Abstract
Objective
To investigate the impact of a high-protein diet (HPD) versus a calorie-restricted diet (CRD) on weight loss and biochemical indicators improvement in overweight and obese individuals.
Methods
63 overweight or obese patients were enrolled, with 32 individuals assigned to the HPD group and 31 to the CRD group, each undergoing a 24-week intensive lifestyle intervention. Changes in key parameters, including body weight, body mass index (BMI), waist circumference, hip circumference, body fat percentage, glycosylated hemoglobin (HbA1c), blood glucose, insulin, adiponectin, free fatty acids, homeostasis model assessment of insulin resistance (HOMA-IR), and other relevant indicators were observed before and after the intervention.
Results
A total of 63 overweight/obese participants participated in this study, and the baseline characteristics were similar between the two groups. After a 24-week intervention, the HPD group showed significantly greater reductions in body weight, BMI, waist circumference, and body fat percentage (all P < 0.05), as well as a higher proportion of participants achieving clinically significant weight loss (≥ 10%) compared to the CRD group (58.1% vs. 19.4%, P = 0.006). Regarding biochemical indicators, the HPD group also demonstrated superior improvements in HbA1c, 2‑hour postprandial blood glucose, free fatty acids, and adiponectin. However, no significant differences between the groups were observed in changes in HOMA-IR, lipid profiles, and adiponectin levels.
Conclusion
Both HPD and CRD are effective strategies for achieving weight loss, improving biomarkers of metabolic syndrome in overweight and obese patients. Notably, HPD has a superior effect on weight loss, being able to significantly improve central obesity, reduce body fat percentage, and improve glycemic control as well as adipocytokine profiles.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1186/s12986-026-01163-8.
Keywords: Obesity, High-protein diet, Calorie-restricted diet, Weight loss, Body composition
Introduction
According to a comprehensive global pooled analysis of 3663 population-representative studies published in the Lancet, the worldwide prevalence of obesity is increasing dramatically. Since 1990, with prevalence of adult obesity has doubled in women and nearly tripled in men. Concurrently, the situation in China mirrors this global trend, with a multicenter cross-sectional survey conducted in 2022 across 10 provinces and encompassing 62,893 adults indicating that the overweight prevalence among Chinese adults has reached 34.29%, while the obesity prevalence is at 11.24% [1]. This data underscores a significant public health challenge consistent with global patterns. Overweight and obesity are well-established risk factors for a variety of chronic diseases in adults. It is widely acknowledged that obesity-induced inflammatory responses, dysregulation of glucose and lipid metabolism, and insulin resistance are critical contributors to the onset and progression of metabolic diseases such as type 2 diabetes and cardiovascular diseases [2]. The Prolonged and excessive accumulation of adipose tissue can result in its dysfunction, subsequently promoting the release of pro-inflammatory, pro-diabetic, and pro-atherosclerotic signals. These signals include adipokines, elevated free fatty acids due to enhanced lipolysis, various metabolites, and immune mediators. These factors may contribute to end-organ damage, affecting the liver, skeletal muscle, pancreas, and vasculature, and lead to the development of metabolically unhealthy obesity [3, 4].
Current clinical management strategies for obesity primarily involve three approaches: lifestyle interventions, pharmacotherapy, and bariatric surgery. Dietary and exercise interventions are fundamental to weight loss, as they operate on the principle of achieving a negative energy balance. Evidence indicates that personalized dietary and physical activity programs, based on scientific assessment, can effectively facilitate weight control [5]. Numerous studies, both within China and internationally, have demonstrated the efficacy of meal replacements [6], calorie-restricted diets (CRD) [7], and high-protein diets (HPD) [8, 9] in reducing body weight, decreasing adiposity, and improving metabolic parameters. However, there remains a comparative lack of research investigating the effects of CRD versus HPD on weight loss, body composition and biochemical indicators improvement in individuals with overweight and obesity. Therefore, this study aims to evaluate and compare the effects of CRD and HPD on weight loss, body composition and biochemical indicators improvement in overweight or obese patients. The anticipated outcomes are expected to provide a comprehensive evaluation of the benefits associated with these dietary interventions and contribute new evidence and insights for the management of obesity.
Method
Study participants
This retrospective study was conducted on 63 overweight and obese patients who visited the Obesity Clinic at Dongguan People’s Hospital from January 2023 to June 2024. The patients were divided into two groups based on their dietary patterns over 24 weeks: 32 patients received a high-protein diet (HPD), and 31 patients received a calorie-restricted diet (CRD). Inclusion criteria were age 18–65 years, overweight or obesity as defined by Chinese criteria (BMI ≥ 24.0 kg/m²), and provision of written informed consent. Key exclusion criteria included secondary obesity; pregnancy or lactation; severe comorbidities (e.g., hepatic or renal insufficiency, coronary heart disease, malignancy); history of bariatric surgery; psychiatric disorders; substance abuse; use of anti-obesity medication; or recent significant weight change (> 2% within the previous 3 months). The study protocol was approved by the Ethics Committee of Dongguan People’s Hospital (Approval No.: KYKT2021-062; Medical Research Registration Record No.MR-44-23-023870). All participants provided written informed consent prior to enrollment.
