What Is Cholesterol? The Molecule Every Cell Needs and Every Artery Fears

Cholesterol is a waxy, fat-like molecule, a ring structure with a short tail, and it is made by nearly every animal cell. Its first job is structural: inserted between the fatty molecules of a cell membrane, it keeps the membrane firm enough to hold its shape and fluid enough to let things through. Its second job is as a raw material, since the body converts it into the bile acids that digest fat, vitamin D in the skin, and the steroid hormones, cortisol, testosterone and the oestrogens. About four fifths of the cholesterol in the body was made there, mostly in the liver, and the rest came from food; eating more turns the liver's production down, which is why dietary cholesterol, in eggs and shellfish, matters less to blood levels than was believed for fifty years.

Cholesterol does not dissolve in blood, so it is carried in particles of protein and fat called lipoproteins, and the particles, not the cholesterol, are what a blood test counts:

• •LDL, low-density lipoprotein: the particles that deliver cholesterol from the liver to the tissues; when there are too many they lodge in artery walls, which is why LDL is called bad
• •HDL, high-density lipoprotein: particles that collect surplus cholesterol from tissues and return it to the liver; higher levels go with lower risk, though raising HDL with drugs has not reduced heart attacks, so it is a marker more than a cause
• •Triglycerides: the fat carried for energy, high after meals and in people with excess weight or diabetes, and a risk factor in its own right
• •Total cholesterol: the sum, which is less useful than its parts

The disease is atherosclerosis. LDL particles pass into the wall of an artery, become oxidised there, and are engulfed by immune cells that swell into foam cells and die, leaving a core of fat and debris under a fibrous cap: a plaque. Over decades the plaque grows, narrows the vessel and, if the cap cracks, triggers a clot that blocks it, which in a coronary artery is a heart attack and in the brain a stroke. The process begins in childhood, is driven by the number of LDL particles in the blood multiplied by the years of exposure, and is accelerated by smoking, high blood pressure and diabetes, all of which damage the artery lining. The evidence that LDL causes it rather than merely accompanying it is about as strong as evidence in medicine gets: people born with genes that give them lifelong low LDL have far less heart disease, people born with genes that give them high LDL have heart attacks in their thirties, and every intervention that lowers LDL, by whatever mechanism, lowers events in proportion.

A blood test reports LDL, HDL, triglycerides and total, in millimoles per litre in Britain and milligrams per decilitre in America. Guidelines have moved from fixed targets to overall risk: a doctor combines the cholesterol figures with age, sex, blood pressure, smoking and diabetes into an estimate of the chance of a heart attack or stroke in the next ten years, and treats above a threshold. As a rough guide, an LDL below 3 millimoles per litre is desirable for a healthy adult, below 2 for someone who has already had a heart attack, and there appears to be no level below which lowering it further stops helping. Familial hypercholesterolaemia, an inherited condition affecting about one person in 250, produces LDL of 5 to 10 from birth and is badly underdiagnosed; a very high reading in a young, slim person is the signal.

Diet moves LDL by a modest amount, and the lever is saturated fat rather than cholesterol: replacing butter, fatty meat and palm oil with unsaturated fats, and adding soluble fibre from oats, beans and fruit, lowers LDL by around ten percent, as does weight loss; exercise raises HDL and lowers triglycerides. The larger lever is drugs. Statins, introduced in 1987, block the liver's cholesterol-making enzyme, lower LDL by 30 to 50 percent, and reduce heart attacks and strokes by about a quarter for every millimole they remove; they are cheap, taken by tens of millions, and their side effects, chiefly muscle aches, are less common in blinded trials than in practice. Ezetimibe blocks absorption in the gut, and the newer injectable antibodies and gene-silencing drugs that boost the liver's clearance of LDL lower it by a further half for those who need it. The one myth worth dropping is that cholesterol is something to avoid in food; the body makes what it needs, and the question is only how much is left circulating.

Cholesterol is a fat the body makes for its cell membranes, bile and hormones, carried in the blood by lipoprotein particles; the LDL particles that deliver it can lodge in artery walls and build the plaques that cause heart attacks and strokes, and the risk depends on how many there are for how long. Dietary cholesterol matters little, saturated fat and fibre matter somewhat, and statins and newer drugs lower LDL and events in proportion to the reduction.