Skip to Content

Ephedra

Scientific Name(s): Ephedra equisetina Bge., Ephedra intermedia Schrenk et Meyer, Ephedra sinica Stapf.
Common Name(s): Ephedra, Ma huang, Pinellia, Yellow astringent, Yellow horse

Clinical Overview

Use

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.

Dosing

Ephedra-containing dietary supplements are currently banned in the United States. Dosages of ephedra more than 32 mg/day have resulted in adverse reactions.

Contraindications

Cardiovascular and cerebrovascular adverse events have been documented in case reports.

Pregnancy/Lactation

Documented adverse reactions. Avoid use.

Interactions

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.

Adverse Reactions

Reported adverse reactions include arrhythmia and sudden death, myocardial infarction, stroke, psychiatric symptoms, autonomic hyperactivity, seizures, and ischemic colitis and gastric mucosal injury.

Toxicology

Toxicological data are limited. Periconceptional use of ephedra-containing products has been associated with an increased adjusted odds ratio for anencephaly.

Botany

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.Lee 2011, USDA 2007, Chaw 2000, Bowe 2000, Fu 2000

History

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.Lee 2011, Fu 2000

Chemistry

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.Freudenberg 1932 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.Jian 1988 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.Grue-Srensen 1988, Grue-Srensen 1994 The supercritical fluid extraction of ephedrine from E. sinica has been studied using a mixture of carbon dioxide, diethylamine, and methanol.Choi 1999

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.Cui 1991, Betz 1997, Li 2001, Spyridaki 2001 Numerous high-performance liquid chromatography (HPLC) methods have been developedJian 1988, Moriyasu 1984, Gurley 1998, Hurlbut 1998, Li 2002, Hong 2011 including analysis of urine samplesGmeiner 2002 and a liquid chromatography-mass spectrometry method for dietary supplements.Gay 2001 Capillary electrophoresis and isotachophoresis also have been applied, with some methods using cyclodextrin as a matrix to resolve optically isomeric alkaloids.Kasahara 1985, Snopek 1988, Liu 1992, Liu 1993, Flurer 1995, Belder 2011 Carbon-13 nuclear magnetic resonance also has been used to qualitatively and quantitatively analyze ephedra alkaloids.Yamasaki 1979

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.Liu 1993 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.Makino 2002 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.Gurley 2000 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.Terry 1927

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.Spyridaki 2001, Lv 2000, Zhao 2009 In the roots, which do not contain appreciable amounts of ephedrine alkaloids, feruloylhistamineHikino 1984 and ephedradines A-DHikino 1983, Tamada 1979 were isolated. The flavonoid derivative ephedrannin A was also isolated from the root.Hikino 1982 The polysaccharide ephedrans A-E have been isolated from ephedra stems.Konno 1985 The roots of ephedra have yielded a variety of hypotensive compounds, including the flavonoid ephedrannin AHikino 1982 feruloylhistamineHikino 1984 and the spermine alkaloids ephedradines A-DHikino 1983 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.FDA 2012, Greenway 2001

Athletic performance

Animal data

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.Tokish 2004, Avois 2006, Dhar 2005 Few trials evaluating the ergogenic efficacy of ephedrine alone exist, and results suggest slight effects on performance.Tokish 2004, Shekelle 2003 However, combinations of ephedrine and caffeine have been reported to increase endurance in running and cycling experiments.Dhar 2005, Shekelle 2003 Most studies have been conducted by one groupBell 2001, Bell 2002 and because of the different types of exercise studied (endurance and power), the results cannot be pooled for analysis.Shekelle 2003 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.Tokish 2004, Avois 2006

Weight loss

Animal data

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.Greenway 2001 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.Shekelle 2003 Other reviews found similar results.Pittler 2005, Joyal 2004, Dwyer 2005, Dulloo 2002 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.Greenway 2001, Vukovich 2005 Whereas a variety of herbals (including ephedra) were shown to effectively decrease appetite and food intake in a 2009 systematic review of herbals used for management of obesity, significant adverse effects were reported only in studies using supplements containing ephedra and caffeine.Hasani-Ranjbar 2009 A more recent study in 7 volunteers attributed the weight loss activity of ephedra correlated to the changes in gut microbiota induced by ephedra consumption.Kim 2014

Other effects

Antiviral

Activity against a limited range of viruses has been shown in some, but not all, in vitro studies.Soltan 2009, Murakami 2008, Lee 2010 Antimicrobial activity has been demonstrated in vitro by other Ephedra species (Ephedra strobiliacea, Ephedra procera, and Ephedra pachyclada spp.).Parsaeimehr 2010

Inflammatory

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.Li 2009 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.Kim 2010, Yamada 2008 Ephedra constricted isolated rabbit urethra tissue, possibly via arachidonic acid pathways, and alpha-adrenoreceptor stimulation in another laboratory experiment.Ayajiki 2008

Dosing

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.Andraws 2005

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.White 1997 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.Haller 2002