Dietary pattern
A retrospective analysis was conducted on patients who participated in a 24-week lifestyle intervention program. All participants received comprehensive health education on lifestyle modification. Certified dietitians from the research team provided standardized tableware and pre-portioned foods, using the food exchange system to guide daily food choices and portion control.
Individualized nutrition plans were developed according to each participant’s ideal body weight (calculated as height in cm minus 105), body fat percentage, and physical activity level, accompanied by precise calculations of daily caloric requirements. Participants in the HPD group were prescribed a diet with total energy intake controlled at 20–25 kcal·kg⁻¹ ideal body weight per day. Protein intake constituted 20–30% of total daily energy, equating to approximately 1.0–1.9 g·kg⁻¹ ideal body weight per day. Protein was obtained primarily from high-quality natural sources such as lean meats and eggs, supplemented with a daily standardized protein bar. Participants in the CRD group maintained a prescribed daily energy intake of 1000–1400 kcal, creating an estimated deficit of 500–1000 kcal. Protein intake constituted 15–20% of total daily energy, corresponding to approximately 0.7–1.2 g·kg⁻¹ ideal body weight per day. Emphasis was placed on high-fiber, low-energy-density foods to enhance satiety.
All participants followed a structured exercise protocol comprising ≥ 150 min (optimally 200–300 min) of moderate-intensity aerobic activity per week, distributed over 3–7 sessions lasting 30–90 min each, supplemented by resistance training 2–3 times per week on non-consecutive days. To ensure adherence, dedicated dietitians and health coaches conducted daily monitoring via WeChat, requiring participants to photograph and submit all meals before consumption for real-time dietary assessment and adjustment, thereby ensuring strict compliance with the program.
Follow-up and outcome measures
Assessments were conducted at enrollment (V0), 4 weeks (V1), 12 weeks (V2), and 24 weeks (V3) post-enrollment to evaluate the effects of the intervention on body morphology, metabolic parameters, and adipocytokine levels. Basic anthropometric data, including height, weight, waist circumference (WC), and hip circumference (HC), were measured at all four time points. Body composition was assessed using a bioelectrical impedance analyzer (IOI 353), which provided measurements of body fat percentage (PBF), skeletal muscle mass (SMM), and visceral fat area (VFA). Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated as BMI = weight (kg) / height (m)² and WHR = WC (cm) / HC (cm), respectively.
Fasting biochemical parameters—including renal function, liver function, and blood lipids—were assessed at V0, V2, and V3. In addition, fasting adiponectin (measured by immunoturbidimetric assay; reference range: ≥5 µg/mL) and free fatty acids (FFA; measured by enzymatic colorimetric method; reference range: 0.10–0.76 mmol/L) were measured at V0 and V3. All participants underwent a one-time HbA1c test and an oral glucose tolerance test (OGTT) at baseline, with blood glucose, insulin, and C-peptide levels measured at 0 and 120 min. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated as [fasting insulin (FINS, µIU/mL) × fasting plasma glucose (FPG, mmol/L)] / 22.5, and the triglyceride-glucose index (TyG) was derived as ln [fasting triglycerides (mg/dL) × FPG (mg/dL) / 2].
Statistical analysis
Statistical analyses were performed using SPSS 26.0 and R version 4.4.1. Normality of continuous variables was assessed using the Shapiro-Wilk test; the results are summarized in Supplementary Table S1. Variables that followed a normal distribution in both groups are presented as mean±standard deviation (SD) and were compared between groups using the independent-samples t-test (Levene’s test confirmed equal variances). Variables that deviated from normality in either group are presented as median (interquartile range, IQR) and were compared using the Mann-Whitney U test, after visual confirmation that the distribution shapes were broadly similar between groups. Within-group changes across the four time points (baseline, 4 weeks, 12 weeks, and 24 weeks) were analyzed using Friedman’s two-way ANOVA by ranks; significant main effects were followed by post-hoc pairwise comparisons with Bonferroni correction. Categorical variables are expressed as frequencies (percentages) and were compared using the χ² test or Fisher’s exact test. All tests were two‑tailed, with P < 0.05 considered statistically significant. Additionally, to evaluate the interaction between diet type (HPD vs. CRD) and time (baseline, 4-week, 12-week, and 24-week), a two-way repeated-measures ANOVA was performed on four key indicators: body weight, BMI, waist circumference, and body fat percentage. The significance level for the interaction effect was set at P < 0.05.
