TOPICS

COLUMNS

LISTINGS

2001 LISTINGS

HELP

PARTNER LINKS

HEALTH

Code green: Seeing the side effects of alternative supplements

Dietary supplements and alternative medicine are increasingly popular. And physicians are seeing an increasing number of patients with adverse reactions to the pills, potions and teas.

By Victoria Stagg Elliott, amednews staff. March 5, 2001.

The patient showed up in the emergency department with a racing heart, blood pressure shooting through the roof, a throbbing headache and a persistent erection. Timothy Erickson, MD, had seen other cases of priapism among patients with sickle cell anemia, spinal cord injuries or cancer, but this case was unique.

"He was totally healthy," said Dr. Erickson, director of the emergency medicine residency program at the University of Illinois at Chicago. However, after some questioning, the patient revealed that he had taken yohimbine, an herbal derived from yohimbine tree bark and marketed as a possible natural solution for male impotence.

Common dietary supplements
Links

"He had taken way too much because he thought that if one must be good, six must be better. That was an introduction for me in the early '90s that there was this stuff out there," said Dr. Erickson.

Since then, Dr. Erickson has been collecting cases of adverse reactions caused by herbals and other alternative medicines. He gave a presentation on the subject at last year's scientific assembly of the American College of Emergency Physicians.

The dietary supplement industry is rapidly growing, and Dr. Erickson and other physicians are seeing ever-increasing numbers of patients with adverse reactions because the herbal they took conflicted with a prescription medication or another herbal, or because the supplement was not what the package said.

Also, like the patient who took too much yohimbine, patients may overdose because they believe that more must be better and that "natural" automatically equals safe.

Information on possible adverse reactions may sometimes be found in scientific literature. But because Food and Drug Administration regulations require that herbals and supplements be sold as food rather than as drugs, those risks are rarely noted on the packaging.

Questionable quality, bad labeling

The patient had had surgery for a rapid and irregular heartbeat but had been symptom-free for five years. One morning, she woke up with a searing pain in her chest and a racing heart.

The culprit was an herbal supplement for weight loss that contained ephedra. "She required hospitalization," said her doctor, Rebecca Bigoney, MD, an internist with Medicorp Health System in Fredricksburg, Va. "She didn't have insurance and ended up with a big hospital bill. She's taking legal action" against the supplement manufacturer.

The amount of active ingredients in herbal supplements can vary widely.

Adverse reactions from ephedra have been well-documented, most recently in a report published in the Dec. 21, 2000, New England Journal of Medicine, but the supplement that Dr. Bigoney's patient took had no warning label.

"Had the diet supplement that my patient bought said, 'Warning: If you have any history of cardiac disease or cardiac rhythm problems,' there would have been no way she would have taken it," said Dr. Bigoney.

Concerns are also increasingly being raised about the quality of herbal supplements because studies have found that the amount of active ingredients can vary widely.

"They don't say how much is in there, and you don't know how pure it is," said Dr. Erickson. "Doses are all over the board. Impurities are all over the board. Adulterants are all over the board."

And supplements do not always contain what they say they do.

In Alaska last month, a woman was awarded $13.2 million because she had a stroke while on an herbal dietary supplement that was supposed to contain the natural herb ephedra, when in fact it included the manufactured version, ephedrine.

"Does the label on the bottle relate in any way to what's inside the bottle?" said James S. Gordon, MD, chair of the White House Commission on Complementary and Alternative Medicine Policy. "The major problem is that, in many cases, it does not. No matter how well-informed you are, if you're not getting what you're supposed to be getting, then you're in trouble."

Problems can also be caused by conflicts with other medications or herbals. Ginkgo biloba, often taken to enhance memory, can conflict with blood thinners such as warfarin or aspirin. St. John's wort can reduce oral contraceptives' effectiveness.

Tim Gorski, MD, associate clinical professor of obstetrics and gynecology at the University of North Texas Health Science Center in Fort Worth, says that two of his patients became pregnant when the St. John's wort they were taking as an antidepressant interfered with their birth control pills.

"It's rare for people to get pregnant while on the birth control pill, but all the ones I've seen have also been on St. John's wort," he said.

The FDA does have a reporting system for adverse events linked to dietary supplements, but herbals are sometimes difficult culprits to finger. Many patients are taking multiple drugs and supplements, making it hard to single any one out.

Also, supplements rarely show up on toxicology tests, and studies have shown that few users of alternative medicine talk to their physicians about what they are taking besides what a doctor has prescribed.

Physicians' role

If a doctor doesn't ask, a patient won't tell, experts said.

"The patients we see usually come in with vague symptoms, and unless you ask them, 'Do you take herbal medications?' they won't tell you," said Dr. Erickson. "If you interviewed a lot of physicians, they would say they never see it, but I believe they see a lot that they're missing because they don't ask."

Physician responses may also be inappropriate. Patients are sometimes reprimanded by the doctor or wrongly told a product is safe because it's natural.

Some doctors, meanwhile, have incorporated alternative medicine into their practices, but even those who haven't are starting to recognize the issue's importance. Doug Hill, DO, a staff emergency physician at North Suburban Medical Center in Denver, used to skip articles about alternative medicine in the scientific journals but now reads every one.

"We see people coming in with all sorts of reactions," said Dr. Hill.

"Our biggest problem is to figure out that [supplements are] in fact what they take. You have to ask patients very specifically [because] they don't even think about herbal supplements or dietary supplements as an issue."

Physicians practicing alternative medicine say that although not every physician has to know every herb, knowing the most common interactions could make their jobs easier. When Bernd Wollschlaeger, MD, medical director of the Aventura Family Health Center in North Miami Beach, Fla., recommends St. John's wort to patients, he warns them that exposure to the sun can cause redness.

