Obesity is a common metabolic disorder in developed and developing countries [
Current management of obesity by pharmacotherapy includes noncentrally acting antiobesity agents such as Orlistat (Xenical), which inhibits the action of the intestinal lipase enzymes and hence blocks the absorption of fat in the intestines. The most common adverse events of Orlistat include oily faecal spotting, abdominal pain, and flatus with discharge, faecal urgency, fatty/oily stool, increased defecation, and faecal incontinence [
Another pharmacotherapy is the centrally acting antiobesity agent, namely, Sibutramine (Reductil), which produces unwanted side effects such as trouble sleeping, constipation, and dry mouth as well as increased heartbeat, increased blood pressure, awareness of the heartbeat (palpitations), headache, anxiety, or dizziness [
Surgical procedures such as gastric bypass operations are generally reserved for people with morbid obesity (BMI > 40) who instituted but failed an adequate exercise and diet program (with or without adjunctive drug therapy) or patients presenting with comorbid conditions such as hypertension, impaired glucose tolerance, diabetes mellitus, hyperlipidaemia, and obstructive sleep apnoea [
Chinese herbal medicine has been used for weight management both in China and in western countries [
In 2004, Hioki et al. demonstrated the effectiveness and safety of a traditional Chinese formula (Bofutsusho-san) in obese Japanese women with impaired glucose tolerance. Findings from this study revealed significant improvement in both treatment and placebo groups compared to baseline. However, waist and hip circumference measurements of subjects in the Bofutsusho-san treatment group were also significantly improved compared to that of the control group [
A number of animal studies support the use of Chinese herbal medicine formulas for treating obesity and have shown other beneficial effects. For example, the Bofutsusho-san formula has been shown to prevent intimal thickening and vascular smooth muscle cell proliferation in rats [
Until recently, widely used herbal supplements for weight loss contained ephedra alkaloids and herbal forms of caffeine, which are constituents of Mahuang [
RCM-104 is an RMIT Chinese herbal medicine formula with three herbal ingredients that are commonly used in daily practice. These 3 herbs were carefully selected based on both Chinese medicine theory and existing published literature of basic research. A previous study on green tea extract had shown a 4.6% decrease in body weight and 4.5% decrease in waist circumference after 12 weeks, possibly via inhibition of intestinal lipases and stimulation of thermogenesis [
The aim of this study was to evaluate the efficacy and safety of RCM-104 through a rigorous double-blinded, randomized, placebo-controlled clinical trial.
The trial was approved by the RMIT University Human Research Ethics Committee, and a Clinical Trial Notification (CTN) application was filed with the Therapeutic Goods Administration (TGA-2007/313), Department for Health and Ageing, Australian Federal Government, Canberra, Australia. The trial has been registered with Australian and New Zealand Clinical Trial Registry (ACTRN12607000255482).
Subjects and personnel who were involved in the clinical trial were blinded to the participant’s group allocation. A pharmacist, responsible for prepacking and dispensing the RCM-104 and matched placebo capsules into identical packages, was the only person with access to the randomization allocation codes.
Subjects were given written information and a verbal explanation concerning the study prior to obtaining consent for their participation. After the two-week baseline assessment, the subjects were randomly assigned into either the RCM-104 treatment or placebo groups using treatment allocation codes generated by a statistician and designed to ensure balance of gender, age, and severity of obesity between groups (Figure
Clinical trial profile.
Subjects were required to take either the RCM-104 or placebo capsules for 12 weeks with measures of BW, BMI, and body fat taken once every 4 weeks as well as at 12 weeks after intervention.
Subjects’ ages ranged from 18 to 60 years with a BMI ≥ 30 kg/m2. The exclusion criteria were (1) losing more than 5 kg in the past 3 months; (2) endocrine disorders other than type 2 diabetes mellitus; (3) uncontrolled hypertension; (4) autoimmune or cardiovascular diseases or carrying a pace-maker; (5) lactating or pregnant women; (6) those using drugs affecting the central nervous system or lipid lowering drugs; (7) obesity known to be caused by pharmacotherapy; (8) therapy for weight control in the last 6 months; (9) renal or hepatic disease; (10) unable to read or understand English. The subjects were not allowed to receive other obesity management and were asked to keep to their existing diet and life style during the study period. All subjects were free to withdraw at any time during the course of the study.
The study was advertised in the local newspapers and websites. Flyers advertising the study were displayed in local medical centers and university campuses. After a brief telephone screening interview, subjects were invited to a face-to-face interview to ensure they understood the aims of the trial and satisfied the inclusion and exclusion criteria.
