Medically reviewed on May 11, 2018.
Scientific Name(s): Ephedra sinica Stapf., Ephedra intermedia Schrenk et Meyer, or Ephedra equisetina Bge. Family: Ephedraceae (ephedra)
Common Name(s): Ephedra , ma huang , yellow horse , yellow astringent , pinellia .
The whole Ephedra sinica plant has traditionally been used to treat symptoms of bronchial asthma, colds, influenza, allergies, and hives in teas or tinctures. Because of adverse events and lack of efficacy, use is not recommended for weight loss or increased athletic performance. Ephedra-containing supplements are banned for sale in the United States.
Ephedra-containing dietary supplements are currently banned in the United States. Dosages of ephedra more than 32 mg/day have resulted in adverse reactions.
Cardiovascular and cerebrovascular adverse events have been documented in case reports.
Documented adverse reactions. Avoid use.
Interactions are likely to be similar to those established for synthetic ephedrine and include monoamine oxidase inhibitors (MAOIs), the anesthetic propofol, cholinergic agents such as tricyclic antidepressants, caffeine, theophylline, and steroids such as dexamethasone.
Reported adverse reactions include arrhythmia and sudden death, myocardial infarction, stroke, psychiatric symptoms, autonomic hyperactivity, seizures, and ischemic colitis and gastric mucosal injury.
Toxicological data are limited. Periconceptional use of ephedra-containing products has been associated with an increased adjusted odds ratio for anencephaly.
Ephedra species grow as low, shrubby plants with small leaves on jointed, ribbed green stems. They are dioecious (ie, male and female flowers are usually found on separate plants). The 3-source species are native to China, where the aboveground parts are collected in the fall and dried for use. Ephedras are gymnosperms and are most closely related to conifers, although many aspects of their botany are different. About 45 Ephedra species exist, varying in their alkaloid content. American, Chilean, and European species are considered to be relatively low in alkaloid content, while Chinese and Indian varieties contain larger amounts of active alkaloids.
The root of E. sinica or E. intermedia , known as “ma huang gen,” is considered by Chinese traditional practitioners to be a distinct drug product from the aboveground parts. A chapter on ephedra has been included in the Flora of China , a collaborative plant project. 1 , 2 , 3 , 4 , 5
Ma huang is one of the earliest and best known drugs of Chinese traditional medicine. It is mentioned in the Shen Nong Ben Cao Jing , one of the premodern classics of Chinese medicine written around 100 AD. Ma huang was used to induce perspiration and treat the symptoms of bronchial asthma, colds, and influenza; it is still in traditional use today.
The earliest scientific work on ephedra, and consequently on ephedrine, is attributed to the Japanese organic chemist and pharmacologist Nagayoshi Nagai (1844 to 1929), followed by his colleague Kinnosuke Miura (1864 to 1950), who identified the potential toxicity of the alkaloids. As a weight loss agent, ephedra has been commonly combined with caffeine; however, more recently the ephedra component has been replaced with bitter orange in US dietary supplements. 1 , 5
Chemical investigations of ephedra in the early 20th century resulted in the isolation of the alkaloids ephedrine and pseudoephedrine, which were identified as the major pharmacologically active compounds in the aboveground portions of the plant. The ephedra alkaloids possess 2 adjacent chiral atoms that could generate 4 possible isomers for every planar structure; however, the plant produces only 2 of the possible isomers. 6 Synthetic ephedrine and pseudoephedrine are usually produced as a racemate, and therefore contain all of the possible isomers. A total of 6 major alkaloids of this type are found in the 3 species known as Ephedrae herba ; the major alkaloid of all species is ephedrine, with pseudoephedrine the next most abundant, and norephedrine, norpseudoephedrine, methylephedrine, and methylpseudoephedrine making up the balance. 7 The proportion of single alkaloids and total alkaloid content of the aboveground portions can vary widely, from 0.5% to 2.5%, with the highest concentration of alkaloids found in the fall. Biosynthesis of ephedra alkaloids has been studied; ephedrine is formed from pyruvate and benzoic acid. 8 , 9 The supercritical fluid extraction of ephedrine from E. sinica has been studied using a mixture of carbon dioxide, diethylamine, and methanol. 10
