InteractionsGuide Index Page

 
Case Analysis Toolclose
Enter Each Substance:


Analysis Search Terms:

Ephedra

Botanical Names: Ephedra sinica Stapf., Ephedra equisetina Bunge., Ephedra intermedia Shenk and CA Meyer.
Pharmacopoeial Name: Ephedrae herba.
Common Names: Ephedra, Ma-huang, Ma huang , jointfir.

Summary Table
herb description

Related Species

The three main Ephedra spp. ( E. sinica, E. equisetina, E. intermedia ) are official in the Chinese and Japanese pharmacopoeias. Commercial sources also include E. distachya L. and E. geradiana Wall. ex Stapf. The latter is common in medicinal use in India. The North American species known as Mormon or Brigham Tea ( E. nevadensis S. Wats.) contains little or no alkaloid and is not used medicinally.

Habitat and Cultivation

Widespread perennial shrub native to China, Mongolia, Tibet, Siberia, Japan, India, Pakistan, and Afghanistan; it is also extensively cultivated.

Parts Used

Dried aerial parts (stems); the roots and rhizomes, known as Ma Huang gen , are a separate medicinal agent in Chinese medicine with distinct actions and uses.

Common Forms

  • Dried:   Powdered stems.

  • Tincture:   1:4, 45% alcohol (BHP).

  • Standardized Extracts:   Unavailable.

Alkaloid content of ephedra-containing dietary supplement combinations in the United States and elsewhere are often not accurately labeled, and significant product variability has been demonstrated. 1-3Crude herb extracts are subject to seasonal and species variations in alkaloid content. 4 Ephedra is a component of several commercially available Chinese standard formulae.

herb in clinical practice

Overview

Ephedra has a long history of use in Chinese medicine, dating from 3100BCE. Some authorities consider ephedra to be the mythical soma plant of the Vedas. 5,6Traditionally, ephedra, or Ma Huang, has been used as a bitter warming herb for feverish and catarrhal conditions of the respiratory tract. Currently, regulatory restrictions permitting, it continues to be used clinically for its traditional indications, including bronchial asthma, allergic rhinitis, and as a diaphoretic in colds and influenza in both Western and Chinese medical formulations.

The activity of the crude herb is dominated by sympathomimetic phenethylamine alkaloid constituents, principally ephedrine and pseudoephedrine. Synthetic (racemic) ephedrine itself was produced by Merck in 1926 and introduced into clinical medicine as a treatment for pediatric asthma in 1927; thereafter it rapidly replaced epinephrine because it could be orally administered. Then, as now, the undesirable central stimulating effects of ephedrine were considered limiting factors on its clinical use.

Ephedra monographs by both the World Health Organization (WHO) 7 and the German Commission E support its traditional use for catarrhal conditions of the respiratory tract. 8 The clinical literature on ephedra appears extensive but actually is dominated by a persistent confusion of the crude herb with isolated ephedrine alkaloid. To a limited degree, pharmacokinetic and pharmacodynamic data suggest a similarity between crude ephedra and ephedrine, and the general sympathomimetic activity of ephedra is broadly correlated with ephedrine content. However, aspects of ephedra pharmacology, such as cytotoxicity or phosphodiesterase inhibition, cannot be attributed to ephedrine alone. 9-11In answer to the question of whether there is full equivalence between synthetic ephedrine and ephedra, eminent German phytotherapist Weiss replied, “On the whole yes, but not quite.” 5

The problems of literature interpretation and data comparison are compounded by the variable ingredients and combinations of agents contained in dietary supplements marketed as “weight loss” products that have been used in clinical trials. 2,9Caffeine or caffeine-containing herbs such as guaraná (Paullinea cupana) may be present, with aspirin or salicylate-containing herbs such as willow bark (Salix alba) sometimes combined with micronutrients such as trivalent chromium. Most recent trials have invariably examined these combination products and often incorrectly describe the results as referring to “ephedra.” This in turn casts some methodological doubts on metastudies such as the Cantox and RAND reports, and although both reviews acknowledged the problem, their conclusions should be critically qualified in this regard. 12,13

In the U.S., ephedra-containing supplements previously permitted under the Dietary Supplement Health and Education Act (DSHEA) have been banned since 2003, largely because of inappropriate consumption of ephedrine-containing weight loss and “natural stimulant” products resulting in a significant number of adverse events (see Note: Regulation, Safety, and Ephedra Weight Loss Products).