Results
Baseline characteristics
This study ultimately enrolled 63 overweight/obese patients, with 32 assigned to the HPD group and 31 to the CRD group. The sample size of this study has been confirmed through post hoc power analysis, indicating that the current research has an adequate sample size to detect the statistical differences observed. As presented in Table 1, the two groups demonstrated comparable baseline characteristics regarding demographic features, anthropometry, body composition, and metabolic profiles. Specifically, no statistically significant differences (all P > 0.05) were observed in gender distribution, age, body weight, BMI, or WHR. Body composition analysis further confirmed balanced baseline parameters including PBF, VFA, and SMM (all P > 0.05). Metabolic indicators—HbA1c, FPG, 2hPBG, and HOMA-IR—also showed no significant intergroup differences. Additionally, lipid profiles, hepatic and renal function markers, and adipocytokine levels (adiponectin and FFA) exhibited consistent baseline values (all P > 0.05). Notably, although waist circumference and LDL-C approached borderline significance, all other measured parameters satisfied the criterion of P > 0.05, collectively demonstrating the comparability of baseline characteristics between the two groups.
Table 1.
Baseline characteristics of study participants
| HPD (n = 31) | CRD (n = 31) | Test statistic | P value | |
|---|---|---|---|---|
| Gender, n (%) | χ² (1) = 0.076 | 0.783 | ||
| Male | 10 (31.3%) | 9 (29.0%) | ||
| Female | 21 (68.7%) | 22 (71.0%) | ||
| Age (years) | 32.7 ± 8.8 | 30.9 ± 7.4 | t (60) = 0.85 | 0.402 |
| Height (cm) | 164.4 ± 8.0 | 163.3 ± 9.2 | U = 431.0, Z=-0.698 | 0.49 |
| Weight (kg) | 80.20 (70.60, 92.20) | 75.50 (67.40, 89.73) | U = 363.5, Z=-1.647 | 0.1 |
| BMI (kg/m2) | 30.19 (27.11, 32.74) | 28.42 (26.35, 31.86) | U = 360.0, Z=-1.697 | 0.091 |
| Waist circumference (cm) | 98.00(91.00, 107.00) | 92.00(86.00, 102.00) | U = 331.0, Z=-1.697 | 0.035 |
| Hip circumference (cm) | 104.00 (96.00, 111.38) | 101.00 (95.00, 108.00) | U = 399.0, Z=-1.148 | 0.254 |
| Waist-hip ratio | 0.95 (0.90, 0.98) | 0.94 (0.90, 0.97) | U = 371.0, Z=-1.546 | 0.124 |
| Body fat percentage (%) | 35.20 (31.30, 38.00) | 34.20 (31.90, 36.10) | U = 442.0, Z=-0.542 | 0.593 |
| SMM (kg) | 48.05 (43.45, 57.33) | 43.80 (40.23, 53.95) | U = 337.0, Z=-2.021 | 0.043 |
| VFA (cm2) | 110.00 (77.25, 127.75) | 114.50 (86.00, 128.75) | U = 473.0, Z=-0.106 | 0.919 |
| HbA1c (%) | 5.60 (5.30, 6.03) | 5.60 (5.40, 5.80) | U = 354.5, Z=-1.779 | 0.076 |
| FBG (mmol/L) | 5.05(4.60, 5.47) | 4.85(4.50, 5.20) | U = 363.0, Z=-1.655 | 0.099 |
| 2 h PBG (mmol/L) | 7.40 (6.60, 9.72) | 7.50(6.30, 8.50) | U = 322.0, Z=-2.232 | 0.025 |
| FINS (uIU/mL) | 12.82 (9.62, 15.91) | 16.60(10.50, 22.70) | U = 476.0, Z=-0.063 | 0.953 |
| 2hINS (uIU/mL) | 70.59 (44.23, 105.42) | 116.32(66.72, 168.37) | U = 393.5, Z=-1.225 | 0.224 |
| HOMA-IR | 2.99(2.08, 4.42) | 3.74 (2.24, 5.18) | U = 438.5, Z=-0.591 | 0.559 |
| Creatinine (umol/L) | 60.60 (52.00, 68.00) | 62.00 (52.00, 74.00) | U = 430.0, Z=-0.711 | 0.482 |
| Uric acid (umol/L) | 388.50 (331.50, 460.90) | 388.60 (330.20, 460.20) | U = 441.0, Z=-0.556 | 0.585 |
| Total cholesterol (mmol/L) | 5.1 ± 0.8 | 4.8 ± 0.6 | t (60) = 1.47 | 0.148 |
| Triglycerides (mmol/L) | 1.37(1.12, 1.83) | 1.15(0.98, 1.67) | U = 371.5, Z=-1.535 | 0.126 |
| LDL-C (mmol/L) | 3.3 ± 0.6 | 3.1 ± 0.5 | t (60) = 1.78 | 0.081 |
