{"id":45635,"date":"2019-09-16T16:01:28","date_gmt":"2019-09-16T15:01:28","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=45635"},"modified":"2019-09-20T14:13:58","modified_gmt":"2019-09-20T13:13:58","slug":"jeffrey-aronson-when-i-use-a-word-hormesis","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2019\/09\/16\/jeffrey-aronson-when-i-use-a-word-hormesis\/","title":{"rendered":"Jeffrey Aronson: When I Use a Word . . . Hormesis"},"content":{"rendered":"

\"\"<\/a>Last week<\/a> I discussed the different types of concentration-effect curves that R P (Steve) Stephenson reported in 1956, by using alkylated trimethylammonium salts to induce contractions in guinea-pig ileum in vitro. Most of the curves were monotonic: low concentrations had no effect, higher concentrations caused increasing contraction, with log-linearity at 20\u201380% of the maximum effect, but then no further increases after the maximal efficacy had been reached. However, in one case the curve was biphasic, with increased contractions at low concentrations and reversal of the effect at higher concentrations.\u00a0<\/span><\/p>\n

Stephenson attributed this biphasic effect of the decyl salt to reduced surface tension of water at high concentrations, causing frothing. However, it could have been due to a phenomenon called hormesis, which had been described in 1943, but which related to effects on fungal and bacterial growth and had achieved little currency. Indeed, as Figure 1 shows, discussion of the concept only took off at the end of the 20<\/span>th<\/span> century.<\/span><\/p>\n

\"\"<\/p>\n

The term hormesis was introduced by Chester M Southam and John Ehrlich in 1943 (Phytopathology 1943; 33: 517-24). They observed that water-soluble extracts from the heartwood of Western red cedar trees (<\/span>Thuja plicata<\/span><\/i>) included a substance, a phenol they thought, that was toxic to the fungus <\/span>Lenzites saepiaria<\/span><\/i> (<\/span>Lenzites lepideus<\/span><\/i> or <\/span>Fomes annosus<\/span><\/i>) and that protected the heartwood from fungal decay. They then investigated the effects of different concentrations of the extract on a range of fungi. Some of their results are shown in Figure 2. Low concentrations increased the growth of some of the fungi, reflected in the average of all the 11 species they studied (top panel). The example of <\/span>Lentius lepideus<\/span><\/i> is shown in the bottom panel. They called this \u201chormesis\u201d: \u201cThe term <\/span>hormesis<\/span><\/i> (adj. <\/span>hormetic<\/span><\/i>) is proposed to designate such a stimulatory effect of subinhibitory concentrations of any toxic substance on any organism.\u201d They did not explain the origin of the term.<\/span><\/p>\n

\"\"<\/p>\n

Actually, the term \u201chormetic\u201d was by no means new, although rare and by then long obsolete. The <\/span>Oxford English Dictionary<\/span><\/i> cites a single instance from 1666, in a <\/span>book<\/span><\/a> called <\/span>\u0393\u03b7\u03c1\u03bf\u03ba\u03bf\u03bc\u03af\u03b1 \u0392\u03b1\u03c3\u03b9\u03bb\u03b9\u03ba\u1f74:<\/span><\/i> King Solomon\u2019s Portraiture of Old Age<\/span><\/i> by John Smith “[The muscles] By their hormetick power and contraction into their own bodies … can readily perform whatsoever motion the Organ is capable of.” He got it from the Greek, \u1f41\u03c1\u03bc\u03b7\u03c4\u03b9\u03ba\u03cc\u03c2, impulsive.<\/span><\/p>\n

The IndoEuropean root ER meant to move or set in motion and hence to stimulate. This gives us parts of the verb to be, are and art; the name Ernest, meaning vigour, typically in battle; earnest; and uplifting words, such as arise, rise, and raise. The o-grade form OR, gave the verbs \u1f44\u03c1\u03bd\u03c5\u03c3\u03b8\u03b1\u03b9 in Greek and oriri in Latin, both meaning to arise, from which we get origin, the orient, where the sun rises, and abort. The Greeks also aspirated the o-grade form and added a mu, giving them the noun \u1f41\u03c1\u03bc\u03ae, rapid onward motion, and the verb \u1f41\u03c1\u03bc\u03ac\u03b5\u03b9\u03bd, to set in motion or urge on. From these we get hormone, coined by Ernest Henry Starling in the Lancet<\/em> in 1905: \u201cThese chemical messengers, however, or \u201chormones\u201d (from \u1f41\u03c1\u03bc\u03ac\u03c9, I excite or arouse), as we might call them\u201d. And of course hormesis.<\/span><\/p>\n

After Southam and Ehrlich\u2019s observations on fungi, <\/span>antibacterial drugs<\/a> were also shown to produce hormesis, as were <\/span>insecticides and herbicides<\/a>. And radiation hormesis, the controversial theory that low doses of radiation can be beneficial, emerged for discussion in the <\/span>1980s<\/a>. <\/span>Elements<\/a> such as vanadium, iron, manganese, cobalt, nickel, copper, and zinc have also been regarded as hormetic, since trace amounts are necessary for life but large amounts are toxic. The term \u201c<\/span>hormetin<\/a>\u201d has also been coined to denote a substance that demonstrates hormesis. And hormology is the study of such effects.<\/span><\/p>\n

Hormetic effects tend to be rather small, as the data in Figure 2 show. For example, cardiac glycosides, which act by inhibiting Na\/K-ATPase (the Na\/K pump), have also been shown to <\/span>stimulate<\/span><\/a> it at very low concentrations, although the size of this effect is too small to be convincingly relevant to clinical practice. Occasionally, however, a sizeable effect may be demonstrated, as in the case of the effects of dopamine on pituitary secretion of prolactin (Figure 3), leading to the <\/span>use<\/span><\/a> of dopamine receptor agonists in hyperprolactinaemia.<\/span><\/p>\n

\"\"<\/p>\n

Jeffrey Aronson<\/strong>\u00a0is a clinical pharmacologist, working in the Centre for Evidence Based Medicine in Oxford’s Nuffield Department of Primary Care Health Sciences. He is also president emeritus of the British Pharmacological Society.<\/em><\/p>\n

Competing interests:<\/strong> None declared.<\/p>\n","protected":false},"excerpt":{"rendered":"

Last week I discussed the different types of concentration-effect curves that R P (Steve) Stephenson reported in 1956, by using alkylated trimethylammonium salts to induce contractions in guinea-pig ileum in […]<\/p>\n

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