All subjects were instructed to take 4 capsules per time, three times per day. The treatment group received RCM-104 capsules containing 500 mg granule extract from dried herbals according to the pre-set standard procedures with certificate of analysis. The standard markers were Chrysophanol (0.0317 mg/g), Epicatechin (EC—10.89 mg/g), Caffeine (31.24 mg/g); Epigallocatechin gallate (EGCG—52.34 mg/g); Epicatechin gallate (ECG—13.63 mg/g) and Rutin (62.09 mg/g). The ingredients include
All anthropometric measurements were carried out using standardized methods and performed at the beginning of each 4 weekly visit. Height was measured with a wall-mounted stationmaster without wearing shoes to the nearest 0.1 cm; weight was measured while wearing light clothes without shoes on a calibrated balance beam scale to the nearest 0.1 kg. BMI was calculated according to the formula: BMI = body weight (BW)/squared height (kg/m2). Waist circumference (WC) was measured mid-way between the lateral lower rib margin and the iliac crest, and hip circumference (HC) was measured at the levels of the prominence of greater trochanters. Body fat (BF) composition was determined using a standard Bioimpedance Analyzer (BIA, Model HBF-522; Omron, Kyoto, Japan) which calculated lean mass and fat mass using an algorithm based on electrical resistance, weight, age, height, and gender.
The resting metabolic rate was determined by Fitmate (Biomedex Pty. Ltd. 1/1 Pioneer Drive, Bellambi, NSW, Australia). Subjects were instructed not to exercise or consume stimulants such as alcohol, tea, or coffee at least 2 hours prior to the test. Blood pressure and heart rate were measured three times in a resting seated position with the rest period of 1 minute between the measurements using ITO blood pressure monitor, and the average of all three measurements was recorded.
Blood collections for serological data were conducted only at the first and the last visit (week 12). The serological data included cholesterol, low density lipoprotein cholesterol (LDL), high-density lipoprotein (HDL) cholesterol, triglycerides, fasting insulin and glucose for calculation of insulin sensitivity (HOMA-IR), and renal and liver functions tests.
Self-assessment questionnaires were used to monitor quality of life using validated Weight-Related Symptom Measure (WRSM) and the Obesity & Weight-Loss Quality of Life measure (OWLQOL) questionnaires (University of Washington, 2004) prior to each visit.
Subjects were asked to maintain their normal diet and routine activities. They were instructed to record their diet in the dietary record form. The forms include day by day, meal by meal records of all food and liquids consumed over 3 days at the beginning of the trial and further random 3 days in each treatment period. The food intake records were subsequently analysed using a standard dietary software package (FoodWorks, Xyris, Brisbane, Australia) incorporating the latest Australian database of food composition (NUTTAB 2006, FSANZ, Canberra, Australia). Nutrient intake was averaged over the initial 3-day period to determine the daily intake of macro- and micronutrient, fat subtypes, and total energy as the subject’s baseline diet. Dietary data collected during study periods were compared to baseline to determine any change in dietary intake (data not provided).
All data were analysed using the Statistical Package for the Social Sciences (
The data from nonrepeated measures including blood tests were analyzed using
Of 133 obese subjects screened, 117 fulfilled the inclusion criteria and were randomized into placebo (
Demographic and baseline health characteristics of all randomized subjects by group.
RCM-104 ( | Control ( | ||
---|---|---|---|
Gender | |||
Male | 10 | 10 | 0.97 |
Female | 49 | 48 | |
Age (years) | 0.61 | ||
Weight (kg) | 0.67 | ||
Male | 0.41 | ||
Female | 0.67 | ||
BMI (kg/m2) | 0.47 | ||
Heart rate (beats/min) | 0.84 | ||
Systolic blood pressure (mmHg) | 0.30 | ||
Diastolic blood pressure (mmHg) | 0.16 | ||
HbA1c (%) | 0.008 | ||
Triglyceride (mmol/L) | 0.50 | ||
Total Cholesterol (mmol/L) | 0.71 | ||
LDL Cholesterol (mmol/L) | 1.00 | ||
HDL Cholesterol (mmol/L) | 0.002 | ||
Insulin (mIU/L) | 0.001 | ||
Glucose (mmol/L) | 0.058 | ||
Homa-index (%) | <0.001 |
Thirteen (13) subjects of the treatment group and 17 subjects of the placebo group prematurely withdrew before the commencement of the treatment phase or did not return for the assessment after the first treatment period due to personal and other reasons. Ninety-two subjects were included in an ITT analysis. No subjects were removed or withdrew from the study due to serious adverse events (Figure
At baseline, the placebo group had a mean weight (
Average weights (Kg) after 12-week treatment. The plotted line graphs indicate the means ± SD of change of weight at each assessment visit, RCM-104 group (
Average body weight index (Kg/m2) after 12-week treatment. The plotted line graphs indicate the means ± SD of change of BMI at each assessment visit, RCM-104 group (
The analysis showed that after 12 weeks of treatment, there was no significant reduction in the BF composition between the RCM-104 group and the placebo group (
Change in body fat composition (%) after 12-week treatment. The plotted line graphs indicate the means ± SD of change of body fat composition at each assessment visit, RCM-104 group (
At baseline, there were no statistically significant differences in any of the 20 quality of life measures (Weight-Related Symptoms and How Much They Bother You) between the two groups. The RCM-104 group showed significant improvement compared to baseline on only two items of the quality of life measure, which assessed shortness of breath and physical stamina (
Weight-related symptoms and how much they bother you.
