Helen B. Brown

Hyperlipoproteinemia and Pancreatitis

Abstract A prospective study was begun in 1969 to investigate the relationship between hyperlipoproteinemia and pancreatitis. Ten patients were observed at the Cleveland Clinic Hospital. All had discrete, recurrent, acute pancreatitis with typical pain, hyper-amylasemia and hypertriglyceridemia during the acute phase, but without biliary tract disease or alcoholism. Acute pancreatitis usually occurred when serum triglyceride levels were above 1,000 mg/100 ml. In all patients during the acute phases, chylomicronemia and prebeta lipoproteinemia were present; serum cholesterol levels were normal or slightly elevated. Lipoprotein electrophoretic patterns were similar to the type V pattern described by Fredrickson. Serum lipids became normal in five patients given low fat diets (10 to 15 g/day), and they had no further abdominal pain; three others had satisfactory, but not complete remissions on diet therapy. Two others continued to have recurrent abdominal pain. It is concluded that the most consistent feature of one kind of pancreatitis is hyperlipoproteinemia with chylomicronemia. This condition probably occurs more frequently than has been previously recognized. Because of the favorable response to a low fat diet, this kind of pancreatitis can be treated adequately and further recurrence prevented.

Induced Hypercholesterolemia and Atherogenesis

An attempt has been made to elicit atherosclerosis in rats by duplicating as far as possible those conditions which in other animals are atherogenic. By making the rats hypothyroid and feeding cholic acid and cholesterol, severe hypercholesterolemia and abnormal beta-lipoproteins appeared along with heavy lipid infiltration of the kidneys, liver, heart and aorta. Aortic and coronary atherosclerosis might have been expected in rats exposed to so much atherogenic material in the blood, but it was not found. Despite lipid infiltration in the intima of the vessels, no appreciable tissue reaction to it occurred; we believe the lack of tissue response is one of the chief causes for the failure of atherosclerosis to develop. Thus tissue response and receptivity to lipid deposition seem to be important mechanisms in atherogenesis.

Some Observations on the National Diet-Heart Study

THE National Diet-Heart Study which was supported by the National Heart Institute, has been completed, and the final report appears as a supplement to CIRCULATION. This was a large double-blind, 2-year study on the effects of diet on blood cholesterol levels in both free-living and closed populations. The relevance of such a study originated in our minds as a result of a study we conducted for 10 months with 55 volunteer couples using commercially prepared, fat-modified foods. These foods were low in saturated fat and relatively high in polyunsaturated oils. Individual diet instruction was not given. The average reduction in serum cholesterol was 14%.1 The general principles on which it was designed have already been presented.2 Its great importance lies in the demonstration that adequate techniques have now been developed for large experimental studies using volunteers. This is the first study of its kind in which so complex and important a factor as diet was controlled double-blind in a freeliving population. Centers were established in Baltimore, Minneapolis-St. Paul, Oakland, Chicago, and Boston, where studies of free-living partici-

Mixed hyperlipemia, a sixth type of hyperlipoproteinemia

Abstract A study of 132 hyperlipidemic patients that included dietary treatment of 81 for 1 to 10 years was reviewed to examine the thesis that mixed hyperlipemia, now called type II B, should be classified as type VI. Serum lipids in type VI had an elevated beta or low density lipoprotein level characteristic of type II and an elevated pre-beta or very low density lipoprotein level characteristic of type IV, yet all lipid levels were relatively moderate in elevation and normal in proportion. Type VI was present in 32 % of these hyperlipidemic patients and was closely associated with atherosclerotic vascular disease. Unlike type II, serum beta lipoprotein and cholesterol in type VI were reduced to relatively normal levels with a polyunsaturated-fat diet; unlike type IV, serum pre-beta and triglycerides were reduced to normal levels with diet. Triglyceride and pre-beta lipoprotein levels were increased with high dietary carbohydrate so that the polyunsaturated-fat diet with moderate amounts of carbohydrate was more effective in maintaining reduced serum lipid levels than the low-fat (high carbohydrate) diet. Because of these distinctive characteristics, mixed hyperlipemia or type II B should be classified as type VI.