A large number of analytical methods for ephedra alkaloids have been devised. Gas chromatography has been used, as well as chiral gas chromatography and gas chromatography-mass spectrometry of both plant material and urine specimens. 11 , 12 , 13 , 14 Numerous high-performance liquid chromatography (HPLC) methods have been developed, 7 , 15 , 16 , 17 , 18 , 19 including analysis of urine samples 20 and a liquid chromatography-mass spectrometry method for dietary supplements. 21 Capillary electrophoresis and isotachophoresis also have been applied, with some methods using cyclodextrin as a matrix to resolve optically isomeric alkaloids. 22 , 23 , 24 , 25 , 26 , 27 Carbon-13 nuclear magnetic resonance also has been used to qualitatively and quantitatively analyze ephedra alkaloids. 28
Several systematic studies of alkaloid content in commercial ephedra samples have been conducted. One study used capillary electrophoresis to analyze 22 samples from Taiwan herbal markets and found that E. sinica samples were generally higher in alkaloid content than E. intermedia samples (1.6% vs 1.2%, respectively). The relative amounts of specific alkaloids in aboveground parts correlated well with the species studied, while root samples had no detectable alkaloids. 29 Because crude ephedra can be used as a starting substance for the synthesis of amphetamines, the profile of impurities was used to determine the origin of illicit amphetamine in Japan. 30 Another study examined 20 different dietary supplements from the United States market by HPLC and found that some products had no ephedra alkaloids, some had only ephedrine (suggesting the use of synthetic material), and others were properly labeled and contained the specified amount of alkaloid. 31 American species of ephedra have been found to be devoid of or have very low amounts of alkaloids. Thus, species such as Ephedra nevadensis (Mormon tea) are not appropriate substitutes. 32
Other types of compounds also have been isolated from ma huang. Tetramethylpyrazine has been identified as a pharmacologically active constituent of stems, and analytical methods have been developed. 14 , 33 , 34 In the roots, which do not contain appreciable amounts of ephedrine alkaloids, feruloylhistamine 35 and ephedradines A-D 36 , 37 were isolated. The flavonoid derivative ephedrannin A was also isolated from the root. 38 The polysaccharide ephedrans A-E have been isolated from ephedra stems. 39 The roots of ephedra have yielded a variety of hypotensive compounds, including the flavonoid ephedrannin A, 38 feruloylhistamine, 35 and the spermine alkaloids ephedradines A-D, 36 which were not found in the aboveground parts.
Uses and Pharmacology
The US Food and Drug Administration (FDA) first banned the sale of all dietary supplements containing ephedra in April 2004 based on a lack of evidence to support efficacy claims and more than 16,000 reported cases of adverse reactions. The ban was later overturned by a federal judge in April 2005 for products containing ephedra 10 mg or less. However, in May 2007, the ban was upheld by the US Supreme Court based on a final FDA regulation declaring dietary supplements containing adulterated ephedrine alkaloids as presenting an unreasonable risk of illness or injury under conditions of use recommended or suggested in the labeling, or if no conditions of use are suggested or recommended, under ordinary conditions of use. 40 , 41Athletic performance
Ephedra-containing dietary supplements are banned by the FDA, making data from animal studies of their use as a performance enhancer irrelevant.Clinical data
The use of ephedra-containing products in sports has been reported. 42 , 43 , 44 Few trials evaluating the ergogenic efficacy of ephedrine alone exist, and results suggest slight effects on performance. 42 , 45 However, combinations of ephedrine and caffeine have been reported to increase endurance in running and cycling experiments. 44 , 45 Most studies have been conducted by one group, 46 , 47 and because of the different types of exercise studied (endurance and power), the results cannot be pooled for analysis. 45 Because most classes of amphetamines are banned by the International Olympic Committee (except for medical use of ephedrine) and ephedra-containing supplements are banned by the FDA, further trials evaluating their efficacy are unlikely. 42 , 43Weight loss
Ephedra-containing supplements are banned by the FDA, making data from animal studies for use as a weight-loss aid irrelevant.Clinical data
