Jo, Ok, Kim, and Lim: Review on the Efficacy and Safety of Mahuang and Ephedrine in the Treatment of Obesity -Focused on RCT-



The objective of this study was to summarize randomized clinical trials (RCTs) that have assessed efficacy and safety of mahuang and ephedrine on treatment of obesity and to propose better process of study.


NLM Medline (pubmed), the Cochrane library, Scopus, Science Direct, RISS, KISS were systemically searched for clinical trials investigating the efficacy, safety of mahuang and ephedrine on treatment of obesity from 2000 to 2017.


16 RCTs met all the inclusion criteria. In most reports, mahuang and ephedrine significantly reduced body weight, body fat mass. There were no serious adverse events associated with mahuang and ephedrine in all studies.


In appropriate dose of mahuang and ephedrine for healthy adult was safe, and weight loss effect of mahuang and ephedrine was better than control group. Improved clinical practice guidelines should be developed for safe use of mahuang and ephedrine.

Fig. 1
Flow chart of the trial selection process
Table 1
Summary of Randomized Controlled Studies
First author Year Country Study design Sample size (treatment/control) Duration Subject condition Age Experimental intervention Control intervention Outcome measure
Liu, A. G 2013 USA17) 3-arm parallel 90 (CE:30/L:30/LCE: 30) 24 weeks BMI 30–40kg/m2
18–60 years
  1. CE: caffeine 200mg, ephedrine 20mg orally tid, placebo subcutaneously daily(qd)

  2. L: leptin A-200 20mg subQ qd, 2 placebo pills tid

  3. LCE: caffeine 200mg, ephedrine 20mg orally tid, leptin A-200 20mg subQ qd.

non BW, BMI, body fat mass, lean mass (by DXA), visceral adipose tissue mass (CT scan), lipid panel, glucose, insulin, TSH, T3, CBC, UA, EKG
Kim, Ho-Jun 2008 Korea18) parallel 125 (ephedra:41, evodia:45, placebo: 39) 8 weeks healthy, premenopausal Korean women (BMI≥25)
21–50 years
  1. ephedra extract in capsules (pseudo-ephedrine 31.52mg)

  2. evoida extract in capsules (evodiamine 6.75mg, rutaecarpine 0.66mg)

placebo RMR, BW, WHR, lean body mass, BMI, percent fat, FBS, BUN, creatinine, HDL-chol., TG, total chol., AST/ALT, C-reactive protein, platelet count, RBC, WBC, Hg, Hct, MCV, BP
Hackman, R. M. 2006 USA19) parallel 61(29/32) 9 months healthy, premenopausal women (BMI 27–39)
25–47 years
dietary supplement (40mg/day ephedra alkaloids, 100mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) placebo Efficacy: BW, lipids, insulin, leptin, adiponectin, ghrelin, self-reports of physical activity, diet and quality of life indices
Safety: BP, HR, EKG, UA, blood histology, serum chemistry measures, self-reported symptom
Vukovich, M. D. 2005 USA20) cross over 8 5–7days healthy subjects (4 men, 4 women)
23.4±0.8 years
150mg caffeine, 20mg ephedrine placebo REE, HR, BP, plasma glucose, plasma free fatty acids
\Haller, Ca 2005 USA21) 3-arm crossover study 16 29 hours 1-week washout healthy adults (8 women, 8 men)
18 to 45 years
  1. Ephedra + guarana (20mg ephedrine, 83.3mg caffeine)

