Binding the Cholesterol

Although it is not yet certain that low- ering the cholesterol level in a man's blood will protect him against artery disease, heart attacks and strokes, many doctors think it may and are willing to try using drugs to prove it. The first such drug, MER/29, had to be yanked off the market because of its severe side effects. Two others, Atromid-S and Choloxin, are now approved and so far appear to be safe, but because they work through metabolic and hormonal mechanisms, many physicians are keep ing their fingers crossed. Last week a Duke University surgeon reported that a plastic resin, which works more like a chemical sponge than a true drug, pro duces sharp reductions in blood cholesterol levels. Whether it can therefore forestall or reverse the development of heart-and-artery disease (mostly atherosclerosis), which is America's No. 1 killer, accounting for 54% of all deaths, remains to be seen.

The substance is cholestyramine, developed by Dow Chemical Co. as a water softener because impurities in the water become bound to its particles and can be precipitated out. By a similar process, the chemical can bind to itself bile acids in the digestive tract so that they are expelled in the feces.

Depressing History. Cholestyramine's power to lower cholesterol levels was noted early, and Merck Sharp & Dohme tried to develop a medicinal form for this purpose. One trouble was that it smelled like decayed fish and tasted lit tle better. Merck settled for selling its product, trade-named Cuemid, as a rem edy for the intolerable itching that often goes with jaundice. Duke University's Dr. Robert L. Fuson wondered wheth er, with its flavor improved, cholestyramine might not be used to lower cholesterol. Mead Johnson Laboratories, famed for many-flavored Metrecal, had the same idea. They gave it an orangeade taste, trade-named it Questran.

Any physician or surgeon would be delighted to find a preventive or treat ment for atherosclerosis. Dr. Fuson had an added personal reason for investigating cholestyramine, he told the American College of Surgeons last week. In his early 30s, he already had a cholesterol reading above 250 mg., on the edge of the danger zone, and he weighed 226 Ibs. There was a depressing history of heart disease in his family.

Dr. Fuson fed 101 dogs a high-fat diet; 79 of them got no cholestyramine.

At autopsy, 13 out of 14 of these showed severe atherosclerosis of the type that causes heart attacks and most strokes. But of ten dogs that got cholestyramine, only two showed arterial changes and these were minimal.

The doctor and his colleagues have also put 65 human patients on cho- lestyramine. The patients take two packets of powder in a glass of water three times a day before meals. Almost half of the 65 have been bothered at first by constipation, though only two have quit the test because of that. All patients have shown marked reductions not only in blood cholesterol but in other circulating fats that, in excess, may be still more damaging.

Of 36 test patients who had been suffering from angina pectoris or recurrent small strokes, or who were unable to walk more than a few yards because of leg pain from deficient blood flow, 32 say they now feel better and some can walk farther. Dr. Fuson himself has slimmed to 172 Ibs. and has sent his cholesterol crashing down to the 40-50 mg. range that is normal for a newborn baby. He has done this without denying himself steaks and creamy desserts. "So," he says, "you can have your cake and eat it too."

Only Suggestive. When the cholestyramine resin particles latch onto bile acids in the intestine and cause them to be excreted, the body's automatic governor reacts to this loss by telling the liver to make more bile acids. To do so, the liver uses cholesterol already in the body as its main source of raw material, thus reducing the stored cholesterol. By parallel mechanisms, cholestyramine also appears to reduce the absorption of fats into the blood and their deposition at various sites in the body, including artery walls.

Though the Food and Drug Administration has approved both drug companies' forms of cholestyramine for the itching of jaundice, it still has pending Mead Johnson's bid to have it approved for lowering cholesterol.

Duke's chief surgeon and Dr. Fuson's boss, Dr. David C. Sabiston Jr., staunchly endorsed the animal studies with cholestyramine. But he insists cautiously that there is as yet no scientific evidence that patients with artery disease have benefited. Their subjective impressions, he emphasized, are still only suggestive. Not until many of the test patients have had arterial examinations, both before and after taking cholestyramine, will it be possible to find physical proof.

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