Introduction

Obesity typically results from an energy imbalance caused by excessive caloric intake.1 Appetite is the body’s response to the need for nutrients and energy, directly influencing eating behavior.2 Differences in appetite between lean and obese individuals extend beyond satiety; obese individuals exhibit a heightened sensitivity to food stimuli and derive more pleasure from eating.3,4 Previous study has shown that more than 70% of obese or overweight people have factors that increase eating abnormally, and some of them have special ingestion behaviors such as overeating and involuntary eating.5

Despite the adverse health effects of increased appetite on overweight and obese individuals, effective treatment options are limited. Current weight loss strategies, including dietary control, pharmacotherapy, and bariatric surgery, have shown some effectiveness in reducing appetite.6 However, dietary control requires long-term adherence, which is often challenging for patients;7 pharmacotherapy can lead to many side effects, including nausea, insomnia, and headaches;8 and bariatric surgery, while effective, is constrained by high safety requirements, high costs, strict indications, and postoperative complications.9 These limitations have prompted the search for alternative therapeutic approaches.

Currently, various alternative therapies, such as mindfulness-based interventions, behavioral therapies, and acupuncture, are widely used for weight management.6,10,11 Mindfulness-based interventions and behavioral therapies promote self-regulation by modulating cognitive and emotional aspects of eating behavior.12,13 However, their effectiveness heavily relies on patient motivation and consistent professional guidance, which limits their practical applicability.14,15 In contrast, acupuncture offers a low-effort intervention by stimulating specific acupoints associated with hunger and satiety, helping regulate appetite through physiological mechanisms rather than conscious cognitive control.16 However, acupuncture typically requires frequent treatments over several months, which can be challenging for patient adherence.17

Acupoint Catgut Embedding (ACE) is an innovative acupuncture technique that combines traditional acupuncture principles with modern materials.18 It embeds absorbable catgut into acupoints, where catgut undergoes softening, liquefaction, and absorption, providing prolonged stimulation.19 Compared with traditional acupuncture, ACE offers stronger and longer-lasting stimulation, requiring fewer sessions and reducing the discomfort from repeated needling. These advantages address the limitations of traditional acupuncture and improve patient compliance.20 Recent clinical studies have demonstrated ACE’s potential in obesity management.21–23 A network meta-analysis of 35 clinical trials involving 3040 obese patients found that ACE outperformed manual acupuncture, electroacupuncture, and exercise diet therapy in reducing body mass index (BMI), improving waist-to-hip ratio, and promoting weight loss.24 Despite these promising findings, research on the impact of ACE on subjective appetite remains underexplored. To address this gap, we conducted a preliminary study to quantify and compare the effects of ACE on the subjective appetite of patients with different appetite levels. We tested the hypothesis that the effectiveness of ACE does not differ between adults reporting strong and moderate appetite at baseline.

Methods Study Design and Setting

This study is a secondary analysis of appetite data from a multicenter, double-blind, parallel randomized clinical trial.25 The trial aimed to examine the effect of ACE intervention on the subjective appetite of overweight and obese adults with strong and moderate appetites. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR1800016947) and approved by the Ethics Committee of Yunnan Sports Trauma Specialist Hospital (2018CK-001). All participants provided written informed consent. The study adhered to the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines (Supplementary Material 1).

Study Population

The study was conducted from July 2018 to March 2020 at four hospitals in China: the Second Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming Traditional Chinese Medicine Hospital, Yunnan Sports Trauma Specialist Hospital, and Sheng’ai Traditional Chinese Medicine Hospital. Eligibility criteria included: (1) meeting the diagnosis of overweight and obesity, BMI ≥ 24 kg/m²;26 (2) age between 18–60 years; (3) signing informed consent. Exclusion criteria included: (1) secondary obesity caused by medication or endocrine diseases; (2) light appetite (Appetite Visual Analogue Scale (VAS) at baseline < 4 points); (3) chronic obstructive pulmonary disease, coronary heart disease, liver cirrhosis, nephritis, and other severe organ diseases; (4) severe mental and neurological disorders; (5) allergies to alcohol or catgut; (6) pregnancy, breastfeeding, and childbirth within the past six months; (7) receiving weight loss treatment within the past three months.

Randomization and Blinding

The randomization was computer generated by the Clinical Research Center of Yunnan University of Chinese Medicine. Stratified randomization was performed in the 4 clinical centers. Opaque envelopes with a random number were managed by an independent coordinator. Participants and inspectors were all blinded to the allocation. The acupuncturist performed the catgut embedding after the assistant laid the drapes. Therefore, the acupuncturists were also blinded to the allocation.

