Efficacy and Safety of Mixed Oriental Herbal Medicines for Treating Human Obesity: A Systematic Review of Randomized Clinical Trials

Abstract

The objective of this systematic review was to assess the evidence from rigorous clinical trials evaluating the efficacy of mixed herbal medicine formulations used in traditional Oriental medicines for the treatment of obesity and to describe the safety and types of adverse events reported in such trials. To accomplish this, 14 databases were searched from inception to July 31, 2009. The search terms used were “obesity” or “obese” and “herb,” “herbal,” or “herbal medicine” without language restriction. All randomized clinical trials using mixed herbal medicines on obese or overweight subjects were considered for inclusion. Of the publications in the identified databases, 1144 results were searched and reviewed, and in total 12 studies were included. Their methodological quality was assessed using the Jadad score. The results of our review provide evidence suggesting that mixed Oriental herbal medicines may be safe and effective for the treatment of obesity when compared with conventional medicine, placebos, or lifestyle control. Many trials also reported improved concomitant conditions including impaired glucose tolerance, hypertension, and inflammation. Small numbers of adverse events were reported, but most were mild or not related to the intervention in itself. No significant mortality was observed in any of the trials. However, the evidence provided by the trials reviewed is not fully convincing because of their poor methodological quality. Therefore, more research and well-designed clinical trials are necessary to address these issues, as well as to assess the safety of mixed Oriental herbal medicines used to treat obesity.

Introduction

T he prevalence of obesity is increasing at an alarming rate, and obesity has become one of the most important avoidable risk factors for morbidity and mortality.¹ Standard treatment options for obesity include reducing caloric intake and increasing energy expenditure; however, such methods are often accompanied by an adaptive decrease in metabolic rate, making further body weight loss or maintenance difficult.² Additionally, although pharmacologic treatment and surgical interventions are occasionally used, these methods are not always appropriate. For example, sibutramine has been found to induce common adverse events, including dry mouth, insomnia, anorexia, and constipation, in 10–20% of users,³ while orlistat has side effects that include gastrointestinal problems, fecal urgency, oily spotting, and fatty stools in 10–30% of users.⁴ These considerations and the notoriously poor compliance of individuals to conventional weight management programs emphasize the importance of effective, safe, and acceptable therapeutic options for obesity.⁵

Accordingly, there is a tendency for individuals to use complementary and alternative medicine for the treatment of obesity. Herbal medicine is one of the most widely used therapies for the treatment of obesity among current modalities of complementary and alternative medicine. The growing popularity of these remedies is fueled by increasing scientific interest in herbal medicines.⁶ However, there are still conflicting opinions regarding the efficacy of such treatments because of the lack of evidence of their effectiveness and safety. Herbal supplements are marketed as food supplements in many countries and are therefore subject to less stringent control than drugs. In the United States, some herbal weight loss supplements have been tested for effectiveness in clinical trials, but there is little evidence available for most supplements on the market.⁷ Additionally, the use of some herbal supplements containing ephedrine has been controversial because of the possibility of adverse events.⁸ For these reasons, there is a need to evaluate scientific evidence regarding the effectiveness of herbal medicines using rigorous clinical trials.

Herbal medicines are generally used as a mixture of various herbs based on traditional Oriental medical theory, which usually does not prescribe a single herb for the patients. The effects of mixed herbal medicines are influenced by the interaction of various herbs.⁹ More specifically, in a mixed herbal formulation, the component herbs produce synergistic beneficial effects, while the adverse side effects of any individual component are attenuated by the others. Therefore, it is conceivable that the mode of action of a formulation of mixed herbal medicines is complex in nature, and the therapeutic efficacy of the formulation is not simply the sum of the effects of the individual component herbs. Accordingly, the clinical trials that were conducted to evaluate the treatment effects of mixed Oriental herbal medicines were evaluated in this study rather than the effects of single herbs.

The goal of this systematic review was to assess the evidence produced by rigorous randomized clinical trials (RCTs) conducted to evaluate the effectiveness of Oriental herbal medicines for obesity. In addition, the safety and types of adverse events reported in clinical trials are discussed, and future studies regarding the present subject are suggested.

