Experiments That Changed Nutritional Thinking - TUUM EST

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1040S SUPPLEMENT TABLE 1 TABLE 2 Effects of food restriction on life span of rats1 Effects of food restriction on the weight and density of the femur of rats1 Median age Group Ave. age at death Group Mean weight Density d I Unrestricted Males (n Å 11) 0.741 1.22 I Unrestricted Females (n Å 18) 0.540 1.21 Males (n Å 14) 483 522 II Restricted at weaning Females (n Å 22) 801 820 Males (n Å 7) 0.486 1.15 II Restricted at weaning Females (n Å 13) 0.398 1.13 Males (n Å 13) 820 797 III Restricted 2 wk after weaning Females (n Å 23) 775 904 Males (n Å 9) 0.484 1.09 III Restricted 2 wk after weaning Females (n Å 10) 0.432 1.14 Males (n Å 15) 894 919 Females2 (n Å 19) 826 894 1 Data taken from McCay et al. (1935). 1 Data taken from McCay et al. (1935). 2 Two female rats in this group died at a young age due to high Table 2 provides data regarding the weight and density of the temperatures in the animal room. They were not included in the calcula- femur at the time of death. tion of results. Confirmation of the Relationship of Diet to Longevity publishing the first report from this work in 1934 while some In a second experiment, McCay and his group fed all rats of the rats were yet alive (McCay and Crowell 1934). McCay and his co-author remarked on the long-held viewpoint that identical amounts of a nutrient-dense diet, feeding that nutrition and life span were related (Darby 1990). Yet, they amount required to just maintain the weight of the restricted rats. This allowed them to determine whether the unlimited noted, the science of nutrition had focused on the young, consumption of a nutrient-dense diet had shortened the life growing animal to the exclusion of the study of the adult or of the control group from the first experiment, and they conaging animal. cluded it had not. The growth of the rats was controlled by They wrote: ‘‘In this day when both children and animals varying the amount of a mixture of sucrose, cooked starch and are being fed to attain a maximum growth rate, it seems a lard (38:57:5) that was fed, with the control rats being allowed little short of heresy to present data in favor of the ancient to eat as much as they chose. In addition, the control group theory that slow growth favors longevity.’’ They cited the earwas divided, with half the rats being fed cod liver oil and half lier work of Osborne et al. (1917) and their own previous (as well as all rats with restricted intakes) being fed irradiated observations that trout with very low protein intake ‘‘failed to grow [but remained alive and] lived twice as long as those yeast and carotene as sources of fat-soluble vitamins. Supple- mentation with these different sources of fat-soluble nutrients that grew.’’ They postulated that ‘‘something was consumed in growth that is essential for the maintenance of life’’ (McCay and Crowell 1934). Accordingly, McCay and Crowell selected from their colony TABLE 3 106 rats, both male and female, and divided them into Effects of various lengths of food restriction on three groups. They fed them all the same nutrient-dense diet the life span of rats1 from the time of weaning. However, Group I was fed unlimited amounts of the diet, whereas the others were fed restricted Age at death amounts of the diet, either from the time of weaning (Group II) or after 2 wk (Group III). Restricted rats were maintained at a constant weight until once about every 100 d when they Group Ave. Range were allowed to grow about 10 g because of the feeding of d sucrose or beef liver to all rats. I Unrestricted2 A full report was published on this initial experiment a year Males (n Å 17) 670 308–896 after the preliminary report (McCay et al. 1935). Table 1 presents Females (n Å 16) 643 404–965 data concerning the length of life of these rats. The female rats II Restricted until d 300 that were fed unrestricted amounts of diet lived significantly Males (n Å 4) 865 805–1018 longer than the comparable males (median age at death 820 vs Females (n Å 5) 811 555–1183 522 d). Male rats that were fed restricted amounts of diet, how- Restricted until d 500 Males (n Å 5) 806 366–1103 ever, lived as long, and in some cases longer, than did the females Females (n Å 5) 990 793–1078 whose intake was restricted. The life of the male rats was clearly Restricted until d 700 lengthened by food restriction and the slower rate of growth, Males (n Å 4) 874 772–1025 whereas the life of the slower-growing females was not lengthened Females (n Å 6) 912 406–1320 greatly, if at all, by food restriction. Restricted until d 1000 McCay et al. (1935) also observed the effects of food restric- Males (n Å 5) 882 336–1127 Females (n Å 4) 1033 815–1320 tion on the growth and composition of several tissues. Their most striking observation was of the fragility of the bones taken 1 Data taken from McCay et al. (1939). from the rats fed restricted amounts of diet. They reported that 2 Data for controls, fed either carotene / irradiated yeast or cod some of the bones ‘‘crumbled in the course of dissection.’’ liver oil, were combined. / 4p09$$0062 04-07-97 14:02:12 nutras LP: J Nut May Suppl Downloaded from jn.nutrition.org by on June 3, 2010
