Is Too Low Cholesterol A High Health Risk?

by Jonathan Wilson Health Consultant

Impressive new data show that low total cholesterol may be just as hazardous as high. Is HDL all we really need to worry about?

One of the over-riding concerns of medical journalism in recent years has been high cholesterol. The dangers of LDL (the bad cholesterol) have been unremittingly highlighted, prefaced only by the caveat that cholesterol is necessary to good health.

But no one has ever really warned against the dangers of too low cholesterol. Certainly, no one has said that a depleted cholesterol supply can raise your mortality risk.

Now they are saying so. And they are backed by research evidence that’s solid and impressive. The evidence was reported last year in medical journals including BMJ (British Medical Journal), Cancer, and Circulation, a publication of the American Heart Association. Low cholesterol, the research shows, is more than a trivial concern.

The most dramatic conclusion:

“There is an association between low blood cholesterol and non-cardiovascular deaths in men and women.” There is no longer any doubt, report the experts, that the 6 per cent of middle-aged adults with cholesterol values below 160 milligrams/deciliter are at increased risk of dying from a variety of causes, which includes lung cancer, other non-colon cancers, respiratory disease, digestive disease, trauma, hemorrhagic stroke, and other residual causes.

And how solid and believable is the evidence? The report is based on a meta-analysis (a statistical pooling of data) of 19 studies on low cholesterol, and it’s likely to be quite some time before anyone produces scientific evidence that’s more conclusive.

One by one, these studies did not carry a lot of statistical power, but put together they are enough to draw conclusions – not necessarily that low cholesterol causes excess deaths but certainly that more men with low cholesterol die than those with “normal” (160-199 mg/dl) cholesterol.

How many more? For men with cholesterol lower than 160 mg/dl, risk is elevated between 14 and 22 per cent for all causes of death, compared to those with cholesterol between 160 and 200 mg/dl. That’s just about the same risk that men with cholesterol greater than 200 mg/dl had from heart disease. When you graph the death rate at increasing cholesterol levels, the curve forms a U, with the bottom of the U in the 160-200 mg/dl range.

[Read: Tomorrow I Am Going To Do Something About My Cholesterol]

What are They Dying From?

Heart Disease: Not surprisingly, most of the elevated risk was not from heart disease. Eleven of 18 studies did show some elevated risk of heart disease in low-cholesterol men, but one of the largest and most comprehensive – the Multiple Risk Factor Intervention Trial – actually found an 11 per cent lower risk. It seems fair to conclude that low cholesterol did not significantly increase or decrease heart disease risk compared to the normal group. And risk of cardiovascular disease did rise progressively in men (but not in women) with total cholesterol levels higher than 200 mg/dl.

(This, in fact, was one of the other interesting research conclusions, namely that “there is no association between high blood cholesterol and cardiovascular deaths in women… With the exception of those who already have coronary disease or other reasons for being at a comparably very high risk of CHD (coronary heart disease) death, it no longer seems wise to screen for and treat high blood cholesterol in women.”)

Cancer: Most of the extra risk at low cholesterol levels came from cancer and other problems. In men with cholesterol lower than 160 mg/dl, cancer rates were elevated by approximately 18 per cent compared to rates in the 160-200 mg/dl groups. This holds true for colon cancer, rectal cancer, lung cancer, and several others.

A new study, reported in Cancer, has also found increased risk of colon cancer with low cholesterol. Using the patients from the famous Framingham study – a sample of more than 5,000 men and women followed for nearly 40 years – the team, led by Bernard E. Kreger, M.D., M.P.H., found that a 20 mg/dl increase in total cholesterol lowered the risk of colon, but not rectal, cancer by about 15 per cent. Just as interesting, these researchers found a strong interplay between low cholesterol and body mass index (weight/height). The greatest risk of colon cancer – an elevation of 4.53 times – was in men with low cholesterol and high body mass index (overweight).

Other: Risk was elevated the most for a collection of non-heart, non-cancer causes of death, such as respiratory and digestive disease and injuries. In fact, both men and women with low, compared to normal, cholesterol had about 40 per cent greater risk. What’s more, the risk of these types of deaths dropped – down 11 to 25 per cent – for men with cholesterol over 200 mg/dl. compared to the normal group.

Injuries were a particularly deadly risk to men. Their increased risk was 40 per cent, compared to only 26 per cent of women. And data from the BMJ article suggest that much of that 14 per cent disparity may be self-inflicted. Swedish researchers followed over 26,693 men and 27,692 women for more than 20 years. During that period, 376 men and 139 women died from injuries. Of those sub-groups, 146 men and 44 women committed suicide. (All people with cancer were excluded from the data, because they may have had special incentive to take their own lives.)

That so many more men than women commit suicide is disturbing, but it’s not news. Higher suicide rates in men are well documented. But the Swedish scientists also cross-checked deaths from injuries and suicide with total cholesterol levels, and the numbers are dramatic.

In the first six years of the study period, the risk of injury for men with the lowest cholesterol turned out to be 2.75 times higher than for those in the highest cholesterol group, and suicide was elevated by 4.1 times! Strangely, though, the elevated risk disappeared by the end of the 20.5 year follow-up. This led the researchers to speculate that a decrease in cholesterol to below a person’s normal value may be more important than a habitually low level.

Why should low cholesterol make a person suicidal? No one knows, and it may, in fact, just be a side-effect of some other disorder. The Swedes did note, however, that low cholesterol has been found in criminals, aggressive people and those with low self-control. And studies of monkeys have shown behaviour changes when the animals are fed a diet low in saturated fat and cholesterol.

What to Do?

Understand, no one is questioning whether lowering total cholesterol is beneficial to people who have been diagnosed with heart disease. On that, at least, that data are clearly and consistently positive. But when you examine studies of otherwise healthy people who try to lower cholesterol, the results aren’t so clear or consistent.

Lowering total cholesterol definitely does reduce deaths from heart disease. But other causes of death increase, particularly if the patients are simply treated with cholesterol-lowering drugs. Treatments that include several approaches – drugs, diet and exercise, for example – don’t show such strong increases in non-heart-disease deaths.

The experts who were involved in extracting the data showing low cholesterol to be bad for you are very tentative about drawing conclusions that would suggest you change your behaviour. They want to be absolutely sure that this “sacred cow” really needs slaughtering to feed you hamburgers.

So where does this leave us? At the very least, with the same healthful skepticism we always carry toward taking drugs. If your doctor wants to put you on a cholesterol-lowering drug, ask questions. Get him to explain the rationale. Make sure he’s aware of this research and has taken it into consideration.

We also see no reason for you to make changes in diet based on this work. A low-fat, high-fibre diet has many other benefits besides lowering cholesterol, including reduced risk of several cancers and diabetes, just to name a couple.

Mainly, though, we’re left with the same impression we’ve had for some time: Total cholesterol just doesn’t tell the total story. Numerous studies have shown that HDL cholesterol (the good type) and its ratio to LDL or total cholesterol is a better predictor of heart disease risk. It’s not impossible for a person to have relatively high total cholesterol and lots of HDL at the same time. And it seems likely that very low total cholesterol is likely to go along with low HDL.

Big changes in cholesterol policy may be on the horizon, but those of us who’ve already adopted a healthful, preventive lifestyle have probably already implemented them.

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