Subjects and Methods

Data sources

The following databases were searched from inception to July 31, 2009: National Library of Medicine Medline (PubMed), EMBASE, Science Direct, the Cochrane Library, EBSCOhost, one Japanese database (CiNii [Scholarly and Academic Information Navigator]), one Chinese database (CAJ [China Academic Journal]), four Korean databases (DBPIA, National Assembly Library, Research Information Service System, and Korean Studies Information Service System), and four Korean medical journals relevant to obesity (Journal of Oriental Medicine, Journal of Oriental Physiology and Pathology, Journal of Oriental Rehabilitation Medicine, and Journal of Korean Oriental Association for Study of Obesity). The search terms used were “herb,” “herbal,” or “herbal medicine” and “obesity” or “obese.”

Study selection

RCTs were searched to assess the efficacy of mixed herbal medicines in traditional Oriental medicines for the treatment of obesity in human subjects. A study that stated the phrase “randomization” in its text was regarded as a randomized trial. Trials using mixed herbal medicines that were based on traditional Oriental medicine theory were included. Participants clearly defined as overweight or obese at baseline were included. Overweight or obesity definitions were either body mass index (BMI) cutoff points (≥25 kg/m²) or obesity degree cutoff points (≥110%).¹⁰ Trials comparing herbal medicines with any type of control interventions were included, and the primary outcome measures were BMI, body weight, body fat percentage, and waist or hip circumference.

Studies utilizing herbal treatments that did not comply with Oriental medical theory were not included in this review. Accordingly, we excluded trials in which only a single herb or dietary supplement was used for treatment intervention. Trials that compared different forms of herbal medicines with each other or did not use a herbal medicine for the main treatment intervention were also excluded. In addition, trials with incorrect descriptions of herbal prescriptions or unavailable statistical analysis were excluded. No language restrictions were imposed, and only publications with available abstracts were reviewed. The search process is further detailed in Figure 1.

FIG. 1.

Flowchart of trials excluded versus selected for systematic review.

Results

Study description

An initial search identified 1144 potentially relevant articles, of which 12 met our inclusion criteria. Key data regarding the included RCTs are summarized in Table 1. All 12 RCTs were parallel two-arm design. Types of interventions considered in this review included herbal medicines, herbal medicines plus lifestyle control (such as dietary or exercise interventions), herbal medicines plus conventional medicines, and herbal medicines plus acupuncture treatment. The use of herbal medicines as the only intervention was used in six trials, and adjuvant interventions were used in six trials. Regarding types of control groups, a placebo procedure was used in five trials, conventional medicines were included in five trials, other treatments (e.g., acupuncture treatment) were used in one trial, and lifestyle control was used in one trial.

Table 1.