  2. Xenadrine RFA (multicomponent dietary supplement. 10.1mg ephedrine, 92.6mg caffeine)

placebo HR, BP, plasma (Pharmacokinetic analysis, Pharmacodynamic analysis), urine sample analysis
McBride, B.F. 2004 USA22) Crossover 15 Each 1 day 1-week washout healthy volunteers (mean weight 72.7kg) mean age 26.7 years ephedrine 12mg, caffeine 40mg placebo maximal QTc interval, SBP assessed at 1,3, and 5 hours after dosing for the DSEC relative to placebo
Hioki, C. 2004 Japan23) Parallel 81 (41/40) 24 weeks 81 obese women
BMI 36.5±4.8
age 53.8±12.9
bofu-tsusho-san 24mg/day ephedrine in Ephedra Herba and an efficacy equivalent of 280mg caffeine placebo BP, HR, TG, total cholesterol, LDL, HDL, uric acid, HbA1c, glucose, insulin, RMR
Haller, Ca 2004 USA24) 4-arm crossover 16 24hr 1-week washout 16 healthy nonsmokers
18–45 years
  1. 25mg ephedrine

  2. 200mg caffeine

  3. 1+2

placebo HR, BP, serum hormonal and metabolic markers, Pharmacokinetic analysis, Pharmacodynamic analysis
Greenway, F. L. 2004 USA25) cross over phase 1: 12
phase 2,3: 40
phase 1: 1 week phase 2,3: 6 months healthy subjects (BMI 25–35)
18–65 years
dietary supplement (caffeine 70mg, ephedra 24mg) placebo metabolic rate, BW, BP, HR, total cholesterol, TG, HDL-chol., LDL-chol.
Coffey, C. S. 2004 USA26) parallel 102 (52/50) 12-week s overweight/obese volunteers (30<BMI≤39.9kg/m2)
14 men, 88 women
18–65 years
anti-obesity product 125mg Mahuang(10mg ephedrine), 250 Kola nut(60mg caffeine), 100mg White willow bark(15mg salicin) placebo BW, percent body fat, fat mass, waist circumference, BMI, BP, pulse
Kalman, D. 2002 USA27) parallel 30 (15/15) 14 days healthy volunteers (19 female, 11 male) BMI ≥ 25kg/m2
21–60 years
335mg Mahuang(20mg ephedrine alkaloids), 910mg gaurana(200mg caffeine), 85mg bitter orange(5mg synephrine) placebo BP, HR, EKG, Doppler echocardiograms. Screening: FBS, urinary pregnancy screen, temperature, VAS-SQ.
Boozer, CN 2002 USA28) Parallel 167 (83/84) 6 months healthy volunteers 25≤BMI≤40
18–80 years
ephedrine 90mg/day + caffeine 192mg/day placebo BP, heart function, BW, metabolic changes
Zaragoza, Rm 2001 Mexico29) Parallel 208 (formula 1: 69, formula 2: 70, placebo: 69) 6 months Healthy volunteers
18–60 years
formulation 1: d-norpseudoephedrine hydrochloride 50mg, triyodotironine 75mg, diazepam 5mg, atropine sulphate 0.36mg and aloine 16mg
formulation 2: d-norpseudoephedrine hydrochloride 50mg, atropine sulphate 0.36mg and aloine 16mg
placebo BW, WC
Boozer, CN 2001 USA30) Parallel 67 (35/32) 8 weeks healthy volunteers
25–55 years
herbal dietary supplement (72mg/day ephedrine alkaloids and 240mg/day caffeine) placebo BW, body fat mass, WC, HC, BP, HR, Total Chol, HDL-chol, LDL-chol, TG, glucose
Molnar, D. 2000 Hungary31) Parallel 29 (16/13) 20 weeks obese adolescents (16 males, 16 females)
14–18 years (tanner stage: 3–4)
relative body weight >140%
tablet: caffeine 100mg, ephedrine 10mg
80kg ≤ : 1tab tid
80kg >: 2tab tid
placebo BMI, relative body weight, WHR, RMR, glucose, insulin, Total Chol, HDL-chol, TG, BP, HR
Kalman, DS 2000 USA32) Parallel 30 (16/14) 8 weeks Healthy adults BMI>27kg/m2
under 70 years
capsule containing ephedrine alkaloids 20mg, synephrine 5mg, caffeine 200mg, and salicin 15mg twice daily placebo WHR, BP, BW, body fat, fat-free mass