Pregnancy / Lactation

Documented adverse reactions. Avoid use.Ernst 2002, Fleming 2008 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.Bitsko 2008

Interactions

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.Ulbricht 2008, Scott 2002, Tang 2011

Adverse Reactions

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.Dhar 2005, Shekelle 2003, Andraws 2005, Figueredo 2011, Maglione 2005 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.Shekelle 2003 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).Andraws 2005

A clinical trial in which 20 healthy adults were given ephedra 1 g dry extract (or placebo) daily for 14 days found increases in heart rate after taking ephedra.Chen 2010, Chen 2010

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.Dhar 2005, Shekelle 2003, Joyal 2004, Vukovich 2005, Andraws 2005, Fleming 2008, Maglione 2005, Haller 2005, Haller 2005, Flanagan 2010, Nazeri 2009, Singh 2008, Cohen 2010 Unfavorable effects on glucose and potassium homeostasis have also been demonstrated, and case reports of ischemic colitis and gastric mucosal injury also exist.Fleming 2008, Haller 2005, Lillegard 2010, Song 2008

Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases was caused by herbals and dietary supplements whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanic/Latinos compared to non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher from supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, ephedra was among the 22% (116) of the single-ingredient products.Navarro 2014

In the 2016 Scientific Statement by the American Heart Association regarding drugs that may cause or exacerbate heart failure, ephedra (ma-huang) and ephedra-like products have been recognized as products with stimulant effects on blood pressure and heart rate as well as an increased risk of mortality and morbidity, and should be avoided. The guidance noted that naturoceuticals are not recommended for the management of heart failure symptoms or for the secondary prevention of cardiovascular events, and that nutritional supplements are not recommended for the treatment of heart failure [Low-quality; Limited].Page 2016

Toxicology

Toxicological data on ephedra are limited. While ephedra extracts are cytotoxic to cultivated cells, the cytotoxicity is not primarily caused by ephedrine.Joyal 2004, Lee 2000 N-nitrosamines of ephedrine and pseudoephedrine have been found to be formed under physiological conditions. N-nitrosoephedrine has been shown to be a carcinogen.Alwan 1986, Tricker 1987 Periconceptional use of ephedra-containing products has been associated with an increased adjusted odds ratio for anencephaly.Bitsko 2008