Symptoms | Study period | RCM-104 ( | Placebo ( | |
---|---|---|---|---|
Shortness of breath | Baseline | |||
Final | ||||
0.760 | ||||
Sensitivity to cold | Baseline | |||
Final | ||||
0.008 | 0.628 | 0.011 | ||
Leakage of urine | Baseline | |||
Final | ||||
0.521 | 0.005 | 0.005 | ||
Increased sweating | Baseline | |||
Final | ||||
0.030 | 0.547 | 0.057 | ||
Decreased physical stamina | Baseline | |||
Final | ||||
0.660 | 0.049 | |||
Joint pain | Baseline | |||
Final | ||||
0.003 | 0.748 | 0.007 |
Weight-Related Symptom Measure (WRSM) is 7-point scaled: 0 = not at all; 1 = hardly; 2 = somewhat; 3 = moderately; 4 = a good deal; 5 = a great deal; 6 = a very great deal.
*Comparison within the group between baseline and final visits using Wilcoxon-signed rank test.
**Comparison between groups at the end of trial.
For the above, the
#Sample size for treatment group reduced from 50 to 48 as Quality of Life data were unavailable for two participants.
Similarly, after 12 weeks, eleven items of Weight-Loss Quality of Life (your feelings about your weight—Table
Obesity and weight-loss quality of life-your feelings about your weight.
Symptoms | Study period | RCM-104 ( | Placebo ( | |
---|---|---|---|---|
Because of my weight, I try to wear clothes that hide my shape | Baseline | |||
Final | ||||
0.033 | 0.021 | |||
I feel frustrated that I have less energy because of my weight | Baseline | |||
Final | ||||
0.058 | 0.025 | |||
I feel guilty when I eat because of my weight | Baseline | |||
Final | ||||
0.025 | 0.093 | |||
I am bothered about what other people say about my weight | Baseline | |||
Final | ||||
0.033 | 0.047 | 0.590 | ||
Because of my weight, I try to avoid having my photograph taken | Baseline | |||
Final | ||||
0.016 | 0.374 | |||
My weight prevents me from doing what I want to do | Baseline | |||
Final | ||||
0.045 | 0.608 | |||
I worry about the physical stress that my weight puts on my body | Baseline | |||
Final | ||||
0.028 | 0.329 | |||
I feel depressed because of my weight | Baseline | |||
Final | ||||
0.148 | 0.106 | |||
I feel ugly because of my weight | Baseline | |||
Final | ||||
0.072 | ||||
I worry about the future because of my weight | Baseline | |||
Final | ||||
0.231 | 0.702 | |||
I envy people who are thin | Baseline | |||
Final | ||||
0.382 | 0.267 | |||
I feel that people stare at me because of my weight | Baseline | |||
Final | ||||
0.014 | 0.254 | 0.332 | ||
I have difficulty accepting my body because of my weight | Baseline | |||
Final | ||||
0.006 | 0.170 | 0.179 | ||
I am afraid that I will gain back any weight that I lose | Baseline | |||
Final | ||||
0.019 | 0.149 | |||
I get discouraged when I try to lose weight | Baseline | |||
Final | ||||
0.848 |
Obesity & Weight-Loss Quality of Life measure (OWLQOL) questionnaires are 7-point scaled: 0 = not at all; 1 = hardly; 2 = somewhat; 3 = moderately; 4 = a good deal; 5 = a great deal; 6 = a very great deal.
*Comparison within the group between baseline and final visits using Wilcoxon signed-rank test.
