Weight Loss and Adverse Events According to Baseline Skeletal Muscle Mass in Overweight Patients Treated with Gamitaeeumjowee-tang : A Retrospective Chart Review
Article information
Abstract
Objectives
This study evaluated the associations of the Gamitaeeumjowee-tang–based weight reduction program with body weight, body composition, and adverse events in overweight patients, stratified by baseline skeletal muscle mass.
Methods
A retrospective chart review was performed on 155 women aged 20 to 59 years who were overweight (body mass index [BMI], 23 to 24.9 kg/m2) and participated in a 12-week weight reduction program with Gamitaeeumjowee-tang from 2019 to 2024. Participants were classified into a low muscle group (80% to <90% of reference skeletal muscle, n = 75) and a normal muscle group (100% to <110%, n = 80). Changes in body weight, BMI, fat mass, fat-free mass (FFM), and skeletal muscle mass were assessed before and after treatment. Adverse events were also evaluated.
Results
Both groups showed significant reductions in body weight, BMI, body fat mass, and body fat percentage (p < 0.05). Skeletal muscle mass showed no significant change in the low muscle group but decreased slightly in the normal muscle group. The proportion achieving ≥5% weight loss was 84% in the low muscle group and 75% in the normal muscle group; ≥10% was achieved in 32% and 18.8%, respectively. Adverse events occurred mainly during the early phase, decreased over time, and were mostly mild.
Conclusions
The Gamitaeeumjowee-tang–based weight reduction program was associated with fat-focused weight loss with relative muscle preservation in overweight women. These findings should be interpreted with caution due to the lack of control for diet and physical activity.
Introduction
Obesity is a chronic disease strongly associated with cardiovascular disease, metabolic disorders, neoplastic disease, and musculoskeletal disorders. It also serves as an independent risk factor for cardiovascular disease, contributing to increased mortality.1) The global prevalence of obesity continues to rise. According to the World Health Organization (WHO), adult obesity prevalence was approximately 13.4% in 2016, 14.9% in 2020, and 15.8% in 2022.2) In South Korea, 37.2% of all adults were obese as of 2023.3) The 2025 World Obesity Atlas projects that more than half of the world’s population will be overweight or obese by 2030.4)
Obesity is commonly diagnosed using body mass index (BMI) and is classified into pre-obesity (23.0–24.9 kg/m2), class I obesity (25.0–29.9 kg/m2), class II obesity (30.0–34.9 kg/m2), and class III obesity (≥35.0 kg/m2).5) However, BMI, calculated from weight and height does not accurately reflect muscle mass, body fat mass, or fat distribution. These limitations are especially apparent in conditions such as sarcopenic obesity,6) normal weight obesity,7) and overweight. Overweight is not merely a transitional state before obesity but represents a metabolically high-risk group, with increased risks of cardiovascular disease, diabetes, and cancer compared to individuals of normal weight.8,9) Furthermore, increases in BMI within the overweight group are associated with higher medical costs and reduced quality of life, making preemptive weight reduction cost-effective.10)
Conventional treatment and management of obesity focus on lifestyle modifications, including dietary changes, exercise, and behavioral therapy, with pharmacological treatment added when necessary.5) In this process, skeletal muscle plays an essential role in effective weight loss, prevention of adverse effects, and maintenance of reduced weight. Skeletal muscle functions as a metabolic organ, performing fatty acid oxidation, regulating insulin sensitivity, and secreting anti-inflammatory cytokines. It is also recognized as an independent indicator of metabolic health.11,12) Skeletal muscle accounts for a significant portion of resting energy expenditure (REE) and has approximately three times the metabolic rate of adipose tissue.13) In overweight and obese patients, REE is independently associated with muscle mass, increasing about 24 kcal/day for each 1 kg increase in muscle mass.14)
Excessive dietary restriction or activity disproportionate to food intake during weight loss can cause hypoglycemic symptoms. In such cases, skeletal muscle provides metabolic compensation by reducing glucose uptake during hypoglycemia and contributing to gluconeogenesis through lactate release.15)
Preservation of skeletal muscle mass during weight loss is therefore crucial for metabolic homeostasis and hypoglycemia prevention. Nonetheless, some loss of fat-free mass (FFM), including skeletal muscle mass, is inevitable during weight reduction, typically accounting for 20–40% of total weight lost.16) Approximately half of FFM consists of skeletal muscle, and changes in FFM are largely attributable to changes in muscle mass,16,17) Previous studies have shown that the greater the proportion of fat free mass loss (FFML) during weight reduction, the higher the risk of weight regain, often within one year.18) Thus, preserving skeletal muscle mass is important not only for achieving weight loss but also for maintaining it.
