1 184 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



to remain elevated or to rise. When highly unsatu- 

 rated liquid fats such as corn oil and menhaden oil 

 are substituted isocalorically for the "hard" fats in 

 the diet, serum cholesterol levels usually fall appre- 

 ciably. A reasonable correlation can be made between 

 the physical state of a fat and its effect on serum 

 cholesterol. It has been suggested that the cholesterol- 

 lowering effect of the liquid oils may be a function of 

 the constituent polyunsaturated fatty acids and that 

 these fatty acids have an effect by virtue of their 

 polyethenoid configuration. 



Recently, it was reported that a synthetic medium- 

 chain triglyceride, a liquid with a melting point below 

 o C, made up entirely of saturated fatty acids of chain 

 lengths ranging from C 6 to C12, can lower serum cho- 

 lesterol significantly when substituted for butter in a 

 formula diet (96). Such results are of interest since 

 medium-chain triglyceride (MCT) is devoid of poly- 

 ethenoid fatty acids and has an iodine value of less 

 than 1.0 (that of butter is approximately 40). Al- 

 though the preparation is highly saturated, its shorter 

 chain fatty acids confer upon it many of the physical 

 characteristics of the natural vegetable oils rich in 

 long-chain polyunsaturated fatty acids. 



Since medium-chain fatty acids may be metab- 

 olized differently from longer chain fatty acids, the 

 results with medium-chain triglyceride may not help 

 one interpret the cholesterol-lowering effects of the 

 highly unsaturated oils. On the other hand, such 

 studies have again called attention to the possible 

 importance of the physical properties of fatty acids 

 apart from the number and location of their double 

 bonds. 



There remains a great need for further character- 

 ization of dietary glycerides in order that their physi- 

 cochemical characteristics may be better related to 

 their effects on serum lipids. The mechanisms whereby- 

 dietary fats influence cholesterol metabolism still are 

 not well understood. The picture is further compli- 

 cated by the complex nature of the dietary glycerides. 

 As pointed out earlier, 64 different fatty acids have 

 been identified in butter. For a time it was believed 

 by some investigators that the hypercholesteremic 

 effect of butter was due to its relatively high content 

 of shorter chain saturated fatty acids. Studies em- 

 ploying synthetic glycerides of simplified fatty acid 

 composition were helpful in clarifying this problem 

 inasmuch as it was possible to study the effect on 

 serum lipids (96) of a synthetic medium-chain tri- 

 glyceride (MCT) containing predominantly the very 

 fatty acids thought to be hypercholesteremic. As a 

 result of such experiments it was shown that in rela- 



tion to butter the MCT preparation was actually 

 hypocholesteremic. 



Dietary Cholesterol 



Since the early work of Ignatowski (110) and 

 Anitschkow (10) on experimental atherosclerosis in 

 rabbits, dietary cholesterol has been an essential 

 ingredient of diets used to induce hypercholesteremia 

 and atherosclerosis in a variety of animal species. Not 

 long ago, it was fashionable to prescribe diets low in 

 cholesterol for patients with an elevated serum choles- 

 terol. As cholesterol metabolism in man was studied 

 more intensively, it became evident that the liver 

 normally synthesizes about three times as much choles- 

 terol per day as is consumed in the average diet. It 

 was further learned that an increased intake of 

 cholesterol is likely to result in a proportionate inhibi- 

 tion of cholesterol manufacture. Subsequently, care- 

 fully controlled studies by Keys et al. (119) and others 

 have suggested that, within wide limits, variations in 

 the cholesterol content of an ordinary diet do not 

 affect serum cholesterol levels to any significant de- 

 gree, provided other elements in the diet are constant. 

 Such results have encouraged many physicians to 

 abandon use of diets specifically low in cholesterol 

 in treating patients with hypercholesteremia. 



Despite such negative reports, the influence of 

 dietary cholesterol on serum cholesterol in man con- 

 tinues to be a subject of investigation and contro- 

 versy. Beveridge et al. (23) have recently reported 

 that the addition of relatively small amounts of choles- 

 terol to formula diets can raise serum cholesterol 

 levels, depending on the nature of the accompanying 

 fat. Indeed, these investigators attribute the hyper- 

 cholesteremic effect of butter in part to its content of 

 cholesterol. Keys (121) has reviewed the results of 

 Beveridge and associates and has questioned their 

 significance. Connor et al. (45) have studied the effect 

 of adding or subtracting moderate amounts of choles- 

 terol as egg yolk in diets equivalent in amounts and 

 composition of fat. In their studies, the addition of 

 475 to 1425 mg cholesterol (the amount present in 

 one to three large eggs) raised serum total cholesterol 

 by an average of 68 mg per 100 ml. On the other 

 hand, crystalline cholesterol added to the diet in 

 amounts ranging from 1 200 to 3600 mg per day 

 increased the mean cholesterol level by only 18 mg 

 per 100 ml. 



It would seem that the effect of crystalline choles- 

 terol added to the diet cannot be equated with the 

 effect of the cholesterol that occurs naturally in food. 



