Beneficial role of dietary phytoestrogens in obesity and diabetes

Vascular diseases such as atherosclerosis, stroke or myocardial infarction are a significant public health problem worldwide. Attempts to prevent vascular diseases often imply modifications and improvement of causative risk factors such as high blood pressure, obesity, an unfavorable profile of blood lipids or insulin resistance. In addition to numerous preventive and therapeutic drug regimens, there has been increased focus on identifying dietary compounds that may contribute to cardiovascular health in recent years. Food-derived bioactive peptides represent one such source of health-enhancing components. They can be released during gastrointestinal digestion or food processing from a multitude of plant and animal proteins, especially milk, soy or fish proteins. Biologically active peptides are considered to promote diverse activities, including opiate-like, mineral binding, immunomodulatory, antimicrobial, antioxidant, antithrombotic, hypocholesterolemic and antihypertensive actions. By modulating and improving physiological functions, bioactive peptides may provide new therapeutic applications for the prevention or treatment of chronic diseases. As components of functional foods or nutraceuticals with certain health claims, bioactive peptides are of commercial interest as well. The current review centers on bioactive peptides with properties relevant to cardiovascular health.

The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death in the United States.1 Diet has a major impact on several modifiable risk factors for heart disease: hypercholesterolemia, hypertriglyceridemia, elevated LDL cholesterol, low HDL cholesterol, hypertension, obesity, and diabetes. The recommended low-saturated-fat, low-cholesterol diet1 does help lower risk of CVD.2 3 However, other dietary factors may offer additional benefits.

There is increasing evidence that consumption of soy protein in place of animal protein lowers blood cholesterol levels and may provide other cardiovascular benefits. Epidemiologists have long noted that Asian populations who consume soy foods as a dietary staple have a lower incidence of CVD than those who consume a typical Western diet.4 Soy protein consumption in Japan is reported to be as much as 55 g/d,5 compared with <5 g/d in the United States.6 In 1998, deaths from CVD per 100 000 people between the ages of 35 and 74 years were as follows: 401 for US men, 201 for Japanese men, 197 for US women, and 99 for Japanese women.1 There are many differences in dietary patterns and lifestyle factors that could account for differences in disease patterns among countries.

The American Heart Association (AHA) Dietary Guidelines for Healthy American Adults2 stated that although there was some evidence that when soy protein was substituted for animal protein, total and LDL cholesterol could be reduced, the findings were inconclusive. The AHA Nutrition Committee concluded that the use of soy foods was consistent with the AHA Dietary Guidelines, but no recommendation was made to include soy protein in the diet. More research on the mechanisms explaining the effects of soy protein and related phytochemicals on blood lipids was recommended. This AHA Science Advisory provides an update on recent research reports.

The following description is …

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Soy Protein and Cardiovascular Disease A Statement for Healthcare Professionals From the Nutrition Committee of the AHA

Identification of Novel Hypocholesterolemic Peptides Derived from Bovine Milk β-Lactoglobulin

Dietary proteins and amino acids are important modulators of glucose metabolism and insulin sensitivity. Although high intake of dietary proteins has positive effects on energy homeostasis by inducing satiety and possibly increasing energy expenditure, it has detrimental effects on glucose homeostasis by promoting insulin resistance and increasing gluconeogenesis. Varying the quality rather than the quantity of proteins has been shown to modulate insulin resistance induced by Western diets and has revealed that proteins derived from fish might have the most desirable effects on insulin sensitivity. In vitro and in vivo data also support an important role of amino acids in glucose homeostasis through modulation of insulin action on muscle glucose transport and hepatic glucose production, secretion of insulin and glucagon, as well as gene and protein expression in various tissues. Moreover, amino acid signaling is integrated by mammalian target of rapamycin, a nutrient sensor that operates a negative feedback loop toward insulin receptor substrate 1 signaling, promoting insulin resistance for glucose metabolism. This integration suggests that modulating dietary proteins and the flux of circulating amino acids generated by their consumption and digestion might underlie powerful new approaches to treat various metabolic diseases such as obesity and diabetes.

