We should love Cholesterol?

Arguably, cholesterol is one of the most overrated reasons people pin on cardiovascular diseases. Not only do they simply blame cholesterol levels in serum, they also blame fatty diet to be the reason for the diseases. But one should not confuse cholesterol with fats; they are unique from each other such that fats are fatty acids (carboxylic acids containing fatty tails) while cholesterol is a type of sterol.

It is important to note that cholesterol doesn’t simply build up in the body due to diet, but rather, the body itself biosynthetically produces cholesterol from various precursors (most abundantly is from Acetyl-CoA). In this light, it can be seen that cholesterol plays an important role in the functioning of the human body. Not only is it an important membrane component, but it also acts as a precursor to the production of bile acids and steroid hormones. Moreover, the body also has its own mechanism of regulating cholesterol levels in the body by activating nuclear receptors that would instigate the conversion of cholesterol to bile acids.

The importance of cholesterol in human physiology has been recognized in the past –Nobel Prize winners for Physiology Konrad Bloch (1963), M.S. Brown and J.L. Goldstein (1985) for their work in metabolism and regulation of cholesterol in the human body. Based on their work, it was discovered that cholesterol plays many roles in different biological processes and is relatively a common compound in the body. Another important biological process that involves the compound cholesterol is the production of Vitamin D – a type of fat-soluble vitamin that helps the blood absorb and maintain concentration levels of calcium and phosphorus to construct strong bones.

 Ancel Keys, an American Physiologist who studied health effects of diet, was among the few that postulated the correlation between cholesterol levels in serum with cardiovascular diseases. In his study – Seven Countries Study – there was a claim that the rate of getting cardiovascular diseases was associated with the average serum cholesterol levels and per capita intake of saturated fats. Critics were quick to point out that Keys didn’t point out which type saturated fats were ingested (in terms of length). Moreover, various studies done parallel to Keys showed that the association of high cholesterol and saturated fat intake with cardiovascular diseases was isolated to American countries while some Asian countries such as Japan didn’t show such correlation.

It is important to point out however that there are generally two kinds of lipoproteins known as low-density and high-density lipoproteins – which are coined as “bad” and “good” cholesterol respectively due to associations with increasing or decreasing the risk of coronary heart diseases respectively. Saturated fat in the diet is actually what determines the lipoprotein formation. Long-chain saturated fats are what cause increased levels of low-density lipoproteins. So rather than simply blaming cholesterol, there are also other factors that cause the increased risk of getting cardiovascular diseases.

Recent studies (in the US) show that there’s actually no correlation between the risk of getting cardiovascular diseases and intake of saturated fats. In fact, the incidence of obesity and type II diabetes actually increased despite the decreased consumption of dietary fat.

With the hype of decreasing cholesterol levels in serum, people not only focused on diet, but as well as the use of medication. Inhibition of cholesterol synthesis in the body gained research interest, which then paved the way to the development of the drug known as lovastatin – belonging to the class of compound known as statins that block endogenous cholesterol biosynthesis. It is important to note however that statins have been found to have side-effects such as muscle aches, memory loss, deteriorating cognitive functions, and liver damage. This may be attributed to the fact that statins have the tendency to inhibit the biosynthesis of other important endogenous compounds in the body.

Based on this diagram from (Ferranti and Ludwig, NEJM, 2008), it can be said that by inhibiting the biosynthesis of cholesterol, antioxidant activity, intracellular processes and steroid hormone synthesis are also affected.

One alternative that has been developed in decreasing blood cholesterol levels is actually the discovery of phytosterols – sterols that act as structural components in plant membranes similar to how cholesterol act in mammalian cells. Phytosterols have been found to decrease total cholesterol level and low-density lipoprotein level without compromising high-density lipoprotein level. It’s a better alternative to decreasing cholesterol levels compared to statins such that it works on a different mechanism than statins. Rather than inhibiting cholesterol biosynthesis, phyosterols instead compete with cholesterol with regards to intestinal absorption. Phytosterols are available in various vegetable oils such as corn oil and soybean oil. Rather than just relying on drug intake, it seems that dieting is still the safest answer with regards to controlling serum levels.

Did you know?

·      A large percentage of our brain is actually made up of cholesterol

·      Cholesterol in the body is obtained not only through diet but also because of natural biosynthesis

·      Lovastatin is one of the most widely used statin in the world

·      Biosynthesis of Ubiquinones – which are rumored to work as anti-oxidants – are interrupted by intake of statins

·      Statins also inhibit the biosynthesis of carrier lipids

Reference:

Dayrit, Fabian. Sterols in Human Physiology, (2010)