Possible herbal medicine contribution to mushroom poisoning recoveries

A thoughtful reader of mine and Kevin MD’s just brought to my attention the plight of six members of a California family who apparently ingested Amanita phalloides (deathcap) mushrooms following a New Year’s Day outing.
Jondi Gumz of the Santa Cruz Sentinel reported today on the circuitous route the attending physicians took to obtain a source and FDA emergency approval to try an intravenous formulation of an herbal medicine from Europe.

Using Google Scholar, a search engine of scholarly literature, he [Dr Todd Mitchell] found a promising avenue of treatment: Extract from milk thistle, a nuisance weed for farmers and used as a liver tonic in European folk medicine.
Milk thistle extract, or silymarin, has been used in Europe to treat cirrhosis of the liver, scarring that often proves fatal.
In a 1970s experiment, beagles that received milk thistle intravenously were protected from mushroom poisoning
That treatment, intravenous milk thistle extract, is not available in the United States and is not approved by the Food and Drug Administration.

The mushroom toxins from the Amanita family, amatoxins, are heat-stable cyclic peptides that inhibit RNA polymerase II and cause severe liver damage, often requiring liver transplant. German researchers in the 1960s first identified hepatoprotective compounds from extracts of milk thistle seeds, known also as silymarin or silibinin. In 1984, the German phytopharmaceutical company, Madaus AG, first offered an intravenous preparation called Legalon (silibinin hemisuccinate) that is widely kept in European emergency rooms to treat such cases of mushroom poisoning.

Very early Wednesday morning, Mitchell called the company and got the number of its office in Germany, where the drug is approved for use.
He reached Peter Odenthal of Madaus in Cologne, Germany, and explained the situation. It was already afternoon in Germany. Odenthal agreed to donate enough Legalon to treat all six family members.

However, the US FDA prohibits the explicit marketing of botanical medicines for disease treatment, and certainly is not keen on intravenous preparations of herbal products. Groups wishing to study botanical medicines in clinical trials must first obtain from FDA a botanical investigative new drug approval, a truncated but still laborious form of the IND required before a new prescription drug can be given to patients. And, of course, the physicians required approval of their Institutional Review Board (IRB) to administer an experimental medication.
Oral preparations of milk thistle are available in the US, but the purported active constituents have notoriously poor oral bioavailability, hence the Germans’ development of an intravenous product. The recommended intravenous dose of 20 mg/kg would produce a mean plasma concentration in the neighborhood of 500 micromolar. In contrast, an oral dose of 13 grams daily was shown recently to produce a blood concentration of just over 100 micromolar. (note: these calculations aren’t entirely accurate since milk thistle extracts contain anywhere from two to eight active compounds).

Mitchell also had read up on oral milk thistle in capsules. The FDA hasn’t approved that either, but a lot of companies sell milk thistle extract in that form as a supplement…The patients began taking the capsules that day, but Mitchell wasn’t sure it would be enough. The patients were already nauseous and vomiting.

Ultimately, five of the six family members had to be transferred to a San Francisco hospital capable of performing a liver transplant. The 83-year-old matriarch of the group had unfortunately died.
Long story made short: all of the patients received a standard therapy of N-acetylcysteine (usually used for acetaminophen overdoses), activated charcoal (to bind the amatoxins), and penicillin G (probably inhibits active transport of amatoxins into cells). The intravenous Legalon was reserved for the two of the sickest remaining patients.
Four of the five family members have been released from the hospital.
A blinded, controlled study this is not – always a major challenge in the study of any antidotal regimens for poisonings – and it would have been unethical to withhold the three standard therapies and test the intravenous milk thistle extract alone. But, hopefully, these cases will be written up for the medical literature to provide some insight as to the contribution of the botanical therapy in the recovery of these patients.

2 thoughts on “Possible herbal medicine contribution to mushroom poisoning recoveries

  1. Interesting story. The long version you linked read like a thriller – well it did right up to the point where they were thinking of sending the drug via Fed Express. It been my unfortunate experience that what usually happens to absolutely vital or irreplaceable samples at this point is that Fedex manages to swiftly route them to some strange hub centre (generally in a completely different country and in the exact geographically opposite direction to where you intended it to end up). From there it either sits in a warehouse, twiddling its thumbs for a couple of days, before finally being sent to the correct address. Or else it disappears into thin air. I’m glad to see they took the safe way of personally bringing it on a flight with a courier.

  2. You know I’ve often thought that the European health agencies and the FDA and the like should have full parity with regard to approved drugs.
    It’s pretty easy to connect them – data circuits and database servers are cheap. It’s just hammering out policy.
    But then our FDA is a cruel joke, dominated by corporate interests with only a marginal interest in the actual health and safety of citizens. You only have to look so far as the Vioxx debacle to see that.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s