Growth and Lipotropism I. the Dietary Requirements of Methionine, Cystine, and Choline by C. R. Treadwell*

Since the reviews by McHenry and Patterson (1) and Best and Lucas (2) on the relationships of lipotropic substances to fat metabolism, several publications have appeared which indicate progress in clarifying the somewhat conflicting views regarding the influence of amino acids and proteins on the fat content of the liver. Beveridge and coworkers (3) have shown that certain essential amino acids have a marked effect on the lipotropic efficacy of methionine. They also found no significant difference in the lipotropic effect exerted by methionine when fed as the amino acid or in casein, provided the essential amino acids were approximately equalized in the two diets. The data of Beveridge and coworkers give strong support to the explanation proposed by Treadwell, Groothuis, and Eckstein (4) for the greater lipotropic activity of free methionine in comparison with protein-contained methionine. It was suggested that larger amounts of methionine were used for the synthesis of tissue protein in the casein-fed groups, thus producing a decrease in the amount available for lipotropic activity with a resultant higher level of liver fat. The basal diet (4) contained 5 per cent casein, which is insufficient to support normal growth in young rats irrespective of the level of supplementary methionine. Horning and Eckstein (5) found that with adult male rats (250 gm.) a diet containing 5 per cent casein was, as far as lipotropism is concerned, as effective when supplemented with methionine and cystine as when supplemented with sufficient amounts of cystine and casein to equalize the content of the sulfur-containing amino acids in the two diets. The level of liver fat was low in all the groups receiving supplements, in marked contrast to results with young animals (4) in which the liver fat was low only in those receiving amino acid supplements. In these animals, as the authors (5) point out, the protein and methionine requirements for growth were low, so that a considerable part of the methionine in the supplements was available for lipotropic action. Treadwell, Tidwell, and Gast (6) have extended observations on young rats (130 gm.) to include the effect of diets so designed that the protein and methionine levels could be varied independently of each