CE: caffeine, ephedrine group, tid: ter in die, qd: quaque die, L: leptin only group, subQ: subcutaneously , LCE: leptin+caffeine, ephedrine group, BMI: body mass index, BW: body weight, DXA: dual energy X-ray absorptiometry, CT: computed tomography, TSH: thyroid stimulating hormone, T3: triiodothyronine, CBC: complete blood cell count, UA: urinary analysis, EKG: electrocardiogram, RMR: resting metabolic rate, WHR: waist to hip ratio, FBS: fasting blood sugar, BUN: blood urea nitrogen, HDL: high density lipoprotein, chol.:cholesterol, TG: triglyceride, AST: aspartate aminotransferase, ALT: alanine aminotransferase, RBC: red blood cell, WBC: white blood cell, Hg: hemoglobin, Hct: hematocrit, MCV: mean corpuscular volume, BP: blood pressure, HR: heart rate, REE: resting energy expenditure, SBP: systolic blood pressure, DSEC: multicomponent dietary supplement containing ephedra and caffeine, LDL: low density lipoprotein, HbA1c: glycosylated hemoglobin, VAS-SQ: Visual Analogue Scale for sleep quality, WC: waist circumference, HC: hip circumference

Table 2
Efficacy of Mahuang and Ephedrine for Weight Loss
Author Year Blood pressure Heart rate Cardiac function Serum analysis Other symptoms (Complaints)
Liu, A. G 2013 sBP, pulse: n.s. differences dBP:
CE: 4.4mmHg increased, LCE: 2.5mmHg reduced (p=0.03)
n.r. blood glucose, insulin, TG, LDL-chol.: n.s.c.
HDL-chol.: L (4.6% reduction), LCE(5.0% increased) (p=0.03)
insomnia, anxiety, palpitation, drowsiness, chest pain
Kim, Ho-Jun 2008 n.r. n.r. AST: decreased in ephedra group
BUN: decreased in ephedra, evodia group Total chol., TG: decreased in ephedra group (p<0.05)
palpitation, insomnia, dry mouth, anorexia, nausea, vomiting, constipation (increased in ephedra group)
Hackman, R. M. 2006 BP: n.s. differences (except at 3 month)
HR: decline in treatment group (p=0.0003).
most EKGs were considered within the normal range. significant decline in treatment group: Total chol., TG, glucose, fasting insulin, leptin (p=0.005)
n.s.c.: clinical chemistry measures, blood histology, urinalysis
dry mouth, insomnia, nervousness, palpitations.
Coffey, C. S. 2004 BP: n.s. differences
HR (at 12 weeks): treatment group(0.78±1.15bpm), control group (−2.32±1.19bpm), p=0.06
n.r. Total chol., TG: decreased in treatment group (0.05<p<0.10) n.s.
Kalman, D. 2002 BP, HR: n.s. differences (p>0.05) n.s.c.: EKG (ST waves, QRS complexes), Doppler echocardiogram (heart chamber size, wall motion, valve movements), p>0.05 FBS unchanged (p=0.265) n.s.c.: sleep habits/quality (p=0.427)
no serious AE
Boozer, CN 2002 BP: small change (+3 to −5mmHg, p≤0.05)
HR: treatment(4±9bpm), control(−3±9bpm), p<0.001
n.s.c: EKG
cardiac arrhythmias were not increased. (p>0.05)
improved: LDL-chol.(P: −0.8±24.2, H: −12.9±23.1mg/dl, p=0.026), HDL-chol.(P: −0.5±9.4, H: 4.4±6.6mg/dl, p=0.011), glucose(P: 5.3±12.1, H: −0.8±12.8mg/dl, p=0.036)
n.s.c.: serum electrolytes, AST, ALT, creatinine
Increased: dry mouth, heartburn, insomnia
decreased: diarrhea
Molnar, D. 2000 n.s.c. n.r. normal range: hemoglobin, hematocrit, WBC and platelet count, AST, LDH, bilirubin, ALP, serum albumin, creatinine, UA
n.s.c.: glucose, plasma insulin, Total chol., HDL-chol., ApoA1, thyroid hormone
no serious AE

