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Citrus Aurantium vs. Ephedra
Adverse publicity about Citrus aurantium extract is unfounded!
Recently, there has been much adverse publicity about the dangers of Ephedra (Ma-huang). The FDA has received over 17,000 reports of adverse reactions, up to and including deaths, and a study of these adverse reactions and the literature reported by the Southern California Evidence-Based Practice Center (RAND report) also identified serious concerns about Ephedra. Many media sources have speculated that Citrus aurantium extract (also known as Advantra Z®) will cause similar adverse reactions.
These speculations, which seem to be based on the assumption that the alkaloids in Citrus aurantium extract behave identically to those found in Ephedra, are pertinently unfounded and untrue.
The alkaloids from Citrus species are biologically and physiologically distinct from those found in Ephedra, and possess properties that are not shared with the Ephedra alkaloids. The converse is also true; the Ephedra alkaloids possess properties that are not shared with the Citrus alkaloids. Scientifically, this is in part due to differences in pharmacokinetics and pharmacodynamics. For the layperson, the most obvious difference is that the Citrus alkaloids, unlike the Ephedra alkaloids, do not readily pass into the brain. Consequently, the Citrus alkaloids have no effects on the central nervous system (CNS; in lay language, they do not give a "buzz") and since the CNS actions of the Ephedra alkaloids are responsible for at least some of the reported Ephedra side effects, the Citrus alkaloids are entirely incapable of causing similar side effects. In terms of effects in the rest of the body, while the Citrus alkaloids are indirect-acting adrenergic agents, they are very much weaker than the Ephedra alkaloids. However, it has been shown that both synephrine and octopamine (the latter also present in the Citrus alkaloid mixture) can specifically and directly stimulate so-called β-3 receptors, which are believed to be the receptors mainly responsible for thermogenesis and lipolysis (the breakdown of stored fat). This property appears to be unique to synephrine and octopamine, and is not a property shown by the Ephedra alkaloids. It is obviously a property of considerable value in terms of losing weight (where the real objective is to eliminate unwanted fat) and in terms of making metabolizable substrates (fatty acids from stored fat) available as energy sources.
 The Chinese herb Zhi shi, which is the immature Bitter Orange (Citrus aurantium), is used to manufacture Citrus aurantium extract. This herb, Zhi shi, has been used in Chinese medicine for several centuries for a variety of purposes, including as a digestive aid, generally in doses of 3 - 15 grams as a decoction, but sometimes in doses as high as 45 grams. The herb contains about 0.8% of mixed alkaloids, with synephrine predominating (the natural form of the alkaloid is l-synephrine), so the normal dose of 3 - 15 grams would provide 24 - 120 mg of Citrus alkaloids per dose, with an intake of as much as 360 mg not being unusual. There are no reports of side effects at these dosage levels. In addition to administering the herb itself as a decoction, extracts are also administered by the intravenous route in the treatment of shock, in doses equivalent to 10 - 40 grams (80 - 320 mg alkaloids).
Synthetic dl-synephrine is used therapeutically world-wide, often under the name oxedrine. The recommended dosage is 100 - 150 mg three times daily, with a maximum daily intake of 600 mg. At these dose levels the only reported side effects are rarely bradycardia (slowing of the heart rate; ephedrine, the main constituent of the Ephedra alkaloids, increases the heart rate) and exacerbation of narrow-angle glaucoma.
In comparison to the above, the single and daily intakes of alkaloids from most products based on Citrus aurantium extract are from 12 - 60 mg as a single dose, with 36 - 180 mg total daily intake! To date, there have been at least five clinical studies performed with products containing Citrus aurantium extract in these dose ranges, as well as four metabolic studies in human volunteers. There were no side effects observed in any of these studies. In particular, there were no effects seen on heart rate or blood pressure. Market surveillance covering many thousands of "user-days" has also failed to reveal adverse effects, thus indicating that Citrus aurantium extract is indeed a safe and effective alternative to Ephedra.
djones@zhishin.com Dr. Dennis Jones,
M.A. (Cantab.), Ph.D. (Cantab.), C.Chem.,
http://www.zhishin.com FRSC(UK), C.Biol., M.I.Biol., MBIM.
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