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.
- Journal | Annals of Internal Medicine - July 18th, 2015
- Week 2 of tga genetics, organic medicine - Video - April 14th, 2015
- 3398 how to draw medicine easy step by step video - Video - April 14th, 2015
- Flea Medicine for Cats and Dogs - Best Deal Online! - Video - April 14th, 2015
- The Poisoner s Handbook - Medicine in the Early 20th Century (HD Documentary) - Video - April 14th, 2015
- Dr. K's Medicine Show @ The Compound 4/11 - Video - April 14th, 2015
- 24 In. x 29 In. Recessed or Surface Mount Medicine Cabinet with Bi-View Beveled Mirror in Silver - Video - April 14th, 2015
- 5 Simple Steps To Reduce Stress Fast Naturally (No Medicine) - Video - April 14th, 2015
- Flea Prevention Medicine Harms Dogs, Trifexis - Video - April 14th, 2015
- Foundation Medicine Announces Timing for First Quarter 2015 Financial Results and Conference Call - April 14th, 2015
- Regenerative Medicine Symposium set for April 24 at GRU - April 14th, 2015
- Jason Soklofske assault charge prompts police reminder - April 14th, 2015
- Dr Samantha Anandappa,International Conference on Health & Medicine - Video - April 13th, 2015
- China's cruel 'farms' that harvest bear's bile for medicine - Video - April 13th, 2015
- Magnito - Mr Medicine [Official Video] - Video - April 13th, 2015
- Golf ball & Medicine Ball - Video - April 13th, 2015
- Tornado in Medicine Lodge, KS 4/8/15 Full Version - Video - April 13th, 2015
- 2011 Hyundai Santa Fe in Medicine Hat, AB T1B 3Z9 - Video - April 13th, 2015
- Clint Sock - Medicine - Beat Prod By: TgSoundz - Video - April 13th, 2015
- The Social Transformation of American Medicine The rise of a sovereign profession and the - Video - April 13th, 2015
- Download By Chamberlain s Symptoms and Signs in Clinical Medicine An Introduction to Medical Diag - Video - April 13th, 2015
- The Sims 4: Get To Work Part 3: Medicine Time! - Video - April 13th, 2015
- Full-Body Medicine Workout - Video - April 13th, 2015
- Modernizing Medicine to Showcase Third Generation Cloud, Mobile, Data EHR Technology at HIMSS15 - April 13th, 2015
- Emergency Medicine Physicians and Welsh, Carson, Anderson & Stowe Announce Formation of US Acute Care Solutions - April 13th, 2015
- Study Reveals Why Emergency Medicine Physicians Are Sued - April 13th, 2015
- Penn Medicine pain management study reveals patient confusion about opioid addiction - April 13th, 2015
- South African Sports Medicine Leader Serves as AMSSM International Visiting Fellow - April 13th, 2015
- Great Timing For Athersys, Other Stem Cell Companies Amidst Improving Regulatory Landscape - April 13th, 2015
- Alnylam and Collaborators Publish Pre-clinical Study Results in Nature Medicine on ALN-AT3, an Investigational RNAi ... - April 13th, 2015
- What one of the anti-vaccination movements least favorite doctors discovered about Jesus - April 13th, 2015
- Sports Medicine Physicians of AMSSM to Restore Recreational Area For Boys and Girls Club Carver Ranches Unit - April 13th, 2015
- Medicine Cabinet Makeovers - Video - April 12th, 2015
- April 8, 2015 - Medicine Lodge, KS Hook Slice - Video - April 12th, 2015
- creative medicine - Video - April 12th, 2015
- FOX Sports Keck Medicine of USC Report: Treating Rotator Cuff Injuries - Video - April 12th, 2015
- Admissions for Doctor of Medicine (M.D.) Degree and PreMed Program at IUSOM - Video - April 12th, 2015
- BuildingNY: Jan T. Vilcek, MD: NYU School of Medicine & The Vilcek Foundation - Video - April 12th, 2015
- FROMBall - Medicine Ball - Instructional Performance Training - By Reactsport.com - Video - April 12th, 2015
- Dr Quinn, Medicine Woman Season 2 x Episode 04 The Incident - Video - April 12th, 2015
