Lipotropic substances

Animal experiments have shown that faulty nutrition, i.e. > 90% fat, < 10% protein and < 2 mg choline per day, leads to pronounced fatty fiver and even fatty cirrhosis within a few weeks. The same changes could be observed when the protein intake remained more or less normal, while extremely little methionine and choline was offered. With a partial surplus of certain foodstuffs, the special nature of the excessive nutritional components is also of considerable importance. The term partial malnutrition may, for example, be associated with a pronounced protein deficiency (and thus possibly inadequate production of lipoproteins) or a lack of lipotropic substances (such as methionine, choline, cystine, glycocoUbetaine, pyridoxine, casein and various N- or S-methylated substances). Protein deficiency has particularly severe consequences when toxic substances are absorbed at the same time or when the organism has to fight bacterial or parasitic infections. A diseased liver reacts to both a serious deficiency in and an excessive supply of different nutrients (e.g. proteins, certain kinds of amino acids, various lipids, trace elements) with unfavourable or even complicative developments during the course of disease. 

Lee, S.O., Studies on the influence of diets and lipotropic substances upon the various organ and metabolic changes in rabbits on long-term feeding with red pepper (I) histopathological changes of the liver and spleen, Kor. J. Int. Med., 6, 383, 1963. 

Lipotropic substances compounds directly or indirectly involved in fat metabolism, which can prevent or correct fatty degeneration of the liver. They serve as substrates of phosphatide biosynthesis, or contribute (e.g. by methylation) to the synthesis of these substrates. Thus choline and any substance capable of contributing methyl groups for choline synthesis (e.g. methionine) are L.s. Liver is the major site of synthesis of plasma phosphoglycerides when the availability of choline is restricted, the rate of phosphatidylcholine synthesis decreases, and the rate of removal of fatty acids from the liver falls below normal. If the rate of supply of fatty acids (free and esterified) to the liver remains normal, the resulting accumulation of fat gives rise to the condition of fatty liver, or fatty degeneration of the liver. 

Curtis, A. C., and J. P. Berger Effect of feeding a lipotropic substance to patients with xanthelasma. Arch. Derm. Syph. (Chic.) 62, 252 (1945). 

E. Effect of Lipotropic Substances on Phosphatide Turnover in Liver. 138... 

E. EFFECT OF LIPOTROPIC SUBSTANCES ON PHOSPHATIDE TURNOVER IN LIVER... 

Stable lipotropic OCPs and their metabolytes present a danger to mammals not only through acute exposure, but also through chronic exposure to small doses. In recent years, intensive study of the effect of small doses of contaminants [92] shows that small, and super small, doses (i.e. doses that are thousands, and tens of thousands, of times smaller than those causing acute effects) of biologically active substances affect living organisms in a delayed way, over a protracted amount of time. 

Choline can be replaced by other substances capable of donating methyl groups, such as methionine or betaine. Similarly vitamin a factor in the synthesis of methyl groups, also has a lipotropic effect when administered together with homocysteine (Bennett et al. 1951). 

The absorption and excretion of choline have been studied in normal subjects and in patients with hepatobiliary diseases. After oral administration of 2 to 8 g. of choline base, only small amounts of choline were detected in the urine, while approximately two-thirds of the ingested choline nitrogen was excreted as trimethylamine and its oxide. Incubated stool dilutions were shown to transform choline to trimethylamine. After intravenous administration of choline, urinary trimethylamine excretion did not increase. These findings suggest that trimethylamine is formed from choline in the intestinal tract. Since trimethylamine is a substance without lipotropic activity, it would appear that oral therapy with choline could not be expected to produce markedly beneficial effects. 

Like choline, which is part of the compounds which are commonly called lecithins, inositol is an important component of phospholipids which help to stabilize blood cholesterol and prevent its deposition on the walls of arteries. Sometimes, the administration of inositol has helped to reduce accumulations of fatty substances (lipids) in the blood and the liver. Hence, it is designated as an agent which aids in the utilization of lipids (a lipotropic factor). However, it appears that the actions of inositol are closely tied to those of such other nutrients as choline, essential fatty acids, phospholipids, niacin, and vitamin B-6 (pyri-doxine). Finally, it is noteworthy that the heart muscle contains high levels of inositol, which suggests that it has an important cardiac function. 

A substance that prevents accumulation of fat in the liver. Choline is probably the most important of the lipotropic factors. So, any substance capable of contributing methyl groups for choline synthesis is lipotropic. 

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