Descriptive Data of Randomized Clinical Trials

Reference (year)	Numbers of patients randomized/analyzed	Type of design; blinding	Jadad score	Intervention type (regimen)	Control intervention (regimen)	Treatment period	Control of lifestyle factors	Main outcome measure	Result (intergroup)	Main conclusion	Adverse events
Ignjatovic et al.¹¹ (2000)	140/140	Parallel; open	1	Slimax: Hordeum vulgare, Polygonatum multiflorum, Dimocarpus longan, Ligusticum sinense, Lilium brownie, Zingiber officinale	Placebo	6 weeks	Maintain dietary habits or level of physical activity	1. Body weight 2. BMI 3. Adipose tissue 4. Glycerol release	1. NS 2. NS 3. P<.05 4. P<.05	Slimax provides an effective means for treatment of human obesity, acting via direct modification of lipid metabolism
Pan et al. ¹² (2005)	82/82	Parallel; DB	4	Combination of node of lotus rhizome, green tea, and Panax notoginseng	Placebo	7 weeks	Maintain dietary habits or level of physical activity	1. Body weight2. Body fat (%)3. Fat mass4. BMI5. WC6. HC	P<.01	Herbal medicines significantly reduced body weight and fat in obese adults	Irritability, nausea in both groups; constipation in the control group
He et al.¹³ (2007)	45/45	Parallel; open	1	Yiqi-sanju-formula: radix linderae, radix astragali, rhizoma coptidis, rhizoma alismatis, typhae pollen	Placebo	10 weeks	NR	1. BMI2. WC, WHR3. HOMA-IR4. CRP5. FFA6. PAI-17. t-PA	1. P<.012. P<.013. P<.014. P<.015. P<.056. P<.057. P<.01	Yiqi-sanju-formula can reduce obesity and insulin resistance in central obese men at high risk of metabolic syndrome and improve inflammation and the fibrinolysis index	Vomiting
Hioki et al.¹⁴ (2004)	81/78	Parallel; DB	4	Bofu-tsusho-san: herba ephedrae, radix glycyrrhizae, fructus forsythiae, spica schizonepetae, fructus gardeniae, radix paeoniae, Cnidium rhizome, radix angelicae, herba menthae, radix ledebouriellae, Zingiberis rhizome, talcum, natrium sulfuricum	Placebo	24 weeks	1. Low calorie diet(1200 kcal/day)2. Exercise regimen (300 kcal/day)	1. AVF2. WC3. Body weight4. RMR	1. P<.012. P<.053. NR4. NR	The Bofu-tsusho-san group lost significantly more body weight (P<.01) and abdominal visceral fat without a decrease in the RMR, whereas the placebo group lost body weight (P<.05) and had no significant change in abdominal visceral fat	Diarrhea
Greenway et al.¹⁵ (2006)	24/24	Parallel; open	1	Number Ten (NT): radix et rhizome rhei, radix astrgalia, radix salviae miltriorrhizae, rhizoma curcumae longae, rhizoma Zingiberis officinalis	Placebo	11 weeks	Low calorie diet (700 kcal/day)	1. Body weight2. BMI	NS	NT does not have potential as a herbal supplement in humans because of gastrointestinal toxicity below the dose required for effective for weight loss	Diarrhea (67%), gastrointestinal, musculoskeletal, headache, oral, respiratory, dermatologic, gynecologic problems
Shi et al.¹⁶ (2006)	62/62	Parallel; open	1	Fufang-cangzhu-tang: rhizoma atractylodis, semen coicis, fructus mori, rhizoma dioscoreae, cortex phellodendri, semen litchi, Lumbricus	Conventional medicine	8 weeks	NR	1. Body weight2. Glucose tolerance3. TC, TG4. WHR	NS^a	The Fufang-cangzhu-tang group showed improved body weight, WC, HC, WHR, glucose tolerance, fasting serum insulin, and blood lipid profile equivalent to the conventional medicine group
Xie¹⁷ (2008)	80/80	Parallel; open	1	Qingshenjianzhi-yin: herba artemisiae capillaris, rhizoma atractylodis, radix polygoni cuspidati, semen cassiae, rhizoma rhei, rhizoma alismatis, radix salviae miltiorrhizae, rhizoma polygonati, fructus crataegi, typhae pollen, radix polygoni multiflori, fructus lycii	Conventional medicine	8 weeks	NR	1. Body weight2. TC, LDL-C3. Blood glucose	1. NS^a 2. P<.013. P<.01	The Qingshenjianzhi-yin group showed an improvement in obesity similar to the conventional medicine group as well as positive effects on the lipid profile	Diarrhea, abdominal discomfort
Wang¹⁸ (2006)	156/156	Parallel; open	1	Zinijianzhi formula: rhizoma rhei, fructus gardeniae, fructus aurantii immaturus, radix astragali, radix angelicae gigantis, atractylodis rhizoma alba, radix et rhizoma glycyrrhizae	Conventional medicine	3 months	NR	Body weight	P<.01	Zinijianzhi formula significantly reduced body weight and showed fewer adverse events than conventional medicine	Gastrointestinal problems, diarrhea
Ceng et al.¹⁹ (2006)	74/74	Parallel; open	1	Medicated diet with herbs (radix astragali, rhizoma dioscoreae, radix adenophorae, hoelen, radix puerariae) versus conventional medicine	Conventional medicine	2 months	None	1. BMI2. TC, TG, LDL-C3. Blood glucose	1. P<.012. P<.013. NS	Obese people with IGT taking TCM herbal formula plus conventional medicine showed significantly improved obesity and lipid profiles compared with individuals taking conventional medicine only
Wang et al. ²⁰ (2006)	60/60	Parallel; open	1	Pinggan-yishen-ditan-yin (rhizoma gastrodiae, ramulus et uncus uncariae, rhizoma alismatis, radix cyathulae, atractylodis rhizoma alba, sargassum, semen cassiae, herba visci et ramulus loranthi, Lumbricus, spica prunellae, pinelliae tuber) versus conventional medicine	Conventional medicine	8 weeks	Moderate exercise	1. BMI2. WHR3. Blood glucose4. TC5. TG6. LDL-C7. BP	1. NS2. NS3. P<.014. P<.015. NS6. P<.017. P<.01	Treatment of obese hypertensive patients with herbal medicine can improve BP, blood glucose, and lipid metabolism
Wei et al.²¹ (2008)	60/60	Parallel; open	1	Feikexiao-prescription: herba epimedii, radix astragali, fructus lycii, fructus crataegi, radix salviae miltiorrhizae, pericarpium citri unshii, rhizoma rhei	None	12 weeks	Dietary control and exercise	Body weight	P<.05	Feikexiao-prescription can effectively treat simple obesity in elderly individuals
Zhang et al.²² (2006)	96/96	Parallel; open	1	Medicated diet with spleen-invigorating and phlegm-removing herbs (caulis et rhizoma sinomenii, radix astragali, atractylodis rhizoma alba, hoelen), Acu-Tx, catgut embedment	Acu-Tx, catgut embedment	1 month	Dietary control	1. Body weight2. BMI3. Lipid profiles	P<.05	Medicated diet with spleen-invigorating and phlegm-removing herbs has a synergistic effect with acupuncture for simple obesity and has no obvious side effects