HISTORY OF NUTRITION 1041S TABLE 4 these data for guidance of human beings he might summarize by stating: ‘Eat what you should, after that eat what you will Effects of food restriction on weight and density but not too much.’ ’’ of the femur of rats1 McCay’s scientific work was interrupted by his military ser- vice during World War II, but after the war he continued his Group Weight Density studies of the effects of nutrition on aging and the life span of rats and other species. He is best remembered by his students g for the course he taught for several years on the history of nutrition. A collection of some of these lectures was published I Unrestricted posthumously (McCay 1972). McCay died of a heart attack Males 0.70 1.10 Females 0.57 1.21 in 1967. II Restricted until d 300 Males 0.63 1.18 Females 0.45 1.13 Literature Cited Restricted until d 500 Darby, W. J. (1990) Early concepts on the role of nutrition, diet and longevity. Males 0.54 1.18 In: Nutrition and Aging (Prinsley, D. M. & Sandstead, H. H., eds.). Alan R. Liss, Females 0.47 1.13 New York, NY. McCay, C. M. (1939) Chemical aspects of aging. In: Problems of Aging Restricted until d 700 (Cowdry, E. V., ed.), chapter 21. Williams & Wilkins, Baltimore, MD. Males 0.55 1.15 McCay, C. M. (1952) Chemical aspects of aging and the effect of diet upon Females 0.39 1.11 aging. In: Cowdry’s Problem of Aging (Lansing, A. I., ed.), chapter 6. Williams & Restricted until d 1000 Wilkins, Baltimore, MD. Males 0.38 1.06 McCay, C. M. (1973) Notes on the History of Nutrition Research (Verzar, F., Females 0.37 1.03 ed.). Hans Huber Publishers, Berne, Switzerland. McCay, C. M. & Crowell, M. F. (1934) Prolonging the life span. Sci. Monthly 1 39: 405–414. Data taken from McCay et al. (1939). McCay, C. M., Crowell, M. F. & Maynard, L. A. (1935) The effect of retarded growth upon the length of life span and upon the ultimate body size. J. Nutr. 10: 63–79. did not significantly alter the results, and the data in Tables McCay, C. M., Maynard, L. A., Sperling, G. & Barnes, L. L. (1939) Retarded 3 and 4 represent the combination of these two treatments growth, life span, ultimate body size and age changes in the albino rat after feeding diets restricted in calories. J. Nutr. 18: 1–13. (McCay et al. 1939). Osborne, T. B., Mendel, L. B. & Ferry, E. L. (1917) The effect of retardation of The second experiment, designed to confirm and extend growth upon the breeding period and duration of life of rats. Science 45: the results of the first, began with 106 rats. Thirty-three were 294–295. fed unlimited amount of energy, and 73 were fed restricted amounts. Thirty-five of the restricted rats, however, died due Paper 14: The Dynamic State of Body Constituents (Schoenheimer, 1939) to two failures in the heating system. On d 300, the remaining 38 rats from the restricted group were divided into four subgroups and fed unlimited energy starting on d 300, 500, 700 Presented by Robert E. Olson, Department of Pediatrics, College or 1000 (McCay et al. 1939). of Medicine, University of South Florida, Tampa, FL 33606 as All groups of rats with restricted intakes contained longerpart of the minisymposium ‘‘Experiments That Changed Nutritional lived individuals than did the control group. At the time that Thinking’’ given at Experimental Biology 95, April 11, 1995, in the longest-lived control rat died (d 965), 18 out of the 38 Atlanta, GA. rats whose intakes were restricted were still alive. When the restricted rats were allowed to eat normally, they resumed The discoveries of Rudolf Schoenheimer and his colleagues growth with few exceptions. Those exceptions were certain at Columbia University in the period from 1933 to 1941 revoindividuals whose food intake had been restricted for 1000 d. lutionized our understanding of the metabolism of fatty acids Restricted rats did not attain the full size of the control rats. and amino acids and led to the concept of metabolic turnover. Table 4 presents the weight and density of the femur of Rudolf Schoenheimer was born in Berlin in 1898 and rerats in the second experiment. Again, both measures tended ceived his medical degree from the University of Berlin in to decrease with increasing length of time of food restriction. 1922. Following a year of clinical training he did postdoctoral Bone growth (length) was also measured, and the authors con- work in Leipzig with Karl Thomas from 1923 to 1926 and cluded: ‘‘The bones of the males respond to the realimentation then in Freiburg with Ludwig Aschoff from 1926 to 1933, more promptly than those of the female. The bones of the where he began work on the metabolism of cholesterol. In male retain the power to grow larger than those of the female’’ 1933, following the political upheaval in Germany, he emi- (McCay et al. 1939). grated to the United States to take up an appointment in the Department of Biochemistry at Columbia University, where he came in contact with Harold Urey, who had discovered Conclusions McCay summarized the conclusions he drew from these experiments in a chapter he wrote (McCay 1939) and later revised (McCay 1952) as a contribution to a book on aging. ‘‘This indicated that the life span was flexible and that the possibility of its extension was unknown as well as that the retarded animals tended to outlive those that matured normally’’ (McCay 1952). ‘‘The second experiment gave essentially the same results as the first and indicated clearly that the retarded growth was the essential feature’’ (McCay 1952). He went on to say: ‘‘If one were to draw conclusions from deuterium in 1932, and David Rittenburg, one of Urey’s students who had also joined the biochemistry faculty at Columbia. Together they planned experiments with various isotopic compounds, including heavy water, and substrates labeled with deuterium and 15 N; these experiments were to revolutionize concepts of fat and protein metabolism. At the time that Schoenheimer initiated his isotopic studies of intermediary metabolism it was generally believed that the major components of the body, including body fat and protein, were chemically stable. It was assumed that there was very little exchange of nutrient molecules between the diet and the / 4p09$$0062 04-07-97 14:02:12 nutras LP: J Nut May Suppl Downloaded from jn.nutrition.org by on June 3, 2010
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