Herbert P. Sarett

Nutritional evaluation of medium-chain triglycerides in the rat.

Nutritional evaluation of a medium-chain triglyceride (MCT) preparation, containing about 75% octanoic acid and 25% decanoic acid, was carried out in short- and long-term experiments in rats. A casein diet containing 19.6% MCT and 2.5% safflower oil, the latter to supply essential fatty acids, was compared with similar diets containing conventional dietary fats. Data obtained in a 47-week study showed that the MCT diet supported normal growth and development. At autopsy, carcass protein and ash levels, vital organ weights and composition were similar to those in rats fed conventional fats. Histological study showed that intestinal and liver sections were normal after 47 weeks on the MCT-containing diet. In general, rats fed MCT had slightly lower growth rates and caloric efficiency values, less carcass fat and smaller epididymal fat pads than animals fed conventional dietary fats. Little C8 and C10 were found in depot fat. The MCT diet also supported normal reproducton, as indicated by litter size and number. During lactation the volume of milk secreted by the rats receiving the MCT diet was smaller and contained a lower level of fat than that secreted by the rats receiving an oleo oil diet, resulting in slower gains in weight in the MCT group. After weaning, growth of the rats fed MCT compared favorably with that attained by the animals on the diet containing oleo oil.

Effect of Cholestyramine on Cholesterol Metabolism in Young Adult Swine

Summary Nine-week-old swine were fed the bile acid sequestrant, cholestyramine, at 2% and 4% of the diet for successive 4-week periods. Cholestyramine increased bile acid excretion about 10-fold, but the rate of liver biosynthesis of cholesterol was 19 times higher in the cholestyramine fed pigs than in the control pigs. This marked increase in cholesterol synthesis was apparently sufficient to prevent a decrease in plasma cholesterol levels. Feeding 4% cholestyramine (approximately 70 g/day) had no effect on growth, food efficiency, organ weights, plasma lipids and aorta cholesterol. Liver cholesterol levels were decreased slightly, liver vitamin A stores were decreased about one-third, and excretion of fecal fat and cholesterol-like (Lieberman-Burchard reactive) materials were increased in the cholestyramine fed pigs.

The Species Specificity of Cholestyramine in Its Effect on Synthesis Of Liver Lipids and Level of Serum Cholesterol

Summary The effect of dietary cholestyramine on plasma and liver sterol levels, and on in vitro hepatic lipid synthesis from acetate-1-C14 were compared in the rat and chicken at intervals up to 35 days. The resin had no effect on plasma or hepatic cholesterol levels in the rat. In the chicken, plasma cholesterol levels were significantly reduced by cholestyramine although liver cholesterol was not changed. Sterol synthesis by rat liver homogenates was significantly increased within 24 hours after addition of cholestyramine to the diet, and a significant reduction in sterol synthesis occurred within 24 hours after removal of cholestyramine from the diet. Cholestyramine also stimulated sterol synthesis by chicken liver homogenates, but the increase was of considerably lesser magnitude than in the rat. The results are in accord with the hypothesis that cholestyramine significantly lowers plasma cholesterol levels in species which cannot increase hepatic sterol synthesis sufficiently to compensate for increased fecal loss of bile acids and other steroidal substances.

Fat Utilization in Rats Fed Gholestyramine, a Bile Acid Sequestrant

Summary In the young weanling rat, 2% cholestyramine in the diet increased the loss of fecal fat, particularly in diets of high fat content. Administration of cholestyramine to the mature rat resulted in a moderate decrease in fat retention, but after one week the effect was minimal.

Comparison of in vitro Bile Acid Binding Capacity and in vivo Hypocholesteremic Activity of Cholestyramine

Summary Methods for in vitro assay of cholate binding capacity and for in vivo assay of hypocholesteremic activity of preparations of cholestyramine, an anion exchange resin, were developed and compared. In the in vitro assay, 20 ml of 0.3 M phosphate buffer at pH 6.0, 20 or 40 mg of the resin and 40 mg of sodium cholate were mixed and shaken for 30 minutes; the filtrates were assayed for cholate spectrophotometrically, and the cholate bound by the resin determined by difference. In the in vivo method, a hypercholesteremic diet was fed to day-old chicks for 2 weeks; graded levels of the anion exchange resin were added to the diet during the second week. Plasma cholesterol levels were then determined as an indicator of the activity of the resin. The relative activities of the various preparations of cholestyramine and other anion exchange resins compared very well when tested by the two methods of assay. Addition of excipients in preparations of cholestyramine for clinical use had no effect on cholate binding or hypocholesteremic activity.

Plasma and Liver Cholesterol Levels in Chicks Fed Medium Chain Triglycerides (MCT) and Cholestyramine

Summary Substitution of medium chain triglycerides (MCT) for coconut oil in a 15% fat diet fed to young chicks resulted in lower plasma and liver cholesterol levels, lower liver fat levels, and less body weight gain than were observed in chicks continued on the coconut oil diet. Plasma cholesterol was lower with corn oil than with MCT, but liver cholesterol was lower with MCT. Addition of cholestyramine to these diets reduced plasma and liver cholesterol levels with each of the dietary fats, but reduced liver fat only with the diet containing MCT. Cholestyramine did not significantly affect body weight gains.

Hydrolysis and Absorption of Medium-Chain Triglycerides and Soy Oil

Summary Studies were conducted on in vitro hydrolysis of MCT and soy oil emulsified in gum arabic and Tween 80 solutions by pancreatic lipase and in vivo hydrolysis and absorption of these emulsions in normal and washed isolated sections of the small intestine of rats.

Weight loss and body composition

Body fat accounts for much of the excess weight in obese persons; but the amount of lean body tissue (muscle and other protein tissue) in the obese individual is similar to that found in the normal individual. In weight loss primarily excess fat should be lost; not essential protein tissue.Complete fasting has been proposed as a technique for losing weight, in lieu of partial caloric restriction. The present studies were carried out to evaluate these techniques for weight loss. Changes in body composition of obese rats were determined after the animals lost one third of their body weight on different regimens. Obese animals which were restricted to 37.5 and 60% of ad libitum caloric intakes required 53 and 93 days, respectively, to lose this weight, whereas those which were totally fasted required only 24 days. There were significant differences in body composition of these groups after weight loss.Fasted animals lost more protein and less fat than did animals restricted in caloric intake; the fasted animals lost 18% of their total body protein, whereas the calorically restricted animals lost only 8–9%. Epididymal fat pads were twice as large in the fasted animals as in the calorically restricted animals. In fasted animals, liver weight loss was greater than in restricted animals, but liver fat levels were still high, as in the obese rats. Liver cholesterol levels were also elevated in fasted animals.Neither the amount of fat nor the type of fat (unsaturation) in the diet had any significant effect on the rate of weight loss or on gross body composition. Type of fat affected fatty acid composition of plasma, but not of liver or depot fat.The development of new methods for determining body composition in man has permitted reasonably accurate estimates of the amount of excess body fat in obese individuals. In obese subjects who lost weight on restricted caloric intakes of an otherwise nutritionally complete diet, most of the weight loss was as body fat, without significant loss of lean body tissue. The studies in man confirm the findings in animals.The extra weight in obesity is mainly fat, with very little protein and some water; when weight is lost by restricted intake of a good diet, the composition of the tissue burned is quite similar to that comprising the extra weight. Fasting gives more rapid weight loss, but apparently less favorable changes in body composition.