Meanwhile, herbal medicine is widely used for weight loss. Gamitaeeumjowee-tang is one of the most commonly prescribed formulas in clinical practice. Its key constituent, Ephedra (mahuang), contains ephedrine, which suppresses appetite, increases thermogenesis, and raises metabolic rate through sympathetic nervous system stimulation, thereby accelerating fat breakdown.19) However, when herbal medicines containing Ephedra are used for weight loss, adverse effects such as palpitations, insomnia, excessive sweating, dry mouth, thirst, nausea, and vomiting may occur due to sympathetic nervous system activation.20) In addition, excessive dietary restriction during weight loss may cause other adverse reactions such as hypoglycemic symptoms.
Therefore, when combining herbal medicine with lifestyle modifications for obesity treatment, professional diagnosis, individualized prescriptions, and careful management are required. Of particular importance is monitoring baseline muscle mass and subsequent changes during weight loss, since lower muscle mass may lead to poorer weight-loss outcomes and increased risk of hypoglycemia-related adverse effects. Indeed, previous studies in overweight and obese patients have reported that greater initial muscle mass is associated with greater weight-loss effects.21)
Most previous studies on herbal medicine for obesity treatment have focused either on patients with simple obesity, including overweight individuals,22) or on obese patients with comorbidities such as diabetes,23) hypothyroidism,24) and depression.25) As described earlier, overweight itself represents a metabolically high-risk group. Large-scale international cohort studies have shown that many patients with sarcopenia fall into the overweight category, and that overweight with sarcopenia is more prevalent than sarcopenic obesity.26) Recent chart review studies on normal-weight obesity,27) and sarcopenic obesity28) have examined the efficacy and safety of herbal medicine in patients with low muscle mass. However, to date, no studies have divided overweight patients into groups based on baseline muscle mass to compare patterns of weight loss, body composition changes, and adverse reactions following herbal medicine–based weight reduction program.
The purpose of this study is to classify overweight patients into normal-muscle and low-muscle groups according to baseline muscle mass, to compare weight loss, muscle mass changes, and adverse reactions before and after the Gamitaeeumjowee-tang–based weight reduction program, and to share these findings with researchers and clinicians involved in obesity management.
Methods
1. Study Participants
Adults aged 20–59 years who visited the Gangnam branch of Nubebe Korean Medical Clinic in Seoul between January 1, 2019, and December 31, 2024, and who provided informed consent for the use of personal information, were screened for eligibility. Participants were selected based on the inclusion criteria: (1) baseline BMI between 23.0 kg/m2 and <25.0 kg/m2, and (2) skeletal muscle mass relative to standard skeletal muscle mass, as measured by InBody bioelectrical impedance analysis (BIA), of either 80% to <90% (below the standard range) or 100% to <110% (within the standard range).
From this population, individuals were included in the final analysis if they (1) enrolled in a 12-week weight-loss program, (2) received Gamitaeeumjowee-tang with ≥75% medication adherence, and (3) completed follow-up visits within 70–120 days of the initial consultation, which included comprehensive body composition analysis (weight, body fat percentage, skeletal muscle mass) and clinical evaluation to obtain complete clinical data.
This retrospective chart review was conducted in accordance with a research protocol exempted by the Institutional Review Board (IRB) designated by the Ministry of Health and Welfare (approval number: P01-202507-01-019).
2. Prescription and Diet
Participants received Gamitaeeumjowee-tang in divided doses over a 12-week program. The daily composition of the prescription is presented in Table 1. The herbal medicine was prepared in tablet form (550 mg per tablet) following decoction extraction, evaporation, concentration, and freeze-drying. Patients took 3 tablets per dose, 3 times daily, for a total of 9 tablets per day.
