Ephedra Medical Issues

What are the effects of ephedra alkaloids?

Ephedrine, the most significant ephedra alkaloid, excites the sympathomimetic system to produce the "fight or flight" response. Ephedrine primarily affects the cardiovascular system, where therapeutic doses cause vasoconstriction, increased cardiac output and heart rate, and increased peripheral resistance, producing a lasting rise in blood pressure (systolic, diastolic, and pulse pressures). The pharmacological action of ephedrine is comparable to amphetamine at about one-fifth of amphetamine's potency.

What are ephedra's toxic effects?

The ephedrine alkaloid and, to a lesser degree, the pseudoephedrine alkaloid are responsible for the toxic effects that primarily impact the cardiovascular and central nervous systems. According to Dr. Steven Dentali, a pharmacognosist and member of FDA's ephedrine alkaloid working group, ephedrine alkaloids are toxic at levels only a few times greater than the therapeutic dose, and particularly sensitive individuals can experience untoward effects even at recommended dosages.

Ephedrine and related alkaloids have been associated with such adverse cardiovascular events as acute myocardial infarction, severe hypertension, myocarditis, lethal cardiac arrhythmias, strokes, and death. Adverse effects of the central nervous system include nervousness, agitation, anxiety, irritability, palpitation, restlessness, weakness, tingling, dizziness, insomnia, psychosis, tremors, and seizures. Other signs of ephedrine toxicity include nausea, vomiting, headache, flushing, numbness and tingling, difficult urination, and precordial pain.

What types of adverse events have been related to the FDA?

The analysis published in NEJM regarding 140 adverse events indicated that: "Thirty-one percent of cases were considered to be definitely or probably related to the use of supplements containing ephedra alkaloids, and 31 percent were deemed to be possibly related. Among the adverse events that were deemed definitely, probably, or possibly related to the use of supplements containing ephedra alkaloids, 47 percent involved cardiovascular symptoms and 18 percent involved the central nervous system.

Hypertension [high blood pressure] was the single most frequent adverse effect (17 reports), followed by palpitations, tachycardia [increased heart rate], or both (13); stroke (10); and seizures (7). Ten events resulted in death, and 13 events produced permanent disability, representing 26 percent of the definite, probably, and possible cases."

The UCSF scientists stated "health risks are so serious - especially to young, healthy consumers - that federal regulators should immediately set maximum dosages and require stronger warning labels on products that contain the stimulant."

Neal Benowitz, MD, USCF Professor of Medicine, Psychiatry and Biopharmaceutical Sciences, stated: "We think that as currently marketed these supplements are unreasonably hazardous . . . When used as labeled, ephedrine-containing nutritional supplements present a significant and unreasonable risk of injury."

What conditions rule out the use of ephedra?

The UCSF researchers stated that, since ephedrine-containing supplements are stimulants, they suspect the supplements should be avoided by individuals with "kidney disease, those with pre-existing heart disease, high blood pressure, overactive thyroid, or psychiatric disorders, and those with autonomic insufficiency - abnormalities in the nerves controlling their cardiovascular system - and those with histories of seizures and diabetes."

Canada's Therapeutic Products Programme, analogous to the US FDA, treats ephedra as a medical drug and requires the label to warn patients not to exceed the recommended dosage or take for more than seven days except on the advice of a physician and to consult a physician prior to use if they have heart or thyroid disease, high blood pressure, diabetes, glaucoma, difficulty in urination due to an enlarged prostate gland or if they are taking any prescription drugs.

Does ephedra interact with other substances?

Many ephedra alkaloid products contain caffeine, and many individuals who use EADS also ingest beverages containing caffeine. Caffeine intensifies the effects of ephedrine on the cardiovascular and central nervous systems.

The Physicians' Desk Reference for Herbal Medicines reports the following interactions: heart rhythm disturbances with heart glycosides or halothane; increased sympathomimetic effect with guanethidine and MAO-inhibitors; and high blood pressure with secale alkaloid derivatives or oxytocin.

Is there a relationship between ephedra and substance abuse?

The May 1999 article "The Hazards of Psychotropic Herbs," published by the Minnesota Medical Association in Minnesota Medicine, reports that the US Drug Enforcement Administration has known for some time that ephedrine and pseudoephedrine are used in the illegal manufacture of methamphetamine. This should come as no surprise to Michael Ellis, CEO and founder of Metabolife International Inc., who pleaded guilty to charges linking him to an illegal methamphetamine lab in the 1980s and received five years' probation.