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What is Cholesterol?

Cholesterol is the most important sterol synthesized by animals. It is mostly produced in the liver through a synthetic pathway devoted to the production of a number of essential sterols and lipids.

Cholesterol is an important organic molecule in the body. For example, it is essential for the formation of cell membranes because it provides the structural integrity and permeability needed for membranes to protect cells while still allowing the inflow and outflow of certain molecules.

Other important roles of cholesterol in the body include the syntheses of bile acids, vitamin D and steroid hormones (including sex hormones and hormones released from the adrenal gland).

The production of cholesterol proceeds by a series of reactions. This complex synthesis involves 37 steps and starts with a key enzyme known as HMG-CoA reductase (inhibited by statins, a class of cholesterol-lowering drugs).

To regulate the amount of cholesterol in the body, a feedback mechanism turns down cholesterol synthesis in the liver when dietary cholesterol intake rises. This synthesis is also raised when the amount of cholesterol obtained from foods is lowered.

When cholesterol synthesis is poorly regulated, a state characterized by an abnormally high cholesterol level may be reached. This state is known as hypercholesterolemia.

During hypercholesterolemia, LDL (low-density lipoprotein) is high while HDL (high-density lipoprotein) is low.

Hypercholesterolemia increases the risks of heart attack, stroke, and peripheral vascular disease.

More than cholesterol, it is the abnormally high level of LDL cholesterol that has been linked to increased heart disease. However, because LDL is often called “bad cholesterol”, bringing down cholesterol level is commonly, but mistakenly, believed to reduce the risk of heart disease.

Cholesterol and Lipoproteins

Lipoproteins are biochemical packages made out of proteins and lipids. They are used to move fats across cellular membranes and also through the circulatory system.

To transport fats, lipoproteins bind to them and then emulsify the fats.

Lipoproteins are classified by density. Large lipoprotein molecules are less dense than smaller lipoproteins. Large lipoproteins are also made up of more fats than proteins.

VLDL is produced in the liver from cholesterol and apolipoprotein B. Once released into the blood, VLDL is then broken down into IDL. The fatty acids released from this breakdown is taken up by the adipose tissue and muscles.

IDL is either returned to the liver or further broken down into LDL. The breakdown of IDL is also accompanied by the release of fatty acids.

The LDL released from IDL has a very high cholesterol content. Once released, LDL molecules circulate through the body until they are returned to the liver or taken up by muscle cells.

Besides apolipoprotein B, a related lipoprotein (lipoprotein a) is found in the blood. Lipoprotein is also a combination of LDL and apoprotein a. The level of this lipoprotein is a very accurate predictor of the risk of heart disease.

Cholesterol and the Risk of Heart Disease

Although LDL cholesterol is commonly called bad cholesterol and HDL cholesterol is referred to as good cholesterol, the truth is that there is only one type of cholesterol and it is neither good nor bad.

Lipoproteins such as LDL and HDL are carrier proteins used to package and transport cholesterol. The difference between the two types of lipoproteins is their sizes.

In addition, HDL molecules come in different sizes and so do LDL molecules. For example, while some LDL particles are too big to pass into the pores of artery walls, some LDL particles are small enough to lodge in the lining of arteries.

Therefore, even LDL cholesterol is not inherently bad. In fact, LDL cholesterol becomes “bad” only when it is oxidized and forms a fatty deposit on the walls of the arteries. Only then can it increase the risks of atherosclerosis and heart disease.

Currently, health experts recommend anyone over the age of 20 to take cholesterol tests at least once every 5 years. Such tests will provide a measure of total cholesterol as well as the levels of VLDL, LDL and HDL cholesterol.

The American Heart Association recommends keeping total blood cholesterol below 200 mg/dL.

However, total blood cholesterol is actually a poor predictor of the risk of heart disease unless it rises above 300 mg/dL.

Clinical data show that HDL cholesterol and triglycerides are better indicators of the risk of cardiovascular complications. The two ratios to watch out for are:

• HDL cholesterol/total cholesterol ratio (above 0.24 or 24%)
• Triglyceride/HDL cholesterol ratio (below 2)

Demonizing Cholesterol

Lowering blood cholesterol is a treatment goal that emerged only after doctors learned how to measure blood cholesterol. Some experts would argue that lowering cholesterol is an artificial problem created as we try to understand the link between lipids and cardiovascular health.

Even now that we know HDL cholesterol and non-HDL cholesterol, such as LDL cholesterol, are more important than total cholesterol, most doctors still aim to lower total cholesterol.

In 2004, the National Cholesterol Education Program constituted a panel of 9 doctors to provide recommendations for reducing the risk of heart disease. The panel submitted that LDL cholesterol should be kept lower than the old limit of 130 mg/dL.

The new guideline-recommended LDL cholesterol level less than 100 mg/dL and as low as 70 mg/dL for people deemed to have a very high risk of heart disease.

While this panel quoted a number of past studies to support their recommendations, a 2006 review published in the Annals of Internal Medicine failed to find strong evidence and support for those recommendations even in the studies quoted by the panel.

It was later discovered that 8 out of the 9 doctors on the panel had received financial support from drug companies that sell cholesterol-lowering drugs such as statins.

Unfortunately, the official guidelines from the American Heart Association still follow the recommendation of such biased experts.

The Dangers of Lowering Cholesterol

One of the dangers of significantly lowering cholesterol levels is its impact on vitamin D production.

