Review on the Efficacy and Safety of Mahuang and Ephedrine in the Treatment of Obesity -Focused on RCT-

Article information

J Korean Med. 2017;38(3):170-184

Publication date (electronic) : 2017 September 30

doi : https://doi.org/10.13048/jkm.17034

Ga-Won Jo ¹^,, Ji-Myung Ok ¹, Seo-Young Kim ¹, Young-Woo Lim ¹

¹Nubebe Korean Medical Clinic

Correspondence to：조가원(Ga-Won Jo) 서울특별시 강남구 선릉로 515 동인빌딩 3층 누베베 한의원 Tel：+82-2-2652-3601, Fax：+82-2-3288-3700, E-mail : jogawon@naver.com

Received 2017 September 5; Revised 2017 September 15; Accepted 2017 September 18.

Abstract

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords: Mahuang; ephedrine; efficacy; safety; obesity; weight loss

Fig. 1

Flow chart of the trial selection process

Table 1

Summary of Randomized Controlled Studies

Table 2

Efficacy of Mahuang and Ephedrine for Weight Loss

Table 3

Safety of Mahuang and Ephedrine

Table 4

Short Term Effect of Mahuang and Ephedrine

References

1. World Health Organization. Reducing Risks -Promoting healthy life. World Health Report 2002 Geneva: WHO; 2002.

2. Ministry of Health and Welfare. Korea Centers for Disease Control and Prevention. Korea Health Statistics 2014 Korea National Health and Nutrition Examination Survey (KNHANES VI-2).

3. Kopelman P. Health risks associated with overweight and obesity. Obesity Reviews 2007;8(1):13–17.

4. Kopelman PG. Obesity as a medical problem. Nature 2000;404(6778):635–643.

5. Lee KW. Correct Obesity Drug Therapy. Korean Journal of International Medicine 2009;77(4):971–976.

6. Lee TH. Treatment of Obesity. Korean Journal of Medicine 2001;61(3):227–233.

7. Song YK, Lim HH. Clinical Application of Ma Huang in the Obesity Treatment. Journal of Society of Korean Medicine for Obesity Research 2007;7(1):1–7.

8. Hwang MJ, Shin HD, Song MY. Literature review of herbal medicines on treatment of obesity since 2000-Mainly about Ephedra herba. Journal of Society of Korean Medicine for Obesity Research 2007;7(1):39–54.

9. Jeong JW, Cho SW. Trend research of the human body-Oriented obesity studies on Korean medicine. Journal of Korean Medicine Rehabilitation 2016;26(1):49–61.

10. Lim SY, Park SW, Joo JH, Kim SR, Kim DJ, Choi WS. The effects of Taeeumjowui-tang (Taiyintiaowei-tang) on obesity in sasang constitution. The Journal of East-West Medicine 2012;37(4):109–116.

11. Professors of formula study of Korean Medicine School. Clinical Traditional Herbalogy Seoul: Yeong-lim Press; 2016. p. 236.

12. Andraws R, Chawla P, Brown DL. Cardiovascular effects of ephedra alkaloids: a comprehensive review. Progress in Cardiovascular Diseases 2005;47(4):217–25.

13. Lee MK, Cheng BW, Che CT, Hsieh DP. Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. Toxicol Sci 2000;56(2):424–30.

14. Jang IS, Hwang EH. The Need for Clinical Practice Guidelines in Usage of Mahuang in Weight Loss. Journal of Society of Korean Medicine for Obesity Research 2007;(1):23–29.

15. Department of Health and Human Services, Agency for Healthcare Research and Quality, Shekelle P, Hardy ML, Morton SC, Maglione M, Suttorp M, et al. Ephedra and ephedrine for weight loss and athletic performance enhancement. Clinical efficacy and side effects Available at: URL:http://www.fda.gov/OHRMS/DOCKETS/98fr/95n-0304-bkg0003-ref-07-01-index.htm . Accessed June, 2007.

16. Kim HJ, Han CH, Lee EJ, Song YK, Shin BC, Kim YK. A clinical practice guideline for Ma-huang(Ephedra sinica) prescription in obesity. Journal of Society of Korean Medicine for Obesity Research 2007;7(2):27–37.