Historical/Ethnomedicine Precedent

Chinese traditional uses include acute wind-cold syndromes (characterized by chills, mild headaches, fevers without sweating, runny or stuffy nose, and body or joint aches) as well as bronchial asthma and allergic rhinitis. Several millennia-old classical Chinese formulae contain Ma Huang, including Ma Huang Tang (ephedra decoction), She Gan Ma Huang Tang (belamcanda and ephedra decoction), Ge Gan Tang (pueraria decoction), and Xiao Qing Long Tang (minor blue dragon decoction). In these combinations, ephedra comprises 15% to 25% of the total prescription, delivering 60 to 90 mg total alkaloid daily at normal adult dose levels.

In Chinese medicine, a further distinction is made between the stems of the plant, Ma Huang, and the root, Ma Huang gen . The roots contain dimeric flavonols and macrocyclic alkaloids not found in the aerial parts. In Chinese medicine the root is considered antisudorific, used for night sweats and excessive perspiration, whereas the stem is diaphoretic.

Known or Potential Therapeutic Uses

Asthma, coryza of common colds, fevers, allergic and vasomotor rhinitis, hives, and topical use for insect bites, stings, and allergic irritations of the skin and enuresis.

A recent comprehensive meta-analysis of these trials supports a moderate short-term weight loss effect from ephedra alkaloids when combined with stimulants such as caffeine. 14,15Ephedrine and pseudoephedrine are approved for use in over-the-counter (OTC) bronchodilator and nasal decongestant products. Ephedrine has limited use in the hospital setting for the management of hypotension during epidural block and inhalational anesthesia in the operating room (intravenous and intramuscular). Ephedrine has been historically used as a mydriatic and also as a pharmacotherapeutic agent for Stokes-Adams heart block, for enuresis, and for myasthenia gravis, in which latter its mechanism of action is unclear. 16 Some herbal texts also mention the latter two indications, but these are not general practice today, although some urologists continue to investigate the use of ephedrine for enuresis. 17

Key Constituents

Phenylethylamine alkaloids, from approximately 0.5% to more than 2.4% total. (See Note.)

Catechin tannins, including epicatechin and epigallocatechin as well as catechin and gallocatechin.

Volatile oil, including terpinol, cineole, and tetramethylpyrazine; biflavonols.

The roots contain dimeric flavonols and spermine alkaloids not found in the stems.

Note: Proportions of the different alkaloids vary. The majority is 1R,2S-ephedrine (up to 80%), which occurs alongside the optical isomer 1S,2S-pseudoephedrine and their corresponding nor- and methyl- derivatives. The ratio of ephedrine to pseudoephedrine is variable and even reversed in some minor species of Ephedra . 4 Alkaloid composition can be used to “fingerprint” product samples containing ephedra herb because of the four possible optical isomers of ephedrine, only 1R,2S-ephedrine and 1S,2S-pseudoephedrine occur naturally. 18

Therapeutic Dosing Range

Adults

  • Dried prepared herb for traditional decoction:   3 to 9 g daily. Typical recommended doses in Chinese and Western herbal practice deliver between 60 to 90 mg total alkaloid daily.

  • Commission E:   15 to 30 mg single dose and maximum of 300 mg daily total ephedra alkaloid.

  • OTC ephedrine:   Up to 150 mg alkaloid daily.

  • OTC pseudoephedrine:   Up to 240 mg alkaloid daily.

Children

Not to be administered to children under 6 years of age.

Pediatric dose up to 0.5 mg total alkaloid per kg body weight daily; according to Commission E and WHO figures. 7,8

interactions review

Strategic Considerations

Ephedra alkaloids act as combination direct and indirect sympathomimetic agents at all alpha and beta adrenoceptor subtypes and have multiple effects on catecholamine pathways. 19 As a result, ephedra may interact with a variety of drugs that directly target the sympathetic nervous system. They may also indirectly interact with other classes of drug, such as antihypertensives or antiarrhythmics that do not directly affect the adrenergic pathways.