Composition of Gamitaeeumjowee-tang
Ephedra dosage was prescribed in graduated increments within a daily range of 16–24 g, adjusted for individual body weight and sensitivity to the herbal ingredient. Dietary therapy consisted of counseling on regular three-meal consumption and low-calorie, balanced diet. Participants were advised to maintain a daily energy intake of 1,200–1,500 kcal, with 45% from carbohydrates and approximately 1.0 g of protein per kilogram of body weight. They were also encouraged to include at least one to two types of vegetables at each meal. Light physical activity was recommended, and counseling regarding weight reduction, including dietary therapy, was provided at each clinic visit.
3. Outcome Measures
1) Body Weight and Body Composition
To assess weight reduction patterns, body weight, BMI, body fat mass, body fat percentage, skeletal muscle mass, and FFM were measured before and after the program. Measurements were obtained using the InBody 770 bioelectrical impedance analyzer (InBody Co., Ltd., Seoul, Republic of Korea), and height was measured separately using the BSM 330 automatic height and weight scale (InBody Co., Ltd., Seoul, Republic of Korea). Participants were instructed to remove metal accessories and electronic devices, stand barefoot, wear light clothing, maintain a standardized standing posture with full electrode contact, and minimize movement during measurement. Room temperature was maintained at 24–26 °C in summer and 22–24 °C in winter, with relative humidity kept above 35%.
Additionally, in line with obesity management guidelines that recommend a primary goal of reducing initial body weight by 5–10% within 6 months for adults with obesity,5) the proportions of participants achieving ≥5% and ≥10% weight reduction were calculated.
2) Adverse Events
Adverse events that occurred during the medication period were collected through chart review. Three Korean medicine physicians independently evaluated the causality and severity of these events. When the evaluators were not concordant, consensus was reached through discussion. If two or more evaluators provided identical assessments, those findings were adopted.
The frequency of adverse reactions was categorized by organ system according to System Organ Classes (SOC). Causality was assessed using the World Health Organization–Uppsala Monitoring Centre (WHO-UMC) criteria, and severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
4. Statistical Analysis
Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) Statistics, version 26 (IBM Corp., Armonk, NY, USA). Continuous variables were presented as mean ± standard deviation, and categorical variables as frequency (n, %). Between-group comparisons of continuous variables were conducted using the independent t test or Mann–Whitney U test, depending on normality. Within-group pre- and post-treatment comparisons were conducted using the paired t test or Wilcoxon signed-rank test. Normality was assessed using the Shapiro–Wilk test. Multiple linear regression analysis was performed to assess the potential effects of baseline BMI and age on changes in body weight, and the chi-square test was used to compare the incidence of adverse events between groups. A p-value < 0.05 was considered statistically significant.
Results
1. Baseline Characteristics of Participants
Between January 1, 2019, and December 31, 2024, 5,559 female adults aged 20–59 years who visited the Nubebe Korean Medicine Obesity Clinic in Seoul and provided informed consent were classified as overweight at the initial consultation. Of these, 2,115 patients had skeletal muscle mass ratios of 80% to <90% or 100% to <110% relative to the standard skeletal muscle mass based on InBody analysis. After excluding 1,956 patients due to lack of follow-up records (failure to return within 70–120 days), medication adherence <75%, participation in a 4-week instead of 12-week program, or other factors, 159 patients remained. Following exclusion of 4 statistical outliers, 155 patients were included in the final analysis (Figure 1).
Flowchart of a retrospective chart review
The mean age of participants was 33.85 ± 9.53 years. Mean baseline values were as follows: body weight, 63.20 ± 3.93 kg; BMI, 24.07 ± 0.55 kg/m2; body fat percentage, 35.47 ± 4.53%; and skeletal muscle mass, 22.12 ± 2.49 kg. The mean duration of Gamitaeeumjowee-tang administration was 93.31 ± 12.03 days.
Participants were classified into two groups based on skeletal muscle mass relative to InBody standards: low muscle (80% to <90%, n = 75) and normal muscle (100% to <110%, n = 80). Statistically significant between-group differences were observed in age, initial body weight, BMI, skeletal muscle mass, body fat mass, body fat percentage, skeletal muscle percentage, and FFM. Multiple linear regression analyses were performed to assess the potential effects of baseline BMI and age on changes in body weight. Neither baseline BMI (β = −0.323, p = 0.301) nor age (β = −0.0276, p = 0.117) showed a statistically significant association with these outcomes (p > 0.05). Therefore, no additional adjustment for these variables was applied in subsequent analyses. (Table 2).
