Gyromitrin poisoning: more questions than answers Denis R. Benjamin, MD some dedicated mycophagist, who had Many of these clues to the toxin never eaten the mushroom for many years made any coherent sense, even though it “It is perhaps ironic for a mushroom, without any ill effects, would suddenly was known for some years that the toxins Gyromitra esculenta, whose very name and unaccountably take ill. This too could be destroyed by cooking.” (From means edible, to be so poisonous under was passed off as the development of an Benjamin, 1995.) certain circumstances. Surprisingly, allergy in the unfortunate individual, the toxins were only characterized as that the mushrooms had been mistaken ll the enigmas related to this recently as 1968. A number of factors for a poisonous variety, or a rotten toxin remain unresolved. The conspired against the investigators of this batch had been eaten. To compound the current literature merely repeats mushroom poison (Lincoff and Mitchel, difficulties, Gyromitra esculenta caused Awhat was published before 1990. A 1977). The first was the observation that many poisonings in Europe, while in the deluge of “cut and paste.” No meaningful only a few of the participants eating the western USA, the seemingly identical research has been done in the past same quantity of the same mushroom species appeared largely harmless. All three decades. This is due to a number would become ill. Because of this, the sorts of explanations were proposed of factors. The first was the demise of poisoning was immediately ascribed to to explain this discrepancy, including academic pharmacognosy departments, ‘allergy’ or ‘individual idiosyncrasy.’ The such fanciful ones as suggesting that responsible for investigating the biology next problematic observation was that Americans cook their vegetables better. and chemistry of products found in nature. Patent law does not issue patents on “natural” products so they cannot be monetized. The pharmaceutical industry seized this opportunity to create designer molecules, ignoring those produced by plants and fungi. Mycology research has been swallowed up by cell biology and lately molecular biology, so few scientists remain to do the field work or the chemistry. Funding for these types of investigations is almost nonexistent. The final issue was the passage of the HIPAA regulations. Obtaining reliable and comprehensive medical information from suspected poisonings is virtually impossible. What is known The main toxin in Gyromitra esculenta, and a few of its relatives, is gyromitrin. It is a highly volatile and unstable molecule. After ingestion this compound is converted into monomethylhydrazine (MMH) in the acid environment of the stomach and passage through the liver. A number Gyromitra esculenta from Washington, courtesy M. Beug. of other hydrazine and hydrozone 36 FUNGI Volume 13:1 Spring 2020 Gyromitra korfii (G. gigas) from Wisconsin, courtesy B. Bunyard. molecules are also present in varying Compounding the problem, gyromitrin and only organ to be affected, with a amounts, and probably contribute to has a number of pharmacological sense of bloating, nausea, vomiting, the toxicity. The chemistry and effects effects that may manifest themselves abdominal pain, and diarrhea. In more of hydrazines are well studied, as they in different ways from one person to severe cases the liver may be damaged are used in the aerospace industry the next. Symptoms of toxicity usually resulting in jaundice, which develops as propellants. However it after 48–72 hours. This may should be noted that there are progress to liver failure. Very significant species differences, rarely kidney failure may occur. such that data derived from In some cases there are serious animals cannot be extrapolated neurological effects (confusion, to humans. For example, convulsions, coma) due the dogs frequently develop effect of MMH interfering with methemaglobinemia, while this enzymes that rely on pyridoxal is quite rare in humans. It is also 5-phosphate (vitamin B6). known that the therapeutic/ In the brain this inhibits the toxic range is very narrow, synthesis of the important varying from one person to neurotransmitter, GABA the next, depending on one’s (Michelot and Toth, 1990). individual metabolism. This In rare circumstances means that no two people may patients have succumbed, have the same reaction to the although no deaths have identical dose of toxin. There been reported in the USA is no relationship between the in the past 30 years. Other dose and the response. “Thus, Gyromitra caroliniana in Missouri, courtesy B. May. pharmacological effects like rockets, MMH-containing mentioned in reviews, mushrooms have the potential of occur after six hours. Mild cases may but poorly documented in human moving the human body from an earthly be delayed even further, up to 48 hrs. cases, include red cell hemolysis and existence to heaven” (Trestrail, 1994). In most people, the GI tract is the first methemoglobinemia. Spring 2020 FUNGI Volume 13:1 37 Treatment is largely supportive. these in North America, none of