Cholesterol

We all have quite a lot of cholesterol in our blood, and it is there for the excellent reason that it is an essential chemical for the efficient running of the human body. Only a small amount of this cholesterol comes directly from the food we eat: most of it is made by our own body. Nevertheless, it is not a good thing to have too much. Unfortunately, some individuals have very high cholesterol levels, and the cause is hereditary; about 25 people in 10,000 carry this trait. This is a worrying condition which requires constant monitoring and medical attention to correct it. For such people the battle against cholesterol is never-ending because they are prone to heart disease. The rest of us are lucky by comparison, but that is little comfort to many people who now fear that they too are at risk unless they can reduce the amount of cholesterol in their blood. If you find your blood cholesterol level is too high you can generally reduce it by following the advice of a trained dietitian, which generally means eating less fat and more fibre, and especially soluble fibre.

Cholesterol is not a life-threatening toxin, but a medium-sized molecule that is really a building block for important parts of the body. In particular it is an essential component of cell membranes. Cholesterol also stabilizes a cell against temperature changes. It is a major part of the membranes of the nervous system, the brain, the spinal cord and the peripheral nerves. In particular it is incorporated into the myelin sheath that insulates the nerves from the surrounding tissue. Cholesterol is also the forerunner of important hormones such as the female sex hormone, oestradiol, and the male sex hormone, testosterone, and of vitamin D, which we need in order to utilize calcium and form bone. Nearly all body tissues are capable of making cholesterol, but the liver and intestines make the most. We require cholesterol to produce the bile we need to digest the fats in our food, and the name itself comes from the Greek words for 'bile solids'.

Essential though cholesterol is, there can be too much of it, and too much causes a build-up of deposits in the arteries, constricts them, and may even block them, with dire consequences.' The causes which are now seen as contributing to higher-than-normal cholesterol levels are: hereditary factors, which are the most important; then high blood pressure; followed by stress, smoking, obesity and dietary cholesterol.

We can do nothing about the first of these since it is written in the genes we inherited from our parents. It is also difficult to change the pressures of work, but we can give up smoking and we can change our diet and lose weight, and maybe reduce the level of blood cholesterol at the same time. Dieting as a course of action is relatively easy to undertake and perhaps this is why it has received most attention, although the focus of that attention has tended to be directed at cholesterol. This is perhaps not surprising in view of the known danger of heart disease suffered by those with naturally high levels of cholesterol in their blood. In their case the high blood cholesterol level can be brought down with medical treatment using potent pharmaceutical drugs, but for most people a change of diet may be all that is required. The drug treatment works in that it prolongs the life of the high risk group, and there is a growing tendency to believe that it will do the same for the rest of us. Regular cholesterol monitoring is possible, even using a home test kit. The simple message that most people have now picked up is that cholesterol is bad news and that foods with high levels of this should be avoided.

Only a little of the cholesterol in our blood comes from our food. The eating of oils and fats has much more effect in boosting it. Our bodies produce bile acids in order to digest these food molecules, and bile acids are made from cholesterol. The more fat we eat, the more bile acid we need. The more bile acid we use, the more cholesterol we make, and the more of this gets in our intestines. When it has done its job it can be reabsorbed by the body and reused.

Food manufacturers have responded to the public's heightened awareness of cholesterol as a dangerous chemical, and today you can even see 'no cholesterol' or 'low cholesterol' on some product labels on supermarket shelves. The public has got the message, but is it a helpful one? Cholesterol itself does not cause heart attacks or high blood pressure. We make four times as much cholesterol a day as we could possibly absorb from our food, even assuming we were to eat a lot of dairy foods such as eggs and cream which contain relatively high amounts.

Cholesterol is so important that together our cells, intestines, and especially our liver make about a gram of it every day. The average adult has 150 grams (5 ounces) in their body, enough to fill a wine glass. Very little of this has come from the cholesterol in their food, and if a person is a vegan vegetarian and eats no animal products, they take in none at all. Their own bodies have to produce all the cholesterol they need. Those who eat meat, fish or dairy products generally consume about half a gram of cholesterol a day, and their body can absorb a little of this. How much depends upon other components of their diet, such as soluble fibre which scavenges cholesterol.

In theory the ideal level of cholesterol in the blood is 200 milligrams per 100 millilitres of blood, and this is the target to aim for in the USA. In Europe the magic number is 5.2, with the cholesterol being measured in the chemical units of millimoles per litre of blood. These numbers are just different ways of expressing the same amount. Because cholesterol is chiefly a hydrocarbon-type molecule, it is insoluble in water, yet it has to be transported by the blood. To do this it combines with lipoproteins, tiny globules which are a combination of fatty acids and proteins. The low density lipoproteins (LDLs) are where most of the cholesterol in our blood is to be found, and this explains why LDL is regarded as threatening because it deposits as plaque and clogs up our arteries, and may even trigger the formation of a blood clot. There is also another type of lipoprotein called high density lipoprotein (HDL), but this is considered less harmful - indeed some claim it acts as a protective factor. HDL is thought to be responsible for removing cholesterol and transporting it safely to the liver.

Given a balanced diet, our bodies regulate the production, use and removal of cholesterol, and it stays at around the 200 mg (or 5.2 mmole) level. There are several factors that may push it above this figure, such as a fatty diet, smoking, stress, and drinking too much coffee.2 There are some foods which can reduce our cholesterol, such as garlic, alcohol, oats and baked beans. These last two contain a lot of soluble fibre, and a diet which includes them regularly will reduce your blood cholesterol level by about 10%.

