Inside This Issue AED Lockbox News Restarting Small Hearts Deadly Dangers of Ephedra Fast Stroke Treatment Saves Lives Good Health in a Nutshell Shaping the Future of Medicine
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Ephedra, an over-the-counter herbal drug, is marketed as a dietary supplement for weight loss and to boost energy. For many users, however, it can increase the odds of heart attack, stroke, and death.

"Ephedra can absolutely kill you," warns NHW editor Dr. Douglas Zipes, who recently testified before the House Energy and Commerce Committee on the use of ephedra medications. "In my opinion, the risk far outweighs the benefit. I recommend that ephedra at minimum be called a drug and placed under FDA supervision. More probably, it should be taken off the market.

"Just because something is called 'natural' and added to dietary supplements does not mean that it is safe," Dr. Zipes adds. "Hemlock is natural but is obviously a poison. A snakebite is natural, but it can kill you."

The following are excerpts of Dr. Zipes' comments delivered on Capitol Hill in July:

On Normal Heart Function
The normal heart beats approximately 38 million times per year, or about 3 billion times in an average lifespan. The sinus node, a small group of specialized cells in the top right portion of the heart's upper chamber, serves as the pacemaker, initiating and orches- trating each heartbeat. Other tissues in the heart wait for the arrival of each sinus-generated beat (almost like electricity traveling over a wire) and fire in an orderly sequence from the atria to the ventricles to produce each heartbeat.

On Disorders of the Heartbeat
Multiple factors can influence the rate of discharge of the sinus node and can cause other tissues in the heart to fire prematurely and usurp control of the heartbeat. Among these factors, the autonomic nervous system is most prominent. Predominantly, two groups of nerves make up the autonomic nervous system: vagus nerves and sympathetic nerves. The vagus nerves exert an inhibitory effect on heart function by release of a substance called acetylcholine, slowing the heart rate and dilating blood vessels. Sympathetic nerves release substances known collectively as catecholamines, causing an increase in the heart rate and, for the most part, a constriction of the blood vessels. These actions can provoke spontaneous discharge of the heartbeat from areas other than the sinus node and result in arrhythmias. The extent of the heartbeat disorder can range from a single premature beat (often felt as a "thump" in the chest or palpitation) to a lethal heart rhythm called ventricular fibrillationÑa disorganized, rapid (400 to 600 times per minute) heart rhythm originating in the bottom chambers (ventricles) and preventing blood flow to the brain, which causes death in three to five minutes unless reversed.

Action of Ephedra on the Heart and Blood Vessels
Ephedra contains primarily ephedrine, which is sympathomimetic amine. That means its actions mimic those actions produced by stimulation of the sympathetic nerves, as noted above. Ephedra does this by both a direct effect on stimulating alpha and beta 1 and beta 2-adrenergic receptors (as the body's own catecholamines do) and indirectly by stimulating the release of the body's store of catecholamines and another compound called dopamine (20 to 30 percent increase).

On Caffeine in Ephedra Supplements
Most of these ephedra products also contain caffeine, typically extracts from guarana seed. Caffeine causes an antivagal effect by antagonizing the actions of adenosine, and can therefore promote vasoconstriction and increase the release of epinephrine, norepinephrine, and dopamine.

Importantly, an exercising individual normally activates the autonomic nervous system to decrease vagal, and increase sympathetic, activity. These changes summate with the actions of ephedra and caffeine.

Physiologic Effects
The result of the actions of ephedra and caffeine noted above is to:

1. Elevate the blood pressure.
2. Elevate the heart rate.
3. Put more stress on the heart (needs more oxygen).
4. Reduce the potassium level in the blood.

No controversy exists about the physiologic actions of these drugs. More than 1,200 serious reactions related to ephedra have been reported to the FDA, and it is suspected that the actual number of events is far greater. These include strokes, arrhythmias, myocardial infarction (heart attack), psychosis, and death. Apparently, 13,000 complaints have been registered with the manufacturer of Metabolife 356, including several hundred patients who required hospitalization and 80 incidents of serious injury or death.

Recommendations
Because of our inability to predict who might have an adverse response to these drugs, the minimal (if any) therapeutic effect, and the potential for major adverse responses, I would recommend the following:

1. Recognize that ephedra and ephedrine are drugs, not dietary supplements.
2. Recognize that they are capable of provoking harm, including ventricular fibrillation and sudden death.
3. Eliminate over-the-counter use based on minor proven benefit and potential for major harm.
4. Regulate their use by applying FDA criteria to distribution of ephedra-caffeine compounds, as is done for all other drugs.