What Milk Thistle did for one Family

[Guest guest]

Family poisoned by mushrooms first to receive experimental treatment

January 14, 2007

A life-or-death situation: Family poisoned by mushrooms first to

receive experimental treatment

By Jondi Gumz

Sentinel staff writer

Santa Cruz

When a family of six showed up at Dominican Hospital complaining of

nausea, vomiting and diarrhea, it was more than a routine case for

doctors Todd and Knapp.

Once they heard all six had eaten tacos made with wild mushrooms,

they knew what to suspect. Most likely the family had eaten " death

cap " mushrooms, a fungus that could destroy their liver and kidneys

and eventually cause death.

The hard part was telling the family.

" Oh my God, " said one family member, a 29-year-old man. " I just ate a

ton of this stuff. Am I going to need a liver transplant? Am I going

to die? "

The family, ranging in age from 17 to 83, lives in Aptos. They had

picked several varieties of mushrooms in Wilder Ranch State Park on

New Year's Day.

Now they faced the fight of their lives. In the United States, there

is no known antidote for mushroom poisoning. Unless doctors could

find one, the meal they had eaten could be their last.

Deadly history

Even experts can mistake Amanita phalloides, known as the " death

cap, " for similar-looking nontoxic mushrooms.

Ten years ago, one person in Santa Cruz County and another in Sonoma

County died after eating death cap mushrooms. Five years ago, a

couple from Jordan visiting ville fell gravely ill and spent

weeks in the hospital before recovering. Typically, wild mushrooms

appear in wooded areas in Northern California late in December or

early January. Often people who pick them are immigrant families

familiar with mushrooms in their native country. Of the 5,000 known

mushroom species, about 100 are poisonous, with the death cap

accounting for most fatalities.

Mushroom poisoning sent nearly 400 people to the hospital in

California last year.

For , who had worked at Dominican Hospital for 10 years, this

case was his first.

, 49, is married with three children, ages 14, 12 and 9. He's

slender with short brownish hair. If he has to work late, he likes to

eat at Cafe La Vie for its vegetarian entrees.

He knows medical miracles are possible.

The staff at Dominican Hospital, he said after finishing a salad late

one Friday night, saved the life of his wife last year.

The way doctors confirm mushroom poisoning is with a blood test.

When the Aptos family came into the hospital Jan. 2, the levels of

liver enzymes were in a normal range, from 25-50. Six hours later,

the numbers jumped into the 100s, and doubled every six hours after

that.

Those counts were like fingerprints, confirming the presence

of " amatoxin " poison.

Even when the uneaten mushrooms were brought in for the doctors to

examine, and none was a death cap, and Knapp felt it was

prudent to " prepare for the worst and hope for the best "

Like an overdose of the painkiller Tylenol, amatoxin shuts down the

liver over a period of days.

knew of no " ironclad " antidote. He could not give the family

any guarantees.

" We're going to do everything humanly possible, " the two physicians

told the family. " We're pulling out all the stops "

Overseas solution

The morning after being admitted to the hospital, the patients were

feeling better, but they actually were getting more sick. The toxin

was binding to the RNA in their cells, shutting down the liver's

normal operations, and refusing to let go.

The liver turns food into chemical components for use in other parts

of the body, stores sugar and vitamins and filters waste and poisons

out of the bloodstream. Without a liver, the body can't function.

is not only a physician, he's also a volunteer at Mount

Madonna School, run by a spiritual community. Asked if he's the kind

of doctor who turns to prayer, he demurred.

" If it's God's will for them to recover, they will, " he said. " If

it's not, they won't. It's not kosher for me to determine what's

God's will. My time is better spent figuring out what they need to

heal "

Into the night that Tuesday and early Wednesday morning,

looked for information.

Using Google Scholar, a search engine of scholarly literature, he

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.

found a pharmaceutical company, Madaus Pharma, in Brussels,

Belgium, that produced Legalon-Sil, milk thistle extract in an

intravenous form. But it was too late to call because of the time

difference.

Red tape

Very early Wednesday morning, called the company and got the

number of its office in Germany, where the drug is approved for use.

He reached 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.

Shortly thereafter, got a call from Joe Veilleux, U.S.

president of Madaus whose office is in Pittsburgh.

It was bad news.

The medication could be stopped at the border unless the FDA approved

its use.

