Toward a Nutritional Concept of Host Resistance to Malignancy and Intracellular Infection

TOWARD A NUTRITIONAL CONCEPT OF HOST RESISTANCE TO MALIGNANCY AND INTRACELLULAR INFECTION JOHN MURRAY and ANNE MURRAY* Man has not always been well fed and still is not in many parts of the world. As primitive hunter-gatherer, early nomadic herdsman, and, later, subsistence agriculturalist, he depended almost exclusively for survival on the productivity of the soil. Sometimes his stomach was full, more often than not it was empty. Added to his daily and frequently unrewarded search for food were recurrent cycles of famine and plenty. Through selective pressure, these vicissitudes must have favored the early evolution of biological mechanisms to save him from the double jeopardy of famine and disease. We propose that these mechanisms still exist and are continually operative as protective devices against intracellular disease, whether malignant or infective; that they are most obvious in tribal societies and the undernourished; that their suppression by "improved" nutrition may be responsible for the higher incidence of these diseases in developed societies; and that their explication may permit a rational approach to prevention and perhaps management of intracellular infection and malignancy. Introduction The experimental evidence for the protective effect of starvation against malignancy is unequivocal; it began in the modern era with the observation of Moreschi (1909) that sarcomas were less frequent in mice losing weight on a diet restricted in energy [I]. The next 40 years saw repeated but more precise confirmation of his work with a variety of malignancies in small animals, including breast cancer in inbred strains of mice [2-4]. But the dietary restriction needed to attain this effect was ?Department of Medicine, University of Minnesota, Box 385, Mayo Building, University Hospitals, Minneapolis, Minnesota 55455.© 1981 by The University of Chicago. 003 1-5982/81/2402-02 12$01.00 290 I John Murray and Anne Murray ¦ Nutrition and Host Resistance considerable—to two-thirds or less of the energy of an ad libitum diet [5], a reduction which led inevitably to reduced growth of tissues [6]. As a recent and interesting variation on the theme of starvation and malignancy , the growth of transplantable thymomas has been shown to be less vigorous in untreated diabetic mice (a form ofcellular starvation) than in treated diabetic mice [7]. In humans, the evidence is not unequivocal. Uncontrolled observations during the two World Wars point strongly to a reduced mortality from cancer during times of maximum deprivation. There was a sharp drop during the years of the First World War in the otherwise steady rise (1905-1935) in mortality from cancer of Germans aged 60-69 [8]. In Athens and Piraeus, through the lean years of 1942 and 1943, fatality from cancer fell, while death from all other causes rose [9]. The reported incidence of malignancies in most underdeveloped countries is low [10], but diagnosis and reporting leaves much to be desired. Physicians working in the field (and not in referral hospitals), however, cannot help but be impressed with the lower incidence and the different nature of malignancies in tribal societies on restricted diets. During fieldwork among famine-stricken African nomads (Fulani, Maasai, Turkana, and some 16,000 Somali in the Ogaden feeding camps) from 1973 to 1978, we actively searched for malignant tumors. We encountered two; one was a hepatoma in a sedentary Fulani and the other a carcinoma in the schistosome-infected bladder of an elderly Buduma from Lake Chad. While this was not a controlled epidemiological study, the findings did suggest an unusual rarity of malignancies in these groups. Invariably such societies are classified as undernourished by Western norms, but there is no certainty about the proper nutritional status of a society for optimum host resistance to malignancy and intracellular infection. As for infection, we have already reviewed the case for suppression of intracellular infections by undernutrition and for its activation by refeeding [H]. The evidence was conclusive enough in many experimental models and sufficiently strong in the field for us to formulate the idea that the phenomenon represented a biological mechanism designed to prevent the extinction of man from disease in the event of famine [12]. We believe that the mechanisms involved are identical with those responsible for the nutritional suppression oftumorigenesis. Interestingly, when nutritional state...