Influence of human diets containing casein, soy protein isolate, and soy protein concentrate on serum cholesterol and lipoproteins in humans, rabbits and rats

It is well known that feeding animals such as rabbits with semipurified diets containing animal proteins, as for example casein, results in hypercholesterolemia and atherosclerosis. On the other hand, diets containing vegetable proteins such as soybean protein maintain low levels of serum cholesterol. Little is known about the effects of the type of protein in the diet in humans.<p/>This thesis deals with the effects of casein and soy protein on serum cholesterol and lipoproteins, as observed in two experiments with human subjects and four experiments using animals. Three principle sources of protein were compared: caseinate; soy protein isolate, which is the purest soy protein preparation available commercially; and soy protein concentrate, a less refined soy protein preparation.<p/>In the first human experiment (Chapter 2), 69 young healthy students aged between 18 and 28 years were given for a period of 38 days diets containing 13% of energy as protein of which 65% consisted of protein from caseinate, or soy protein isolate, or a 2:1 mixture of caseinate and soy protein isolate. After a control period of 10 days during which all the subjects received the casein-soy diet, the subjects were divided into three groups, each group receiving one of the test diets for a test period of 28 days. In the second human experiment (Chapter 3), 57 healthy subjects aged between 29 and 60 years were given for a period of 45 days diets containing 16% of energy as protein of which 60% consisted of protein from caseinate, or soy protein isolate, or soy protein concentrate. After a control period of 17 days during which they received the casein diet, the subjects were divided into three groups, each group receiving one of the test diets for a test period of 28 days. Subjects in both studies were under strict dietary control. Apart from 0.5 MJ (120 kcal) per day in the first study and 1.0 MJ (240 kcal) per day in the second, all of the food eaten was supplied daily to the subjects in amounts appropriate to individual energy requirements. Food records and chemical analysis of the diets indicated that within each study, there were essentially no differences between the experimental diets except for the type of protein and/or the amount of non-protein material derived from the protein preparations. Blood samples were taken at the end of the control and test periods.<p/>During the experiments with human volunteers, two extra portions of each diet were collected. These were later homogenised and fed to animals in two experiments with rabbits and one with rats. A further experiment with rabbits was carried out using semipurified diets, the total protein content of which was test protein. The designs of the animal experiments were similar to those of the human experiments (Chapter 4).<p/>In the two human studies, there was no clear difference in response with respect to total serum cholesterol between the casein and the soy diets. A decrease in low-density-lipoprotein (LDL)- cholesterol and an increase in high-density-lipoprotein (HDL)- cholesterol were observed in those on the soy isolate diet when compared with those on the casein diet. The results on apolipoprotein-B and -A, suggest that the changes in cholesterol concentrations in the lipoprotein fractions resulted mainly from changes in the number of lipoprotein particles. However, these effects were only observed in those on the diets containing soy isolate and not in those on diets containing soy concentrate. With regard to the risk of coronary heart disease, the soy isolate diet can be considered to be beneficial, but the effects are small when compared with the effects of the fat composition and cholesterol content of the diet.<p/>The results of the animal studies using human diets confirm the results reported for semipurified diets. In rabbits, casein was found to be highly hypercholesterolemic when compared with the soy preparations, while in rats the effects were much smaller. The results stress the danger of extrapolating too readily from data from animal experiments on the effect of protein on serum cholesterol directly to man.<p/>Large decreases in level of serum cholesterol have been reported in hypercholesterolemic patients on diets containing soybean protein. Therefore, with regard to prevention of coronary heart disease, it has been suggested that animal protein in the diet should be replaced by vegetable protein. However, the results of the present studies with healthy subjects suggest that the normocholesterolemic human is probably relatively insensitive to the type of protein in his diet. It should be noted, however, that these experiments were of short duration and that the subjects were adults. Effects of a long-term intake of various proteins commencing at an early age have still to be determined.<p/>Although the effects of the type of protein are probably small in normocholesterolemic subjects, the replacement of foods containing animal protein with foods containing vegetable protein in the normal diet may still lead to changes in the concentration of serum lipids, because the main sources of animal protein are often also rich in saturated fat and cholesterol.<p/>In modifying the diet in order to influence certain physiological parameters, it should be realised that other parameters may also be affected (see Chapter 5). Caseinates are practically free of purines, while soy protein preparations like other protein sources such as meat. contain considerable amounts of purines. Uric acid is the end product of human purine metabolism and the subjects on the soy diets showed significantly higher levels of serum urate than the subjects on the casein diets. It is well known that the prevalence of gout is directly related to serum urate concentration