| HDL-C (mmol/L) | 1.17 (1.04, 1.28) | 1.14 (1.03, 1.28) | U = 476.0, Z=-0.063 | 0.953 |
| ALT (U/L) | 30.00(18.00, 59.00) | 23.00 (16.00, 46.25) | U = 390.0, Z=-1.275 | 0.205 |
| AST (U/L) | 25.00(18.00, 33.50) | 20.00 (16.00, 28.80) | U = 370.0, Z=-1.557 | 0.121 |
| Adiponectin (µg/ml) | 6.42 (5.44, 7.65) | 8.12(5.48, 9.12) | U = 333.0, Z=-2.077 | 0.038 |
| FFA (mmol/L) | 0.72 (0.58, 0.86) | 0.71 (0.64, 0.86) | U = 356.5, Z=-1.747 | 0.081 |
HPD: high protein diet; CRD: calorie restricted diet; BMI: body mass index; SMM: skeletal muscle mass; VFA: visceral fat area; HbA1c: glycosylated hemoglobin; FPG: fasting plasma glucose; 2hPBG: 2-hour postprandial blood glucose; FINS: fasting insulin; 2hINS: 2-hour insulin; HOMA-IR: homeostasis model assessment of insulin resistance; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; ALT: alanine aminotransferase; AST: aspartate aminotransferase; FFA: free fatty acids
Changes in body composition following intervention
Both dietary interventions led to significant improvements in anthropometric parameters over the 24-week study period. However, the HPD demonstrated a superior effect on key measures of weight loss and body composition compared to the CRD. As illustrated in Fig. 1, the HPD group achieved significantly greater body weight reduction than the CRD group at all follow-up assessments (4 weeks: P = 0.001; 12 weeks: P < 0.001; 24 weeks: P < 0.001). This superior efficacy was further confirmed by the absolute change data at 24 weeks (Table 2) and the distribution of weight loss responders presented in Fig. 4. After 24 weeks, a significantly higher proportion of participants in the HPD group achieved clinically meaningful weight loss (≥ 10%) compared to the CRD group (58.1% vs. 19.4%, P = 0.006).
Fig. 1.
Value of weight loss between HPD and CRD during follow-up
Table 2.
Absolute changes in anthropometric and body composition indicators in the completers of both diet groups from baseline
| Baseline | 4 weeks | 12 weeks | 24 weeks | Absolute change | ||||
|---|---|---|---|---|---|---|---|---|
| median (IQR) | median (IQR) | median (IQR) | median (IQR) | median (IQR) | Test statistic | P value | ||
| Weight (kg) | U = 211.00, Z=-3.795 | < 0.001 | ||||||
| HPD | 80.20 (70.60, 92.20) | 82.60(70.60,93.50)a | 79.70 (68.20, 90.6)b | 77.80(65.40, 85.70)b | -10.2(-15.00,-7.00) | |||
| CRD | 75.50 (67.40, 89.73) | 76.00(67.40,90.30)a | 74.90 (66.40, 89.20)b | 72.30(65.80, 86.20)b | -5.4(-7.90,-4.00) | |||
| BMI (kg/m2) | U = 206.00, Z=-3.865 | < 0.001 | ||||||
| HPD | 30.19 (27.11, 32.74) | 31.02(27.51,32.67)a | 29.92(26.41, 31.57)b | 29.69 (25.55, 30.49)b | -3.77(-5.46,-2.54) | |||
| CRD | 28.42 (26.35, 31.86) | 28.51(26.47,31.49)a | 27.91 (25.87, 30.89)b | 27.23 (25.21, 30.43)b | -2.03 (-2.97, -1.51) | |||
| Waist circumference (cm) | U = 259.50, Z=-3.119 | 0.002 | ||||||
| HPD | 98.00(91.00, 107.00) | 101.00(92.50,108.00)a | 97.00(89.00,104.00)b | 94.00 (85.00, 99.00)b | -12.50 (-14.00, -11.00) | |||
| CRD | 92.00(86.00, 102.00) | 92.00 (87.00,102.00)a | 90.00(85.00,100.00)b | 88.00 (82.00, 93.00)b | -9.50(-12.00, -8.00) | |||
| Hip circumference (cm) | U = 382.50, Z=-1.384 | 0.169 | ||||||
| HPD | 104.00 (96.00, 111.38) | 106.00(97.00,112.00)a | 104.00(95.00,110.00)a | 101.00(92.00,105.00)b | -11.00(-14.00, -8.00) | |||
| CRD | 101.00 (95.00, 108.00) | 102.00(96.00,110.00)a | 99.00 (93.00,107.00)b | 96.00 (92.00,103.00)b | -10.00 (-12.00, -8.00) | |||