A combination of ephedrine with a caffeine-containing supplement, such as guarana or cola nut, has been most frequently used for weight loss. 41 A meta-analysis evaluating the efficacy of ephedra in weight loss published in 2003 found few published high-quality trials. Of those trials included, the pooled data favored ephedra and ephedrine over placebo in the short-term (less than 6 months), with about 0.9 kg/month weight loss compared with placebo but with wide confidence limits. 45 Other reviews found similar results. 48 , 49 , 50 , 51 The few trials that have been published since the 2004 ban on ephedra products came to similar conclusions, with enhanced thermogenesis proposed as the mechanism of action. 41 , 52Other effects
Activity against a limited range of viruses has been shown in some, but not all, in vitro studies. 53 , 54 , 55 Antimicrobial activity has been demonstrated in vitro by other Ephedra species ( Ephedra strobiliacea , Ephedra procera , and Ephedra pachyclada spp.). 56Inflammatory
Ephedra extracts have shown anti-inflammatory and immune effects in experiments in rodents and in vitro studies. Complement activation was inhibited and E. sinica showed protective effects against sequelae of spinal cord injury in one experiment. 57 Chemical constituents ephedrannin A and B suppressed the transcription of tumor necrosis factor-alpha and interleukin-1 beta in macrophages and in induced hepatic failure in mice. 58 , 59 Ephedra constricted isolated rabbit urethra tissue, possibly via arachidonic acid pathways, and alpha-adrenoreceptor stimulation in another laboratory experiment. 60
There is a ban on the sale of all ephedra-containing dietary supplements in the United States. Doses of ephedra greater than 32 mg/day have resulted in adverse reactions. 61
The pharmacokinetics of ephedra in humans have been studied, with ephedrine in crude herb requiring twice as long to reach the peak plasma concentration as pure ephedrine dosage forms. 62 Similarly, the combination of a single dose of ephedra and caffeine has been studied; ephedrine and pseudoephedrine had similar peak concentrations at 140 to 150 minutes, while caffeine blood levels peaked at 90 minutes. Overall results were similar to those of individual compounds in pure form. 63
Documented adverse reactions. Avoid use. 64 , 65 It may increase blood pressure and heart rate, cause CNS activity, and stimulate uterine muscle. Periconceptional use of ephedra-containing products has been associated with an increased adjusted odds ratio for anencephaly. 66
Although natural forms of ephedra may contain different chemical constituents than those of ephedrine, in general, interactions are likely to be similar to those established for the synthetic form of the latter and include MAOIs, the anesthetic propofol, cholinergic agents such as tricyclic antidepressants, caffeine, theophylline, and steroids such as dexamethasone. 67 , 68 , 69
A clear temporal association for cardiovascular and cerebrovascular adverse reactions and psychiatric symptoms has been shown with ephedra use, but a direct causal relationship is difficult to establish. 44 , 45 , 61 , 70 , 71 A 2- to 3-fold increased odds for risk of adverse psychiatric reactions and heart palpitations was found in one meta-analysis, with a trend toward an increase in risk for hypertension. 45 A review of case reports found a trend toward an increased risk for cardiovascular and cerebrovascular adverse reactions at doses lower than those used for weight loss (ephedra 32 mg/day vs 90 to 150 mg/day, respectively). 61
Case reports of adverse reactions continue to appear in the literature despite the FDA ban on ephedra products and include cardiomyopathies, arrhythmia and sudden death, myocardial infarction, coronary artery aneurysm, stroke, psychiatric symptoms, autonomic hyperactivity, and seizures. 44 , 45 , 49 , 52 , 61 , 65 , 71 , 74 , 75 , 76 , 77 , 78 , 79 Unfavorable effects on glucose and potassium homeostasis have also been demonstrated, and case reports of ischemic colitis and gastric mucosal injury also exist. 65 , 74 , 80 , 81
Toxicological data on ephedra are limited. While ephedra extracts are cytotoxic to cultivated cells, the cytotoxicity is not primarily caused by ephedrine. 49 , 82 N-nitrosamines of ephedrine and pseudoephedrine have been found to be formed under physiological conditions. N-nitrosoephedrine has been shown to be a carcinogen. 83 , 84 Periconceptional use of ephedra-containing products has been associated with an increased adjusted odds ratio for anencephaly. 66
Bibliography1. Lee MR. The history of Ephedra (ma-huang). J R Coll Physicians Edinb . 2011;41(1):78-84.
