If you’ve been fortunate to live in the parts of the US that were soggier than usually as of late – or unfortunate enough to have had flooding from hurricanes and tropical storms – then you’ve be noticing a tremendous burst of mushrooms.
For mycologists – mushroom enthusiasts – there are two classic chestnuts: “There are old mushroom collectors and bold mushrooms collectors, but there are no old, bold mushroom collectors.”
Or, in a more concise Croatian proverb, “All mushrooms are edible, but some only once.”
As such, this is the time of year that emergency rooms and regional poison centers begin to see a burst in poisonings from mushroom ingestion, due primarily to amateur misidentification of the fruiting bodies.
Just this past week, Jason McClure at Medscape Oncology News (free reg req’d) wrote about the unusual bloom of mushrooms in the northeastern US and the concomitant bloom of mushroom poisonings this fall.
But “mushroom poisoning” is an imprecise diagnosis for the ER physician. The constellation of symptoms caused by toxic mushrooms is as diverse as the colors and shapes of these wonders of nature. From another Medscape article on emergency management of mushroom poisoning by Dr. Rania Habal from the Emergency Medicine department of NYU:
Mushrooms are best classified by the physiologic and clinical effects of their poisons. The traditional time-based classification of mushrooms into an early/low toxicity group and a delayed/high toxicity group may be inadequate. Additionally, many mushroom syndromes develop soon after ingestion. For example, most of the neurotoxic syndromes, the Coprinus syndrome (ie, concomitant ingestion of alcohol and coprine), the immunoallergic and immunohemolytic syndromes, and most of the GI intoxications occur within the first 6 hours after ingestion.
Ingestions most likely to require intensive medical care involve mushrooms that contain cytotoxic substances such as amatoxin, gyromitrin, and orellanine. Mushrooms that contain involutin may cause a life-threatening immune-mediated hemolysis with hemoglobinuria and renal failure. Inhalation of spores of Lycoperdon species may result in bronchoalveolitis and respiratory failure that requires mechanical ventilation.
Mushrooms that contain the GI irritants psilocybin, ibotenic acid, muscimol, and muscarine may cause critical illness in specific groups of people (eg, young persons, elderly persons). Hallucinogenic mushrooms may also result in major trauma and require care in an intensive care setting. Lastly, coprine-containing mushrooms cause severe illness only when combined with alcohol (ie, Coprinus syndrome).
Among the poisonous mushrooms, Amanita phalloides is perhaps the most deadly. If you’ve spent any time in a biochemical laboratory you will have learned of the primary toxin of the mushroom, α-amanitin. This potency of this toxin comes from its remarkably high affinity for RNA polymerase II, the primary RNA polymerase for making messages that are converted into proteins.
The challenge in treating α-amanitin poisoning is that it has a relatively long half-life in the body because it is conjugated with glucuronic acid in the liver and secreted in the bile. But then microbes that normally inhabit our gut cleave the glucuronide sugar molecule off the toxin, released the toxic α-amanitin.
Throughout the history of folk medicine in the Middle East and Europe, extracts of the seeds of milk thistle (Silybum marianum) were determined to have protective effects against liver toxins. I’m still not terribly pleased with understanding the history of how this came about but answering this question is one of my liberal arts pursuits. As an aside, I should make the disclosure that my laboratory and colleagues have been investigating the anticancer effects of compounds from milk thistle and still receive NIH funding to do so; however, I do not (yet) study how milk thistle compounds prevent liver toxicity.
Nevertheless, milk thistle products are quite popular in Europe and the US for the general prevention of liver toxicity from statins, acetaminophen, and alcohol. Several of my friends have joked that one could make create a successful market for an alcoholic product containing milk thistle extract.
But one of the primary roadblocks in using milk thistle extracts or pure compounds for any indication is that the compounds have rather poor bioavailability. The seven major flavonolignans and one flavonoid in the typical extracts are very avidly conjugated by glucuronidation. In studies by collabortors at the University of Colorado, we now know that it takes daily doses of approximately 10-13 grams of milk thistle extract to achieve plasma concentrations consistent with known anticancer effects in vitro. It can be done, but it means taking much more than the typical 180 mg capsules you can buy at your local health food store.
However, an intravenous preparation of milk thistle extract has been available in Europe for over 20 years: Legalon SIL. This GMP-manufactured product is common to emergency rooms in Germany, France, and Belgium for the treatment of mushroom poisoning. The preparation is comprised of silybin A and silybin B – known collectively as silibinin – as a hemisuccinate that both improves the solubility and bioavailability of the compounds.