Sample Size

The sample size was calculated using G*Power software (version 3.1)27 based on findings from prior studies,28 which reported a mean BMI reduction of 1.32 kg/m² in the intervention group and 1.02 kg/m² in the control group, with a standard deviation (SD) of 0.31 kg/m². Accounting for differences in study design, we anticipated a slightly lower BMI reduction of 1.14 kg/m² in the ACE group and 0.9 kg/m² in the NACE group, both with an SD of 0.31 kg/m². Using a two-tailed test, we set the significance level at ɑ = 0.05 and statistical power at 1-β = 0.95. The minimum required sample size was calculated as 84 participants (42 per group). Considering the 8% dropout rate, the sample size was adjusted to 92 participants with 46 participants in each group. A total of 137 participants were initially recruited; however, 14 participants were excluded due to recruitment errors. Additionally, one participant with light appetite (outside the scope of this secondary analysis focusing on participants with moderate and strong appetite levels) was excluded. The final sample size was 122, comprising 59 participants in the ACE group and 63 in the NACE group.

Interventions

Before treatment, participants in both groups were placed in a comfortable supine position. For the ACE group, true acupoints were selected based on previous research and classical Traditional Chinese Medicine theory, including Zhongwan (CV12), Tianshu (ST25), Zhangmen (LR13), Pishu (BL20), Weishu (BL21), and Dachangshu (BL25). Standardized techniques for location were used.29 To ensure rigorous trial design, a sham procedure that mimicked the actual treatment but was inactive was employed. Although standardized protocols for placebo control in acupoint embedding trials are lacking, it is recommended to use non-active points as controls. For this study, non-acupoints located near the true acupoints but outside recognized meridian lines were selected and labeled as NA1–NA6 (see Figure 1 and Table 1). Previous research has shown that non-acupoints do not elicit specific therapeutic effects, making them effective inert controls.30 Moreover, brain imaging research indicates that stimulation of non-acupoints does not activate the same brain regions as true acupoints, further validating their use as a reliable placebo control.31

Table 1 Location of the Points and the Details Operation of Catgut Embedding

Figure 1 The location of acupoints.

Assistants marked the locations of acupoints and non-acupoints and performed routine disinfection of the surgical area before placing a sterile drape. A 1–2 cm sterile medical catheter (length depending on the location of the acupoint) was positioned at the end of a trocar, connected to a stylet. The skin was raised slightly with the thumb and index finger of one hand while the other hand performed the puncture. When the required depth was reached, the catgut was implanted into the subcutaneous tissue or muscle layer. After removing the needle, a dry cotton ball was pressed on the puncture site for half a minute to stop bleeding, followed by bandaging to protect the site. Participants were instructed not to bathe for 24 hours and to keep the embedding area dry. Participants’ diet and physical activity were not restricted during treatment and follow-up, and they could continue their usual lifestyle.

The embedding needle used was a No. 8 disposable needle (Jiangxi Glance Medical Equipment Co. Ltd. Production, Nanchang, China). The medical catgut was an absorbable collagen thread, specification 2–0, 2cm*20 (Jiangxi Longteng Biotechnology Co., Ltd., Nanchang, China).

ACE was performed by certified acupuncturists designated at each site, including SWZ, QFL, and six other acupuncturists. The study acupuncturists met national licensing requirements, held medical practitioner certificates, and had a minimum of three years of clinical acupuncture experience. They received standardized training before the commencement of the study.

Outcome

Outcome measurements were performed at baseline, 6 and 12 weeks in the intervention period, and 16 weeks in the follow-up phase. Patients were required to undergo measurements at 8 AM after fasting for 12 hours before each measurement. Appetite was measured using a VAS ranging from 0–10 mm, with higher scores indicating stronger appetite. The VAS is a well-established tool for assessing subjective appetite, widely recognized for its validity, reliability, and reproducibility.32 In this study, baseline strong appetite was defined as a baseline appetite score of 7–10, and baseline moderate appetite was defined as a baseline appetite score of 4–6. The appetite VAS scale is shown in Figure 2.

Figure 2 The scale of VAS of appetite.

Statistical Analysis

Differential intervention effects over time were tested for adults categorized into moderate and strong appetite groups at baseline, using an intention-to-treat principle. Under the assumption of data missing at random, we analyzed the full dataset using mean imputation for missing values. Changes in appetite scores were analyzed using generalized linear mixed-effects models (GLMM) with a Gamma distribution and log link function, appropriate for non-normal outcome data. This model accounts for repeated measurements within individuals by including random intercepts for participants to control for intra-individual variability over time. The following model was used:

(VASit: VAS score for participant i at time t. β0: Intercept (overall baseline value), β1, β2, β3: Fixed effects of group, time, and appetite status. β4×(Groupi×Timet×Appetite Statusi): Interaction effect of group, time, and appetite status. γ1, γ2, γ3: Covariate effects of age, gender, and BMI. bi: Random intercept for participant i, accounting for individual variability. : Residual error for participant i at time t).