2. Ephedra sinica Stapf. USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , 1 August 2007). National Plant Data Center, Greensboro, NC 27401-4901 USA.
3. Chaw SM, Parkinson CL, Cheng Y, Vincent TM, Palmer JD. Seed plant phylogeny inferred from all three plant genomes: monophyly of extant gymnosperms and origin of Gnetales from conifers. Proc Natl Acad Sci USA . 2000;97(8):4086-4091.
4. Bowe LM, Coat G, dePamphilis CW. Phylogeny of seed plants based on all three genomic compartments: extant gymnosperms are monophyletic and Gnetales' closest relatives are conifers. Proc Natl Acad Sci USA . 2000;97(8):4092-4097.
5. Fu L, Yu Y, Riedl H. Ephedraceae. In: Wu Z, Raven PH, eds. Flora of China . Beijing: Science Press; St. Louis, MO: 2000:97.
6. Freudenberg K, Schoeffel E, Braun E. Study on the configuration of ephedrine. J Am Chem Soc . 1932;54:234-236.
7. Jian Z, Zhen T, Zhi-cen L. Simultaneous determination of six alkaloids in ephedrae herba by high-performance liquid chromatography. Planta Med . 1988;54(1):69-70.
8. Grue-Srensen G, Spenser ID. Biosynthesis of ephedrine. J Am Chem Soc . 1988;110:3714-3715.
9. Grue-Srensen G, Spenser ID. Biosynthetic route to the Ephedra alkaloids. J Am Chem Soc . 1994;116:6195-6200.
10. Choi YH, Kim J, Kim YC, Yoo KP. Selective extraction of ephedrine from Ephedra sinica using mixtures of CO2, diethylamine, and methanol. Chromatographia . 1999;50:673-679.
11. Cui J, Zhou T, Zhang J, Lou ZC. Analysis of alkaloids in Chinese Ephedra species by gas chromatographic methods. Phytochem Anal . 1991;2:116-119.
12. Betz JM, Gay ML, Mossoba MM, Adams S, Portz BS. Chiral gas chromatographic determination of ephedrine-type alkaloids in dietary supplements containing Má Huáng. J AOAC Int . 1997;80(2):303-315.
13. Li HX, Ding MY, Lv K, Yu JY. Separation and determination of ephedrine alkaloids and tetramethylpyrazine in Ephedra sinica Stapf. by gas chromatography-mass spectrometry [in Chinese]. J Chromatogr Sci . 2001;39(9):370-374.
14. Spyridaki MH, Tsitsimpikou CJ, Siskos PA, Georgakopoulos CG. Determination of ephedrines in urine by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl . 2001;758(2):311-314.
15. Moriyasu M, et al. High-performance liquid chromatographic determination of organic substances by metal chelate derivatization. III. Analysis of Ephedra bases. Chem Pharm Bull . 1984;32:744-747.
16. 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(12):1547-1553.
17. Hurlbut JA, Carr JR, Singleton ER, et al. Solid-phase extraction cleanup and liquid chromatography with ultraviolet detection of ephedrine alkaloids in herbal products. J AOAC Int . 1998;81(6):1121-1127.
18. Li HX, Ding MY, Lv K, Yu JY. Simultaneous separation and determination of ephedrine alkaloids and tetramethylpyrazine in Ephedra sinica Stapf. by HPLC. J Liq Chrom Relat Technol . 2002;25:313-320.
19. Hong H, Chen HB, Yang DH, et al. Comparison of contents of five ephedrine alkaloids in three official origins of Ephedra Herb in China by high-performance liquid chromatography. J Nat Med . 2011; 65(3-4):623-628.
20. Gmeiner G, Geisendorfer T, Kainzbauer J, Nikolajevic M, Tausch H. Quantification of ephedrines in urine by column-switching high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci . 2002;768(2):215-221.
