Rethinking Cholesterol

By Donald R. Davis, Ph.D.

At mid-century, few Americans had heard of cholesterol, and fewer still worried about it. Cardiovascular disease was the leading killer, but many explanations of “hardening of the arteries” focused
on “calcium deposits,” not cholesterol. Less than 40 years later, cholesterol obsession reigned, and a

••• most U. S. heart attack deaths occur at relatively low blood cholesterol levels •••

federal agency launched the National Cholesterol Education Program (NCEP) to advise us to lower our dietary and blood cholesterol. Most medical scientists view this transformation as progress, as they point to our 25-year decline in heart disease (still our leading killer). Some of us are skeptics. There have always been basic “flies in the ointment” of the cholesterol theories, but these are usually ignored. For example, the low rate of heart disease in Japan and in native Eskimos is not explainable by their cholesterol levels and intakes. And most U. S. heart attack deaths occur at relatively low blood cholesterol levels (under 200 mg/100 mL). But these pesky facts have barely slowed the cholesterol bandwagon.

Finally, irresistible evidence is starting a new era of rethinking cholesterol. There is much to ponder, and even if the outcome is, as I expect, to clear cholesterol’s “bogeyman” status, still it will take many years to overcome old ideas pervading our health professions, our media, and our advertising. Here I will highlight four areas needing rethinking. Total Mortality Until recently, researchers focused only on the effect of cholesterol lowering on heart disease. Now they are shocked to find (or still deny) that cholesterol lowering increases death rates from cancer, accidents, and many other causes, with no net reduction in total mortality. So three researchers in 1992 published an editorial in Circulation, titled: “Health Policy on Blood Cholesterol: Time to Change Directions.” Even the NCEP acknowledges the problem briefly in its recent introduction to several pages of detailed advice to physicians on how to-yes-lower cholesterol.

The total mortality problem appears both in studies using diet and studies using drugs. It may be caused by cholesterol lowering as such, by the methods used to accomplish the lowering, or both.  Very recently, a Scandinavian trial of the drug simvastatin found a major reduction in cardiovascular deaths and, for the first time, in total mortality. Proponents of cholesterol lowering are ecstatic, and claim vindication, but prematurely. It was a fairly short (5.4 year) study of a new drug.  Skeptics may point to the dismal record of other cholesterol lowering drugs and to past unpleasant surprises when new drugs failed in further testing, or showed unexpected side-effects after long use.

Another bright hope for cholesterol fighters is the proof of regression of atherosclerotic plaques by strict cholesterol lowering methods(Dean Ornish and others). But these studies are not yet long or large enough to address the total mortality issue. Because they use extreme versions of the cholesterol lowering methods that previously increased mortality from cancer and other causes, even greater problems with total mortality seem likely. But like many new medical procedures, regression therapies are now advocated without much testing.

Biased Reporting Cholesterol fighters still say that cholesterol lowering at least reduces coronary mortality, if not total mortality. However, even this claim is suspect. A citation study of 22 controlled cholesterol lowering trials found that supportive trials are cited about six times more often than the many unsupportive trials. Since 1970,key unsupportive trials are entirely unacknowledged in the major journals, although their number almost equals the supportive trials (British Medical Journal, 1992;305:15). All22 trials considered together point to only a 6% reduction in coronary mortality, too small to be statistically reliable even with the huge number of subjects involved. Selective reporting causes unrealistic beliefs about the benefits of cholesterol
lowering, which needs rethinking in full view of neglected data.

Exceptions Cholesterol lowering began with the undisputed observation that high blood cholesterol is statistically linked to heart disease. But this observation applies mainly to middle-aged men (and is of little use even to them, as noted). Failure to consider exceptions sadly misleads the aged to needless worry about “high cholesterol,” and misleads them and their doctors into useless, risky and often costly therapies. This view is strengthened by a recent report in The Journal of the American Medical Association (November 2, 1994). Mtera4-year study of 997 persons older than 70 years, the authors found no evidence that high blood cholesterol, high LDL cholesterol, or low HDL cholesterol are associated with cardiac mortality, total mortality, or hospitalization for cardiac causes. In fact, women with the highest cholesterol levels lived significantly longer than those with low or medium cholesterol levels. Surely we. must rethink our ideas about cholesterol in those over 70.

Better Ways Even if cholesterol lowering were as successful as is widely claimed (10% to 15% reduction in cardiac mortality), it fails miserably to even approach the minuscule rates of heart disease in Americans of a century ago, or in modern (but non-westernized) Eskimos who eat large amounts of cholesterol. Yet few researchers wonder whether cholesterol lowering might be “barking up the wrong tree.” Those who do are finding striking results. Preliminary studies suggest roughly a 50% reduction in heart disease associated with each of the following: (I) Eating seafood frequently (U. S. men, Europeans, Japanese, Eskimos), (2) Eating nuts frequently (Seventh-Day Adventists, Iowa women), (3) Taking (3- carotene supplements (U. S. physicians), (4) Taking vitamin E supplements (U. S. nurses), and (5) Avoiding margarine, vegetable shortening, and other partially hydrogenated fats (U. S. nurses). At least the fish studies show both reduced cardiac mortality and reduced total mortality. If even some of these ways are confirmed, cholesterol lowering will be discarded as we move on to better ways.

After we rethink these and other aspects of cholesterol lowering, I expect that Americans one day will enjoy much of the blissful ignorance about cholesterol that they had prior to mid-century, as heart disease nevertheless continues to decline. Might Americans 40 years from now regard the current era of cholesterol phobia and the NCEP as medical relics, akin to bloodletting and snake oil? I hope to live long enough to find out, as I personally ignore cholesterol but take many other steps to build my health.