Diet and serum lipids: Controlled studies in the United States

The influence of dietary fat on serum lipids is well established. The general principles of a fat-modified diet--calorie control and the amount and composition of dietary fat--are demonstrated in studies in which nutrient composition was systematically altered. Weight loss, even when caloric deficit involves no other changes in nutrients, reduces serum lipids. With isocaloric diets, the fatty acid composition rather than the amount of fat influences the serum cholesterol concentration. Saturated fatty acids are twice as effective in raising serum cholesterol levels as polyunsaturated fatty acids are in reducing them. The amount of cholesterol in the diet alters the amount in the serum by approximately 5 mg/dl for every 100 mg of change in diets with less than 300 mg/1000 kcal. Cholesterol in excess of this amount has no additional effect. With no dietary cholesterol, serum lipids are unaffected by the fat composition. In the presence of dietary cholesterol, serum lipids are affected by saturated and polyunsaturated fatty acids through an interaction with cholesterol. Polyunsaturates counteract the influence of both saturated fatty acids and cholesterol. The more cholesterol there is in the diet, the more polyunsaturated fatty acids are required to counteract its effect. Both the fatty acid composition of the lipoproteins and lipid metabolism are affected by the fat and cholesterol composition of the diet.

The additive effect of probucol on diet in hyperlipidemia

The effect of probucol, a hypocholesteremic drug, in reducing blood lipids below the level achieved with diet alone, was studied in 19 free‐living hyperlipidemic patients (13 type IIA, 4 type VI [IIB], 1 type III, 1 type V). Diet prescriptions were a4justed to lipid type. The study consisted of a 4 week adjustment period with patients on their usual diet, a 3 month period with fat‐modified diet and placebo, and a 3 month period with the same diet and 500 mg probucol twice a day. The mean serum cholesterol level of type IIA patients was the same for the placebo and probucol periods, but there were large differences among individual patients. One type IIA patient had an increase of 19.2% with probucol, 5 had no change, and 7 had an additional reduction of 8.1 %. There was a mean reduction of serum cholesterol level of 8.8% in 4 type VI, 1 type III, and 1 type V patient; serum triglyceride levels in these 6 patients were reduced by 22%. Lipoprotein patterns were unchanged. There were no side effects from probucol.

The Effect of Oral Iodide on Serum Butanol-Insoluble Protein-Bound Iodine in Various Species

It is possible that there is an association between the butanol-insoluble protein-bound iodine developed in plasma when potassium iodide is fed and the reduction of serum and hepatic cholesterol. This fraction constitutes most of the protein-bound iodine increase observed in iodide-fed rabbits, dogs, rats and hypertensive human beings. It appears a few days after iodide feeding is begun and disappears four to eight weeks after discontinuing iodide. The dose required to produce minimum and maximum concentrations has been determined in all of these animals and in men. Further, it was found that hypothyroidism reduced the iodide requirement to one-tenth that necessary to produce comparable amounts of butanol-insoluble protein-bound iodine in normal animals.

Effects of clofibrate and a fat-modified diet on serum lipids.

The combined effect of clofibrate and a fat‐modified diet was determined in 17 hyperlipidemic patients: 7 type IIA, 7 type IV, 2 type VI(IIB), and I type III. Control serum lipid levels and lipoprotein patterns and their alteration with a fat‐modified diet had been determined previously 1/2 to 2 years for 3 patients, and 6 to 10 years for 14 patients. Two grams of clofibrate a day (0.5 gm four times daily) was taken along with the fat‐modified diet for 2 to 6 months by 5 patients and for 2 years by 13 patients. The effect of clofibrate and a fat‐controlled diet was also determined in 10 normolipidemic men who were subjects of an 18‐day test in which the polyunsaturated fat diet was quantitatively prepared and eaten along with 2 gm clofibrate a day (0.5 gm four times daily). The effect of clofibrate on serum cholesterol levels was a further mean reduction in type IIA patients by 19%, in type III by 23%, in type IV by 12%, in type VI by 7%, and in normolipidemic subjects by 8%. The extent of the additional serum cholesterol reduction with clofibrate in individual hyperlipidemic patients varied from + 10% to −44 % and was not related directly to the type of hyperlipidemia. The extent of reduction appeared related directly to the level of −S 40‐70 (similar to Sf 12‐20) lipoproteinjraction in the control serum sample. Serum triglyceride levels were unaffected in type IIA and normolipidemic subjects. Serum triglyceride levels did not change consistently in the 2 type VI patients, rising by 11 % in 1 and dropping by 31% in the other. Serum triglyceride levels were significantly (p = 0.001) and consistently reduced by 39% only in type IV patients.

Atypical Hyperlipoproteinemia and Pancreatitis.

Excerpt A prospective study was begun in 1969 to investigate the relationship of hyperlipidemia and pancreatitis. Ten patients were studied. All had discrete, recurrent, acute pancreatitis, with ty...

A Point of View on Dietary Management of Hyperlipidemia

The description of dietary management for treating hyperlipidemia in the previous paper by Valerie McGuire makes several important points I wish to emphasize. You are aware that conditions at Saint Michaels Hospital are close to ideal. Both the facilities and the time available are adequate for the necessary activities.