that seem most closely related to the results 

 reported in this bulletin. Blood cholesterol levels 

 vary considerably among species and only reports 

 dealing with rat as the experimental animal will 

 be considered, along with a few of the reports 

 dealing with humans because of interest in the 

 possible application to humans of the results 

 obtained with rats. The results for rats will be 

 confined to those reported for male rats. 



The response of serum cholesterol levels to 

 diet often differs, depending upon the absence or 

 presence of cholesteiol in the diet. Comparison 

 of serum cholesterol values, therefore, must take 

 into account whether we are dealing with en- 

 dogenous cholesterol or with serum cholesterol 

 levels that may be reflecting both endogenous and 

 exogenous cholesterol. 



The liver is the chief source of endogenous cho- 

 lesterol and not only is able to synthesize this 

 sterol but also is active in its breakdown and 

 excretion. Serum cholesterol values in the ab- 

 sence of dietary cholesterol generally reflect the 

 balance of activity in the liver with regard to these 

 two processes. 



With humans, serum cholesterol levels reflect 

 lifetime dietary habits which generally include 

 the consumption of cholesterol-containing foods. 

 With the rat, however, many investigations deal 

 with diets that contain little or no cholesterol so 

 that blood cholesterol is strictly endogenous in 

 origin. Even in the absence of dietary cholesterol, 

 the results relating the kind and/or level of fat to 

 serum cholesterol levels of rats are not entirely 

 consistent. 



In the absence of dietary cholesterol, several in- 

 vestigators report a tendency for blood cholesterol 

 levels in rats to increase with increasing unsatura- 

 tion of dietary fat. Klein {105), feeding diets 

 containing 5- and 30-percent levels of Crisco or 

 corn oil found plasma cholesterol levels to increase 

 as the intake of linoleic acid increased. Swell, 

 Flick, Field, and Treadwell (179) reported in- 

 creased levels with increasing unsaturation of fat 

 when rats were fed diets containing soybean fat 

 hydrogenated to different iodine values. Nath, 

 Wiener, Harper, and Elvehjem (136) reported 

 little effect on serum cholesterol levels in rats as 

 the result of feeding increasing quantities of hy- 

 drogenated coconut oil but a slight increase when 

 1 percent corn oil was added to the diet. Sun- 

 flower seed oil (79) has also been reported to 

 elevate blood cholesterol. 



With diets in which sucrose was the carbo- 

 hydrate, Marshall, Hildebrand, Dupont, and 

 Womack (126) obtained significantly higher cho- 

 lesterol levels with 15 percent corn oil than with 

 3 percent corn oil or with 15 percent lard or HVO. 

 In contrast, no significant differences in serum 

 levels were observed when the carbohydrate was 

 starch. Okey, Lyman, Harris, and others (145) 

 reported that the degree of saturation of dietary 

 fat exerted little influence on serum cholesterol 

 levels when 10 percent of fat was added to a nutri- 



tionally adequate synthetic diet. Best, Lucas , 

 Patterson, and Bidout (23) also reported that the 

 kind of fat had little effect on serum cholesterol 

 when the diet contained sufficient choline to pre- 

 vent fatty fivers. 



Aftergood, Deuel, and Alfin-Slater (6) found no 

 significant difference in the plasma cholesterol 

 levels of rats fed a diet containing 15 percent 

 cottonseed oil or lard after a 12-week feeding 

 period. After 24 weeks, however, plasma choles- 

 terol levels were significantly lower in rats fed 

 cottonseed oil than in those receiving lard. Avigan 

 and Steinberg (15) reported an increase in serum 

 cholesterol when either coconut oil or corn oil was 

 added to a Purina chow diet, but the increase was 

 somewhat greater with coconut oil than with corn 

 oil. 



There is at present no satisfactory explanation 

 for these divergent findings. The results for BHE 

 rats reported in this publication indicate that, in 

 the absence of dietary cholesterol, serum levels 

 change slowly with diet, and suggest that some of 

 the discrepancies in the literature may be due to 

 the relatively short feeding periods generally 

 studied. Another factor that may be responsible 

 for some of the differences observed is the hered- 

 ity of the strain of rats under investigation. 

 Kohn (106) reported evidence for considerable 

 variation among strains of rats in their average 

 serum cholesterol values which varied from 65 

 to 132 mg./lOO ml. 



Investigations of the influence of dietary cho- 

 lesterol on the serum cholesterol levels in the rat 

 have dealt chiefly with the addition of cholesterol 

 per se rather than with the use of cholesterol- 

 containing foods. The response to feeding these 

 cholesterol-containing diets is apparently in- 

 fluenced by accompanying dietary components. 

 Dietary cholesterol may be absorbed by the rat 

 in the absence of dietary fat, but the presence of 

 fat in the diet results in an appreciable increase in 

 serum cholesterol levels (S3). The fatty acid 

 component, not glycerol, is reported to be the 

 important factor (179, 189). Dietary cholesterol 

 may result in elevated values in the blood in the 

 absence of fat if sufficient bile salts are fed (179). 

 Wflgram, Lewis, and Best (189) reported increased 

 cholesterol levels when choline was added to a diet 

 containing cholesterol. 



Unsaturated fats tended to lower serum cho- 

 lesterol levels of rats fed cholesterol in contrast to 

 the elevated values reported by several investi- 

 gators when this sterol was absent from the diet. 

 Okey and Stone (147) and Aftergood, Deuel, and 

 Alfin-Slater (6) reported lower serum values with 

 cottonseed oil than with lard, and small but com- 

 parable differences in liver lipids. The latter 

 investigators report that the differences in serum 

 levels observed were not due to differences in the 

 absorption of these two fats. The addition of 

 large amounts of vitamin E to the lard diet eli- 

 minated the differences observed in the fiver lipid 

 but did not influence blood cholesterol levels. 



32 