Showed positive effects similar to those observed in response to treatment with Western medicine.

Acu-Tx, acupuncture treatment; ASF, abdominal subcutaneous fat; AVF, abdominal visceral fat; BP, blood pressure; BMI, body mass index; CRP, C-reactive protein; DB, double-blind; FFA, free fat acid; HC, hip circumference; HOMA-IR, homeostasis model assessment of insulin resistance; IGT, impaired glucose tolerance; LDL-C, low density lipoprotein-cholesterol; NR, not reported; NS, not significant; PAI-1, plasminogen activator inhibitor-1; RMR, resting metabolic rate; t-PA, tissue plasminogen activator; TC, total cholesterol; TCM, traditional Chinese medicine; TG, triglycerides; WC, waist circumference; WHR, waist–hip ratio.

Study quality

Methodological quality was evaluated using the Jadad scoring system, and the highest possible score was 5 points. Trials with more than 3 points were considered to be of high quality.²³ The methodological quality of the trials was generally low. The average Jadad score was 1.5, and the range was from 1 to 4. Only two^12,14 of the 12 RCTs exhibited a Jadad score greater than 3. Only two trials^12,14 described the appropriate methods of randomization and double blinding. Sufficient details regarding dropouts and withdrawals were only given in two trials.^12,14 The average sample size was 74.8, and the range was from 24 to 156. We also considered whether a description of the ethical approval procedure was included and informed consent was obtained from the participants. Ethical approval procedures were mentioned in only two trials,^14,15 and informed consent was only obtained in five trials.^{11,12,14,15,20}

Outcomes

Herbal medicines versus placebo

All of the three trials^11
–13 in which the effects of herbal medicines for maintaining dietary habits or physical activity were compared with a placebo reported improved outcomes for obesity. The most rigorous trial¹² reported that the herbal medicine–only group showed significant improvement in indicators of obesity (body weight, body fat, BMI, etc.) when compared with a placebo group (P<.01).

Herbal medicines plus lifestyle control versus placebo plus lifestyle control

Two trials^14,15 compared the effectiveness of herbal medicines plus lifestyle controls such as dietary control or enhanced moderate exercise with the effects of placebo plus lifestyle control for obesity. One trial¹⁴ reported that visceral fat area reduction was significantly greater in the herbal medicines plus lifestyle control group than in the placebo plus life style group (P<.01). In addition, the adjusted resting metabolic rate in the herbal medicines group was not decreased, whereas that in the placebo group showed a mild decrease. Body weight and body fat reduction in the herbal medicines group was greater after treatment (P<.01) compared with baseline than what occurred in the placebo group (P<.05). However, the differences between groups were not available in the article. The other trial¹⁵ found no significant differences in body weight reduction or BMI between groups.