CE:caffeine, ephedrine group, LCE: leptin+caffeine, ephedrine group, L: leptin only group, BMI: body mass index, chol.: cholesterol, BW: body weight, RMR: resting metabolic rate, LDL: low density lipoprotein, HDL: high density liproprotein, n.s.: no significant

Table 3
Safety of Mahuang and Ephedrine
Author Year Weight loss Body fat reduction Others
Liu, A. G 2013 CE: 5.9±1.2%, LCE: 6.5±1.1%, L: 1.8±0.9% (p<0.05) CE: 9.6±2.4%, LCE: 12.4±2.3%, L: 1.8±1.9% (p<0.05) reduction visceral adipose tissue
CE: 10.3±3.4% (p=0.08), LCE: 11.0±3.3% (p=0.049), L: 0.6±2.8%
Kim, Ho-Jun 2008 BMI(kg/m2): baseline, after 8 weeks (p<0.05)
Ephedra: 27.4±2.3, 25.7±2.1
evodia: 29.1±2.9, 28.0±3.2
Placebo: 27.9±2.0, 27.3±2.5
body fat(%): baseline, after 8 weeks (p<0.05)
Ephedra: 36.0±4.0, 33.7±4.0
evodia: 37.1±3.5, 36.0±3.9
Placebo: 36.1±3.3, 35.2±3.9
Total chol.(mg/dL): baseline, after 8 weeks
Ephedra (194.3±25.7, 170.1±23.9), Evodia (174.9±29.1, 176.4±34.2), Placebo (180.4±21.7, 173.7±28.7)
Triglyceride (mg/dL): baseline, after 8 weeks
Ephedra (138.3±74.1, 100.3±56.3), Evodia (130.0±76.4, 111.4±43.4), Placebo (122.9±49.2, 114.8±55.0)
Hackman, R. M. 2006 treatment group: 7.18kg
control group: 2.25kg (p<0.01)
treatment group: 5.33kg
control group: 0.99kg (p<0.01)
Total chol.(mg/dL): baseline, after 9 months
treatment (182±5.8, 174±7.1), control (197±6.6, 184±7.9)
Hioki, C. 2004 BW(kg): baseline, after 24 weeks (p<0.05)
treatment group: 90.8±17.9, 80.0±10.3
control group: 90.3±12.2, 83.4±13.4
body fat(%): baseline, after 24 weeks (p<0.05)
treatment group: 42.0±6.8, 35.8±5.7
control group: 42.1±7.4, 38.0±3.5
Total chol.(mg/dL): baseline, after 24 weeks (p<0.01)
treatment group (231.5±38.5, 197.1±33.0), control group (231.0±39.8, 190.8±19.7)
fasting glucose(mg/dL): baseline, after 24 weeks
treatment group (112.3±13.0, 103.7±4.5), control group (115.8±8.4, 108.7±9.5)
Greenway, F. L. 2004 treatment: 3.5 ± 0.6 kg, placebo: 0.8 ± 0.5kg (p<0.02) treatment: 7.9 ± 2.9%, placebo: 1.9 ± 1.1% (p<0.05) rise in RMR: 8 ± 0.1% (compared with placebo) (p<0.01)
Coffey, C. S. 2004 treatment group: 2.1±0.35kg
control group: 0.46±0.37kg (p<0.01)
treatment group: 1.13±0.40%
control group: 1.59±0.41%
decrease waist circumferences (cm)
treatment group: 2.57±0.42
control group: 0.91±0.43 (p<0.01)
Boozer, CN 2002 treatment group: 5.3±5.0kg
control group: 2.6±3.2 kg (p<0.001)
treatment group: 4.3±3.3kg
control group: 2.7±2.8kg (p=0.020)
decrease LDL-cholesterol(mg/dL)
treatment group: 8±20, control group: 0±17 (p=0.013)
increase HDL-cholesterol(mg/dl)
treatment group: 2.7±5.7, control group: −0.3±6.7 (p=0.004)
Boozer, CN 2001 treatment group: 4.0±3.4kg
control group: 0.8±2.4kg (p<0.006)
treatment group: 2.1±3.0%
control group: 0.2±2.3%
Hip circumferences (cm)
treatment group: −4.7±4.2, control group: −0.4±2.4
Serum Triglyceride(mg/dl)
treatment group: −15.7±38.3, control group: 8.5±29.2
Molnar, D. 2000 BW(kg)
CE: 7.9±6.0, PL: 0.5±4.3 (p<0.01) relative body weight (%)
CE: 14.4±10.5, PL: 2.2±5.8 (p<0.05)
BMI (kg/m2)
CE: 2.9±1., PL: 0.5±1.6 (p<0.05)
CE: 6.6±6.0 kg, PL: 0.5±2.7kg (p<0.05) n.s.
Kalman, DS 2000 treatment group: 3.14kg
control group: 2.05kg (p<0.05)
treatment group: 2.33kg
control group: 0.24kg
decrease fat free mass
treatment group: 0.92kg, control group: 3.47kg

