Although its name is often suggestive of something
bad, cholesterol is not a poison and it is not a disease. It is a vital molecule that
performs key structural and regulatory functions in our body. Cholesterol is the most important sterol in
our body. By looking at its structure, you can tell that it’s quite different from
triglycerides and phospholipids. It is still made of the same stuff, carbon, hydrogen and
oxygen but now they are arranged in a completely different way, and in particular they form
four carbon rings, which is distinctive of all sterols. A thing to remember about cholesterol is that
it’s exclusively an animal molecule. For this reason, it is only present in animal
foods. You will never find any cholesterol in vegetable food, so for example, there’s
no cholesterol at all in olive oil or in peanut butter. Cholesterol is nutritionally non-essential,
because our cells can make it starting from fatty acids or glucose, so just like for phospholipids,
we don’t need to worry about getting enough cholesterol from food. Our body can make all
the cholesterol it needs. However, since it’s present in animal food and we can absorb it,
we can also get some of our cholesterol from food, already made. About 2/3 of our body
cholesterol in made by our own cells, the remaining 1/3 comes directly from food. So why is cholesterol important? First of all, it is a structural molecule.
It is an important component of the structure of our cell membranes, and gives them rigidity
to balance the fluidity contributed by phospholipids. Another important structural function of cholesterol
is as constituent of the myelin sheath that protects our nerves and allows proper signal
transmission. Then, it’s the starting material that our
liver uses to build bile salts, which we need to emulsify lipids during fat digestion. It is also a precursor of vitamin D. We can
get some vitamin D directly from food, but we can also build it ourselves in our skin,
as long as we are exposed to sunlight. But to do that, we have to have cholesterol as
starting material. Cholesterol is also the precursor of many
hormones that are called steroid hormones, such as the sexual hormones, like testosterone
or estrogens, and cortisol, involved in our chronic stress response. If cholesterol does so many important things,
why does it have a bad reputation? An old nutritional axiom stated that dietary cholesterol
increases blood cholesterol which in turn increases cardiovascular risk. However, we
know today that this does not hold true. High blood cholesterol will indeed increase cardiovascular
risk, so much so that there is a direct correlation between plasma cholesterol levels and incidence
of coronary heart disease. However, a high intake of dietary cholesterol will hardly
ever increase blood cholesterol in a significant way. It’s not cholesterol that raises cholesterol.
A high intake of saturated fats, trans fats, and sugar, will raise blood cholesterol much
more than eating a lot of cholesterol rich foods, like eggs. Soon you will learn why. For now just note that the only place where
we do NOT want too much cholesterol is our bloodstream, because if it stays there and
has nowhere else to go, it ends up depositing in the walls of our arteries, promoting atherosclerosis
and cardiovascular disease. So remember, cholesterol is dangerous only when it is in our bloodstream.
But once it gets inside our cells, it does no harm anymore and instead is a very useful
molecule. The other important point to remember is that
there is only a weak correlation between cholesterol in food and blood cholesterol levels. Cholesterol
absorption is limited and not very efficient. Only about half of dietary cholesterol is
absorbed, and if our intake exceeds 500 mg, it plateaus, meaning that our gut stops absorbing
it. Furthermore, if dietary cholesterol increases, multiple homeostatic mechanisms will decrease
endogenous cholesterol production and increase cholesterol excretion via the bile. As a result
of all this, substantial variations of cholesterol intake induce only minimal fluctuations in
blood cholesterol. In about 15% of the population, however, which carries a particular polymorphism
for apoprotein E, these homeostatic mechanisms work less efficiently and variations in blood
cholesterol are less stable. Every cell in our body is capable of cholesterol
synthesis for its own use, while the liver can make cholesterol and send it around in
the circulation for other cells to use. The starting material is acetyl-coenzymeA, which
is usually readily available in every cell and can come from fatty acids, glucose and
some amino acids. The metabolic pathway leading to cholesterol
production is non reversible: in other words, our body can make cholesterol but cannot destroy
it, converting it back to acetyl coenzyme A to be used for other things.
The key regulator of the cholesterol synthesis pathway is an enzyme, called hydroxy-methyl-glutamyl
coenzymeA-reductase, from now on we will refer to it as the cholesterol enzyme.
This enzyme can be induced, so that a lot of cholesterol is made, or inhibited, so that
cholesterol synthesis slows down. An important class of cholesterol-lowering medications,
statins, act precisely by inhibiting this enzyme.
Some short-chain fatty acids derived from the intestinal fermentation of fiber, like
butyric acid, have a similar effect and this is one of the reasons why dietary fiber can
lower blood cholesterol levels. Conversely, other dietary factors can induce
the cholesterol enzyme, and therefore raise blood cholesterol levels by promoting its
endogenous synthesis. High dietary fat, and in particular saturated
and trans fats, depresses endogenous synthesis of fatty acids, thus making more Acetyl-CoA
available be used for other purposes, including cholesterol formation.
Another inducer of the cholesterol enzyme is insulin, which is why an excess of high-glycemic
index foods such as simple sugar and refined grains can have a detrimental effect on blood
cholesterol. Ironically, four slices of white bread can end up raising blood cholesterol
more than four eggs. Plant sterols, like beta-sitosterol which
is the most abundant, are structurally similar to cholesterol but we normally cannot absorb
them, so they are not considered nutrients and we could see them as a particular type
of dietary fiber. Plant sterol have a potentially important extra-nutritional function in our
diet in that they interfere with the absorption of cholesterol in our gastrointestinal tract.
In individuals with problems of high blood cholesterol, a moderate intake of about 2
grams of plant sterols every day has been shown to lower blood cholesterol. Inhibiting
intestinal cholesterol absorption is a very effective strategy not so much because it
lowers absorption of dietary cholesterol, which we already know is only marginally relevant,
but above all because it prevents recycling of bile salts, forcing the liver to build
new ones with significant consumption of blood cholesterol.
Nuts and seeds, wheat germ, oat bran, and legumes are good sources of plant sterols,
however the recommended intake of 2 grams for controlling high blood cholesterol can
only be achieved through sterol-fortified foods, such as yogurts, margarines or juices.
Marine sterols, that are especially abundant in shellfish, are also not absorbed and they
act in a similar way to plant sterols.