Within an integrative medical setting, however, the use of ephedra-containing formulae for traditional indications is limited and largely unproblematic when used by professionals trained in botanical medicine. Using traditional formulation models, ephedra is combined with other herbs that mitigate its “warming” energetics and the central nervous system (CNS) stimulatory aspects of its actions. The proportion of ephedra in a given formula is rarely more than approximately 15% to 20% of the total. Administered at therapeutic doses for traditional indications, ephedra is generally considered safe. This is supported by the complete absence of adverse event reports associated with administration of the crude herb or crude herb extracts either alone or in traditional formulations, as opposed to isolated alkaloid in multi-ingredient commercial preparations. Ephedra alkaloids are not degraded by monoamine oxidase, lacking the necessary hydroxyl configuration, and are excreted almost entirely unchanged renally, with a half-life of 3 to 5 hours. 20

Adverse effects of the herb result from the CNS stimulatory actions and sympathomimetic actions and include insomnia, anxiety, tachycardia, tremors, and at higher doses, arrhythmias and increased blood pressure. Prolonged and repetitive use may induce tachyphylaxis, but suggestions of “dependency” are not corroborated by clinical reports. Nonclinical toxicological data is based on studies of the isolated alkaloids, principally ephedrine. Clinical data on safety are derived from adverse drug reactions (ADRs) noted in clinical trials on weight loss, and anecdotal reports following initial use or with abuse of ephedrine-containing combination weight loss products.

Assuming normal clinical practice and basic professional physiology and pharmacology knowledge, ephedra herb and its crude extracts do not present any hazardous interactions issues, despite the recent increases in adverse reports related to weight loss dietary supplements and isolated alkaloids (see Note: Regulation, Safety; and Ephedra Weight Loss Products). Professional management of ephedrine interactions for therapeutic purposes also occurs within the hospital setting, typically in relation to management of anesthesia-induced hypotension.

herb-drug interactions
Acetazolamide and Other Urinary PH Modifiers
Caffeine, Theophylline, and Other Methylxanthines
Dexamethasone and Other Oral Corticosteroids
Guanethidine and Related Peripheral Adrenergic Blocking Agents
Phenelzine and Other Monoamine Oxidase Inhibitors (MAOIs)
Sympatholytic Agents, Including Clonidine, Methyldopa, Opioids, Reserpine
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Cardiac Glycosides
Halothane and Other Halogenated Inhalational Anesthetic Agents
Oxytocin
Oral Hypoglycemic Agents and Insulin
Secale Alkaloids

Commission E suggests an interaction between ephedra and “secale alkaloids” (i.e., ergotamine derivatives from the rye grass fungus Clavicepsspp.), presumably based on theoretical additive pressor effects. 8 Because ergotamine derivatives are primarily used in postpartum hemorrhage or as migraine prophylaxis, the interaction is clinically improbable. The drug interactions literature lacks any reports of this interaction, and its repetition by secondary sources is presumably derived from the original, unsubstantiated claim in Commission E.