Herbal medicines versus conventional medicine

Three trials^16
–18 compared the effectiveness of herbal medicines with conventional medicines used as standard pharmacological treatments for obesity. One trial¹⁸ reported significant body weight reductions for the herbal medicines group compared with the conventional medicine group (P<.01). The other two trials^16,17 reported that the herbal medicines group showed an improvement in obesity similar to that of the conventional medicine groups. Additionally, one trial¹⁹ reported that the improvement in BMI and lipid metabolism was significantly greater in an herbal medicine plus conventional medicine group compared with a group that received conventional medicine alone (P<.01). Furthermore, one trial²⁰ showed an improvement in blood pressure, blood glucose, and lipid metabolism in a group that received herbal medicines plus conventional medicines and moderate exercise compared with a group that received conventional medicines plus moderate exercise (P<.01). However, there was no significant difference in terms of BMI between groups in that study.

Herbal medicines versus lifestyle control

One trial²¹ compared herbal medicines with lifestyle controls such as diet and exercise and found that the group that received herbal medicines showed a significant reduction in body weight compared with the control group (P<.05).

Herbal medicines plus acupuncture treatment versus acupuncture treatment alone

One trial²² reported that improvements in body weight and lipid profile were significantly greater in a group that received herbal medicines plus acupuncture and catgut embedment compared with a group that received acupuncture and embedment alone (P<.05).

Overall, the trials conducted to compare herbal medicines with other interventions revealed that there was greater improvement in BMI or body weight in groups that received herbal medicines than in the various control groups, except for two trials.^15,20 Although no significant reductions in BMI or body weight were observed in the trial by Wang et al.,²⁰ the trial concluded that herbal medicines improved hypertension, blood glucose, and lipid metabolism.

Adverse events and safety

Six RCTs^{12

–15,17,18} reported adverse events. Pan et al.¹² reported irritability and nausea in the treatment group; however, it did not appear to be related to the treatment. In addition, He et al.¹³ reported vomiting in the treatment group, but the symptoms were not serious enough to discontinue the treatment. Hioki et al.¹⁴ reported withdrawal due to the occurrence of loose stool, while improvement of constipation was also observed in the treatment group. Greenway et al.¹⁵ also reported dose-related incidence of loose stools and other symptoms in the treatment group compared with the placebo group; therefore, they concluded that herbal medicines would not be an effective mode of treatment because of the possibility of causing gastrointestinal toxicity. Xie¹⁷ reported diarrhea and abdominal discomfort in the treatment group, but dry mouth, loss of appetite, constipation, headache, and insomnia were observed in the control group. Wang¹⁸ reported a significantly higher incidence of gastrointestinal problems and diarrhea in the treatment group than the control group (P<.01). Most of the reported adverse events appeared to be mild, except in the trial conducted to evaluate NT,¹⁵ which caused adverse events that appeared to be related to the intervention, and in a trial conducted to evaluate Bofutsushosan,¹⁴ which indicated that it caused loose bowel movements.

Five RCTs^{12,14,15,18,20} assessed the effects of herbal medicine on the cardiovascular system and toxicity on renal and liver organs. However, significant changes were not observed after taking the herbal medicine. Despite this, Hioki et al.¹⁴ reported improvements in blood pressure and urine analysis in the treatment group, and Wang et al.²⁰ reported improvement in blood pressure in the treatment group compared with the control group.

Discussion

To the best of our knowledge, this is the first systematic review of RCTs of mixed Oriental herbal medicines for the treatment of obesity. There was no restriction in terms of publication languages; therefore, the authors consider the present search strategy to have minimized bias. Recently, another similar systematic review that assessed the efficacy and safety of herbal medicines for obesity was published. The results of that study indicated that compounds containing Ephedra, Cissus quadrangularis, Ginseng, bitter melon, and Zingiber were found to be effective in the management of obesity.²⁴ That review included all human and animal studies conducted using all types of herbs and plant supplements, whereas our review was limited to RCTs that evaluated humans treated with mixed Oriental herbal medicines.

This systematic review provides evidence suggestive of the effectiveness of herbal medicines for treating obesity. Statistically significant reductions in BMI or body weight were reported in 83% of the included trials. However, the methodological limitations of the searched trials and the degree of evidence did not allow us to definitively conclude that herbal medicines improve obesity.