Group, time, and appetite status were included as fixed effects to assess their influence on intervention outcomes. Additionally, age, gender and BMI were included as covariates to control for potential confounding factors, ensuring the robustness of the model. Although age, gender and BMI did not show statistically significant effects, their inclusion helped mitigate the risk of biased estimates. To assess differential intervention effects over time, we incorporated an interaction term for time × group × appetite status. Post-hoc pairwise comparisons with Bonferroni corrections were applied to identify significant differences between the ACE and NACE groups at each time point. Statistical significance was set at P < 0.05 (two-tailed). All data analyses were performed using SPSS version 28.0 (IBM Corp., Chicago, IL, USA).

Results Participants and Baseline Characteristics

A total of 186 participants entered the baseline period, and 137 participants were randomized, aged 18 to 65 years. A total of 122 participants (one participant was excluded due to a baseline appetite score of less than 4) were included in the ITT population (Figure 3). The mean (SD) age of participants was 36.11 (9.60) years, and 99 participants (81.1%) were female. 59 participants (48.4%) were randomly assigned to the ACE group, while 63 participants (51.6%) were assigned to the Non-acupoint Catgut Embedding (NACE) group. There were no differences in demographic characteristics between the two groups, as shown in Table 2. During the 12-week treatment and 4-week follow-up, 118 participants (96.72%) had complete appetite data.

Table 2 Baseline Participant Characteristics

Figure 3 Study flow diagram.

Appetite Outcome

Figure 4 and Table 3 depict the effects of the intervention on the outcome using interaction plots with marginal estimated values. In participants who reported strong appetite at baseline, the ACE group observed a decrease in the mean appetite VAS score from 7.78 (0.66) at baseline to 5.00 (0.72) at 16 weeks. Meanwhile, the NACE group observed a decrease in the mean appetite VAS score from 7.97 (0.93) at baseline to 6.54 (1.17), as shown in Table 4. In participants who reported moderate appetite at baseline, the ACE group observed a decrease in the mean appetite score from 5.70 (0.61) to 4.5 (0.81), while the NACE group observed a decrease from 5.56 (0.57) to 5.23 (0.99).

Table 3 Intervention Effects Stratified by Appetite VAS at Baseline

Table 4 Observed Outcomes at All Assessment Occasions

Figure 4 Intervention effects on appetite VAS score at different time points stratified by appetite VAS score at baseline. (A) Strong appetite: Appetite VAS scores decreased from baseline to 16 weeks in both groups, with a sharper decline in the ACE group (red line) compared with the NACE group (blue line). (B) Moderate appetite: Appetite VAS scores also decreased, though less steeply compared with strong appetite. The ACE group again showed a greater reduction compared with the NACE group.

Among participants with a strong appetite at baseline, a significant interaction between time and intervention was observed, with a 54.5% reduction in appetite scores at 12 weeks and a 58.9% reduction at 16 weeks in the ACE group compared to the NACE group (adjusted relative rate ratios [ARRR], 0.455 [95% CI, 0.293 to 0.707] at 12 weeks; 0.411 [95% CI, 0.210 to 0.534] at 16 weeks; both P < 0.05), as shown in Table 3. In contrast, among those with moderate appetite at baseline, no significant differences in appetite score changes were observed at either 12 or 16 weeks (P > 0.05). At 12 weeks, intervention effects differed significantly between participants with strong and moderate appetite (ARRR, 0.455 [95% CI, 0.293 to 0.707] vs 0.674 [95% CI, 0.408 to 1.115]; P for group interaction = 0.000). By 16 weeks, this interaction effect was no longer significant (ARRR, 0.411 [95% CI, 0.210 to 0.534] vs 0.608 [95% CI, 0.359 to 1.031]; P for group interaction = 0.114).

Table 5 presents the P values for differences in estimated marginal means (Standard Error [SE]) of appetite scores between participants with strong and moderate appetite statuses at each time point, separately within the ACE and NACE groups. In the ACE group, a significant difference in appetite scores was observed between participants with strong and moderate appetites at baseline (P < 0.05), but this difference was no longer significant by week 16 (P > 0.05). In the NACE group, appetite scores remained significantly different between participants with strong and moderate appetites at all time points (P < 0.05).

Table 5 Appetite Score Comparison Between Strong and Moderate Appetite Status at Each Time Point

Discussion

In this secondary analysis, we found that ACE intervention has a regulatory effect on subjective appetite in overweight and obese individuals, suggesting that this intervention can promote changes in appetite. This finding aligns with previous studies on acupuncture-based interventions, which reported reductions in appetite and improvements in weight management outcomes.33–35 By stratifying participants according to baseline appetite levels, this study provides new insights into the differential effects of ACE that may not have been captured by studies focusing solely on mean outcomes. Specifically, obese and overweight adults with strong baseline appetite in the ACE group showed a sustained reduction in subjective appetite scores, while those with moderate appetite did not exhibit significant changes. By week 16, the significant differences in baseline appetite scores became non-significant, possibly due to ACE intervention balancing appetite without excessively suppressing it.