Vitamin D is synthesized in the skin from the ultraviolet (UVB) irradiation of a cholesterol metabolite. This reaction is important because dietary sources of vitamin D are fewer than for other vitamins.

Given the importance of vitamin D to general health, this synthetic pathway is vital for keeping up the level of the vitamin in the body. However, lowering cholesterol to dangerous levels can severely impair vitamin D synthesis.

The body also uses cholesterol as a precursor in the synthesis of other essential molecules. For example, all steroid hormones depend on optimal blood cholesterol levels.

Without cholesterol, the endocrine and reproductive systems can be severely affected.

To underline the importance of cholesterol in the body, it is important to note that when HDL removes cholesterol from the blood, it returns it to the liver instead of emptying it into the kidneys for excretion.

This means that the body collects cholesterol in the liver to reuse. This conservation only means that the body considers cholesterol to be important to its optimal functioning.

Good HDL. Bad HDL

Just as lowering cholesterol is not always a healthy choice, raising HDL is not always desirable too.

Describing HDL as good cholesterol and LDL as bad cholesterol is too simple. In fact, a 2011 study found out that simply raising HDL does not reduce the risk of heart disease.

Although HDL is used to remove cholesterol from the blood, not everything that raises its level is good and not everything that lowers it is bad. In fact, the efficiency and number of HDL differ from one person to another and are determined by genetic factors.

While people who naturally have a higher number of HDL particles usually have lower risks of heart disease, increasing HDL through diet or drugs does not necessarily translate into lower cardiovascular risk.

A prime example of this irony is the effect of increased dietary intake of saturated fat and cholesterol on blood cholesterol levels.

When High HDL is Bad

By consuming more foods rich in cholesterol, the body may increase the amount of HDL produced to help clear cholesterol away from the blood. However, the amount of LDL released is also increased. An HDL increase followed by an LDL increase offers no advantage and may even be unhealthy.

A similar result is obtained by raising HDL with the cholesterol-lowering supplement, niacin, and the drug, torcetrapib.

Studies show that niacin does not protect against heart attack even though it improves HDL levels. Torcetrapib, on the other, was taken off the market because it significantly increased the risk of a heart attack.

The results of multiple studies also indicate that by dramatically increasing HDL levels, diet and drugs may cause a buildup of HDL in the blood. When HDL cholesterol spends too much time in the blood, the odds that it will be oxidized, much like LDL cholesterol, increases.

When Low HDL is Good

On the other hand, lowering HDL may sometimes reduce the risk of heart disease.

For example, switching to low-fat, low-cholesterol diet will lower your HDL levels as the body reduces HDL production to compensate for lower dietary cholesterol reaching the blood.

Therefore, the HDL reduction that follows the adoption of a raw, plant-based, low-fat diet is good for you.

This is exactly the reason why Asians who eat low-fat diets also have low HDL levels and yet have the lowest rates of heart disease in the world.

All of these examples mean that a change in HDL level needs to be seen in the context of its cause. When HDL levels are lowered by eating a healthier diet, the risk of heart disease is lowered. However, this risk is raised in people who eat high-fat, high-cholesterol foods and yet have low HDL levels. 

Cholesterol-Lowering Drugs: Are they Safe?

Cholesterol-lowering drugs are the second most prescribed medications in the US (after antihypertensive drugs). However, some experts believe that the vast majority of these prescriptions are needless.

Statins are the most commonly prescribed cholesterol-lowering drugs. Yet they are associated with some serious side effects.

Statins work by inhibiting the enzyme, HMG-CoA reductase. This enzyme is involved very early on in cholesterol synthesis. Unfortunately, this synthetic pathway is also responsible for the production of other sterols and functional compounds.

Because of this, statins reduce the level of related sterols such as dolichols (needed to maintain the structural integrity of cell membranes).

The syntheses of sex hormones, adrenal hormones, and vitamin D are also affected.

In addition, statins reduce the level of coenzyme Q10 (CoQ10). Since CoQ10 is an essential cofactor in the generation of energy molecules (ATP) in cells, its depletion leads to muscular weakness and contributes to most of the side effects commonly associated with statins.

Cholesterol-Lowering Drugs: Are they Effective?

Even with all their terrible side effects, some doctors believe that the benefits of statins outweigh their risks. But are statins even very effective at lowering blood cholesterol?

A number of post-marketing surveillance reports and follow-up clinical trials have shown that some key statin drugs do not work as believed.

A good example is Vytorin, a combination of Zocor (a statin) and Zetia (a drug that blocks the absorption of dietary cholesterol).

In fact, the data that confirmed that this drug was ineffective came from the clinical trial conducted by the drug manufacturer. However, during the 2 years in which the results of the trial were delayed, the drug had captured a sizeable chunk of the market for cholesterol-lowering drugs.

The data showed that the combination of Zocor and Zetia doubled the risk of atherosclerosis when compared to Zocor alone.

Pfizer’s Lipitor is another good example of a statin manufacturer manipulating unfavorable data.

In the results quoted from its clinical data and printed in one of its ads, the manufacturer claimed that the drug can reduce the risk of heart attack by 36% when the addendum written in small prints at the end of the ad indicated that Lipitor was barely more effective than placebos.

There are definitely natural alternatives to prescription cholesterol-lowering drugs. For most people, the combination of lifestyle changes, adoption of a healthier diet and regular exercise is effective for improving the blood cholesterol profile.

In fact, for most people, drugs are never needed. When diet and exercise cannot adequately control cholesterol levels, natural supplements should be considered. They are also effective and safer than prescription medications.