sBP: systolic blood pressure, n.s.: no significant, dBP: diastolic blood pressure, CE: caffeine, ephedrine group, LCE: leptin+caffeine, ephedrine group, n.r.: not reported, TG: triglyceride, LDL: low density lipoprotein, chol.: cholesterol, n.s.c.: not significant change, HDL: high density lipoprotein, L: leptin only group, AST: aspartate aminotransferase, BUN: blood urea nitrogen, BP: blood pressure, HR: heart rate, EKG: electrocardiogram, FBS: fasting blood sugar, AE: adverse events, P: placebo group, H: herbal treatment group, ALT: alanine aminotransferase, WBC: white blood cell, LDH: lactate dehydrogenase, ALP: alkaline phosphatase, UA: urinary analysis, ApoA1: apolipoprotein A1

Table 4
Short Term Effect of Mahuang and Ephedrine
Author Year Duration Blood Pressure, Heart Rate Others
Vukovich, M. D. 2005 3hrs changes in 3hrs
HR increase: CE (22.7±5.5%), Placebo (8.9%±2.2%), p<0.05
sBP increase: CE (9.1±2.2%), Placebo (1.9±2.9%), p<0.05
dBP: n.s.c.
REE increase (during last 30min), p<0.05
CE (10.7±2.5%), Placebo (4.5±2.5%)
Haller, Ca 2005 5hrs HR increase (in treatment group)
maximum increase: 9.4±8.6bpm (p=0.002)
BP increase
maximum increase: sBP 11.5±10.7mmHg, dBP 7.3±7.4mmHg (p=0.015)
increase postprandial glucose, insulin concentration
maximum change: glucose (41.0±18.8mg/dl; p<0.001), insulin (41.2±47.8μIU/ml; p=0.005) decrease serum potassium concentration
maximum change: 0.28±0.23mmol/L (p=0.001)
Haller, Ca 2004 24hrs HR increase (in treatment group)
peak difference: 5.9±8.8bpm (p=0.001)
sBP increase
peak difference: 11.7±9.4mmHg (p=0.0005)
fasting glucose, insulin, free fatty acid, lactate concentrations were raised. (p≤0.01)
McBride, B.F. 2004 5hrs sBP increase
treatment group (123.5±10.98 mmHg, placebo(118.93±9.62mmHg), p=0.009
maximal QTc interval increase
treatment group(419.4±11.8ms), placebo(396.1±15.1ms), p<0.001

HR: heart rate, CE: caffeine, ephedrine group, sBP: systolic blood pressure, dBP: diastolic blood pressure, REE: resting energy expenditure, BP: blood pressure,


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