104 CHOLINE 



F. MAN 



W. STANLEY HARTROFT, COLIN C. LUCAS, and CHARLES H. BEST . 



Direct evidence of disease in man due to choline deficiency is still lack- 

 ing, although two decades have elapsed since Best and Huntsman'*'^ dem- 

 onstrated the lipotropic action of choline in the experimental animal. It has 

 been suggested that, in such deficiency states as kwashiorkor, infantile 

 cirrhosis, and related conditions in parts of the world where the nutritional 

 status of much of the population is low, a deficiency of the lipotropic factors 

 as well as of other vitamins, coupled with a low intake of poor protein, 

 may be responsible in part for the lesions in liver, pancreas, and kidney. 

 There are many references to this question in the recent literature,^'^"'*^^ but 

 such a complex problem will not be discussed here. The clinician must await 

 more direct evidence based on controlled therapeutic trials before he can 

 properly assess the role of the lipotropic factors in these perplexing diseases. 

 Experimental research in this field has now progressed sufficiently to justify 

 attempts by physicians to provide clinical data to answer their own ciues- 

 tions. 



In contrast to our ignorance concerning the etiology of those hepatic 

 disorders which are endemic in countries with extremely low standards of 

 living, there is considerable evidence that the cirrhosis frecjuently encount- 

 ered in cases of chronic alcoholism is the direct result of choline deficiency 

 induced by the replacement of a large portion of the individual's food intake 

 by alcohol — an alipotropic source of abundant calories. This conclusion is 

 based on data obtained from animal experiments and also from a few clini- 

 cal trials, which are understandably limited and incompletely controlled. 

 In experiments conducted in this laboratory^- an adequate supplement of 

 choline prevented the development of fatty and fil^rotic hepatic changes 

 that occurred in rats given alcohol (15 %) in their drinking water. This 

 confirmed the earlier investigations of Sebrell and his associates in the U. S. 

 Public Health group .''-^ In addition it w^as shown that in comparable paired- 

 fed animals given an amount of sugar isocaloric with the alcohol consumed, 

 identical lesions (Figs. 4 and 5) developed unless ec^ual amounts of choline 



"6 C. H. Best and M. E. Huntsman, /. Physiol. {London) 83, 255-274 (1934-1935). 

 "7 J. N. P. Davies, Trans. 9th Conf. Liver Injury, New York pp. 151-200 (1950) ; Lancet 



I, 317^320 (1948). 

 "8 J. C. Waterlow, Med. Research Council (Brit.) Spec. Rept. Ser. 263, 78 (1948). 

 «9 J. Gillman and T. Gillman, Lancet I, 169 (1948). 

 ^2° V. Ramalingaswami, P. S. Menon, and P. S. Venkatachalam, Indian Physician 7, 



229-237 (1948). 

 «i Kenneth R. Hill, Trans. 10th Conf. Liver Injury, New York pp. 26.3-320 (1951). 

 «2 C. H. Best, W. S. Hartroft, C. C. Lucas, and J. H. Ridout, Brit. Med. J. II, 1001- 



1006 (1949). 

 «" F. S. Daft and W. H. Sebrell, Publ. Health Repts. (U.S.) 56, 1255-1258 (1941). 