17. Liu AG, Smith SR, Fujioka K, Greenway FL. The effect of leptin, caffeine/ephedrine, and their combination upon visceral fat mass and weight loss. Obesity 2013;21(10):1991–1996.

18. Kim HJ, Park JM, Kim JA, Ko BP. Effect of Herbal Ephedra sinica and Evodia rutaecarpa on Body Composition and Resting Metabolic Rate: A Randomized, Double-blind Clinical Trial in Korean Premenopausal Women. Journal of Acupuncture and Meridian Studies 2008;1(2):128–138.

19. Hackman RM, Havel PJ, Schwartz JH, Rutledge JC, Watnik MR, Nocite EM, et al. Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: A randomized controlled trial. International Journal of Obesity 2006;30(10):1545–1556.

20. Vukovich MD, Schoorman R, Heilman C, Jacob P, Benowitz NL. Caffeine-herbal ephedra combination increases resting energy expenditure, heart rate and blood pressure. Clinical and Experimental Pharmacology and Physiology 2005;32(1–2):47–53.

21. Haller CA, Jacob P, Benowitz NL. Short-term metabolic and hemodynamic effects of ephedra and guarana combinations. Clinical pharmacology and therapeutics 2005;77(6):560–71.

22. McBride BF, Karapanos AK, Krudysz A, Kluger J, Coleman CI, White CM. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. Journal of American Medical Association 2004;291(2):216–21.

23. Hioki C, Yoshimoto K, Yoshida T. Efficacy of bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women with impaired glucose tolerance. Clinical and experimental pharmacology & physiology 2004;31(9):614–9.

24. Haller CA, Jacob P, Benowitz NL. Enhanced stimulant and metabolic effects of combined ephedrine and caffeine. Clinical pharmacology and therapeutics 2004;75(4):259–73.

25. Greenway FL, Jonge L, Blanchard D, Frisard M, Smith SR. Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition. Obesity Research 2004;12(7):1152–1157.

26. Coffey CS, Steiner D, Baker BA, Allison DB. A randomized double-blind placebo-controlled clinical trial of a product containing ephedrine, caffeine, and other ingredients from herbal sources for treatment of overweight and obesity in the absence of lifestyle treatment. International Journal of Obesity 2004;28(11):1411–1419.

27. Kalman D, Incledon T, Gaunaurd I, Schwartz H, Krieger D. An acute clinical trial evaluating the cardiovascular effects of an herbal ephedra-caffeine weight loss product in healthy overweight adults. International journal of obesity and related metabolic disorders. journal of the International Association for the Study of Obesity 2002;26:363–1366.

28. Boozer CN, Daly PA, Homel P, Solomon JL, Blanchard D, Nasser JA, et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. International journal of obesity and related metabolic disorders. journal of the International Association for the Study of Obesity 2002;26(5):593–604.

29. Zaragoza RM, Lonngi G, Ortiz RA, Huerta DR. Comparison of two formulations of d-norpseudoephedrine and placebo in obese patients treated during six months. Medicina Interna de Mexico 2001;17(6):260–71.

30. Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen G, Solomon JL. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. International journal of obesity and related metabolic disorders. journal of the International Association for the Study of Obesity 2001;25(3):316–24.

31. Molnar D, Torok K, Erhardt E, Jeges S. Safety and efficacy of treatment with an ephedrine/ caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. International journal of obesity and related metabolic disorders. journal of the International Association for the Study of Obesity 2000;24(12):1573–8.

32. Kalman DS, Colker CM, Shi Q, Swain MA. Effects of a weight-loss aid in healthy overweight adults: Double-blind, placebo-controlled clinical trial. Current Therapeutic Research - Clinical and Experimental 2000;61(4):199–205.

33. Jang IS, Yang CS, Hwang EH. The need for clinical practice guidelines in usage of Mahuang in weight loss. Journal of Society of Korean Medicine for Obesity Research 2007;7(1):23–29.

Article information Continued

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	CE: caffeine 200mg, ephedrine 20mg orally tid, placebo subcutaneously daily(qd) L: leptin A-200 20mg subQ qd, 2 placebo pills tid 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	ephedra extract in capsules (pseudo-ephedrine 31.52mg) 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	Ephedra + guarana (20mg ephedrine, 83.3mg caffeine) 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	25mg ephedrine 200mg caffeine 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 BMI≥30kg/m₂ 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 29≤BMI≤35 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,