" You can't ship over anything you want even if it's a dire

emergency, " said Veilleux. " Unfortunately it's not registered for us

here. It's awfully expensive to do "

He referred to a researcher at the National Institutes of

Health.

NIH, a federal agency and one of the world's foremost research

centers, takes the position that there is not enough evidence that

milk thistle has medical benefits. The agency says studies of oral

milk thistle conducted outside the United States are flawed.

A multi-year study of using milk thistle orally to treat hepatitis, a

liver disease, is in the beginning stages in the United States. It

has the support of the National Advisory Council for Complementary

and Alternative Medicine.

If the FDA granted an emergency IND number, identifying Legalon as an

investigative new drug, the medication could be shipped to California.

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. One of them was right in Santa

Cruz: Aloha Medicinals.

Once the clock ticked past 8 a.m., when the company opens for

business, called and spoke to company president Powers.

Research director Holliday responded almost immediately,

delivering a case of Aloha's Bio-Silymarin to Dominican Hospital.

Usually it costs $12.95 for a bottle of 60 capsules. In this case,

there was no charge.

The patients began taking the capsules that day, but wasn't

sure it would be enough. The patients were already nauseous and

vomiting.

Candace , the medical librarian at Dominican Hospital, faxed

information to the FDA about the patients, their conditions and the

lab data to bolster 's request for an emergency IND number.

But the FDA wasn't the only roadblock.

would have to get approval from the Institutional Review

Board at Dominican Hospital to administer an investigational drug.

The board consists of a dozen people, including community members,

who consider safety and ethics of using something experimental.

Members heard the results with Legalon in Germany were promising.

They heard that the patients had signed a form consenting to its use.

They too gave their consent.

It seemed worth a try.

That same day, the FDA granted the permission needed. Under FDA

regulations, the agency doesn't discuss investigative new drugs but

Madaus Pharma confirmed that the approval came swiftly.

" Surprisingly he was able to get this within a matter of hours, " said

Veilleux. " People were asking me, 'What are the chances he'll get

permission?' I said, one in 1,000 "

Increasing the odds

While was pursuing the German medication, Knapp was doing

her best to advocate for her patients.

Like , she is a " hospitalist " specializing in the case of

hospital inpatients. At 42, she has been a doctor for 10 years. She

also is a mom with one child.

She called the Poison Control Center, which located a one-day supply

of injectable milk thistle at a compounding pharmacy in New Jersey.

Unlike Madaus, the company was not willing to donate its product.

Carl Washburn, the pharmacist at Dominican Hospital, put the order on

his personal credit card with the blessing of the new president, Dr.

Nanette Mickiewicz.

Everyone hoped it would arrive in time.

By Wednesday evening, some of the patients were much more sick.

If any of them suffered liver failure, a liver transplant would be

their only chance to survive.

Those operations are done only at institutions with transplant

specialists, not at general hospitals like Dominican.

Knapp got on the phone, calling to find a medical center where a

doctor would accept the patients - not an easy task. Often when

multiple patients require treatment, they are divided among hospitals

so as not to overwhelm a single institution.

She found Dr. Gish at the Transplantation Center at California

Pacific Medical Center.

When Gish agreed to take all six patients and to use Legalon, even

though it was experimental, the two doctors at Dominican felt a sense

of relief.

If any hospital could increase the odds for the family in Santa Cruz,

it was Pacific Medical.

It was a place with liver experts and facilities for liver

transplants. Another doctor, Maurizio Bonacini, had treated 17

mushroom poisoning cases in four years. In eight of those cases,

people who were severely ill recovered without needing a liver

transplant. The quicker the treatment, the better the outcome,

Bonacini found. He had co-authored a paper on the subject for the

American Gastroenterological Association.

But there weren't enough beds for all six.

Five patients were taken to San Francisco, and one stayed behind in

Santa Cruz.

got on the phone to Veilleux at Madaus asking him to reroute

the medication to San Francisco.

Another roadblock

By the time the FDA had given its OK to administer Legalon, it was

too late in Germany for Madaus to ship the medication by FedEx. So

Veilleux arranged for a personal courier to pick up the product and

board a plane early Thursday morning to San Francisco.

The antidote fit into a box about the size of four shoe boxes.

The plane ticket cost 3,600 Euros - about $5,000.

