Cholesterol is one of the main building blocks used to make cell
membranes (in particular, the ever-important “lipid
bilayer” of the cell membrane).
role in allowing cells to even exist, it also serves an important
role in the synthesis of vitamins and steroid
hormones, including sex hormones and bile acids. Make sure you
take a look at the picture of steroid
hormones synthesis and compare it to that of cholesterol (above).
If this comparison doesn’t convince you of the vital importance
of cholesterol, nothing I say will.
One of the
unfortunate results of the eternal need to simplify everything is
that we (i.e., the medical establishment) have done the public a
disservice by failing to communicate that there is no such thing
as “bad” cholesterol or “good” cholesterol. All cholesterol
is imperative for life to exist!
The only “bad”
outcome is when cholesterol ends up inside of the wall of
an artery, most famously the inside of a coronary
artery or a carotid
artery, AND leads to an inflammatory cascade which results in
the obstruction of that artery (make sure you check out the pictures
in the links above). When one measures cholesterol in the blood
we really do not know the final destination of those cholesterol
3. The cholesterol
we eat has little to do with the cholesterol we measure in our bloodstream.
We ingest (i.e.,
take in) cholesterol in many of the foods we eat and
our body produces (“synthesizes”) cholesterol de novo from
various precursors. About 25% of our daily “intake” of cholesterol
– roughly 300 to 500 mg – comes from what we eat (called
exogenous cholesterol), and the remaining 75% of our “intake”
of cholesterol – roughly 800 to 1,200 mg – is made by
our body (called endogenous production). To put these amounts
in context, consider that total body stores of cholesterol are about
30 to 40 gm (i.e., 30,000 to 40,000 mg) and most of this resides
within our cell membranes. Nearly every cell in the body can produce
cholesterol, and thus very few cells actually require a delivery
of cholesterol. Cholesterol is required by all cell membranes
and to produce steroid hormones and bile acids.
Of this “made”
or “synthesized” cholesterol, our liver synthesizes
about 20% of it and the remaining 80% is synthesized by other cells
in our bodies. The synthesis of cholesterol is a complex four-step
process (with 37 individual steps) that I will not cover here, but
I want to point out how tightly regulated this process is, with
multiple feedback loops. In other words, the body works very hard
(and very “smart”) to ensure cellular cholesterol levels are within
a pretty narrow band (the overall process is called cholesterol
homeostasis). Excess cellular cholesterol will crystalize and cause
cellular apoptosis (programmed cell death). Plasma cholesterol
levels (which is what clinicians measure with standard cholesterol
tests) often have little to do with cellular cholesterol,
especially artery cholesterol, which is what we really
care about. For example, when cholesterol intake is decreased, the
body will synthesize more cholesterol and/or absorb (i.e., recycle)
more cholesterol from our gut. The way our body absorbs and regulates
cholesterol is really amazing, so I want to spend a bit of time
the rest of the article
September 1, 2012
© 2012 Mark's Daily Apple