Dietary Proteins and Atherosclerosis PDF

Preface

Although food lipids are now recognized as the major nutritional factors in atherosclerosis, it is interesting to remember that the first experimental research projects investigating the possible relationships among nutrition, blood lipids, and atherosclerosis studied the effects of animal proteins and meat in particular. Indeed, dietary meat induces various forms of pathologic damage to hepatic tissues in rabbits (Garnier and Simon 1907) and dogs, and also liver necrosis and arterial lesions (D'Amato 1908). The results of these studies on rabbits were confirmed by Ignatowski (1908a, 1908b) and Fahr (1912). Later, investigators assessed the effects of different animal proteins: meat (Lubarsch 1909, 1910) or various associations such as meat, egg yolk, egg white, and milk (Starokadomsky and Ssobolew 1909; Stuckey 1911, 1912). Anitschkow and Chalatow established the cholesterol-fed rabbit as a model for atherosclerosis research (Anitschkow and Chalatow 1913; Finking and Hanke 1997). On the basis of their results, the investigators came to the conclusion that proteins were not the only factors responsible for arterial injuries and that the initially suspected effects of cholesterol should be accepted (Chalatow 1912; Wesselkin 1913; Anitschkow and Chalatow 1913; Wacker and Hueck 1913).

The respective roles of animal proteins and cholesterol already studied (Kon 1913, 1914; Steinbiss 1913; Knack 1915; Newburgh 1919; Newburgh and Squier 1920; Newburgh and Clarkson 1922, 1923a, 1923b; Diecke 1926; Clarkson and Newburgh 1926) are discussed later. A positive correlation has been established between animal protein consumption and serum cholesterol concentrations and the extent of atherosclerosis, despite the absence of cholesterol in the diet (Newburgh and Clarkson 1923a, 1923b). However, according to Diecke, no correlation can be established between atherosclerosis and hypercholesterolemia (Diecke 1926). The arterial hypertension observed in rabbits on a diet including meat could also be the cause of atherosclerotic lesions (Schmidtmann 1926). The prevalence of cardiovascular diseases, as assessed by epidemiologic studies over the same period, is positively and equally correlated with animal protein or fat consumption (Yerushalmy and Hilleboe 1957; Yudkin 1957).

Meeker and Kestens (1940, 1941) demonstrated that in contrast to animal proteins, vegetable proteins do not induce an increase in serum cholesterol concentrations. Atherosclerosis is not observed in rabbits fed maize oil and casein or wheat gluten. Nevertheless, plasma cholesterol concentrations were higher when the rabbits were fed casein rather than wheat gluten (Enselme et al. 1963).

The experiments by Kritchevsky et al. (1959) and Howard et al. (1965) confirmed the results obtained by Meeker and Kestens. When cholesterol was added to the diet of rabbits, the nonpurified soybean protein provided decreased serum cholesterol concentrations, and not only was harmless but prevented atherosclerosis. Two general reviews have summarized the effects of dietary proteins on plasma holesterol concentrations and atherosclerosis in animals (Yudkin 1957; Enselme et al. 1962).

In young women, the capacity of vegetable proteins compared to animal proteins to lower plasma cholesterol levels was first observed by Walker et al. (1960). In men, Hodges et al. (1967) showed that vegetable proteins decrease the serum cholesterol concentrations induced by diets containing various proportions of fats and simple or complex carbohydrates. In spite of these results, investigations on the relationship between proteins and atherosclerosis have been replaced by others focusing on the rapid development of the lipidic theory of atherosclerosis.

Nevertheless over the past 30 years, there has been renewed interest in the protein theory (Connor and Connor 1972; Carroll and Hamilton 1975; Hermus 1975; Kritchevsky 1976; Hamilton and Carroll 1976; Debry 1976; Carroll 1978a, 1978b; Kritchevsky 1980a, 1980b; Carroll 1981b; Kritchevsky and Czarnecki 1982, 1983; Laurent 1983, Terpstra et al. 1983a, 1983b; Kritchevsky 1983a, 1983b; Kritchevsky et al. 1983, 1984; Debry et al. 1984; Goldberg and Schonfeld 1985; West and Beynen 1986; Forsythe et al. 1986; Kritchevsky et al. 1987; Kritchevsky and Klurfeld 1987; Debry 1987a, 1987b; Guzman and Strong 1987; Kritchevsky 1987; Foley et al. 1988; West and Beynen 1988; Barth and Pfeuffer 1988; Kritchevsky 1990; Debry 2001a, 2001b). The history of these relationships was reviewed by Kritchevsky and Czarnecki (1983) and Terpstra et al. (1983a, 1983b), and more recently by Kritchevsky (1993, 1995). However, in one general review on diet, plasma cholesterol, and coronary heart disease by Smith and Pickney (1989), none of the 1700 references quoted dietary proteins as a possible factor involved in atherosclerosis, and in a recent review on coronary heart disease risk factors (Ferns and Lamb 2001), the eventual role of proteins is not mentioned.

The results of experiments with varying diet components have shown that serum cholesterol concentrations are positively correlated with animal protein content, and casein in particular. However, according to the authors, these effects could also be due to other diet components (Carroll and Hamilton 1975; Hamilton and Carroll 1974, 1976; Carroll 1978a), and cannot be generalized since the serum cholesterol levels induced by certain animal and vegetable proteins are not significantly different. This is the case, for example, with pork protein or raw egg white, wheat gluten, and peanut protein (Carroll and Hamilton 1975) or with beef and vegetable proteins (Kritchevsky et al. 1981). Moreover, since animal growth depends on the biological value of proteins, this value should be taken into account (Hermus 1975).

Although the results of epidemiologic studies and clinical trials support the notion of a positive correlation between the consumption of dietary proteins and the prevalence of atherosclerosis or coronary thrombosis, this theory cannot be attested with certainty since the collection of data on animal and vegetable protein consumption remains relatively inaccurate in humans. In contrast, the numerous experimental studies carried out in animals of various species as well as in humans have partly identified, although only in a limited number of studies, the pathophysiologic mechanisms of the effects of proteins on atherosclerosis.

The damage caused by some animal proteins and the protective effects of certain vegetable proteins have been clearly demonstrated. Although dietary proteins are considered to be of minor importance in the etiology of hypercholesterolemia and therosclerosis in humans (Carroll 1978a; Kris-Etherton et al. 1988), their effects on plasma lipids, various factors of blood coagulation, endocrinologic balance, arterial hypertension, and arterial wall properties have been demonstrated. The effects of nonprotein substances associated with vegetable proteins in plants have been the subjects of numerous studies over recent years. Results have shown that the direct influence of these proteins on plasma lipid levels and the development of atherosclerosis remains unclear and further studies are still required to establish the real effects (Smith 1998).