Note: Regulation, Safety, and Ephedra Weight Loss Products
Citations
  • 1.Gurley BJ, Wang P, Gardner SF. Ephedrine-type alkaloid content of nutritional supplements containing Ephedra sinica (Ma-huang) as determined by high performance liquid chromatography. J Pharm Sci 1998;87:1547-1553.View Abstract
  • 2.Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm 2000;57:963-969.View Abstract
  • 3.Betz JM, Gay ML, Mossoba MM et al. Chiral gas chromatographic determination of ephedrine-type alkaloids in dietary supplements containing Ma Huang. J AOAC Int 1997;80:303-315.View Abstract
  • 4.Zhang JS, Tian Z, Lou ZC. [Quality evaluation of twelve species of Chinese Ephedra (ma huang)]. Yao Xue Xue Bao 1989;24:865-871.View Abstract
  • 5.Weiss R. Herbal medicine. Meuss A, Translator. 6th ed. Beaconsfield, UK: Beaconsfield Publishers Ltd; 1988.
  • 6.Pendell D. Ma Huang, Ephedra spp. Pharmakodynamis: Stimulating Plants, Potions and Herbcraft. San Francisco: Mercury House; 2002:127-141.
  • 7.WHO. Herba Ephedrae. WHO Monographs on Selected Medicinal Plants. 1 vol. Geneva: World Health Organization; 1999:145-153.
  • 8.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs. Austin: American Botanical Council: Integrative Medicine Communications; 1998:685.
  • 9.Gurley BJ, Gardner SF, White LM, Wang PL. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit 1998;20:439-445.View Abstract
  • 10.Lee MK, Cheng BW, Che CT, Hsieh DP. Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. Toxicol Sci 2000;56:424-430.View Abstract
  • 11.Nikaido T, Ohmoto T, Kuge T et al. [The study on Chinese herbal medicinal prescription with enzyme inhibitory activity. III. The study of mao-to with adenosine 3',5'-cyclic monophosphate phosphodiesterase]. Yakugaku Zasshi 1990;110:504-508.View Abstract
  • 12.Cantox. Safety assessment and determination of a tolerable upper limit for ephedra. Mississauga, ON, Canada: Cantox Health Sciences International; 2000.
  • 13.Shekelle PG, Hardy ML, Morton SC et al. Ephedra and ephedrine for weight loss and athletic performance enhancement: clinical efficacy and side effects. Evid Rep Technol Assess (RAND) 2003;76.
  • 14.Shekelle PG, Hardy ML, Morton SC et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003;289:1537-1545.View Abstract
  • 15.Pittler M, Ernst E. Complementary therapies for reducing body weight: a systematic review. Int J Obes Relat Metab Disord 2005.View Abstract
  • 16.Milone M, Engel AG. Block of the endplate acetylcholine receptor channel by the sympathomimetic agents ephedrine, pseudoephedrine, and albuterol. Brain Res 1996;740:346-352.View Abstract
  • 17.El Hemaly AK. Nocturnal enuresis: pathogenesis and treatment. Int Urogynecol J Pelvic Floor Dysfunct 1998;9:129-131.View Abstract
  • 18.Schaneberg BT, Crockett S, Bedir E, Khan IA. The role of chemical fingerprinting: application to Ephedra. Phytochemistry 2003;62:911-918.View Abstract
  • 19.Sulzer D, Sonders M, Poulsen N, Galli A. Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol 2005;75:406-433.View Abstract
  • 20.Sever PS, Dring LG, Williams RT. The metabolism of ephedrine in man. Eur J Clin Pharmacol 1975;9:193-198.View Abstract
  • 21.Wilkinson GR, Beckett AH. Absorption, metabolism, and excretion of the ephedrines in man. II. Pharmacokinetics. J Pharm Sci 1968;57:1933-1938.View Abstract
  • 22.Kuntzman RG, Tsai I, Brand L, Mark LC. The influence of urinary pH on the plasma half-life of pseudoephedrine in man and dog and a sensitive assay for its determination in human plasma. Clin Pharmacol Ther 1971;12:62-67.View Abstract
  • 23.Brater DC, Kaojarern S, Benet LZ et al. Renal excretion of pseudoephedrine. Clin Pharmacol Ther 1980;28:690-694.View Abstract
  • 24.Astrup A, Breum L, Toubro S et al. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet: a double blind trial. Int J Obes Relat Metab Disord 1992;16:269-277.View Abstract
  • 25.Astrup A, Breum L, Toubro S et al. Ephedrine and weight loss. Int J Obes Relat Metab Disord 1992;16:715.View Abstract
  • 26.Astrup A, Buemann B, Christensen NJ et al. The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women. Metabolism 1992;41:686-688.View Abstract