References

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):221-226.3697965
Andraws R, Chawla P, Brown DL. Cardiovascular effects of ephedra alkaloids: a comprehensive review. Prog Cardiovasc Dis. 2005;47(4):217-225.15991150
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-i20.16799095
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):175-180.18544894
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):440-447.21254134
Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc. 2001;33(8):1399-1403.11474345
Bell DG, McClellan TM, Sabiston CM. Effect of ingesting caffeine and ephedrine on 10-km run performance. Med Sci Sports Exerc. 2002;34(2):344-349.11828246
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):303-315.9086588
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):553-562.18553492
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):4092-4097.10760278
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):4086-4091.10760277
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):39-44.20520603
Chen WL, Tsai TH, Yang CC, Kuo TB. Effects of ephedra on autonomic nervous modulation in healthy young adults. J Ethnopharmacol. 2010;130(3):563-568.20573567
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.
Cohen PA, Ernst E. Safety of herbal supplements: a guide for cardiologists. Cardiovasc Ther. 2010;28(4):246-253.20633025
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.
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):1307-1315.16212144
Dulloo AG. Herbal simulation of ephedrine and caffeine in treatment of obesity. Int J Obes Relat Metab Disord. 2002;26(5):590-592.12032740
Dwyer JT, Allison DB, Coates PM. Dietary supplements in weight reduction. J Am Diet Assoc. 2005;105(5 suppl 1):S80-S86.15867902
Ephedra sinica Stapf. USDA, NRCS. 2007. The PLANTS Database (http://plants.usda.gov, August 2007). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed August 2007.
Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235.11950176
FDA issues regulation prohibiting sale of dietary supplements containing ephedrine alkaloids and reiterates its advice that consumers stop using these products. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108242.htm. Accessed July 2, 2012. [article archived on FDA site]
Figueredo VM. Chemical cardiomyopathies: the negative effects of medications and nonprescribed drugs on the heart. Am J Med. 2011;124(6):480-488.21605722
Flanagan CM, Kaesberg JL, Mitchell ES, et al. Coronary artery aneurysm and thrombosis following chronic ephedra use. Int J Cardiol. 2010;139(1):e11-e13.18718687
Fleming RM. Safety of ephedra and related anorexic medications. Expert Opin Drug Saf. 2008;7(6):749-759.18983221
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):133-139.7581877
Freudenberg K, Schoeffel E, Braun E. Study on the configuration of ephedrine. J Am Chem Soc. 1932;54:234-236.
Fu L, Yu Y, Riedl H. Ephedraceae. In: Wu Z, Raven PH, eds. Flora of China. Beijing: Science Press; St. Louis, MO: 2000:97.
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):761-769.11417640
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):215-221.11888049
Greenway FL. The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obes Rev. 2001;2(3):199-211.12120105
Grue-Srensen G, Spenser ID. Biosynthesis of ephedrine. J Am Chem Soc. 1988;110:3714-3715.
Grue-Srensen G, Spenser ID. Biosynthetic route to the Ephedra alkaloids. J Am Chem Soc. 1994;116:6195-6200.
Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm. 2000;57(10):963-969.10832496
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):1547-1553.10189265
Haller CA, Jacob P, Benowitz NL. Short-term metabolic and hemodynamic effects of ephedra and guarana combinations. Clin Pharmacol Ther. 2005;77(6):560-571.15961987
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):421-432.12087345
Haller CA, Meier KH, Olson KR. Seizures reported in association with use of dietary supplements. Clin Toxicol. 2005;43(1):23-30.15732443
Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol. 2009;15(25):3073-3085.19575486
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):478-480.6531409
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.
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.
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):623-628.21465337
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):1121-1127.9850573
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):69-70.17265209
Joyal SV. A perspective on the current strategies for the treatment of obesity. Curr Drug Targets CNS Neurol Disord. 2004;3(5):341-356.15544444
Kasahara Y, Hikino H, Hine T. Determination of ephedrine alkaloids by isotachophoresis. J Chromatogr. 1985;324:503-507.
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):1616-1625.20939997
Kim BS, Song MY, Kim H. The anti-obesity effect of Ephedra sinica through modulation of gut microbiota in obese Korean women. J Ethnopharmacol. 2014;152(3):532-539.24556223
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):162-163.4034736
Lee MK, Cheng BW, Che CT, Hsieh DP. Cytotoxicity assessment of ma-huang (Ephedra) under different conditions of preparation. Toxicol Sci. 2000;56(2):424-430.10911002
Lee MR. The history of Ephedra (ma-huang). J R Coll Physicians Edinb. 2011;41(1):78-84.21365072
Lee SA, Hong SK, Suh CI, et al. Anti-HIV-1 efficacy of extracts from medicinal plants. J Microbiol. 2010;48(2):249-252.20437159
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):370-374.11565946
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.
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):261-266.19000748
Lillegard JB, Porterfield Jr JR. Ephedra-induced gastric mucosal injury. Case Rep Gastroenterol. 2010;4(1):79-83.21103232
Liu YM, Sheu SJ. Determination of ephedrine alkaloids by capillary electrophoresis. J Chromatogr. 1992;600:370-372.
Liu YM, Sheu SJ. Determination of ephedrine and pseudoephedrine in Chinese herbal preparations by capillary electrophoresis. J Chromatogr. 1993;637:219-223.
Liu YM, Sheu SJ, Chiou SH, Chang HC, Chen YP. A comparative study on commercial samples of ephedrae herba. Planta Med. 1993;59(4):376-378.17235993
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):147-152.10843553
Maglione M, Miotto K, Iguchi M, Hilton L, Shekelle P. Psychiatric symptoms associated with ephedra use. Expert Opin Drug Saf. 2005;4(5):879-884.16111450
Makino Y, Urano Y, Nagano T. Impurity profiling of ephedrines in methamphetamine by high-performance liquid chromatography. J Chromatogr A. 2002;947(1):151-154.11873994
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.
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):2334-2337.19043222
Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. drug-induced liver injury network. Hepatology. 2014;60(4):1399-1408.25043597
Nazeri A, Massumi A, Wilson JM, et al. Arrhythmogenicity of weight-loss supplements marketed on the Internet. Heart Rhythm. 2009;6(5):658-662.19328040
Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2016;134(6):e32-69.27400984
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):1668-1678.20336006
Pittler MH, Ernst E. Complementary therapies for reducing body weight: a systematic review. Int J Obes. 2005;29(9):1030-1038.15925954
Scott GN, Elmer GW. Update on natural product-drug interactions. Am J Health Syst Pharm. 2002;59(4):339-347.11885397
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):1537-1545.12672771
Singh A, Rajeev AG, Dohrmann ML. Cardiomyopathy associated with ephedra-containing nutritional supplements. Congest Heart Fail. 2008;14(2):89-90.18401217
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.
Soltan MM, Zaki AK. Antiviral screening of forty-two Egyptian medicinal plants. J Ethnopharmacol. 2009;126(1):102-107.19666102
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):496-499.18581601
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):311-314.11486842
Tamada M, Endo K, Hikino H, Kabuto C. Structure of ephedradine A, a hypotensive principle of Ephedra roots. Tetrahedron Lett. 1979;873-876.
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. .21796703
Terry RE. A study of Ephedra nevadensis. J Am Pharm Assoc. 1927;16:397.
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):1543-1553.15310585
Tricker AR, Wacker CD, Preussmann R. Nitrosation products from the plant Ephedra altissima and their potential endogenous formation. Cancer Lett. 1987;35(2):199-206.3581050
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):1063-1120.19075623
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):47-53.15730434
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):116-122.9055137
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):293-301.18218321
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.
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):168-171.19219730

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Hide