LIPID METABOLISM 



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It is possible that the differences in response to these 

 two forms of cholesterol relate to considerations of 

 solubility of this sterol in dietary fat. Recently, it has 

 been pointed out (37) that cholesterol is more soluble 

 in the saturated than in the polyunsaturated fats. 



Practicable Diets 



It is of considerable practical interest that palatable 

 diets can now be devised that are rich in polyunsatu- 

 rated fatty acid content and provide the same pro- 

 portion of fat to which Americans are accustomed. At 

 present, need exists for controlled studies in man to 

 determine the effects on serum lipids of "normal" 

 diets exhibiting a variety of fatty acid patterns. At- 

 tempts in this direction have begun (46, 93, 111). 

 Earlier experiments with semipurified formula-type 

 regimens suggested that when the ratio of poly- 

 unsaturated to saturated fatty acids (P:S ratio) in 

 the diet was increased, serum cholesterol usually 

 could be lowered. 



Approximately 5 years ago, experiments were 

 begun to determine whether everyday diets could be 

 altered so as to reduce serum cholesterol Levels and 

 yet remain palatable and acceptable to most indi- 

 viduals. From progress reports of these studies, it is 

 now clear that manipulation of the fatty acid pattern 

 of the diet is effective in lowering serum cholesterol 

 in most subjects with cholesterol levels higher than 

 230 mg per 100 ml. The change in pattern is effected 

 principally by substituting one form of dietary fat for 

 another in order to increase the P:S ratio. In prac- 

 tice, this change involves a drastically decreased 

 consumption of butter fat and of certain margarines, 

 and a reduced intake of meats from ruminants, such 

 as bovine animals and sheep. At the same time, con- 

 sumption of poultry, fish, nuts, and plant seed oils 

 is materially increased. A typical diet designed to 

 lower cholesterol prescribes an increase in intake of 

 polyunsaturated fatty acids from approximately 1 5 

 to 42 per cent of total fat and a decrease in intake of 

 saturated fatty acids from approximately 42 to 1 5 per 

 cent. The intake of the monounsaturated fatty acid, 

 oleic acid, remains unchanged. Total dietary fat is 

 reduced from 44 to 36 per cent of calories, although 

 this is not an essential feature of the diet. 



Such diets are acceptable and palatable. The effect 

 of a diet of similar fatty acid composition on serum 

 cholesterol in 97 men of normal weight, 50 to 59 

 years old, was determined by Jolliffe et a/. (113). This 

 study demonstrated the fall in cholesterol by tertiles 

 over a period of 6 months. The upper third, with 



cholesterol levels of 270 mg per 100 ml and over, 

 dropped an average of 45 mg per 1 00 ml. The lower 

 third, with cholesterol values under 230 mg displayed 

 a decrease averaging 16 mg per 100 ml. Similar 

 studies performed on smaller groups of subjects have 

 yielded generally similar results (200). 



The fact that it is indeed feasible to lower serum 

 cholesterol levels by dietary means has had and is con- 

 tinuing to have a tremendous impact on the public, 

 the medical and dietetic professions, and the food 

 industry. The public is being made increasingly aware 

 of the possibly ominous significance of an elevated 

 serum cholesterol level in terms of danger from 

 obstructive coronary artery disease. At the same time, 

 there appears to be decreasing use, per capita, of 

 butter and hydrogenated products, and increasing 

 use of liquid vegetable oils, such as corn, safflower, 

 and cottonseed oils. 



A number of cookbooks on the subject of fatty acid 

 "control" are now appearing, and the demand for 

 them is great. Recently, several food companies have 

 come out with new margarines with an increased 

 content of cis-cis linoleic acid. There is increasing 

 interest in the development of cheeses and spreads 

 and commercial products resembling ice cream, all 

 containing appreciable quantities of linoleate. "Rea- 

 sonable substitution of polvunsaturated for saturated 

 fats, under medical supervision" has been recom- 

 mended by an ad hoc committee of the American 

 Heart Association (8). Whether or not diets of this 

 kind will have a clinically useful effect is one of the 

 most urgent questions facing medicine today. 



Mechanism of Cholesterol Lowering 



The exact mechanism whereby a diet rich in poly- 

 unsaturated fatty acids lowers serum total cholesterol 

 (and low-density lipoproteins) remains unknown. A 

 few studies have indicated that when such a diet is 

 fed more cholesterol and its end products (including 

 bile acids) are excreted in the feces. When a diet rich 

 in saturated fatty acids is fed, less sterols and bile 

 acids are excreted in the feces and the serum choles- 

 terol level rises (85, 99, 1 1 1 ). 



There appears to be no evidence for direct inter- 

 ference by the polyunsaturated fatty acids with 

 cholesterol synthesis in the liver. However, the ability 

 of the liver to excrete cholesterol and to convert 

 cholesterol to bile acids may depend in part on certain 

 physicochemical characteristics of cholesterol esters 

 or of the lipoprotein molecules of which cholesterol 

 and its esters can constitute a significant portion. 