Veilleux didn't want to wait until the next morning for the FedEx

office to open.

" Every hour could mean something, " he said.

is astonished by how much cooperation he got.

" Everyone grasped the gravity of the situation and worked to cut red

tape, " he said.

He didn't realize there was still red tape ahead.

On Thursday morning, called for an ambulance to take the

last patient to San Francisco.

None was available.

Shortly after 2 p.m., got more bad news: Highway 17 was

closed. An armored truck had crashed, closing the northbound lanes.

The backup was immense.

looked into helicopter transport. Too windy.

That left one option: Highway 1.

An ambulance departed at 5 p.m. Thursday, carrying the patient and

the one-day supply of injectable milk thistle to San Francisco.

Its lights were flashing and sirens sounding.

Recovery

In San Francisco, the treatment included the Legalon milk thistle

delivered by courier and three other medications: the antidote for an

overdose of Tylenol, penicillin and activated charcoal. Some of the

patients didn't receive any penicillin because of allergies.

Two of the six patients got well very quickly. Bonacini, who took

over their care a week ago Friday, said he felt they could have

recovered just as well at Dominican.

But it appeared one patient, the 29-year-old man, would need a liver

transplant. Doctors looked for donor organs and even got offers.

Bonacini reserved the Legalon for the two sickest patients, the 29-

year-old and the eldest.

The eldest was not a good candidate for a liver transplant because of

her age. She was 83, and 70 is " about the limit, " according to

Bonacini.

Two more patients were released Wednesday.

By Thursday, the 29-year-old had improved enough to go home.

The matriarch of the family, the eldest patient, died that same day.

The poison moved from her liver to her kidney, the organ that makes

urine and discharges waste from the body. Ironically, her liver

appeared to recover at the same time her kidneys failed.

The hospitals have not released the names of the family members

because of the federal laws on patient privacy.

" I'm humbled by a poison as powerful as amatoxin, " said.

A first

learned Friday that these patients from Aptos were the first

in America to be treated with intravenous milk thistle extract for

mushroom poisoning.

" We took a path not previously blazed, " he said.

He and his physician colleague, Knapp, are sad that one patient

died, but elated to have five survive - and be spared a liver

transplant.

The experience may pave the way for broader changes.

" We're going to work closely with the Poison Control Center, Madaus

and the FDA to allow us to maintain a supply of this medicine in

Northern California so it's available to be used within 12-24 hours, "

said.

If intravenous milk thistle is more readily accessible, doctors can

gather more data on its effectiveness.

" At the end of the day, we can't say whether it was the silymarin or

dumb luck, " said. " But we can say folks at Dominican

Hospital know how to pull together in a crisis, and when that

happens, extraordinary things can happen "

Contact Jondi Gumz at jgumz@santacruzsent inel.com.

About milk thistle

Common names: thistle, holy thistle. Sometimes called silymarin,

after the Latin name silybum marianum.

History: Native to the Mediterranean. Used for thousands of years as

a remedy for ailments, especially liver problems. Typically used to

treat liver cirrhosis, chronic hepatitis and gallbladder disorders.

How it is used

Silymarin can be extracted from the seeds, believed to be the

biologically active part. The seeds are used to prepare capsules

containing powdered herb or seed, extracts and strong teas.

What science says

Some studies have looked at the effect of milk thistle on liver

disease in humans, but these have been small. Some promising data

have been reported, but results are mixed.

Some studies conducted outside the United States support claims of

oral milk thistle to improve liver function, but there have been

flaws in study design and reporting.

The National Center for Complementary and Alternative Medicine is

supporting a research study to better understand the use of milk

thistle for chronic hepatitis C. With the National Institute of

Diabetes and Digestive and Kidney Diseases, the center is planning

further studies of milk thistle for chronic hepatitis C and

nonalcoholic liver disease.

The National Cancer Institute and the National Institute of Nursing

Research are studying milk thistle for cancer prevention and to treat

complications in HIV patients.

Side effects

In clinical trials, milk thistle generally has few side effects.

Occasionally, people report a laxative effect, upset stomach,

diarrhea and bloating. Milk thistle can produce allergic reactions,

which tend to be more common among people who are allergic to plants

in the same family such as ragweed, chrysanthemum and daisies.

Source: National Center for Complementary and Alternative Medicine,

National Institutes of Health.

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