Two cases in the US – one in 2007 and another just this past month – have seen emergency IND approval of this European product. In 2007, Legalon was used to save four of five family members who had ingested Amanita phalloides while on a New Year’s Day picnic outside of Santa Cruz, California. And just last month, a team led by Dr. Jacqueline Laurin at Georgetown Medical Center successfully treated two men for accidental ingestion of Amanita. Georgetown is now an approved referral center for this IV prep of Legalon and their efforts were greatly assisted by the Santa Cruz team who handled the 2007 cases.
Less satisfying to me is the mechanism by which silybin A and silybin B protect the liver from the effects of RNA polymerase II inhibition by α-amanitin. The literature to date seems to converge on the inhibition of toxin uptake into hepatocytes by silibinin. A German group led by Herbert de Groot in Essen, Germany, published a highly-cited 1996 paper proposing that inhibition of inflammatory mediator release from Kupffer cells (the macrophage of the liver) might partly account for the hepatoprotective effects of silibinin. More recent work continues to address the modulation of inflammation.
Regardless, we are now seeing legitimate use of a medicine from a herbal tradition being used in clinical situations where emergency IRB approval and IND status have been given to such a product. Certainly, these stories may be used by marketers to promote use of their oral milk thistle products. But, as I mentioned earlier, such effects required ingestion of large doses of capsules. Instead, I present this story to SBM readers to illustrate that amidst the wooful promotion of herbal therapies, a few gems exist and are most worthy of our scientific investigation.
- Four Timely Memoirs from the Halls of Medicine - New York Times - June 27th, 2017
- Medicine And Metaphor - HuffPost - June 27th, 2017
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- The Relationship of Health Insurance and Mortality: Is Lack of Insurance Deadly? Free - Annals of Internal Medicine - June 27th, 2017
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- Lisa Wong: Conducting an ensemble of music, medicine, and education - STAT - June 26th, 2017
- Dr. David Katz, Preventive Medicine: Truth about the bell curve and health - New Haven Register - June 26th, 2017
- NorthBay redefines community medicine - Fairfield Daily Republic - June 26th, 2017
- Marshall Sports Medicine Offers Concussion Testing for Children - The Exponent Telegram (press release) (registration) - June 26th, 2017
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- Is Modern Medicine a Luxury? - HuffPost - June 23rd, 2017
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- How to respond when medicine's culture causes moral distress - American Medical Association (blog) - June 22nd, 2017
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- Study highlights need for more research in primary care and family medicine - News-Medical.net - June 21st, 2017
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- Stanford Medicine launches health care trends report - Stanford Medical Center Report - June 20th, 2017
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- University of Chicago Medicine will remain in UnitedHealthcare's network - Chicago Tribune - June 19th, 2017
- A hit on alternative medicine - Washington Post - June 19th, 2017
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- Bakersfield man pleads no contest to practicing medicine without a license - The Bakersfield Californian - June 19th, 2017
- Martin Wolfe, doctor specializing in tropical and travel medicine, dies at 82 - Bangor Daily News - June 18th, 2017
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- Dr. David Katz, Preventive Medicine: Saturated fat is weighed, measured, and found wanting - New Haven Register - June 18th, 2017
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- Martin Wolfe, doctor specializing in tropical and travel medicine, dies at 82 - Washington Post - June 17th, 2017
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- Y-Speak: Herbal medicine vs. synthetic drugs: What's better? | SunStar - Sun.Star - June 17th, 2017
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- ct.gov-connecticut's official state website - June 16th, 2017
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- Michigan Medicine health system posts better bottom line - Crain's Detroit Business - June 16th, 2017
- I shunned studying medicine to become a nurse. Here's why - The Guardian - June 16th, 2017
- Disparities of women in medicine and science to be explored in Brown conference - The Providence Journal - June 14th, 2017
- WHO classes HIV drug as an essential medicine - New Scientist - June 14th, 2017
- A precision medicine fight is brewing between clinicians, public health - Healthcare IT News - June 14th, 2017
- New AMA president: Physicians must lead to reshape medicine - American Medical Association (blog) - June 14th, 2017
- Quest to spread precision medicine to oncologists nationwide ... - Healthcare IT News - June 14th, 2017
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- University of Chicago Medicine may soon be out of UnitedHealthcare's network - Chicago Tribune - June 13th, 2017
- Eric Dishman wants precision medicine to move from personal to universal - Healthcare IT News - June 13th, 2017
- Widespread precision medicine is still years away, experts say ... - Healthcare IT News - June 13th, 2017
- Henrik Stenson's advice for US Open: take your medicine - Golfweek.com - June 13th, 2017
- Traditional Chinese medicine may benefit some heart disease patients - Medical Xpress - June 13th, 2017
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- Using Herbs as Medicine - Albany Times Union (blog) - June 12th, 2017
- Regenerative Medicine Can Help Make America Great - Morning Consult - June 12th, 2017