Thursday, May 24, 2012

Mycotoxicology smackdown: Death Cap Mushrooms vs. Milk Thistle


Images: Archenzo (L), and demott9 (R)

In the fall of 2011 four cases of death cap mushroom poisoning were successfully treated at Georgetown University Hospital (GUH) using a controversial remedy – an intravenously delivered chemical extracted from the milk thistle plant. Manufactured by the German pharmaceutical company Madaus (and sold under the somewhat ironic name Legalon), the drug has been available in Europe since the mid 1980s, but lacks FDA approval in the United States. Why are U.S. citizens being denied this wunder drug? Are we simply at the mercy of mushrooms? Can nothing be done?

As the Georgetown story unfolds, a few particularly striking points jump out. For one thing…

Poison control centers are very, very important.
When the first of the fungus-addled patients turned up at GUH – having eaten what he assumed were edible mushrooms picked from his yard – physicians quickly diagnosed him with amanitin poisoning. Amanitin, the principal toxin in the feared death cap mushroom, can be lethal. The ordeal begins with your standard food poisoning gastrointestinal woes, but can progress to organ failure, specifically in the liver and kidneys. In severe cases, organ transplants are required to save a patient’s life.

Having identified the problem, the medical team’s next move was to phone poison control. That’s right, the same people you would call if you found your child taking swigs from a bottle of laundry detergent. Poison control put the doctors in touch with Santa Cruz physician Dr. Todd Mitchell, who was conducting clinical trials of IV milk thistle (also called silibinin).

So if you’ve ever dismissed concerns about government funding cuts to poison control centers with a glib, “Ppfff, we don’t need those things, we’ve got emergency rooms” then you might want to rethink your stance. Poison control doesn’t just handle calls from panicked civilians, they also advise health care professionals tasked with treating panicked civilians.

But let’s get back to the story. Contacting Dr. Mitchell was far from the last step in the GUH patient’s road to recovery, because as it turns out…

Using non-approved drugs in the U.S. is NOT easy
The FDA allows experimental drugs to be tested if there is an established protocol and review board approval, such as in Dr. Mitchell’s clinical trial. This doesn’t mean that every other hospital out there can also start doling out these drugs. Luckily, the FDA does permit emergency one-time use of an Investigational New Drug (IND), which allowed the Georgetown team to procure and administer silibinin to their patient.

Mitchell himself went through the emergency IND process twice, first in 2007 and then again in 2009, to treat several mycotoxin-sickened patients (the first case was an entire family of six), before finally managing to set up his clinical trial, sponsored by Madaus.

It having been an unusually rainy season in the DC area, the Georgetown doctors got to work immediately writing up their protocol for any potential future poisonings. Still, an emergency meeting of the approval committee had to be called when a second patient materialized before everything was in place, soon to be followed by patients three and four. In the end, all four received the coveted silibinin and recovered without major complications (or liver transplants) and GUH is now an approved referral center for the drug.

So why isn’t every hospital in the country running silibinin trials? What are we waiting for? Well, mushroom poisoning isn’t especially common in U.S. While Europeans have a long tradition of strolling through the woods patrolling for tasty fungi, most Americans are content to buy their mushrooms at the store. According to the journal Nature Medicine, only about 50 cases of amanitin poisoning crop up in the U.S. annually, which isn’t enough to motivate hospitals to plan ahead on the off chance that one these unfortunate victims walks into their ER. But while we’re on the subject of clinical trials…

Does anyone know if this stuff actually works?
With all the hustling for silibinin going on, there must be some pretty strong evidence of its efficacy against amanitin poisoning, right? Well… not entirely. The anecdotal tales are certainly impressive. Patients on the brink of liver failure have reportedly perked up soon after the IV treatment began. But in the world of science, anecdotes aren’t worth much (unless they’re anecdotes about the insane lives of famous scientists, which, of course, are pure gold). The small number of people turning up with these maladies limits the scope of any trial, and denying available treatment to a control group is, well, kinda unethical.

Additionally, even in the absence of IV milk thistle, patients do receive some treatment for death cap poisoning – including intense hydration, penicillin, and activated charcoal (don’t worry, silibinin patients can get these too, it’s not an either/or deal.) and many of them survive. It’s thus difficult to determine what portion of any success story can be attributed solely to milk thistle. Silibinin supposedly works by blocking absorption of the poison by liver cells. It has also been tested against non-mushroom-related liver issues, but the data thus far are underwhelming.

Perhaps Mitchell’s trial will shed some light (it’s scheduled to wrap in late 2012), but in the meantime we can at least acknowledge that milk thistle doesn’t seem to be making anyone sicker (which is more than can be said for penicillin, which gives me hives and triggers anaphylactic shock in certain unluckier individuals.) And finally...

Are mushrooms a recipe for disaster?
Given that wild mushrooms are so potentially lethal, it seems reasonable to suggest that we leave their harvesting to the pros. But what fun would that be? My mother (who grew up in Russia, so it may be inaccurate to call her an amateur) has been picking and cooking mushrooms for decades with no reported fatalities. I’ve had them, and they’re thoroughly delicious. (Though I did spend a wee bit more time contemplating my mortality during that meal than I normally I do.)

Roughly 100 species of poisonous mushrooms reside in the U.S. (out of a total of 5,000 species), so if you’re going to try your hand at the art of mushroom hunting, please do some research first. And also note that taste and smell are not indicators of whether you’ve picked an edible mushroom or a toxic toadstool. In fact, the death cap is said to be rather tasty. As aptly summarized in this Croatian proverb, “All mushrooms are edible; but some only once.”

1 comment:

  1. Wow! gorgeous mushrooms. You're brave - I have no faith that I could tell poisonous from tasty and safe.

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