Baseline Characteristics
2. Changes in Body Weight and Body Composition
After 12 weeks of Gamitaeeumjowee-tang administration, the following changes were observed: Low muscle group (n = 75): Body weight decreased by 8.14 ± 3.16%, BMI by 8.17 ± 3.14%, body fat mass by 19.30 ± 8.37%, and body fat percentage by 4.82 ± 2.78 percentage points. FFM decreased by 0.89 ± 3.75%, skeletal muscle mass decreased by 0.27 ± 1.16 kg, and skeletal muscle percentage increased by 2.46 ± 2.06 percentage points. All changes were statistically significant except for skeletal muscle mass. Overall, 63 participants (84%) achieved ≥5% weight loss, and 24 (32%) achieved ≥10% weight loss.
Normal muscle group (n = 80): Body weight decreased by 6.94 ± 3.35%, BMI by 7.17 ± 3.02%, body fat mass by 16.98 ± 9.57%, and body fat percentage by 3.47 ± 2.76 percentage points. FFM decreased by 2.25 ± 4.05%, skeletal muscle mass by 0.66 ± 0.94 kg, and skeletal muscle percentage increased by 1.73 ± 1.80 percentage points. All changes were statistically significant. Sixty participants (75%) achieved ≥5% weight loss, and 15 (18.8%) achieved ≥10% weight loss. Among those who lost weight, the proportion of FFML (%FFML; ΔFFM/ΔWeight) was 18.14 ± 55.80%.
Between-group comparisons showed no significant differences in changes in body fat mass or BMI. However, significant differences were observed for body weight, skeletal muscle mass, and FFM.
3. Evaluation of Adverse Events
Assessment of adverse event causality using WHO-UMC criteria and severity grading with CTCAE version 5.0 in both the low muscle group and normal muscle groups yielded the following results:
A total of 126 out of 155 participants (81.3%) reported adverse events during the intervention period. Of these, 60 (38.7%) were in the low muscle mass group and 66 (42.6%) were in the normal muscle mass group. The chi-square test indicated that the difference in the incidence of adverse events between the two groups was not statistically significant.
During weeks 1–9, a total of 100 adverse events were reported in the low muscle group and 106 in the normal muscle group. These numbers decreased to 47 and 53 cases, respectively, during weeks 10–18, demonstrating a clear declining trend over time. According to WHO-UMC causality criteria, events classified as ‘Possible’ were observed in 37 cases in the low muscle group and 42 in the normal muscle group during weeks 1–9, decreasing to 22 and 25 cases, respectively, during weeks 10–18, again showing a similar declining pattern.
In severity assessment, one case in the low muscle group during weeks 10–18 was graded as ‘moderate.’ This involved recurrence of palpitations of unknown etiology, which had been documented in the patient’s past medical history at baseline. The events occurred in the latter phase of treatment and improved after medical care and short-term pharmacotherapy. In the normal muscle group, one case during weeks 10–18 was graded as ‘severe.’ However, dietary intake records were unavailable at the time of occurrence, the event did not occur during the early treatment phase, and no recurrence was observed at follow-up visits. Consequently, drug causality for both events was assessed as ‘unlikely.’
SOC categorization revealed that in the low muscle group, nervous system disorders were most frequent, with dizziness being the most common symptom (18 cases, 18.0% during weeks 1–9; 9 cases, 16.9% during weeks 10–18). In the normal muscle group, gastrointestinal disorders predominated, with constipation as the most common symptom (17 cases, 16.1% during weeks 1–9; 6 cases, 11.3% during weeks 10–18) (Tables 3 and 4).
Comparison of Changes in Weight, Body Mass Index, Body fat and Skeletal muscle mass
Adverse Events Reported from 155 patients
Discussion
This study examined overweight patients who visited a Korean medicine clinic for weight loss, focusing on two groups defined by baseline skeletal muscle mass: a low muscle group and a normal muscle group. We compared the outcomes of a 12-week program involving Gamitaeeumjowee-tang combined with general dietary modification.