In this study, the standard Jadad scale was used to assess important criteria of methodological quality; however, many trials were of poor quality. Specifically, 83% of the trials (10 of 12 RCTs) scored 1 on the Jadad scale, and no RCTs achieved a full score of 5. In addition, most of the included trials lacked adequate allocation concealment. Such trials are likely to show exaggerated treatment effects. Additionally, only two^11,12 of the five trials evaluated in this study that used a placebo stated that they made the placebo drugs difficult to distinguish from the treatment medicine by adjusting the color or smell; therefore, it was difficult to assess the success of the blinding in the rest of the studies. Because each herb has its own color and smell, indistinguishable placebo medication should be made to ensure appropriate blinding.

Low-quality trials are more likely to overestimate the effects;²⁵ however, in our review, 80% of the low-quality RCTs generated positive results, whereas 100% of the high-quality trials generated positive results. Additionally, it is important to focus on both the methodological quality and the importance of ethical considerations in clinical trials. Ethical approval was reported in only two trials,^14,15 and informed consent was given in only five trials.^{11,12,14,15,20} Considering the importance of protecting participants' rights, researchers should be aware of ethical issues.

Although six trials^16

–22 stated the rationale for the selection of herbal medicines, they did not address concrete diagnostic criteria, which might causes difficulties in diagnosis. Oriental medicine uses unique diagnostic tools that are based on the constitution or individuality of the patient rather than uniformity; therefore, clinicians should conduct trials based on clear diagnosis in future studies. However, standardization of diagnostic criteria for obesity has to be elucidated by further studies before this can be accomplished.

Small numbers of adverse events, primarily gastrointestinal irritation, were reported, and the vast majority of adverse events were mild or not related to the intervention. However, one trial¹⁵ concluded that herbal medicines were not appropriate for treatment because of the possibility of adverse events such as diarrhea, even though the researchers used herbal medicines known to be effective in animal models without serious adverse events. This indicates that the results of clinical trials for humans might differ from those of animal studies; therefore, adverse events and safety should be checked through clinical trials conducted in human trials.

Five trials^{12,14,15,18,20} assessed the safety of herbal medicines on the cardiovascular system and their toxicity on kidney and liver. The results of these trials found no significant changes after treatment with herbal medicines. However, in the other seven trials^{11,13,16,17,19,21,22} there were no attempts to assess the safety of the compounds being tested; therefore, no definitive conclusion regarding safety could be made.

This study has some limitations. First, we attempted to identify all RCTs assessing the efficacy of mixed herbal Oriental medicines for the treatment of obesity, but the potential incompleteness of the citation tracking may have led to some relevant RCTs being overlooked. Additionally, many of the identified trials were of low quality and had methodological shortcomings such as there were no sample size estimations and an inadequate level of blinding, which may have influenced the results of our review. Moreover, most of the studies that have been conducted to date have been of short duration, varying from 4 to 24 weeks. Considering that obesity is a chronic condition, it is recommended that trials evaluate longer periods of treatment. Finally, because the occurrence of obesity may vary without treatments, a longer follow-up period with serial measurements of outcomes is suggested to determine the genuine effects of the herbal medicine being tested, as well as its long-term efficacy.

In conclusion, the present review provides suggestive evidence of the effectiveness of mixed herbal medicines in traditional Oriental medicines for treating obesity when compared with conventional medicines, placebos, or lifestyle control. Many trials have also reported an improvement in concomitant conditions such as impaired glucose tolerance, hypertension, lipid profiles, and inflammatory status. However, the results are of limited value because of the poor methodological quality of the included studies, which prevents us from drawing a definitive conclusion regarding the effectiveness of mixed herbal medicines. More research and well-designed clinical trials are necessary to address these issues and to assess the safety and adverse events associated with herbal medicines. Such trials should be randomized adequately, double-blinded, and controlled for placebo effects. In addition, future trials should adhere to rigorous trial designs that are suitable for the treatment of obesity based on Oriental medicine diagnosis.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

References

Report of a WHO consultation. Obesity: preventing and managing the global epidemic. World Health Organ Tech Rep Ser, 2000; 894:1–253.

Leibel

, Rosenbaum

, Hirsch

. Changes in energy expenditure resulting from altered body weight. N Engl J Med, 1995; 332:621–628.

Bray

, Blackburn

, Ferguson

, Greenway

, Jain

, Mendel

, Mendels

, Ryan

, Schwartz

, Scheinbaum

, Seaton

. Sibutramine produces dose-related weight loss. Int J Obes Relat Metab Disord, 1999; 7:189–198.

