PPA and Ephedrine Health Effects

The recently updated review of FDA's Center for Food Safety and Applied Nutrition's (CFSAN) Special Nutritionals Adverse Event Monitoring System (SN/AEMS), including data collected from January 1993 until February 2001, shows that ephedrine alkaloid dietary supplements are associated with more reports of deaths, myocardial infarctions, cardiac arrhythmias, hypertension, stroke and seizure events than all other dietary supplements combined.

According to the FDA analysis, during this interval there were:

• 3308 adverse events for all dietary supplements, 1398 of these (42%) for the ephedrine alkaloids

• 137 reports of death, 81 deaths (59%) associated with ephedrine alkaloids

• 38 reports of myocardial infarction/heart attack, 32 reports (84%) associated with ephedrine alkaloids

• 98 reports of cardiac arrhythmias, 62 (63%) associated with ephedrine alkaloids

• 144 reports of hypertension, 91 (63%) associated with ephedrine alkaloids

• 85 reports of stroke, 69 (81%) associated with ephedrine alkaloids

• 121 reports of seizure, 70 (58%) associated with ephedrine alkaloids

Two earlier FDA-commissioned reviews of a much smaller number of adverse events reported to the FDA involving the use of ephedrine alkaloids (did not include data from 2000 and 2001) confirmed the cardiac toxicity of these chemicals. The first study found that 47% of cases involved the cardiovascular system (17 cases of hypertension, 13 with palpitations or fast heartbeat, 10 strokes). There were also 7 reports of seizures. The second study found that of the 104 reports in which causation by ephedrine alkaloids was very likely, there were 10 cases of sudden death, 9 cardiac arrhythmias, another 23 possible arrhythmic events, 3 heart attacks, 10 cases of chest pain and 15 severe strokes

The background for the recent well-designed Yale Epidemiological Study that found PPA increases the risk for hemorrhagic stroke includes a long history of published serious adverse events including hemorrhagic strokes attributable to PPA going back to 1979. These cases are attributed to the drug because they usually occur shortly after ingestion -- the design of this study was strokes within the first three days of PPA -- and because of the lack of other plausible explanations, especially in otherwise healthy younger people.

Additionally, there's been evidence for the specific mechanism or for a specific mechanism by which these strokes are induced by PPA. Similar evidence has existed for probably 30 years for the stroke-producing properties of amphetamines, once the most common drugs used for obesity. Both PPA and amphetamines are known to cause cerebral vasculitis, severe inflammation of the blood vessels of the brain which, probably in combination with the blood pressure raising effects of the drugs, can result in cerebral or subarachnoid brain hemorrhage and strokes.

Further information about PPA and strokes comes from FDA's own Spontaneous Adverse Reaction Reporting System. In an FDA memo dated August 6, 19991, FDA Medical Officer, Doctor Heidi Jolson, reported there had been a total of 44 cases of strokes, 35 hemorrhagic in PPA users reported to the FDA until then. Subsequent update of that raised the total to 51 cases of hemorrhagic strokes. Given the reporting artifact, which is generally thought for prescription drugs to be only one in 10 that actually occurred get reported, sometimes thought for others such as over-the-counter to be one in 20, some think one in 100. This means hundreds if not thousands of cases of PPA-induced hemorrhagic stroke have occurred.