| Waist-hip ratio | t(60) = -1.12 | 0.269 | ||||||
| HPD | 0.95 (0.90, 0.98) | 0.96(0.90, 0.98) | 0.95 (0.89, 0.97)b | 0.95 (0.90, 0.97)a | -0.02 (-0.03, 0.00) | |||
| CRD | 0.94 (0.90, 0.97) | 0.94 (0.89, 0.97) | 0.95 (0.90, 0.98) | 0.93 (0.91, 0.96) | -0.01 (-0.03, 0.00) | |||
| Body fat percentage (%) | U = 318.00, Z=-2.290 | 0.021 | ||||||
| HPD | 35.20 (31.30, 38.00) | 33.70 (31.30, 38.70)a | 30.20 (32.60, 37.60)b | 31.40 (27.60, 36.50)b | -4.40 (-6.00, -2.90) | |||
| CRD | 34.20 (31.90, 36.10) | 34.50 (31.90, 36.20)a | 33.60 (31.00, 35.30)b | 32.30 (30.10, 35.00)b | -3.40 (-3.90, -2.60) | |||
| SMM (kg) | U = 416.00, Z=-0.909 | 0.361 | ||||||
| HPD | 48.05 (43.45, 57.33) | 48.30(43.60, 57.60) | 47.80 (43.10, 57.10)b | 46.30(40.60, 57.00)b | -3.30 (-4.50, -2.00) | |||
| CRD | 43.80 (40.23, 53.95) | 44.30 (40.60, 54.50)a | 43.60(40.00, 53.80)b | 42.90 (39.10, 51.20)b | -2.60 (-3.60, -2.10) | |||
| VFA (cm2) | U = 384.00, Z=-1.360 | 0.176 | ||||||
| HPD | 110.00 (77.25, 127.75) | 112.00(80.00,127.00)a | 107.00(75.00,122.00)b | 103.00(71.00,118.00)b | -24.00(-38.00, -18.00) | |||
| CRD | 114.50 (86.00, 128.75) | 118.00(86.00,128.00)a | 112.00(80.00,122.00)b | 103.00(78.00,115.00)b | -19.00(-29.00, -15.00) | |||
HPD: high protein diet; CRD: calorie restricted diet; BMI: body mass index; SMM: skeletal muscle mass; VFA: visceral fat area.Note: aP < 0.05 versus baseline; bP < 0.001 versus baseline
Fig. 4.
The proportion of weight loss percentage between HPD and CRD after 24 weeks
A similar time-dependent advantage for HPD was observed for waist circumference and body fat percentage. Although no significant between-group difference was found at 4 weeks (P = 0.117), the HPD group showed substantially greater reductions in waist circumference at both 12 weeks (P < 0.001) and 24 weeks (P = 0.023) compared to the CRD group (Fig. 2). Likewise, for body fat percentage, the HPD group’s advantage became statistically significant from the 12-week assessment onward (12 weeks: P = 0.011; 24 weeks: P = 0.024, Fig. 3), which was consistent with the significant between-group difference in the absolute change at 24 weeks (Table 2). In contrast, changes in hip circumference, waist-to-hip ratio, skeletal muscle mass, and visceral fat area were comparable between the two groups at the study endpoint (all P > 0.05, Table 2).
Fig. 2.
Value of waist circumference (WC) loss between HPD and CRD during follow-up
Fig. 3.
Percentage of body fat loss between HPD and CRD during follow-up
Changes in biochemical indicators following intervention
Both groups showed significant improvements in metabolic parameters following the 24-week intervention. The between-group comparisons of absolute changes from baseline are summarized in Table 3. Compared with the CRD group, the HPD group achieved significantly greater reductions in HbA1c, 2-hour postprandial blood glucose (2hPBG), adiponectin, and free fatty acids (FFA) (all P < 0.05). No significant intergroup differences were observed in the improvements of fasting plasma glucose (FPG), fasting insulin (FINS), 2-hour postprandial insulin (2hINS), homeostatic model assessment for insulin resistance (HOMA-IR), uric acid, lipid profiles, alanine transaminase (ALT), and aspartate transaminase (AST) (all P > 0.05). An exception was serum creatinine, for which the CRD group showed a significantly greater reduction (P < 0.05).
Table 3.
