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Excerpt
Much controversy currently surrounds the safety and efficacy of herbal dietary supplements containing Ephedra sinica (also known by its Chinese name, ma huang). Ephedra supplements contain a variety of ephedrine-type alkaloids including (−)ephedrine, (+)pseudoephedrine, (−)methylephedrine, (−)norephedrine, and (+)norpseudoephedrine, which function as both cardiovascular and central nervous system stimulants. A growing number of case reports have appeared in the medical literature describing a wide range of adverse reactions related to supplementation with botanical ephedrine alkaloids (1–4). The Food and Drug Administration (FDA) recently proposed guidelines limiting the dosage and duration of use for ephedrine alkaloids contained in dietary supplements. A recent General Accounting Office report, however, criticized the FDA for its approach in formulating these guidelines. In particular, the report noted, the FDA relied too heavily on a large number of questionable adverse event reports in making its recommendation (5). As a result, the recommendations have yet to be implemented.
The onset and intensity of the pharmacologic effects of botanical ephedrine from Ephedra supplements are related to the dose contained in the supplement, the frequency of supplementation, and its pharmacokinetic profile. Only two reports have described the absorption and disposition kinetics of botanical ephedrine following oral administration of Ephedra supplements (6,7). A comparison of the pharmacokinetic parameters from these reports indicates that the apparent volume of distribution and clearance of botanical ephedrine are comparable to those of its synthetic counterpart. One notable difference between the two studies was the rate of ephedrine absorption. This difference appears to be related to formulation. The study by White et al (6) used a single-component supplement containing powdered Ephedra herb, whereas that of Gurley et al (7) used multicomponent supplements formulated with concentrated ma huang extracts, natural sources of caffeine, and other herbs, vitamins, and minerals. Mean values for absorption rate constant and tmax for the powdered herb were 0.49 h−1 and 3.9 hours, whereas those for extract formulations were 1.36 h−1 and 2.8 hours, respectively. Clearly, botanical ephedrine is more rapidly absorbed from supplements formulated with ma huang extracts than from those containing powdered “stems and aerial portions” of the herb. Furthermore, no differences were noted in the pharmacokinetic profile of (−)ephedrine when administered either in its synthetic form or as an Ephedra extract (7).
These findings contrast starkly with assertions made by Ephedra supplement manufacturers and advocates of ma huang as a thermogenic diet aid that “the herb does not behave like the pure substances (ephedrine and pseudoephedrine) . . .[and] the alkaloids are absorbed more slowly from the herb than they are from pharmaceutical formulations so there is no sudden rush of ephedrine and congeners into the body.”(8). Whereas there is some merit in the preceding statement with regard to powdered ma huang, the vast majority of Ephedra supplements are formulated from extracts of the herb. As a result, supplements containing ma huang extracts are likely to exhibit absorption and disposition characteristics indistinguishable from those of conventional (−)ephedrine dosage forms.