But, many acknowledge, patient use of alternative medicine is more often self-directed.

Take the 55-year-old patient who declined surgery, radiation and chemotherapy to treat his sinus cancer, instead choosing his therapy online. He had taken hydrazine sulfate, an ingredient in rocket fuel also marketed as a dietary supplement, for four months before Army Capt. Mark Hainer, DO, an internist at Fort Jackson, Columbia, S.C., saw him. By that time, the patient had developed a rash, pruritis, progressive malaise and jaundice. Two weeks later he was dead.

"This is more than a man who died of liver failure because he took a pill," said Dr. Hainer. "It speaks to the fact that medications are available over the Internet, usurping the physician."

The drug is a close cousin of isoniazid, which must be monitored by liver function tests. But for patients who buy an alternative medicine over the Internet, there is no such monitoring.

"Some of these herbal medications have properties that can be very similar to pharmaceutical drugs," said Dr. Hainer. "It's infringing on your ability to prescribe medication. Hydrazine sulfate is a known vitamin B6 antagonist. It also has monoamine oxidase inhibitor properties. I don't know if I want those types of medicines available over the counter."

He knows his patients are spending hours online looking for information about their illnesses, and he is trying to catch up.

"When I first came across this case, I was very Internet-naïve," said Dr. Hainer. "You do need to be Internet-savvy because your patient is."

Seeking relief

The symptoms of the man who took too much yohimbine were alleviated by the administration of the antihypertensive clonidine. The woman who took ephedra continues to have heart problems and is suing the manufacturer. The man who took hydrazine sulfate lives on in a paper in the December 2000 Annals of Internal Medicine detailing his death.

Many physicians, even those who specialize in alternative medicine, say they believe it is time for the FDA to take a more active role.

"The FDA has chosen to be in the back seat," said Dr. Wollschlaeger.

The 1994 Dietary and Nutritional Supplement Health and Education Act says supplements are regulated as food as long as the manufacturers don't make any claims about curing disease. The FDA can react only after a product is proven unsafe.

The supplements do not have to go through the clinical trials and premarket approval process required of prescription and over-the-counter drugs. But, doctors complain, the result is a limited amount of vital label information about potential side effects and drug interactions.

"It's kind of a 'Catch-22'," said Dr. Gordon. "Because these herbs come under the heading of foods, you can't market them to treat a specific condition, and if they can't treat a specific condition, they're not really regarded the way pharmaceuticals are, then they're not required to have the same kind of information about side effects and interactions. Somehow, we have to break through that impasse."

ADDITIONAL INFORMATION:

Common dietary supplements

EPHEDRA/MA HUANG

Most common reason taken: Weight loss
Possible adverse reactions: Nervousness, anxiety, fear, agitation, restlessness, weakness, irritability, talkativeness, insomnia, dizziness, lightheadedness, tremor, hyperreflexia, heart palpitations, sinus tachycardia, fatal arrhythmias
May conflict with: Cardiac glycosides, general anesthetics, monoamine oxidase inhibitors

ST. JOHN'S WORT

Most common reason taken: Depression, insomnia
Possible adverse reactions: Skin hypersensitivity to light, hypomania, gastrointestinal irritation, lethargy, restlessness
May conflict with: MAOIs, antidepressants, oral contraceptives, levodopa, general anesthetics, digoxin, warfarin, anti-retroviral protease inhibitors, non-nucleoside reverse transcriptase inhibitors

KAVA KAVA

Most common reason taken: Stress, nervousness, anxiety
Possible adverse reactions: Skin discoloration, ichthyosis, dizziness, drowsiness, visual impairment, balance disturbances, involuntary movements
May conflict with: Alcohol, benzodiazepines, barbiturates, anticonvulsants, skeletal muscle relaxants, tricyclic antidepressants, MAOIs, lithium, selective serotonin reuptake inhibitors, warfarin, levodopa

YOHIMBINE

Most common reason taken: Erectile dysfunction
Possible adverse reactions: Antidiuresis, dizziness, flushing, headache, hypertension, increased motor activity, irritability, nervousness, sinus tachycardia, tremor
May conflict with: Antidepressants, antihypertensives

GINKGO BILOBA

Most common reason taken: Improve memory and blood flow; treat Alzheimer's and other forms of mental deterioration in the elderly
Possible adverse reactions: Headache, flatulence, nausea, vomiting, diarrhea, subdural hematoma
Conflicts with: Anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs

Source: Clinical Pharmacology 2000

How one hospital handles herbal supplements

The increasing popularity of herbal supplements has hospitals struggling to form policies that regulate how patients are allowed to use them while in their facilities.

Some hospitals have banned the supplements. Others are debating regulations that provide safeguards to prevent herbals from adversely reacting with prescription medications, but that still allow inpatients to continue taking supplements they take at home.

At New York Presbyterian Hospital, it took two years and several dozen rewrites before the staff agreed on a policy, according to Marc S. Roth, clinical coordinator of nutrition. The staff initially wanted to just ban supplements.

"Nursing doesn't want to dispense anything that they don't understand what the potential consequences are because they are responsible for observing the patient for adverse events," Roth said. "Pharmacy's afraid because most of the profiling is done by computers, and the computers don't have the herbals in them."

The staff also wanted to avoid a situation in which patients hid supplements under the mattress. But, at the same time, they didn't want to open the door to unlabeled herbals of unknown quality and effects. Also, some herbals, such as St. John's wort, can cause as many problems if they are stopped abruptly as they do when taken with other medication.

This hospital's solution: Nurses are required, as part of the screening process, to ask about herbals taken at home, and to advise patients that if they want to continue taking the product as an inpatient, they must bring the original sealed bottle with them upon admission. The pharmacy will research and relabel it. Then the patient can have it, as long as the physician agrees.