Absolute changes in biochemical indicators in the completers of both groups from baseline
| Baseline | 12 weeks | 24 weeks | Absolute change | |||
|---|---|---|---|---|---|---|
| Mean ± SD / Median (IQR) | Mean ± SD / Median (IQR) | Mean ± SD / Median (IQR) | Mean ± SD / Median (IQR) | Test statistic | P value | |
| HbA1c (%) | U = 286.50, Z=-2.776 | 0.005 | ||||
| HPD | 5.60 (5.30, 6.03) | - | 5.40 (5.30, 5.60)b | 0.30(0.30,1.20) | ||
| CRD | 5.60 (5.40, 5.80) | 5.30 (5.20, 5.50)b | 0.20(0.20,0.30) | |||
| FBG (mmol/L) | U = 382.00, Z=-1.388 | 0.167 | ||||
| HPD | 5.05(4.60, 5.47) | 4.78 (4.35, 5.20)b | 5.02(4.60, 5.17)b | 0.45(0.10,1.29) | ||
| CRD | 4.85(4.50, 5.20) | 4.80 (4.60, 5.30) | 4.60 (4.30, 5.10)b | 0.31(0.10,0.60) | ||
| 2hPBG (mmol/L) | U = 303.00, Z=-2.501 | 0.012 | ||||
| HPD | 7.40 (6.60, 9.72) | - | 6.80 (6.18, 7.30)b | 2.38(0.67,4.30) | ||
| CRD | 7.50(6.30, 8.50) | - | 6.70 (5.90, 7.20)b | 0.60(0.20,2.12) | ||
| FINS (uIU/mL) | U = 476.50, Z=-0.056 | 0.958 | ||||
| HPD | 12.82 (9.62, 15.91) | - | 2.35 (1.99, 3.07)b | 3.76(1.10,8.01) | ||
| CRD | 16.60(10.50, 22.70) | - | 11.32 (8.20, 16.72)b | 2.66(1.69,6.30) | ||
| 2hINS (uIU/mL) | U = 412.00, Z=-0.964 | 0.341 | ||||
| HPD | 70.59 (44.23, 105.42) | - | 66.70 (41.88, 86.40)a | 27.50(7.81,64.53) | ||
| CRD | 116.32(66.72, 168.37) | - | 74.62(42.17, 88.73)b | 35.41(18.54,96.26) | ||
| HOMA-IR | U = 429.00, Z=-0.718 | 0.478 | ||||
| HPD | 2.99(2.08, 4.42) | - | 2.35 (1.99, 3.07)b | -1.27(-2.64,-0.48) | ||
| CRD | 3.74 (2.24, 5.18) | - | 2.33 (1.66, 3.64)b | -0.80(-1.65,-0.45) | ||
| Creatinine (umol/L) | U = 298.00, Z=-2.570 | 0.01 | ||||
| HPD | 60.60 (52.00, 68.00) | 62.00 (52.00, 70.40) | 60.00 (52.00, 66.80) | -1.00(-6.00,7.90) | ||
| CRD | 62.00 (52.00, 74.00) | 66.00 (50.00, 75.40)a | 60.00 (47.00, 70.00)a | -7.00(-9.00,-4.00) | ||
| Uric acid (umol/L) | U = 469.00, Z=-0.162 | 0.878 | ||||
| HPD | 388.50 (331.50, 460.90) | 374.70 (303.00, 448.10)b | 370.40 (322.60, 418.90)b | -42.80(-85.00,-28.20) | ||
| CRD | 388.60 (330.20, 460.20) | 388.60(346.20, 479.60)b | 346.20(288.70, 421.80)b | -50.70(-91.80,-19.40) | ||
| Total cholesterol (mmol/L) | U = 465.00, Z = 0.218 | 0.831 | ||||
| HPD | 5.1 ± 0.8 | 4.8 ± 0.8 | 4.7 ± 0.8a | -0.5 ± 0.8 | ||
| CRD | 4.8 ± 0.6 | 4.4 ± 0.9 | 4.2 ± 0.9b | -0.5 ± 0.6 | ||
| Triglycerides (mmol/L) | U = 470.50, Z=-0.141 | 0.892 | ||||
| HPD | 1.37(1.12, 1.83) | 1.40 (0.98, 1.80)b | 1.22 (1.11, 1.61)b | -0.37(-0.89,-0.08) | ||
| CRD | 1.15(0.98, 1.67) | 1.15(0.93, 1.70)a | 1.03 (0.82, 1.52)b | -0.32(-0.64,-0.12) | ||
| LDL-C (mmol/L) | U = 412.00, Z=-0.965 | 0.339 | ||||
| HPD | 3.3 ± 0.6 | 3.0 ± 0.6 | 3.0 ± 0.5 | -0.3 ± 0.5 | ||
| CRD | 3.1 ± 0.5 | 2.8 ± 0.7 | 2.7 ± 0.6 | -0.4 ± 0.7 | ||
| HDL-C (mmol/L) | U = 443.00, Z=-0.528 | 0.602 | ||||
| HPD | 1.17 (1.04, 1.28) | 1.13 (1.02, 1.25) | 1.19 (1.06, 1.29) | 0.04(-0.13,0.20) | ||
| CRD | 1.14 (1.03, 1.28) | 1.08 (1.02, 1.26) | 1.17 (1.07, 1.31)b | 0.05(-0.09,0.09) | ||
| ALT (U/L) | U = 452.50, Z=-0.394 | 0.698 | ||||
| HPD | 30.00(18.00, 59.00) | 30.00 (20.00, 58.00)a | 25.00 (15.00, 32.00)a | -13.00(-58.00,-3.00) | ||
| CRD | 23.00 (16.00, 46.25) | 23.00 (16.00, 47.00)a | 20.00 (13.00, 30.00)b | -7.00(-36.90,-4.00) | ||
| AST (U/L) | U = 457.00, Z=-0.331 | 0.745 | ||||
| HPD | 25.00(18.00, 33.50) | 22.00 (19.00, 33.00)a | 20.00 (15.00, 26.00)b | -8.00(-28.60,-3.00) | ||
| CRD | 20.00 (16.00, 28.80) | 20.00 (17.00, 30.00) | 16.00 (15.00, 20.00)b | -7.00(-18.70,-3.00) | ||
| Adiponectin (µg/ml) | U = 281.00, Z=-2.809 | 0.004 | ||||
| HPD | 6.42 (5.44, 7.65) | - | 7.17 (5.66, 8.03)a | -1.01(-1.38,-0.67) | ||
| CRD | 8.12(5.48, 9.12) | - | 8.88 (5.93, 9.78)b | -0.58(-0.91,-0.41) | ||
| FFA (mmol/L) | U = 280.00, Z=-2.825 | 0.004 | ||||
| HPD | 0.72 (0.58, 0.86) | - | 0.61(0.53, 0.71)a | 0.20(0.12,0.26) | ||
| CRD | 0.71 (0.64, 0.86) | - | 0.61 (0.54, 0.71)b | 0.11(0.07,0.19) | ||
HPD: high protein diet; CRD: calorie restricted diet; HbA1c: glycosylated hemoglobin; FPG: fasting plasma glucose; 2hPBG: 2-hour postprandial blood glucose; FINS: fasting insulin; 2hINS: 2-hour insulin; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; HOMA-IR: homeostasis model assessment of insulin resistance; ALT: alanine aminotransferase; AST: aspartate aminotransferase; FFA: free fatty acids
