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In his book, Diogenes Laertius (1) describes the life ofHeraclitus of Ephesus, the pre-Socratic Greek philoso-pher of the 5th century BC interested in the problem ofthe origin of the universe, who became famous for histheory, which can be summarized by the aphorismπα′ ντα ρει (panta rei, “all things are in a constant flux”).The author says that Heraclitus, disgusted by humans,became a complete misanthrope and suddenly decid-ed to withdraw to the desert “eating only herbs androots”. During this period Heraclitus became affectedby hydropsy, and he died a short time after returning tothe city, at the age of 60.The death of Heraclitus is the object of different inter-pretations in ancient literature. In particular, DiogenesLaertius reports that Heraclitus sought the advice of sev-eral doctors, asking in the form of an enigma whetherthey were “able to produce a drought after wet weath-er”, but none was able to understand him and providethe cure he needed. He finally decided to cover himselfwith cow dung, hoping for the heat from the fermentingdung to cause the wet to evaporate from him.The second version of his death, as told by Hermippus,is that Heraclitus asked the doctors whether anyonecould draw off the water by depressing his intestines.Disappointed by the doctor, who had excluded any pos-sibility of finding a remedy for his problem, he decidedto lie in the sun after covering himself with cow dungand died the day after in the throes of agony and wasburied in the market place. Both reports on the deathof Heraclitus are thus related to hydropsy – diffuse stateof edema – contracted during prolonged consumptionof herbs and roots.We hypothesize that the hydropsy of Heraclitus was re-lated to intoxication by licorice. Diogenes Laertius re-ports that the philosopher went away from Ephesus andate only herbs and roots (1), as quoted above. In thatperiod licorice was very popular in the region and wascommonly used by the local populations. Several au-thors of ancient Rome wrote about the use of licorice (2)and in particular Pliny describes it as native of Cilicia, aregion of today’s Turkey. The city of Ephesus was also lo-cated in today’s Turkey. Licorice plants even todayabound in the Mediterranean area and particularly inTurkey and Iran. In 1929, Sir John Uri Lloyd reported thatthe region of Ephesus and Priene, whose rich valleyshave been cultivated from the beginning of history, aremarvelously fertile and there the licorice plant triumphs(3). Theophrastus reported that Scythians survived in thedesert by eating licorice roots since they were able toreduce hunger and thirst (2). The reduction of thirst is

actually related to the mineralocorticoid-like effect ofglycyrrhetinic acid. This characteristic was known aboutbefore the discovery of aldosterone. Theophrastus’s ob-servation could be the reason for the studies carried outby Jerome Conn, who successively described primaryhyperaldosteronism, during the Second World War tofind the best conditions for soldiers to acclimatize to theAfrican Desert. He studied volunteers exposed to highlevels of humidity by evaluating the regulation of saltloss in sweat and found that acclimatization can beachieved quickly by giving desoxycorticosterone acetate,a mild mineralocorticoid.The hydropsy of Heraclitus could actually be interpretedas a consequence of the exaggerated intake of licoriceroots that can reduce thirst, improve the acclimatizationto the warmth and humidity of the region, and reduceappetite. Most of these factors could be related tolicorice over-ingestion. The clinical status of Heraclitusmight have been made more severe by prolonged star-vation, as a consequence of inadequate food intake,which causes decreased serum albumin concentrationand thus edema.The philosopher talked to doctors in search of cure butapparently he was not understood, since he spoke withinappropriate terms interpreted as an enigma, but thatpossibly were just a sign of mental confusion. Even lowdoses of licorice can induce hypertension encephalopa-thy (4) with neurological impairment.Glycyrrhetinic acid produces sodium and water retentiondue both to the block of 11β-hydroxysteroid dehydro-genase type 2 and to a direct mineralocorticoid effect oflicorice. Inhibition of 11β-hydroxysteroid dehydrogenasetype 2, which physiologically converts cortisol to inactivecortisone, causes an excess of active cortisol thus actingon type 1 mineralocorticoid receptors at the level of clas-sical target tissues (5).The reduction of hunger due to licorice was formerly de-scribed by Plinius the Elder, in his Naturalis Historia (2).This property was already reported in a letter to TheLancet in 1956 and attributed to a possible direct effectof the root on appetite due to the agreeable taste (5).We have recently found that licorice is also able to re-duce the body fat mass when ingested (5) and the thick-ness of subcutaneous fat when applied topically; we haverelated this effect to the block of 11β-hydroxysteroid de-hydrogenase type 1, which activates cortisone to corti-sol at the level of fat, thus increasing the triglyceride con-tent of adypocytes (5).In conclusion, the use of licorice root was popular in AsiaMinor during ancient times, and we hypothesize that Her-aclitus consumed an excess to reduce both thirst andhunger, due to the limited availability of other food out-side Ephesus. The prolonged intake of licorice could haveled to sodium and water retention and probably to se-vere hypertension and dropsy, which in turn caused thedeath of the philosopher.Accepted January 23, 2008.

A hypothesis on the death of the Greek philosopher Heraclitus

J. Endocrinol. Invest. 31: 742-743, 2008

©2008, Editrice Kurtis

LETTER TO THE EDITOR

Heraclitus and licorice

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REFERENCES1. Long HS (translation of). Eraclitus. In: Diogenis Laertii Vitae

Philosophorum. Oxford: Oxonii Typographeo Clarendoniano.Liber IX 1964, 437-45.

2. Fiore C, Eisenhut M, Ragazzi E, Zanchin G, Armanini D. A history ofthe therapeutic use of liquorice in Europe. J Ethnopharmacol 2005,99: 317-24.

3. Lloyd JU. Licorice. Cincinnati, Ohio. Reprinted from The EclecticMedical Journal 1929, 11.

4. Russo S, Mastropasqua M, Mosetti MA, Persegani C, Paggi A. Lowdoses of liquorice can induce hypertension encephalopathy. AmJ Nephrol 2000, 20: 145-8.

5. Armanini D, De Palo CB, Mattarello MJ, et al. Effect of licorice onthe reduction of body fat mass in healthy subjects. J EndocrinolInvest 2003, 26: 646-50.

C. Fiore1, D. Velo Dalbrenta2, E. Ragazzi3,D. Pellati1, and D. Armanini1

1Department of Medical and Surgical Sciences,Endocrinology, University of Padua, Padua;

2Department of Philosophy of Law, University ofVerona, Verona; 3Department of Pharmacology and

Anesthesiology, University of Padua, Padua, Italy