Both groups showed statistically significant reductions in mean body weight, BMI, body fat mass, and body fat percentage. Weight loss rates were 8.14 ± 3.16% in the low muscle group and 6.94 ± 3.35% in the normal muscle group. These reductions were somewhat lower than the 9–11% range reported in previous studies involving overweight or obese patients over a similar duration.22) The lower reduction is likely explained by participants in this study being overweight rather than obese, with correspondingly lower baseline body weight and BMI. In contrast to previous studies that included a broad range of overweight to obese individuals—where higher skeletal muscle mass was often accompanied by higher BMI—this study deliberately limited inclusion to BMI between 23.0 kg/m2 and <25.0 kg/m2 to minimize bias from initial body composition. As a result, individuals with higher skeletal muscle mass may have had proportionally less reducible fat mass, which could partly explain the lower weight loss rates observed in the normal muscle group. The proportions achieving ≥5% weight reduction were 84% (n = 63) and 75% (n = 60), while the proportions achieving ≥10% weight reduction were 32% (n = 24) and 18.8% (n = 15), respectively. Clinically, a 5% weight reduction is considered meaningful, as it reduces the risk of obesity-related comorbidities, and a 5–10% decrease in body weight within 6 months is generally recommended as a primary treatment goal.5) Therefore, the majority of participants achieved clinically significant weight loss, with some in the low muscle group exceeding standard treatment benchmarks.
With respect to skeletal muscle, the low muscle group showed no significant change (−0.27 ± 1.16 kg), whereas the normal muscle group experienced a statistically significant decrease (−0.66 ± 0.94 kg). This relative preservation of muscle in the low muscle group may be partly attributable to clinical practice, where practitioners often emphasize the prevention of further muscle loss in patients with low baseline muscle mass by reinforcing adequate protein intake and regular meals. Such guidance may have encouraged better adherence to dietary recommendations. Moreover, because their baseline muscle mass was already lower, the extent of further reduction may have been inherently limited. Conversely, skeletal muscle percentage increased in both groups, by 2.46 ± 2.06 and 1.73 ± 1.80 percentage points, respectively. For the normal muscle group, which showed a decrease in muscle mass, the proportion of FFML (%FFML; ΔFFM/ΔWeight) was calculated. Typically, about 25% of lost weight is attributable to FFM, and greater losses are undesirable.29,30) In this study, the mean %FFML was 18.14 ± 55.80%, indicating that FFM preservation was achieved and that weight reduction was primarily due to fat loss.
Adverse Events According to System-Organ Classes
The findings are consistent with prior herbal medicine studies in populations with low muscle mass. In sarcopenic obesity, a 12-week Gamitaeeumjowee-tang-based program was associated with a 6.52 ± 3.4% reduction in body weight, without significant decreases in skeletal muscle or FFM.28) In normal-weight obesity, 12 weeks of herbal medicine–based program showed weight by 6.99±3.22%, with a %FFML of 21.89 ± 0.16%, again demonstrating fat-predominant loss.27) In the present study, the low muscle group achieved an even higher mean weight reduction, while skeletal muscle mass remained relatively stable. Collectively, these results suggest that herbal medicine–based programs combined with general dietary management may be linked to fat-focused weight reduction in individuals with low muscle mass, including those with sarcopenic obesity, normal-weight obesity, and overweight.
Previous research on obesity treatment outcomes in overweight and obese patients has identified initial body weight, medication adherence, and initial muscle mass as important factors influencing weight loss, with higher muscle mass generally associated with greater reductions.21) However, in the present study restricted to overweight patients, the low muscle group achieved higher weight loss rates, suggesting that low muscle mass may not necessarily limit weight reduction at this stage.
In the analysis of adverse events, no severe adverse events with established drug causality were observed. Both groups initially reported relatively high rates of adverse events, which then declined markedly over time. This pattern is consistent with the tachyphylaxis phenomenon of Ephedra (mahuang),20) the principal herbal component of Gamitaeeumjowee-tang. Prior studies of Gamitaeeumjowee-tang in overweight and obese patients frequently reported gastrointestinal symptoms, such as constipation and nausea, particularly in SOC classification,31) which parallels the findings in the normal muscle group of this study. In contrast, dizziness was more common in the low muscle group, a symptom often associated with excessive dietary restriction during weight loss. Patients with low muscle mass may be especially vulnerable because of reduced compensatory capacity for hypoglycemia. Accordingly, this population requires quantitative dietary counseling at the initial consultation, including regular three-meal patterns and sufficient protein intake, along with continuous monitoring of lifestyle modifications at subsequent follow-up visits.