- San Juan Bautista School of Medicine Class of 2018 (Goofy Games) - Video - April 12th, 2015
- Witness - Baba Yetu by the UST Medicine Glee Club - Video - April 12th, 2015
- San Juan Bautista School of Medicine Class of 2018 GOOFY GAMES 15 - Video - April 12th, 2015
- Side Effects Of Fertility Medicine - Video - April 12th, 2015
- Full automatic medicine packaging production line manufacture email@example.com - Video - April 12th, 2015
- Download Bicycling Medicine Cycling Nutrition Physiology Injury Prevention and Treatment For Ride - Video - April 12th, 2015
- Download Central Pain Syndrome Pathophysiology Diagnosis and Management Cambridge Medicine PDF - Video - April 12th, 2015
- 4/8/15 - Medicine Lodge, KS Tornado - Time Lapse & Chase Video - Video - April 12th, 2015
- Bad Medicine@captains quarters/Zep/Good time"cover" - Video - April 12th, 2015
- Copy of Lifestyle Medicine Seminar on Mindfulness and Health, 10/1/14, St Clair Hospital - Video - April 12th, 2015
- Homeopathic medicine from snake venom can arrest spread of HIV: Researchers - April 12th, 2015
- IN PHOTOS: Indonesian integration in a medicine shop - April 12th, 2015
- 04-08-15 Justin Hoyt Tennis Ball Sized Hail Medicine Lodge, KS - Video - April 11th, 2015
- Medicine Lodge, KS Tornado 4/8/15 - Video - April 11th, 2015
- Medicine Bear and Son Monarcos LIVE at HASHTAGBAR Staten Island 4/8/15 - Video - April 11th, 2015
- Century Dual Grip Medicine Ball, Black, 16 Pounce - Video - April 11th, 2015
- Tinnitus Goes Away On Its Own Ringing In The Ears Relief Medicine Phone 1 800 314 2910 - Video - April 11th, 2015
- Moreno Boxing Medicine Ball 1 Training NY Kingsway Gym 2011 - Video - April 11th, 2015
- Meet Dr. David Gerst, Podiatric Medicine & Surgery - Advocate Health Care - Video - April 11th, 2015
- The Problem and Promise of Precision Medicine | TIME - Video - April 11th, 2015
- Medicine (Bullying Awareness Short Film) - For LunaLpsTV - Video - April 11th, 2015
- BBC Documentary 2015 The Truth About Your Medicine Cabinet - Video - April 11th, 2015
- Iboga: Tradition, medicine and politics - Dimitri Mugianis interviewed by Haydn Rippon - Video - April 11th, 2015
- Medicine, Science and Football - Video - April 11th, 2015
- The Hush Sound - "Medicine Man," "Not Your Concern" and "Honey" (Live in San Diego 4-9-15) - Video - April 11th, 2015
- Jix tape Great Medicine Ft Spydamonkee - Video - April 11th, 2015
- LIGHT! The Medicine of the Future! short 2015 04 10 1415 - Video - April 11th, 2015
- Steelers LBs' Offseason Workout Includes 'Danney-Ball' - Video - April 11th, 2015
- Journal of Sports Science and Medicine - April 11th, 2015
- Helomics to Present at the Personalized Medicine World Conference in Oxford, England - April 11th, 2015
- Scripps Translational Science Institute Director Dr. Eric Topol to Deliver Keynote Address at the 2015 BIO ... - April 11th, 2015
- AMSSM Launches New Sports Medicine Website Geared Toward Parents and the Public - April 11th, 2015
- Mount Carmel Community Outreach Mobile Coach and Street Medicine Program - Video - April 8th, 2015
- Dr. Tiffany Groen Family Medicine - Video - April 8th, 2015
- Dr. Jerome Daly Family Medicine - Video - April 8th, 2015
- Pokemon Soul Silver - Episode 2 - Ganja Gamers - Cyndaquil = Medicine / Let's Play / Gameplay - Video - April 8th, 2015
- Mumbai doctor develops promising medicine for AIDS patients - Video - April 8th, 2015
- Premier Chiropractic in Highlands Ranch, CO | Premier Chiropractic & Natural Medicine - Video - April 8th, 2015
- Ashley Nicole Greene - Medicine (Official) - Video - April 8th, 2015
- How to stop suffering with Pain and stop with Pain Medicine. - Video - April 8th, 2015