Dose-response curves in the estimation of potency of lipotropic agents.

In the 18 years which have elapsed since the lipotropic activity of choline was discovered, four other naturally occurring substances have been shown to inhibit the deposition or to hasten the removal of excessive amounts of liver fat and to prevent kidney damage. Dimethylpropiothetin, the one most recently discovered (3, 4), was found in the marine alga Polysiphoniu jastigiata, but is not known to occur in vegetable or animal products commonly used in human or animal rations. The three other substances (betaine, methionine, and inositol) resemble choline in that they are widely distributed and are present in most natural food products. No systematic quantitative study of the relative lipotropic activities of these four common dietary components has been reported. Numerous exploratory studies of lipotropic phenomena by many investigators have provided a broad general picture of the factors involved. Sufficient data are now available to justify a more systematic attempt to determine the relative activity of naturally occurring and synthetic compounds which affect the accumulation of fat in the liver. Since choline appears to be the effective factor when methionine or betaine is given (5, S), since it is the most active agent of this type, and since inositol exhibits little, if any, significant lipotropic activity in diets containing a normal amount of fat, it would appear logical to use choline as the standard of reference. Evidence already in the literature indicates that factors which affect appetite and rate of growth influence the choline requirement. For example, Griffith and his colleagues (7, 8) have repeatedly emphasized that dietary supplements which improve the rate of growth should not be considered antilipotropic since there is no evidence for their direct antagonism to choline but there is proof that an increased demand for choline occurs when growth is promoted. A similar situation with respect to the mineral