**Comparison between groups at the end of trial.
For both the above, the
Note: only symptoms showing small
#Sample size for treatment group reduced from 50 to 48 as Quality of Life data were unavailable for two participants.
Both within group and between the groups analyses did not reveal significant changes in RMR (Table
Changes in anthropometric parameters of RCM-104 and placebo groups.
Study period | RCM-104 ( | Placebo ( | ||
---|---|---|---|---|
Body weight (kg) | Baseline | |||
Final | ||||
0.510 | ||||
Body mass index (kg/m2) | Baseline | |||
Final | ||||
0.676 | 0.027 | |||
Body fat (%) | Baseline | |||
Final | ||||
0.104 | 0.935 | 0.151 | ||
Waist circumference (cm) | Baseline | |||
Final | ||||
0.014 | 0.182 | 0.445 | ||
Hip circumference (cm) | Baseline | |||
Final | ||||
0.034 | 0.544 | 0.042 | ||
Waist to Hip Ratio | Baseline | |||
Final | ||||
0.382 | 0.067 | 0.356 | ||
Systolic Blood pressure (mmHg) | Baseline | |||
Final | ||||
0.738 | 0.854 | 0.685 | ||
Diastolic blood pressure (mmHg) | Baseline | |||
Final | ||||
0.853 | 0.855 | 0.934 | ||
Heart rate (beats/min) | Baseline | |||
Final | ||||
0.084 | 0.897 | 0.281 | ||
RMR (Kcal/day) | Baseline | |||
Final | ||||
0.085 | 0.019 | 0.827 |
*Comparison within the group between baseline and final visits.
**Comparison between groups at the end of trial.
(
There were some changes in the food intake by the subjects during the trial. However, the changes were not significant (data will be presented in a future journal article).
There were no significant differences between the two groups with respect to renal and liver function tests before and after the treatment period. Similarly, there were no statistically significant differences in the serological data between the 2 groups.
Overall, the compliance of medication was 88% with 88.6% in the placebo and 87% in the treatment group.
Within the RCM-104 group, there were reports of nausea (4 cases) and headache (9 cases) while there were 2 reports of decrease in appetite in the placebo group. Both of these symptoms occurred during the first treatment period and none of these were serious. No subject withdrew from the study due to adverse events.
This study was designed to evaluate the effect of a Chinese herbal medicine formula RCM-104 in the treatment of simple obesity. There was a high level of willingness to participate in this study as all 117 subjects who satisfied inclusion criteria gave informed consent to participate in the trial.
The results of the present study showed statistically significant differences in BW and BMI between the participants of RCM-104 and placebo groups after 12 weeks of treatment and significant improvements in quality of life of participants in the RCM-104 group.
Because obese individuals often have other associated health issues, guidelines for obesity management prefer modest and safe weight loss and good weight maintenance to target an ideal weight [
The RCM-104 is composed of 3 herbs: Camellia Sinensis (Lu Cha Ye—Green tea), Semen Cassiae (Jue Ming Zi), and Flos Sophorae (Huai Hua). While the mechanism of actions of this formula is unknown, a study has shown that green tea extract stimulated thermogenesis and fat oxidation potentially may influence body weight and body composition by increasing energy expenditure [
It has been suggested that synergistic interactions between catechin-polyphenol and caffeine augment and prolong sympathetic stimulation of thermogenesis and that this may play an important role in the management of obesity [
In Chinese medicine practice, Jue Ming Zi is known to clear heat, moistens and lubricates the intestines, and therefore acts as a mild laxative [
In human studies, green tea has been found to significantly increase energy expenditure, lower body weight, and decrease waist circumference without changing heart rate or blood pressure [
There has been general concern of the lack of safety of specific Chinese herbal medicine. Kidney failure due to herbal weight loss pills has been reported [
RCM-104 is well tolerated and appears to be effective in reducing weight and improving quality of life in obese individuals after 12 weeks. Long-term follow-up studies in larger populations are required to determine if weight loss is sustained.
The authors declare that none of them has any conflict of interests within the last three years that may arise by being named as an author of the paper.
This study was cofunded by the Windermere Foundation Limited, an RMIT Emerging Researcher Grant, and an Australian Acupuncture and Chinese Medicine Association (AACMA) seed grant. The trial medications were manufactured, tested, and supplied by Sun Ten Pharmaceuticals Co Ltd, Taiwan. The use of Quality of Life (OWLQOL) instruments was permitted by Seattle Quality of Life Group, University of Washington. The authors would also like to thank all subjects, nurses, doctors, and research assistants who have contributed to this paper.