21. Gay ML, White KD, Obermeyer WR, Betz JM, Musser SM. Determination of ephedrine-type alkaloids in dietary supplements by LC/MS using a stable-isotope labeled internal standard. J AOAC Int . 2001;84(3):761-769.
22. Kasahara Y, Hikino H, Hine T. Determination of ephedrine alkaloids by isotachophoresis. J Chromatogr . 1985;324:503-507.
23. Snopek J, Jelinek I, Smolkova-Keulemansova E. Use of cyclodextrins in isotachophoresis. IV. The influence of cyclodextrins on the chiral resolution of ephedrine alkaloid enantiomers. J Chromatogr . 1988;438:211-218.
24. Liu YM, Sheu SJ. Determination of ephedrine alkaloids by capillary electrophoresis. J Chromatogr . 1992;600:370-372.
25. Liu YM, Sheu SJ. Determination of ephedrine and pseudoephedrine in Chinese herbal preparations by capillary electrophoresis. J Chromatogr . 1993;637:219-223.
26. Flurer CL, Lin LA, Satzger D, Wolnik KA. Determination of ephedrine compounds in nutritional supplements by cyclodextrin-modified capillary electrophoresis. J Chromatogr B Biomed Appl . 1995;669(1):133-139.
27. Belder D, Tolba K, Nagl S. Rapid quantitative determination of ephedra alkaloids in tablet formulations and human urine by microchip electrophoresis. Electrophoresis . 2011;32(3-4):440-447.
28. Yamasaki K, Fujita K. Qualitative and quantitative analysis of ephedra alkaloids in ephedrae herba by carbon-13 nuclear magnetic resonance. Chem Pharm Bull . 1979;27:43-47.
29. Liu YM, Sheu SJ, Chiou SH, Chang HC, Chen YP. A comparative study on commercial samples of ephedrae herba. Planta Med . 1993;59(4):376-378.
30. Makino Y, Urano Y, Nagano T. Impurity profiling of ephedrines in methamphetamine by high-performance liquid chromatography. J Chromatogr A . 2002;947(1):151-154.
31. Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm . 2000;57(10):963-969.
32. Terry RE. A study of Ephedra nevadensis . J Am Pharm Assoc . 1927;16:397.
33. Lv K, Li H, Ding M. Analysis of tetramethylpyrazine in Ephedrae herba by gas chromatography-mass spectrometry and high-performance liquid chromatography. J Chromatogr A . 2000;878(1):147-152.
34. Zhao W, Deng AJ, Du GH, Zhang JL, Li ZH, Qin HL. Chemical constituents of the stems of Ephedra sinica . J Asian Nat Prod Res . 2009;11(2):168-171.
35. Hikino H, Kiso Y, Ogata M, et al. Pharmacological actions of analogues of feruloylhistamine, an imidazole alkaloid of Ephedra roots. Planta Med . 1984;50(6):478-480.
36. Hikino H, Ogata K, Konno C,Sato S. Studies on the constituents of Ephedra. 12. Validity of the oriental medicines. Part 41. Hypotensive actions of ephedradines, macrocyclic spermine alkaloids of Ephedra roots. Planta Med . 1983;48:290-293.
37. Tamada M, Endo K, Hikino H, Kabuto C. Structure of ephedradine A, a hypotensive principle of Ephedra roots. Tetrahedron Lett . 1979;873-876.
38. Hikino H, Takahashi M, Konno C. Studies on the constituents of Ephedra. 10. The validity of oriental medicines. 33. Structure of ephedrannin A, a hypotensive principle of Ephedra roots. Tetrahedron Lett . 1982;23:673-676.
39. 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;51(2):162-163.
40. US Food and Drug Administration. Sales of Supplements Containing Ephedrine Alkaloids (Ephedra) Prohibited. 2007. http://www.fda.gov/oc/initiatives/ephedra/february2004/ . Accessed March 12, 2008.
41. Greenway FL. The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obes Rev . 2001;2(3):199-211.
42. Tokish JM, Kocher MS, Hawkins RJ. Ergogenic aids: a review of basic science, performance, side effects, and status in sports. Am J Sports Med . 2004;32(6):1543-1553.
