Effects of Undernutrition on Host Cell and Organ Function
Authors: Robert A. Good, Anne West, Noorbibi K. Day, Zhi-Wei Dong, Gabriel Fernandes
Journal: Cancer Research (1982)

Abstract  The destructive effects of malnutrition on healthy bodily functioning have been recognized throughout history. Recent scientific inquiries have begun to analyze the precise relationships between various nutritional factors and immunological function and the consequences of these relationships for pathogenetic processes involving several of the major organ systems. Strikingly different biological relationships have been revealed. Profound immunological crippling by nutritional deficiencies, seen in severely malnourished human populations, is in apparently paradoxical contrast with the enhancement of several aspects of thymus-derived immunity with underfeeding in several experimental models. The major disease processes associated with aging, as they are reflected in certain strains of short-lived, autoimmune-prone mice, may be dramatically inhibited by dietary restriction.  The discrepancy between the profound dual-system immunodeficiency seen in malnourished humans and the preserved or enhanced T-cell function seen in laboratory animals was partially explained by the vital role of a single nutrient, the trace metal zinc, in thymic immunity function. Experimental zinc deficiency produces progressive thymic involution and progressive loss of T-cell immunity functions in mice and rats. Congenital failure to absorb this element normally is the single cause of hereditary acrodermatitis enteropathica in both humans and cattle. Patients with other diseases, including primary and secondary immunodeficiencies (the latter particularly in association with certain forms of cancer), have been shown to have low levels of zinc in their sera and certain tissues. Deficiency of intake of dietary zinc is crucial to the deficiencies of zinc in patients with epithelial cancer. In contrast, apparent zinc deficiency in patients with some lymphoid cancers may be associated with rather dramatic losses of zinc and with shifts in zinc distribution. The vital role of zinc in preserving immunological vigor raises the question of what other individual vitamins and minerals, including vitamin A, vitamin C, pyridoxin, and riboflavin, among others, may also be crucial to effective immunity function.  Experimental studies on the diseases of aging have revealed that dietary excess can have as powerful an effect on immunological disorganization and related pathogenesis as dietary deficiency. Corroborating and extending the findings of early investigators, we have shown that the life spans of several strains of short-lived autoimmune-prone mice, which are genetically predisposed to develop diseases analogous to the major diseases of aging in humans (i.e., atherosclerosis, arteriosclerosis, and other vascular diseases; hyalinizing renal disease; amyloidosis, increased infection, and cancer), may be substantially extended, even doubled and occasionally tripled, by restricting either total food intake or the fat component in the diet. In hybrid NZB × NZW F1 mice, this dietary manipulation leads to inhibition of thymic and T-cell immunological involution, decrease of circulating immune complex formation, reduction of anti-DNA antibodies, and reduction of viral glycoprotein with a molecular weight of 70,000 in circulating immune complexes. In mice of the MRL/Ipr strain, not only their characteristic autoimmune disease but also the extraordinary lymphoproliferative syndrome that mice of this strain develop under normal feeding conditions are dramatically inhibited by restriction of total calories. Here, as with certain other immunological influences, restriction of dietary fat seems crucial. Since Tannenbaum9s work in the early 19409s, it has been known that breast cancer in C3H mice can be prevented by calorie and fat restriction. We have confirmed this finding and also demonstrated that the fat component is the crucial dietary variable. Dietary restriction inhibits development of circulating antibodies to mouse mammary tumor virus proteins and inhibits development of circulating immune complexes. This treatment also inhibits development of murine mammary tumor virus particles in mammary cells but does not interfere with estrus cycles. We have also undertaken studies to determine whether dehydroepiandrosterone, which influences obesity and which Schwartz et al. have reported as inhibiting development of mammary adenocarcinoma in C3H mice, alters immunological functions, malignancy, and life span in short-lived autoimmuneprone mice.