Constipation, frequently reported in the normal muscle group, is a commonly adverse event during low-calorie diets. Previous studies administering Gamitaeeumjowee-tang for similar durations reported persistent constipation into later treatment phases.32,33) However, compared with an incidence rate of 41.7% reported in studies using only diet and exercise therapy,34) the constipation rate observed here was relatively lower. Clinical management in such cases should emphasize adequate fiber intake and hydration, with consideration of adjunct herbal prescriptions in more severe presentations.
This study is noteworthy as the first domestic investigation to compare weight loss efficacy and adverse events between groups stratified by initial muscle mass in overweight patients undergoing herbal medicine treatment. In the low muscle group, which is often considered more vulnerable to unfavorable outcomes, patients treated with the Gamitaeeumjowee-tang–based weight reduction program exhibited a meaningful decrease in body weight while generally preserving skeletal muscle mass. In addition, adverse event rates did not differ significantly between groups throughout the treatment period, and no moderate or severe events with high causality were observed. Taken together, these findings indicate that the Gamitaeeumjowee -tang–based program was associated with fat-focused weight loss and relative muscle preservation in overweight patients, but this observation should be interpreted with caution, as dietary intake and physical activity were not systematically assessed or controlled, and the inherent limitations of bioelectrical impedance analysis (BIA) may have influenced measurement accuracy.
Nonetheless, previous studies have shown that the risk of weight regain varies according to initial FFM and the degree of FFM reduction during weight loss.18) Due to the retrospective chart review design, this study could not assess long-term weight regain risk. Moreover, because this study was based on retrospective clinical records, information on patients who did not return for follow-up was unavailable, including whether they discontinued treatment, experienced adverse events, or showed insufficient effect. Furthermore, despite general dietary and lifestyle counseling during clinic visits, detailed data on actual dietary intake, calorie restriction, and physical activity levels were unavailable, limiting interpretation of the mechanisms underlying the observed weight changes. Additionally, body composition was measured by BIA, which, while widely used in clinical practice for its convenience, is less accurate than dual-energy X-ray absorptiometry (DEXA) or computed tomography (CT) and is subject to hydration-related variability.35)
Future research would benefit from prospective, controlled designs with standardized monitoring of diet and physical activity to confirm these findings and clarify the independent contribution of this herbal treatment. Concurrent interventional strategies such as high-protein dietary therapy or resistance exercise may also strengthen the evidence for safe and integrated obesity management.
Conclusion
This retrospective analysis of 155 overweight female patients treated with the Gamitaeeumjowee -tang–based weight reduction program for 12 weeks at a Korean medicine obesity clinic produced the following key findings:
Both the low muscle and normal muscle groups showed statistically significant reductions in body weight, BMI, body fat mass, and body fat percentage. Mean weight loss rates were 8.14 ± 3.16% and 6.94 ± 3.35%, respectively, with a higher proportion of the low muscle group achieving clinically meaningful weight reduction (≥5% in 84% of participants and ≥10% in 32%).
Skeletal muscle mass remained stable in the low muscle group (−0.27 ± 1.16 kg) but decreased modestly in the normal muscle group (−0.66 ± 0.94 kg). In both groups, skeletal muscle percentage increased, suggesting that weight loss was primarily attributable to fat reduction.
No severe adverse events with confirmed drug causality were observed. Reported events were most frequent in the early treatment phase and declined over time. Dizziness predominated in the low muscle group, while constipation was most common in the normal muscle group.
In summary, the findings of this study indicate that the Gamitaeeumjowee-tang–based weight reduction program was associated with fat-focused weight loss and relative preservation of skeletal muscle in overweight women, including those with low baseline muscle mass. However, these results should be interpreted cautiously due to the lack of dietary and physical activity control inherent to the retrospective design.