Animal feeding experiments, vitamin

The story related here will clarify, to some extent, the roles of these pioneers in the emergence of the vitamin hypothesis. More importantly, it will shed light on some peculiarities of nutritional biochemistry as it was practiced in the first quarter of the twentieth century. In particular, it will focus upon experimental results that helped one investigator win a Nobel Prize, results that could not be reproduced by some of the most competent research workers in animal feeding experiments. 

Nevertheless, it is remarkable that the pioneers of the vitamin hypothesis were able to do so much when for twenty years or more they had no clear conception of the chemical entities with which they were dealing. Contradictory or not, those animal feeding experiments opened up new vistas in nutrition and in all the intervening years since the vitamin hypothesis came into being there has not been any single breakthrough in nutrition of comparable magnitude and of such pervasive influence. 

In the early 1940s nutritional studies of young animals raised on diets lacking animal proteins and maintained out of contact with their own excreta (which contained vitamin B12) demonstrated the need for "animal protein factor" which was soon shown to be the same as vitamin B12. The animal feeding experiments also demonstrated that waste liquors from streptomyces fermentations used in production of antibiotics were extremely rich in vitamin B12. Later this vitamin was recognized as a growth factor for a strain of Lactobacillus lactis which responded with half-maximum growth to as little as 0.013 pg/l(10-nM). 

It was found that vitamin E deficiency in the rat resulted in an increase in the incorporation of formate-C into nucleic acids of liver and skeletal muscle (Dinning, 1955). The rats used in these experiments were only mildly deficient in vitamin E, and subsequent experiments were conducted on rabbits in which it is possible to produce severe vitamin E deficiency with relatively short feeding periods. Vitamin E deficiency in the rabbit led to an increased specific activity of nucleic acids in several tissues following formate-C injection (Dinning et al., 1955). Measurements of the specific activity of CO2 expired by these animals indicated that the overall formate pool size was not affected by vitamin E deficiency. The increased specific activity of the tissue nucleic acids then could represent an altered specific activity of the nucleotide precursors or an altered synthetic rate of the tissue nucleic acids. 

The concept of, and need for, vitamins developed through many feeding experiments with animals and some with humans. These experiments pointed to the fact that substances other than minerals, water, carbohydrate, protein, and essential fats were required for... 

The effects of antioxidants on protein oxidation were also studied in animal experiments. Barja et al. [73] demonstrated that feeding guinea pigs with vitamin C decreased endogenous protein oxidative damage in the liver. Administration of the mixture of antioxidants containing Trolox C, ascorbic palmitate, acetylcysteine, (3-carotene, ubiquinones 9 and 10, and (+)-catechin in addition to vitamin E and selenium to rats inhibited heme protein oxidation of kidney homogenates more efficiently than vitamin E + selenium [74]. 

The need to include a variety of minerals in experimental diets has already been mentioned this was especially stressed (1920-1930) by Boyd-Orr, the director of the Rowett Institute for Animal Nutrition in Scotland. Increasingly refined food sources led to the identification of large numbers of trace elements (e.g., Cu, Mn, Mo, Zn) whose importance in the diet was suggested from hydroponic experiments with plant seedlings. Cobalt is an example of such a trace element. Vitamin Bj2 is synthesized by bacteria in the rumens of sheep and cattle but is absent from their fodder. In Australia, sheep feeding on cobalt-deficient pastures failed to thrive because vitamin B12 could no longer be made. 

Lind had discovered that scurvy can be treated with lemons, but he did not recognize that the illness was actually caused by an insufficient intake of vitamin C. This discovery is credited to Norwegian researchers Axel Holst (1860-1931) and Theodor Frohch (1870-1947). They experimented with guinea pigs and got lucky. Scurvy occurred in animals when their feed consisted solely of various types of grain, but the symptoms were prevented when the diet was supplemented with... 

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