Tuesday, January 12, 2016

Hormesis - Grasping the Concept

The dose makes the poison. - Tenet of Pharmacology

Hormesis derives from the Greek hormo, meaning "I excite," from which we also get the word hormone. While of classic origin, hormesis has only recently found its way into many dictionaries and seems to have had its first modern usage by C.M. Southam and J. Erlich in a 1943 study of fungi reported in an unpronounceable scientific journal. [OK, you try it: Phytopathology. The full citation is "Effects of extract of western red cedar heartwood on certain wood decaying fungi in culture," Vol. 33, p. 517, 1943.] The word refers to a phenomenon stated by the "Arndt-Schulz" Law:

Small doses of poison are stimulatory.

Rudolf Arndt (a psychiatrist) and Hugo Schulz (a pharmacologist) were nineteenth-century German researchers who diluted poisons to the point that they were not only no longer poisonous, but had a positive effect on the growth and reproductive rates of yeast. For example, when mercury chloride is diluted by a factor of 700,000, it becomes a stimulant for bacterial growth instead of an extremely potent germicide. Arsenious acid, poisonous to bacteria in normal concentrations, showed a positive effect when diluted by 40,000 times its volume. The Arndt-Schulz team demonstrated that their principle was - or at least appears to be - universal, with regard to the dilution of inorganic toxins.

While Arndt-Schulz seem to be the first to quantify the "low-dose" effect of chemical poisons, the phenomenon had been described earlier by Bernard in Repair Strengthens Tissue (1867), by Hahnemann in Homeopathic Medicine (1810), and even earlier by a Swiss physician and chemist, Philippus Aureolus Paracelsus, in The Dose is Everything (1520). [His real name was Thophrastus Bombastus von Hohenheim. (Somehow I think I could have come up with an easier no de plume.) Aside from his work in chemistry, he is credited with being the first to point out the relation between goiter in the parent and cretinism in the child.]

A relatively modern work on the subject, The General Adaptive Syndrome, was written by Nobel Laureate Hans Seyle in 1944. While he identified many agents that increased the resistance of the host to disease, his primary emphasis was on the effects of stress - both the excessive mind-destroying stress of battle and his observation that little is accomplished by humans unless there is some minimal amount of stress-stimulation in their lives. Seyle's contention was that minute doses of the hormetin (the hormetic or stimulatory agent) start and alarm reaction, small doses induce the stage of resistance, and still larger doses bring about a stage of exhaustion in which the organism is no longer able to cope with the stressing agent. X-rays were one of the stress agents he often mentioned. [In describing his experiments, Seyle remarked, "I could find no noxious agent that did not elicit the syndrome" - meaning, of course, the "reverse effect."]

Walter A. Heiby shows numerous examples of low-dose stimulation - and the problem of over-stimulation - in his 1988 book, The Reverse Effect: How Vitamins and Minerals Promote Health and CAUSE Disease. [MediScience Publishers, Dearfield, Ill., 1988. Available for $59.50 from MediScience Publishers, Box 256A, Dearfield, IL 60015.] As you may have already deduced, his term for hormesis is "the reverse effect," expressing the change in response due to different levels of the same stimulant.

Prior to Southam and Erlich's use of the word hormesis in 1943 and Luckey's subsequent popularization of the term in his 1980 and 1991 books, another even worse tongue-torturer was used to characterize the phenomena: hormoligosis - which better defines the action of a small dose from the Greek olig meaning small or few, as in oligarchy.