Davidson

, Hauptman

, DiGirolamo

, Foreyt

, Halsted

, Heber

, Heimburger

, Lucas

, Robbins

, Chung

, Heymsfield

. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA, 1999; 281:235–242.

Pittler

, Schmidt

. Adverse events of herbal food supplements for body weight reduction: systematic review. IASO Obes Rev, 2005; 6:93–111.

Aschwanden

. Herbs for health, but how safe are they? Bull World Health Organ, 2001; 79:691–692.

Pittler

, Ernst

. Systematic review: dietary supplements for reducing body weight. Am J Clin Nutr, 2004; 79:529–536.

Shekelle

, Hardy

, Morton

, Maglione

, Mojica

, Suttorp

, Rhoeds

. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA, 2003; 289:1537–1545.

Kim

. Metabolism of herbal medicines by human intestinal bacteria and their relation to biological activities. Int Symp East West Med, 1999; 1:76–81.

10.

Kasper

, Braunwald

, Hauser

, Longo

, Jameson

, Fauci

. Harrison's Principles of Internal Medicine, 16 ^th. MHP Publishing Co.: Seoul, 2004; 456.

11.

Ignjatovic

, Ogru

, Heffernan

, Libinaki

, Lim

, Ng

. Studies on the use of “Slimax,” a Chinese herbal mixture, in the treatment of human obesity. Pharm Biol, 2000; 38:30–35.

12.

Pan

, Li

, Lei

, Zhang

, Zhou

. Preparation-containing node of Lotus Rhizome, green tea and Panax notoginseng for obese adults. Chin J Clin Rehabil, 2005; 9:231–233.

13.

, Wang

, Li

, Xu

, Chen

, Ying

, He

. Clinical research of Yiqi Sanju Formula in treating central obese men at high risk of metabolic syndrome. J Chin Integr Med, 2007; 5:263–267. (In Chinese.)

14.

Hioki

, Yoshimoto

, Yoshida

. Efficacy of bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women with impaired glucose tolerance. Clin Exp Pharmacol Physiol, 2004; 31:614–619. (In Chinese.)

15.

Greenway

, Liu

, Martin

, Kai-yuan

, Nofziger

, Rood

, Yu

, Amen

. Safety and efficacy of NT, an herbal supplement, in treating human obesity. Int J Obes, 2006; 30:1737–1741.

16.

Shi

, Hu

, Wang

. Fufang cangzhu tang for treatment of senile obesity or overweight complicated with impaired glucose tolerance—a clinical observation in 32 cases. J Tradit Chin Med, 2006; 26:33–35.

17.

Xie

. Clinical research of Qing shen ji zhi-yin in treating simple obesity. Clin J Tradit Chin Med, 2008; 20:301–303. (In Chinese.)

18.

Wang

. Clinical research of Zi ni jian shi-pang in treating 80 cases of simple obesity. J Sichuan Tradit Chin Med, 2006; 24:69. (In Chinese.)

19.

Ceng

, Jing

, Long

. Efficacy of traditional Chinese medicine on blood glucose and lipid metabolism in obese type 2 diabetic subjects. J Guangxi Med, 2006; 2:199–201. (In Chinese.)

20.

Wang

, Yang

, Cheng

. Improvements of Pinggan Yishen Ditan Yin in blood pressure, body weight and quality of life in patients with obesity hypertension. Chin J Clin Rehabil, 2006; 10:24–26. (In Chinese.)

21.

Wei

, Hao

, Huang

, Li

. Clinical research on Feikexiao Prescription for treatment of simple obesity in old persons. Pract Clin J Integr Tradit Chin West Med, 2008; 8:6–7. (In Chinese.)

22.

Zhang

, Dong

, Tao

. Clinical observation on medicated diet with spleen-invigorating and phlegm-removing herbs for simple obesity. J Guangzhou Univ Tradit Chin Med, 2006; 23:209–211. (In Chinese.)

23.

Jadad

, Moore

, Carroll

, Jenkinson

, Reynolds

, Gavaghan

, McQuay

. Assessing the quality of reports of randomized controlled trial: is blinding necessary? Control Clin Trials, 1996; 17:1–12.

24.

Shirin

, Neda

, Bagher

. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol, 2009; 15:3073–3085.

25.

Schulz

, Chalmers

, Hayer

, Altman

. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA, 1995; 273:408–412.