a P < 0.05 versus baseline; b P < 0.001 versus baseline.
Interaction analysis
To further assess the interactive effects of diet type and time on body composition indicators, a two-way repeated-measures ANOVA was conducted. The results revealed no statistically significant interaction in the temporal trends of changes in body weight, BMI, waist circumference, or body fat percentage between the two groups (as shown in Figs. 5, 6, 7 and 8: body weight: P = 0.173; BMI: P = 0.395; waist circumference: P = 0.612; body fat percentage: P = 0.415). Nevertheless, as illustrated in Figs. 1, 2, 3 and 4, the HPD group exhibited substantially greater reductions across all measures compared to the CRD group, suggesting that HPD yields more favorable outcomes in weight loss and body composition improvement, although the change patterns between the two groups did not differ statistically.
Fig. 5.
Trajectories of body weight change over time in the HPD and CRD groups
Fig. 6.
Trajectories of BMI change over time in the HPD and CRD groups
Fig. 7.
Trajectories of waist circumference change over time in the HPD and CRD groups
Fig. 8.
Trajectories of body fat percentage change over time in the HPD and CRD groups
Discussion
Obesity, as a globally prevalent chronic progressive disease, is not only a central risk factor for various metabolic and cardiovascular diseases but has also emerged as a major public health issue impacting the population in China [3, 10]. Imbalance in adipocytokines plays a critical role in obesity-related metabolic disorders. Medical nutrition therapy serves as the foundation for the comprehensive management of obesity, and comprehensive lifestyle management—combining physical activity and behavioral interventions—has been proven to be an effective weight control strategy for overweight or obese patients [11]. However, the effects of different dietary patterns on adipocytokine levels during weight loss remain a subject of debate.
Regarding weight loss efficacy, this study demonstrated that after 24 weeks of intervention, both the high-protein diet (HPD) and the calorie-restricted diet (CRD) significantly reduced body weight and improved body composition. However, HPD was superior to CRD in terms of the magnitude of reduction in body weight, BMI, and percentage body fat (PBF), as well as the rate of successful weight loss, suggesting that HPD holds an advantage in short-term weight loss interventions. Previous studies have shown some inconsistency when comparing the weight loss effects of HPD and CRD. A meta-analysis by Long Ge et al. indicated that among overweight/obese adults, the differences in weight loss effects between various dietary patterns are limited, and the focus of interventions should be more on patients’ dietary adherence [12]. In contrast, a systematic review by Santesso et al. found that HPD was more effective than a balanced diet in reducing body weight and waist circumference [13]. Another randomized controlled trial (RCT) involving patients with metabolic syndrome showed no significant differences between HPD and a standard-protein diet in waist circumference and blood glucose indicators, apart from body weight [13]. Overall, most studies support the notion that HPD has favorable effects on weight loss. In the present study, the HPD group exhibited a higher rate of successful weight loss (56.3% vs. 19.4%), which may be attributed to the greater satiety it provides, thereby potentially enhancing dietary adherence among participants. Interaction analysis revealed no significant diet-by-time interaction for changes in body weight, BMI, waist circumference, or body fat percentage, indicating that the pattern of change over time did not differ statistically between the two dietary regimens. Nonetheless, the consistently greater absolute reductions observed in the HPD group across all follow-up time points suggest that HPD confers a more pronounced effect on weight loss and body composition within the 24-week intervention period, even in the absence of divergent trajectories of change.