43. Avois L, Robinson N, Saudan C, Baume N, Mangin P, Saugy M. Central nervous system stimulants and sport practice. Br J Sports Med . 2006;40(suppl 1):i16-i20.
44. Dhar R, Stout W, Link MS, Homoud MK, Weinstock J, Estes NA 3rd. Cardiovascular toxicities of performance-enhancing substances in sports. Mayo Clin Proc . 2005;80(10):1307-1315.
45. 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(12):1537-1545.
46. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc . 2001;33(8):1399-1403.
47. Bell DG, McClellan TM, Sabiston CM. Effect of ingesting caffeine and ephedrine on 10-km run performance. Med Sci Sports Exerc . 2002;34(2):344-349.
48. Pittler MH, Ernst E. Complementary therapies for reducing body weight: a systematic review. Int J Obes . 2005;29(9):1030-1038.
49. Joyal SV. A perspective on the current strategies for the treatment of obesity. Curr Drug Targets CNS Neurol Disord . 2004;3(5):341-356.
50. Dwyer JT, Allison DB, Coates PM. Dietary supplements in weight reduction. J Am Diet Assoc . 2005;105(5 suppl 1):S80-S86.
51. Dulloo AG. Herbal simulation of ephedrine and caffeine in treatment of obesity. Int J Obes Relat Metab Disord . 2002;26(5):590-592.
52. Vukovich MD, Schoorman R, Heilman C, Jacob P III, Benowitz NL. Caffeine-herbal ephedra combination increases resting energy expenditure, heart rate and blood pressure. Clin Exp Pharmacol Physiol . 2005;32(1-2):47-53.
53. Soltan MM, Zaki AK. Antiviral screening of forty-two Egyptian medicinal plants. J Ethnopharmacol . 2009;126(1):102-107.
54. Murakami T, Harada H, Suico MA, et al. Ephedrae herba, a component of Japanese herbal medicine Mao-to, efficiently activates the replication of latent human immunodeficiency virus type 1 (HIV-1) in a monocytic cell line. Biol Pharm Bull . 2008;31(12):2334-2337.
55. Lee SA, Hong SK, Suh CI, et al. Anti-HIV-1 efficacy of extracts from medicinal plants. J Microbiol . 2010;48(2):249-252.
56. Parsaeimehr A, Sargsyan E, Javidnia K. A comparative study of the antibacterial, antifungal and antioxidant activity and total content of phenolic compounds of cell cultures and wild plants of three endemic species of Ephedra. Molecules . 2010;15(3):1668-1678.
57. Li L, Li J, Zhu Y, Fan G. Ephedra sinica inhibits complement activation and improves the motor functions after spinal cord injury in rats. Brain Res Bull . 2009;78(4-5):261-266.
58. Kim IS, Park YJ, Yoon SJ, Lee HB. Ephedrannin A and B from roots of Ephedra sinica inhibit lipopolysaccharide-induced inflammatory mediators by suppressing nuclear factor-kB activation in RAW 264.7 macrophages. Int Immunopharmacol . 2010;10(12):1616-1625.
59. Yamada I, Goto T, Takeuchi S, et al. Mao ( Ephedra sinica Stapf) protects against D-galactosamine and lipopolysaccharide-induced hepatic failure. Cytokine . 2008;41(3):293-301.
60. Ayajiki K, Kimura T, Yamamizu K, Okamura T. Mechanisms underlying mechanical responses to Ephedra herb of isolated rabbit urinary bladder and urethra, a possible stress urinary incontinence therapeutic. J Pharmacol Sci . 2008;107(2):175-180.
61. Andraws R, Chawla P, Brown DL. Cardiovascular effects of ephedra alkaloids: a comprehensive review. Prog Cardiovasc Dis . 2005;47(4):217-225.
62. White LM, Gardner SF, Gurley BJ, Marx MA, Wang PL, Estes M. Pharmacokinetics and cardiovascular effects of ma-huang ( Ephedra sinica ) in normotensive adults. J Clin Pharmacol . 1997;37(2):116-122.
63. Haller CA, Jacob P III, Benowitz NL. Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clin Pharmacol Ther . 2002;71(6):421-432.
64. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109(3):227-235.
65. Fleming RM. Safety of ephedra and related anorexic medications. Expert Opin Drug Saf . 2008;7(6):749-759.
66. Bitsko RH, Reefhuis J, Louik C, et al; National Birth Defects Prevention Study. Periconceptional use of weight loss products including ephedra and the association with birth defects. Birth Defects Res A Clin Mol Teratol . 2008;82(8):553-562.
67. Ulbricht C, Chao W, Costa D, Rusie—Seamon E, Weissner W, Woods J. Clinical evidence of herb-drug interactions: a systematic review by the natural standard research collaboration. Curr Drug Metab . 2008;9(10):1063-1120.
68. Scott GN, Elmer GW. Update on natural product-drug interactions. Am J Health Syst Pharm . 2002;59(4):339-347.
69. Tang J, Zhou X, Ji H, Zhu D, Wu L. Effects of ephedra water decoction and cough tablets containing ephedra and liquorice on CYP1A2 and the pharmacokinetics of theophylline in rats [published online ahead of print July 27, 2011]. Phytother Res . 10.1002/ptr.3565 .
70. Figueredo VM. Chemical cardiomyopathies: the negative effects of medications and nonprescribed drugs on the heart. Am J Med . 2011;124(6):480-488.
71. Maglione M, Miotto K, Iguchi M, Hilton L, Shekelle P. Psychiatric symptoms associated with ephedra use. Expert Opin Drug Saf . 2005;4(5):879-884.
72. Chen WL, Tsai TH, Yang CC, Kuo TB. Acute effects of ephedra on autonomic nervous modulation in healthy young adults. Clin Pharmacol Ther . 2010;88(1):39-44.
73. Chen WL, Tsai TH, Yang CC, Kuo TB. Effects of ephedra on autonomic nervous modulation in healthy young adults. J Ethnopharmacol . 2010;130(3):563-568.
74. Haller CA, Jacob P, Benowitz NL. Short-term metabolic and hemodynamic effects of ephedra and guarana combinations. Clin Pharmacol Ther . 2005;77(6):560-571.
75. Haller CA, Meier KH, Olson KR. Seizures reported in association with use of dietary supplements. Clin Toxicol . 2005;43(1):23-30.
76. Flanagan CM, Kaesberg JL, Mitchell ES, et al. Coronary artery aneurysm and thrombosis following chronic ephedra use. Int J Cardiol . 2010;139(1):e11-e13.
77. Nazeri A, Massumi A, Wilson JM, et al. Arrhythmogenicity of weight-loss supplements marketed on the Internet. Heart Rhythm . 2009;6(5):658-662.
78. Singh A, Rajeev AG, Dohrmann ML. Cardiomyopathy associated with ephedra-containing nutritional supplements. Congest Heart Fail . 2008;14(2):89-90.
79. Cohen PA, Ernst E. Safety of herbal supplements: a guide for cardiologists. Cardiovasc Ther . 2010;28(4):246-253.
80. Lillegard JB, Porterfield Jr JR. Ephedra-induced gastric mucosal injury. Case Rep Gastroenterol . 2010;4(1):79-83.
81. Song HJ, Shim KN, Ryu KH, Kim TH, Jung SA, Yoo K. A case of ischemic colitis associated with the herbal food supplement ma huang. Yonsei Med J . 2008;49(3):496-499.
82. Lee MK, Cheng BW, Che CT, Hsieh DP. Cytotoxicity assessment of ma-huang (Ephedra) under different conditions of preparation. Toxicol Sci . 2000;56(2):424-430.
83. Alwan SM, Al-Hindawi MK, Abdul-Rahman SK, Al-Sarraj S. Production of nitrosamines from ephedrine, pseudoephedrine and extracts of Ephedra foliata under physiological conditions. Cancer Lett . 1986;31(2):221-226.
84. Tricker AR, Wacker CD, Preussmann R. Nitrosation products from the plant Ephedra altissima and their potential endogenous formation. Cancer Lett . 1987;35(2):199-206.
Copyright © 2009 Wolters Kluwer Health
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.