  • 27.Astrup A, Madsen J, Holst JJ, Christensen NJ. The effect of chronic ephedrine treatment on substrate utilization, the sympathoadrenal activity, and energy expenditure during glucose-induced thermogenesis in man. Metabolism 1986;35:260-265.
  • 28.Astrup A, Toubro S. Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man. Int J Obes Relat Metab Disord 1993;17 Suppl 1:S41-43.View Abstract
  • 29.Astrup A, Toubro S, Cannon S et al. Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study. Metabolism 1991;40:323-329.
  • 30.Vukovich MD, Schoorman R, Heilman C et al. Caffeine–herbal ephedra combination increases resting energy expenditure, heart rate and blood pressure. Clin Exp Pharmacol Physiol 2005;32:47-53.View Abstract
  • 31.Hackman RM, Havel PJ, Schwartz HJ et al. Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial. Int J Obes (Lond) 2006;30:1545-1546.View Abstract
  • 32.Dulloo AG, Miller DS. The thermogenic properties of ephedrine/methylxanthine mixtures: animal studies. Am J Clin Nutr 1986;43:388-394.View Abstract
  • 33.Dulloo AG, Miller DS. The thermogenic properties of ephedrine/methylxanthine mixtures: human studies. Int J Obes 1986;10:467-481.View Abstract
  • 34.Dulloo AG, Seydoux J, Girardier L. Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition? Metabolism 1992;41:1233-1241.
  • 35.Myers MG. Effects of caffeine on blood pressure. Arch Intern Med 1988;148:1189-1193.View Abstract
  • 36.Myers MG. Caffeine and cardiac arrhythmias. Ann Intern Med 1991;114:147-150.View Abstract
  • 37.McBride BF, Karapanos AK, Krudysz A et al. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA 2004;291:216-221.View Abstract
  • 38.Ray S, Phadke S, Patel C et al. Short-term and long-term in vivo exposure to an ephedra- and caffeine-containing metabolic nutrition system does not induce cardiotoxicity in B6C3F1 mice. Arch Toxicol 2005;79:330-340.
  • 39.Nikaido T, Iizuka S, Okada N et al. [The study of Chinese herbal medicinal prescription with enzyme inhibitory activity. VI. The study of makyo-kanseki-to with adenosine 3',5'-cyclic monophosphate phosphodiesterase]. Yakugaku Zasshi 1992;112:124-128.View Abstract
  • 40.Weinberger M, Bronsky E, Bensch GW et al. Interaction of ephedrine and theophylline. Clin Pharmacol Ther 1975;17:585-592.View Abstract
  • 41.Tinkelman DG, Avner SE. Ephedrine therapy in asthmatic children: clinical tolerance and absence of side effects. JAMA 1977;237:553-557.View Abstract
  • 42.Boozer CN, Daly PA, Homel P et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord 2002;26:593-604.View Abstract
  • 43.Yanovski SZ, Yanovski JA. Obesity. N Engl J Med 2002;346:591-602.View Abstract
  • 44.Brooks SM, Sholiton LJ, Werk EE Jr, Altenau P. The effects of ephedrine and theophylline on dexamethasone metabolism in bronchial asthma. J Clin Pharmacol 1977;17:308-318.View Abstract
  • 45.Jubiz W, Meikle AW. Alterations of glucocorticoid actions by other drugs and disease states. Drugs 1979;18:113-121.View Abstract
  • 46.Flegin OT, Morgan DH, Oates JA, Shand DG. The mechanism of the reversal of the effect of guanethidine by amphetamines in cat and man. Br J Pharmacol 1970;39:253P-254P.View Abstract
  • 47.Gulati OD, Dave BT, Gokhale SD, Shah KM. Antagonism of adrenergic neuron blockade in hypertensive subjects. Clin Pharmacol Ther 1966;7:510-514.View Abstract
  • 48.Starr KJ, Petrie JC. Drug interactions in patients on long-term oral anticoagulant and antihypertensive adrenergic neuron-blocking drugs. Br Med J 1972;4:133-135.View Abstract
  • 49.Stockley I. Stockley’s Drug Interactions. 6th ed. London: Pharmaceutical Press; 2002.
  • 50.Hoffman B, Lefkowitz R. Catecholamines, sympathomimetic drugs and adrenergic receptor antagonists. In: Hardman J, Limbird L, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill; 1995.
  • 51.Kalix P. The pharmacology of psychoactive alkaloids from ephedra and catha. J Ethnopharmacol 1991;32:201-208.View Abstract
  • 52.Ulus IH, Maher TJ, Wurtman RJ. Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors. Biochem Pharmacol 2000;59:1611-1621.View Abstract
  • 53.Scorza MC, Carrau C, Silveira R et al. Monoamine oxidase inhibitory properties of some methoxylated and alkylthio amphetamine derivatives: structure-activity relationships. Biochem Pharmacol 1997;54:1361-1369.View Abstract