Regarding biochemical indicators improvement, both HPD and CRD in this study improved glycemic parameters and insulin resistance; HPD demonstrated greater reductions in HbA1c and 2‑hour postprandial blood glucose. Mechanistically, high-protein diets primarily act by slowing gastric emptying and reducing postprandial glucose absorption, which selectively improves postprandial glucose excursions rather than basal fasting glucose levels. This explains why the benefit of HPD was more evident for 2-hour postprandial blood glucose than for fasting glucose in the present study. This outcome is not entirely consistent with the findings of a 12-month RCT by Larsen et al., which did not identify a superior advantage of HPD in improving HbA1c [7]. The discrepancy may be attributed to the 24-week intervention period in our study falling within a pronounced effect phase where HPD exerts its metabolic benefits—such as significantly enhancing insulin sensitivity and reducing postprandial glucose. In contrast, during longer-term interventions, the influence of other factors (e.g., overall weight maintenance) may become more prominent, thereby diminishing the differences between dietary patterns [8]. Future studies should extend the follow-up duration to verify the sustained metabolic benefits of HPD. Regarding adipocytokines, this study found that both HPD and CRD increased adiponectin, the HPD group achieved markedly superior outcomes in modulating the adipocytokine profile. Specifically, HPD led to a significantly greater elevation in adiponectin and a more pronounced reduction in free fatty acids (FFA) compared to the CRD group [14]. Multiple studies [15–17] have indicated that weight loss promotes an increase in adiponectin, independent of diet type [18]. Furthermore, studies have shown that the benefits of lifestyle interventions on FFA and insulin resistance can persist for several years [19]. The present study indicates that by achieving greater weight loss, HPD may exert an indirect positive effect on modulating a beneficial adipocytokine profile. Future research should include additional inflammatory and adipokine markers to further elucidate the underlying mechanisms.
Although the HPD has demonstrated various metabolic benefits, the safety of its long-term application requires continued attention. The findings of this study further support its safety in populations with normal renal function: during the 24-week intervention, patients in the HPD group achieved significant reductions in body weight, percentage body fat, and serum uric acid levels, without exhibiting a clinically significant increase in serum creatinine. These findings suggest that short-term HPD intervention did not adversely affect renal function. The results align with previous studies indicating that HPD, while improving metabolic parameters, does not cause clinically meaningful deterioration in glomerular filtration rate or creatinine clearance in individuals with normal renal function [14]. In summary, from the perspectives of weight control, metabolic improvement, and renal safety, this study demonstrates that HPD is an effective and safe dietary intervention for overweight or obese individuals with normal renal function.
This study is subject to several limitations. Its single-center design and focus on the Guangdong population may limit generalizability due to geographical bias. Furthermore, the sample size was relatively small and predominantly comprised young and middle-aged adults, highlighting the need for future studies with larger, more age-diverse cohorts. Finally, the 24-week intervention period and the limited number of adipocytokines assessed warrant extended follow-up and the inclusion of additional biomarkers in future research to evaluate long-term efficacy and elucidate the molecular mechanisms.
Conclusion
For overweight or obese patients, both HPD and CRD serve as viable strategies for weight loss and metabolic improvement. Nonetheless, HPD demonstrates superior efficacy in reducing body weight, fat percentage, and blood glucose, making it a preferable choice for individuals with concurrent glucose-lipid metabolism disorders.
Supplementary Information
Acknowledgements
Not applicable.
Author contributions
ZT, HL, and DL conceived the study. HL, DL and XH prepared and analyzed the data. XH and DL carried out literature search. HL, XH and DL drafted the manuscript. XZ and ZT revised the manuscript. All authors have approved the final draft of the manuscript.
Funding
This work was supported by the Famous Doctors Talent Introduction and Cultivation Project of Dongguan (2022) and the Dongguan Science and Technology of Social Development Program (grant numbers: 20211800905442; 20211800903532).
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval
The study protocol was approved by the Ethics Committee of Dongguan People’s Hospital (Approval No.: KYKT2021-062; Medical Research Registration Record No.: MR-44-23-023870). All participants provided written informed consent prior to enrollment.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Xiuwei Zhang, Email: dgzxw@163.com.
Zhanyang Tan, Email: tanzhanyangsmu@163.com.
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Supplementary Materials
Data Availability Statement
No datasets were generated or analysed during the current study.