which saprobe, G. esculenta may also When neurological effects are present, have been formally tested for gyromitrin. establish mycorrhizal relationships. the use of pyridoxal phosphate is This includes the so-called “snow bank” The importance and frequency of advised. It should not be employed in mushroom (G. gigas complex, including this has yet to be determined. mild toxicity. Mild cases usually recover the western G. montana and the 4. Which other species of Gyromitra in 48–72 hours. midwestern/eastern G. korfii). The toxin and Helvella contain gyromitrin, also has been detected in some related The epidemiology of and in what concentration? species in Europe, including Cudonia 5. Does the altitude at which they grow gyromitrin poisoning circinans and Leotia lubrica, Helvella determine the amount of toxin, as The epicenter for Gyromitra esculenta crispa, H. lacunosa, H. elastica, and H. suggested in a single study in France consumption is the Nordic countries, macropus (Andary and Privat, 1985). (Andary and Privat, 1985)? especially Finland, where this mushroom This latter group is seldom collected 6. As hydrazines are known is regarded as a delicacy. The collection, for the table except by exceptionally carcinogens, is there any evidence processing and sale is carefully adventurous mycophagists. that occasional consumption of regulated, and the Finnish health The experiences of toxicity with this properly prepared G. esculenta department publishes explicit guidelines group of mushrooms in North America poses any human health risk? And about methods of preparation (www. was well reviewed by Dr. Michael Beug if so, is it any different from eating ruokavirasto.fi). Poisoning is extremely (2014). This was based on reports he many other mushrooms known rare. In over 100 years (from 1875–1988) received through the toxicology program to contain hydrazines, such as only four fatalities were recorded, and of NAMA, as well as his expertise with Agaricus bisporus (Chiarelli et al., in each case the mushrooms were eaten ascomycetes in general. Beug highlighted 1984; Toth, 1979)? raw (www.dlc.fi/~marian1/gourmet/ some of the taxonomic and identification morel.htm#instrc). The instruction difficulties, as well as the lack of reliable 7. Why do some people develop pamphlet produced by Evira, the Finnish information in a number of cases. Most hemolysis and not others? Food Safety Authority, explicitly states striking was the absence of convincing 8. Although the possibility of that this preparation should only be evidence of toxicity with well-cooked methemaglobinemia is mentioned used for Finnish mushrooms. Either G. montana. Beug (2014) suggested that in many reviews, documentation they don’t trust the rest of us to follow G. korfii is similarly safe if appropriately that it occurs is marginal. Careful instruction or are concerned about prepared, although cautioned that there evaluation of future poisoning cases liability, or both. may be unreported cases of toxicity. could settle this issue. The largest number of reported cases Importantly, there is no documented 9. Is the toxin cumulative? of poisoning are from eastern Europe, evidence of gyromitrin in morels or where Gyromitra is both abundant With so little known about this Verpa species. Claims to the otherwise and widely consumed. This is followed mushroom in North America and its are based on speculation, not fact. by western Europe, with only a small legendary vagaries, it is prudent to number of cases documented in North Questions needing answers avoid its consumption. For those that insist, or have eaten it for years, the America. Most of these have occurred There is only one study on the presence pejorative Australian “good-on-ya” in the Midwest. Despite claims that G. and concentration of gyromitrin in is appropriate—you are winning in a esculenta does not contain gyromitrin collections of G. esculenta in North game of Russian roulette. But as John west of the Rocky Mountains, there is America, but this was limited to counties Trestrail, a past chairman of the NAMA at least one well documented example in in Michigan (Liang et al., 1998). For the which a couple was sickened after eating rest of North America and for other toxicology committee has written raw specimens of G. esculenta (Leathem, species, there is an absolute dearth of (1993): “Persons who decide to continue 2007). The files of the toxicology data. That has not stopped unbridled with this gastronomic gamble should committee of the North American speculation. It would be most beneficial have the numbers of their regional Mycological Association (NAMA) have if we had satisfactory answers to the poison centers permanently engraved on reports of cases in Idaho, California, following questions: their eating utensils.” and Alaska (Beug et al., 2005). Themost 1. Which collections of Gyromitra recent “outbreak” of poisonings in General reviews esculenta from different ecological the USA occurred in Michigan in the StatPearls. Gyromitra mushroom regions contain gyromitrin? spring of 2011, when at least 11 people toxicity.