People with naturally high levels may have cholesterol in excess of 300 mg (or 8 mmole), and some even exceed 800mg (20 mmole). The cause is a hereditary defect in those receptors of.the liver that remove cholesterol from the blood. In addition to con trolling their diet such people need drug therapy, and there are two kinds of drug they can be prescribed. One type binds the cholesterol in our intestines and prevents it from being absorbed. This type is a more effective form of scavenger than soluble fibre, and requires the patient to take an ounce or two of the prescription a day. To compensate for this loss of cholesterol, the body then uses more cholesterol to make bile and so the level in the blood falls. A modified form of wood cellulose has also been discovered to lowet cholesterol by up to 33% within two weeks. The rnaterial HPMC (short for hydroxypropyl-methylcellulose) is manufactured by Dow Chemical as a thickening agent for cheesecake and desserts, but health and safety tests revealed quite by accident that it dramatically lowers cholesterol levels, and especially LDL levels, by as much as 50%.

The other treatment aimed at reducing cholesterol uses drugs and actually interferes with the way cells produce this chemical; in other words the drugs turn off the supply at source. These pharmaceuticals now have worldwide sales in excess of $1 billion annually, and they are one of the fastest growing drugs. The anti-cholesterol drugs most commonly used are lovastatin and mevastatin which are derived from a natural substance found in fungi. They work by deactivating an enzyme that is needed to produce mevalonic acid, the molecule from which cholesterol is made, and it will reduce cholesterol levels by up to 50%.

Only the few people with naturally high levels of cholesterol really require such a drug; the rest of us can keep ourselves at the normal level with very little effort, just by eating less fat and more fibre. A common course of action is to target high cholesterol foods and cut out dairy products such as butter and eggs, although the effect this has on the level-of cholesterol in the blood is minimal. In fact four ounces of chicken contains more cholesterol than an ounce of butter. Eating those high in cholesterol should not worry us, because only a small fraction of the cholesterol we eat ends up in our bloodstream.

Fat intake is much more important in determining cholesterol levels because it stimulates bile production which in turn stimulates cholesterol production. Not only that, but the fat that is absorbed by the gut is then the raw material for more cholesterol to be made in the liver. Cooks and chefs of the future may well design meals which combine high cholesterol foods with foods high in soluble fibre.

Reducing cholesterol in the diet is not without its risks, however, as an epidemiological survey in 1992 discovered. Fifty thousand Swedish men and women over 45 who lived in Varmland were studied over a period of 20 years by Dr Gunnar Lindber of the Centre for Public Health Research at Kadsttad. The results were not quite as reassuring as people had hoped: the group of men with low blood cholesterol did not have a much lower death rate than the group with high cholesterol levels. Admittedly they were less likely to die of heart disease, but they made up for this by being more likely to commit suicide or to die prematurely in accidents. Curiously these effects were not found in women. For the rest of us the best advice, if we suspect our cholesterol level is too high and is putting us at risk, is to eat less fat and more fibre. This advice is also the same as that of many weight-reducing diets, and since being overweight is now thought to put a greater strain on the heart than cholesterol, the advice is still good, although for the wrong reasons.

Molecule of the Month for December 1997 (see the other Molecules of the Month)

The text of this web page is from the book: The Consumer's Good Chemical Guide by John Emsley (Science Writer in residence at Imperial College of Science, Technology and Medicine, London), ISBN 0-552-14435-5, Corgi 1996.

cholesterol C₂₇H₄₆O, the most common animal sterol (steriod alcohol). It can be isolated as white pearly granules which melt at 149 C. It is only sparingly soluble in water but soluble in oils, fats and solutions of the bile salts. The main commerical source has been from the spinal cord of beetle cattle. Cholesterol as a chemical has been used as an emulsifying agent in cosemtics and pharmaceuticals (view its 3-D model - chime plug-in required).

oestradiol C₁₈H₂₄O₂, a female sex hormone, present in the urine of pregnant women.

testosterone 17-beta-hydroxy-4-androsten-3-one, C₁₉H₂₈O₂, the androgenic hormone formed in the testes: it controls the devolopment and maintenance of the male sex organs and secondary sex characteristics. It is used, together with synthetic analogues, in treating disorders due to impaired production of the natural hormone. Testosterone can be prepared commerically from dehroepiandrosterone.

vitamin D is needed for the absorption of calcium and the regulation of calcium levels in the blood. Both vitamins, which have almost identical actions, are used for the prevention and cure of infantile rickets The absence of vitamin D in the food of young animals leads to the development of rickets unless the animal is exposed to sunlight or u.v. irradiation.; they are essential for the normal development of teeth, and are used for treating osteomalacia and dental caries. They are necessary for the absorption of Ca and P from the gut. Sunlight activates the metabolism of vitamin D in the body. The first vitamin D to be discovered was a crude mixture called vitamin D1. Irradiation of erggoterol with u.v. light gives calciferol or vitamin D2. Irradiation of 7-dehydrocholesterol gives the natural vitamin D or vitamin D2, which differs in the structure only in the side chain. Good sources of vitamin D are butter, margarine, cheese cream, yogurt, milk eggs and sunlight. It is soluble in fats, milk, butter and eggs. The richest sources of vitamin D are fish-liver oils, particularly those of the halibut and the cod.

lovastatin, given as a treatment to control high cholesterol levels in the body.

mevastatin, given as a treatment to control high cholesterol levels in the body.

mevalonic acid, precursor to cholesterol formation.