Our findings suggest that ACE has potential as an alternative approach for appetite regulation. Beyond weight management, ACE may also be beneficial for treating appetite-related disorders such as binge eating disorder and metabolic syndrome.36,37 In addition, a key advantage of ACE is its ability to adaptively modulate appetite, enhancing satiety without completely suppressing hunger. This balanced regulation promotes healthy eating behaviors, which are essential for long-term weight control, and reduces the risk of compensatory behaviors, such as binge eating, which could undermine weight loss efforts.38,39

The mechanism by which ACE regulates appetite remains unclear. As an evolved form of acupuncture, ACE is based on the efficacy of acupoints and shares similar mechanisms with acupuncture.18 Prior studies have shown that acupuncture activates vagal afferents, which enhance satiety perception and regulate appetite.40 This vagal activation allows for timely detection of gastric distension and changes in gut hormone levels, transmitting satiety signals to the central nervous system. Subsequently, this triggers the release of anorexigenic peptides, such as pro-opiomelanocortin (POMC), to terminate feeding behavior.41,42 Prolonged excessive energy intake in individuals with obesity can impair these mechanisms, reducing vagal excitability and increasing the expression of orexigenic peptides such as neuropeptide Y (NPY), leading to disrupted appetite control and energy imbalance.43 By activating the vagus nerve, acupuncture may help restore the balance between anorexigenic and orexigenic signals, thereby improving appetite control. Acupuncture has also been shown to regulate dopaminergic pathways from the ventral tegmental area (VTA) to the nucleus accumbens, and serotonergic pathways from the dorsal raphe nucleus to the VTA.44 These pathways are essential components of the reward system, which plays a key role in regulating food intake.45 In individuals with obesity, these pathways are often disrupted, resulting in heightened sensitivity to food-related pleasure, excessive eating, and compulsive eating behaviors.46 By modulating these pathways, acupuncture may help reduce the reward-driven urge to overeat and restore normal appetite control. With embedded sutures providing prolonged acupoint stimulation, ACE may enhance these regulatory effects, resulting in more stable appetite control over time. These potential mechanisms may help explain our findings, the sustained reductions in appetite observed among participants with strong baseline appetite following ACE intervention. In contrast, participants with moderate appetite showed no significant changes, suggesting that ACE helps balance appetite rather than simply suppress it. Future studies should further explore these pathways to better understand the mechanisms involved and enhance the clinical use of ACE for appetite management.

This study has several limitations. The small sample size and secondary nature of the analysis limit the generalizability of our findings. Additionally, the study focused only on participants with moderate and strong appetite, excluding those with light appetite. Future research should include a larger and more diverse sample to validate these findings and explore the impact of ACE across different appetite states. Longer follow-up periods are also necessary to assess the sustainability of ACE’s effects. Furthermore, mechanistic studies are essential to better understand the pathways involved and inform strategies for effective clinical use of ACE.

Conclusion

In a secondary analysis of this randomized clinical trial, ACE significantly reduced appetite scores in overweight and obese individuals with high baseline appetite, while those with moderate appetite showed no significant change. These findings suggest that ACE effectively reduces appetite without over-suppressing it. This balanced regulation fosters healthy eating behaviors, making ACE a promising strategy for sustainable, long-term obesity management. However, further research is needed to validate these findings across more diverse populations and explore the long-term sustainability of ACE. Mechanistic studies are especially required to clarify the neural and metabolic pathways involved, thereby strengthening the theoretical basis for ACE as an effective approach to appetite management.

Data Sharing Statement

Data will be available upon request from the corresponding author.

Ethics and Consent Statements

This study was conducted in strict adherence to the Helsinki Declaration of Principles. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR1800016947) and approved by the Ethics Committee of Yunnan Sports Trauma Specialist Hospital (2018CK-001). Informed consent was obtained from all patients to be included in the study.

Acknowledgments

We would like to express our sincere gratitude to the Yunnan Sports Trauma Specialist Hospital for providing supervision and support during the original data collection process, which laid the foundation for the reanalysis reported in this study.

Funding

This work was funded by the National Natural Science Foundation of China (82260964), the “Liang Fanrong Expert Workstation” of Yunnan Province-Yunnan Provincial Science and Technology Plan Project (202305AF150072), the Youth Special of Yunnan Province Ten-thousand Plan (YNWR-QNBJ-2019-257). The funding bodies do not play any role in the design of the study, collection, analysis, or writing manuscripts.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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