Role of Dietary Proteins and Amino Acids in the Pathogenesis of Insulin Resistance

Given evidence of a hypocholesterolemic effect in rats, soy protein compared with casein showed the following effects on cholesterol dynamics: a) lower cholesterol absorption and greater fecal steroid excretion, b) more rapid turnover of serum cholesterol, c) a marked size reduction of the rapidly exchangeable cholesterol pool (pool A) through a significant increase in the removal rate in that compartment without influencing the production rate, and d) greater hepatic sterogenesis both in vitro and in vivo. In contrast, the amino acid mixture equivalent to soy protein compared with casein-type mixture showed: a) no effects on cholesterol absorption and fecal steroid excretion, b) no effects on the turnover of serum cholesterol, c) the reduction of pool A size as a result of decreased production, and d) the reduction of hepatic steroidogenesis in vitro, but not in vivo. These results indicate that decreased intestinal absorption of cholesterol, and increased fecal steroid excretion are primarily responsible for the antihypercholesterolemic effect of soy protein compared with casein. The fecal loss of steroids far outweighs the activation of hepatic steroidogenesis. In the case of the soy protein-type amino acid mixture, the depression of hepatic cholesterol synthesis seems accountable for reducing serum cholesterol levels.

Studies on the Mechanism of Antihypercholesterolemic Action of Soy Protein and Soy Protein-Type Amino Acid Mixtures in Relation to the Casein Counterparts in Rats

1. The effect of variation in arginine: lysine on the relative cholesterolaemic effects of dietary soya-bean protein and casein was studied. Male rats received semi-purified diets containing soya-bean protein isolate or casein supplemented respectively with varying amounts of lysine or arginine for 40 d and blood samples were taken after a 5 h fast. 2. Neither the addition of arginine to casein nor lysine to soya-bean protein modified the intrinsic effect of these proteins on serum cholesterol. 3. Serum triglyceride levels tended to rise with increasing amounts of lysine supplementation. The opposite trend was obtained with arginine supplementation. 4. Casein caused an increase in the concentration of serum insulin, but not glucagon. The glucagon level was increased proportionately with increasing amounts of arginine, while the addition of lysine showed no effect. The effects of added amino acids on serum insulin were inconclusive. 5. There was a parallel increase in serum apo E and glucagon in response to arginine supplementation, while lysine supplementation increased serum apo E. 6. Thus, arginine: lysine was more effective in regulating serum triglyceride than serum cholesterol. Insulin was associated with different effects of these proteins on serum lipids.

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Effects of arginine and lysine addition to casein and soya-bean protein on serum lipids, apolipoproteins, insulin and glucagon in rats.

Male rats were fed for 4 weeks cholesterol-free diets containing proteins from different sources, milk, fish, egg yolk, soybean, rice and peanut. The antihypercholesterolemic effect of vegetable proteins compared to animal proteins was certified. There was a negative correlation (gamma = -0.74) between the serum cholesterol level and the arginine/lysine ratio of dietary protein, suggesting a role of this ratio in determining the serum cholesterol level. In general, the fasting level of circulating insulin was lower whereas that of glucagon was higher on feeding vegetable proteins, thus resulting in a fall of the insulin/glucagon ratio. Changes in the hormonal status may be relevant to the protein effect.

Naomu Ishiwaki

Papers

Studies on the Mechanism of Antihypercholesterolemic Action of Soy Protein and Soy Protein-Type Amino Acid Mixtures in Relation to the Casein Counterparts in Rats

Effects of arginine and lysine addition to casein and soya-bean protein on serum lipids, apolipoproteins, insulin and glucagon in rats.

Dietary protein-dependent modification of serum cholesterol level in rats. Significance of the arginine/lysine ratio.