  • 54.Dingemanse J. An update of recent moclobemide interaction data. Int Clin Psychopharmacol 1993;7:167-180.View Abstract
  • 55.Martyr JW, Orlikowski CE. Epidural anaesthesia, ephedrine and phenylephrine in a patient taking moclobemide, a new monoamine oxidase inhibitor. Anaesthesia 1996;51:1150-1152.View Abstract
  • 56.Dawson JK, Earnshaw SM, Graham CS. Dangerous monoamine oxidase inhibitor interactions are still occurring in the 1990s. J Accid Emerg Med 1995;12:49-51.View Abstract
  • 57.Furukawa T, Morishita H. Modifications of responses to adrenergic drugs in arterial strip by treatment in vivo with ephedrine and reserpine. Jpn J Pharmacol 1975;25:441-451.View Abstract
  • 58.Kim JM, Stevenson CE, Mathewson HS. Hypertensive reactions to phenylephrine eyedrops in patients with sympathetic denervation. Am J Ophthalmol 1978;85:862-868.View Abstract
  • 59.Nishikawa T, Kimura T, Taguchi N, Dohi S. Oral clonidine preanesthetic medication augments the pressor responses to intravenous ephedrine in awake or anesthetized patients. Anesthesiology 1991;74:705-710.View Abstract
  • 60.Lee A, Ngan Kee WD, Gin T. Prophylactic ephedrine prevents hypotension during spinal anesthesia for cesarean delivery but does not improve neonatal outcome: a quantitative systematic review. Can J Anaesth 2002;49:588-599.
  • 61.Kanaya N, Satoh H, Seki S et al. Propofol anesthesia enhances the pressor response to intravenous ephedrine. Anesth Analg 2002;94:1207-1211, table of contents.View Abstract
  • 62.Webb AA, Shipton EA. Re-evaluation of i.m. ephedrine as prophylaxis against hypotension associated with spinal anaesthesia for caesarean section. Can J Anaesth 1998;45:367-369.View Abstract
  • 63.Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001;286:208-216.View Abstract
  • 64.Konno C, Mizuno T, Hikino H. Isolation and hypoglycemic activity of ephedrans A, B, C, D and E, glycans of Ephedra distachya herbs. Planta Med 1985:162-163.View Abstract
  • 65.Xiu LM, Miura AB, Yamamoto K et al. Pancreatic islet regeneration by ephedrine in mice with streptozotocin-induced diabetes. Am J Chin Med 2001;29:493-500.View Abstract
  • 66.Strosberg AD. Association of beta 3-adrenoceptor polymorphism with obesity and diabetes: current status. Trends Pharmacol Sci 1997;18:449-454.View Abstract
  • 67.Vansal SS, Feller DR. Direct effects of ephedrine isomers on human beta-adrenergic receptor subtypes. Biochem Pharmacol 1999;58:807-810.View Abstract
  • 68.Dionne IJ, Turner AN, Tchernof A et al. Identification of an interactive effect of beta3- and alpha2b-adrenoceptor gene polymorphisms on fat mass in Caucasian women. Diabetes 2001;50:91-95.
  • 69.Buscher R, Herrmann V, Insel PA. Human adrenoceptor polymorphisms: evolving recognition of clinical importance. Trends Pharmacol Sci 1999;20:94-99.View Abstract
  • 70.Kernan WN, Viscoli CM, Brass LM et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000;343:1826-1832.View Abstract
  • 71.Morgenstern LB, Viscoli CM, Kernan WN et al. Use of Ephedra-containing products and risk for hemorrhagic stroke. Neurology 2003;60:132-135.View Abstract
  • 72.Inokuchi J, Okabe H, Yamauchi T et al. Inhibitors of angiotensin-converting enzyme in crude drugs. II. Chem Pharm Bull (Tokyo) 1985;33:264-269.View Abstract
  • 73.White LM, Gardner SF, Gurley BJ et al. Pharmacokinetics and cardiovascular effects of ma-huang (Ephedra sinica) in normotensive adults. J Clin Pharmacol 1997;37:116-122.View Abstract
  • 74.Powell T, Hsu FF, Turk J, Hruska K. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis 1998;32:153-159.View Abstract
  • 75.Yokozawa T, Fujioka K, Oura H et al. Decrease in uremic toxins, a newly found beneficial effect of Ephedrae Herba. Phytother Res 1995;34:277-282.
  • 76.Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood) 2004;229:698-704.View Abstract
  • 77.Dentali SJ. Comment on Citrus aurantium minireview. Exp Biol Med (Maywood) 2005;230:102; discussion 103.View Abstract
  • 78.Haaz S, Fontaine KR, Cutter G et al. Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update. Obes Rev 2006;7:79-88.View Abstract