This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
Alpha hydroxy fatty acids were obtained by fixing an OH at the carbon adjacent to the carboxyl. Some of these acids exist in nature—in significant amounts in the brain and skin, and in very small amounts in the kidneys. In our research, they were originally prepared from natural sources, such as animal brain and skin. Most of the studies however, were made with synthetic alpha hydroxy fatty acids. For experimental purposes in animals and humans, we principally used pure synthetic alpha hydroxy fatty acids. Mixtures of these members obtained through the treatment of acid lipidic preparations also were employed.
In animals and humans, alpha hydroxy fatty acids induce less systemic, organic, tissue and cellular changes than do the corresponding untreated acids. However, we would like to mention a striking exception: the response of lymphosarcoma 6C3HED in mice to the administration of alpha hydroxy caprylic acid. Although this tumor uniformly kills control animals within 10-12 days, it disappears in over 80% of animals treated with alpha hydroxy caprillic acid, even if treatment is instituted late, that is, when the tumor has already grown to 1 cm. in diameter, a size usually reached 2 or 3 days before death. In the few animals in which the tumor does not disappear, its growth is so slowed down that survival time is extended to three or more weeks. (Note 6)
Other alpha hydroxy fatty acids close to caprylic acid, such as alpha hydroxy caproic and capric acids, show no influence upon evolution of this tumor. We could not obtain similar effects with any of the other saturated alpha hydroxy fatty acids that have chains with 4-20 carbons, nor with alpha hydroxy oleic or linoleic acids. Nor did alpha hydroxy caprylic acid or any of its homologues appear to have any influence upon other transplanted tumors in mice, the Walker tumor in rats or, spontaneous mammary tumors in mice.
The fading effect seen with naturally occurring fatty acids is so great a handicap for therapeutic use of these substances that we searched for heterogeneous fatty acids which the organism does not normally encounter and against which it would not be prepared to defend itself. This brought us to the study of fatty acids having different nonpolar groups than those of the normal and abnormal constituents. While most of these were prepared synthetically in the laboratory, we utilized on a substantially large scale two natural fatty acids which exist in plants and are sufficiently heterogeneous, ricinoleic and crotonic acids.
Ricinoleic acid has a double bond between 9 and 10 and a hydroxyl at carbon 12 instead of the second double bond found in linoleic and linolenic acids. As a result of the induction effect propagated from the carboxyl through the chain, the C11 is a positive carbon. The positive character is enhanced by the adjacent double bond between C9 and C10, and by the hydroxyl bound to C12. C11 thus is very strongly positive. We related the intense local alkalosis with consequent water excretion corresponding to the alkaline watery diarrhea to the effect of ricinoleic acid liberated in the intestine, and have considered it to correspond to a local organic offbalance similar to that induced in tissues by unsaturated fatty acids. This would explain the intensive laxative effect of castor oil.
We utilized ricinoleic acid parenterally with the aim of obtaining a similar effect in abnormal cellular and tissue lesions. The oily solution of ricinoleic acid has low toxicity when administered parenterally. However, no manifest effect upon tumors or at different levels of organization was obtained. Crotonic acid did not show the expected influence at these levels.
Other heterogeneous agents, polyhydroxy fatty acids, were studied. They were prepared by adding one or more OH groups to the nonpolar groups at the double bonds of unsaturated fatty acids. 9, 10 dihydroxy and 9, 10, 12, 13 tetrahydroxy fatty acids were no different than the corresponding unsaturated fatty acids in their effects upon pain or systemic analyses in humans, or upon tumor growth in animals and humans.
Peroxides and epoxides of fatty acids were prepared and studied. They showed more manifest effects upon viruses and bacteria in vitro and in vivo than the other fatty acids. Investigations of the effects of these fatty acids upon higher levels have been limited until now. It seems that the effects upon systemic and organic manifestations are somewhat different than those obtained with use of the fatty acids from which the peroxides and epoxides were derived. Influence upon pain and upon tumors was greater for the corresponding unsaturated fatty acids. This research—especially with polyepoxide fatty acids—is still in progress.