Abstract
BACKGROUND/OBJECTIVES
A 5:2 intermittent fasting (IF) program is an effective dietary intervention for patients who are overweight or obese, but the effects of a 5:2 IF diet on the Chinese population are unclear. This study examined the impact of a modified 5:2 IF dietary intervention on Chinese adults who were overweight or obese.
SUBJECTS/METHODS
In this self-controlled clinical trial, 45 overweight or obese participants received a modified 5:2 IF dietary intervention for 24 weeks. The body weight, body mass index (BMI), waist circumference (WC), glycolipid metabolism indicators, adipokines, and inflammatory factors were measured in all participants at weeks 0 and 24. The changes in body weight and glycolipid metabolism indicators were the primary outcomes. Serum metabolomics analysis was conducted to identify the differences in metabolites and potential metabolic pathways after dietary intervention.
RESULTS
Thirty-one participants completed the trial and were included in the final analysis. After 24 weeks of a modified 5:2 IF dietary intervention, the participants showed significant decreases in the BMI, WC, body weight, levels of fasting plasma glucose, fasting plasma insulin, total cholesterol, low-density lipoprotein-cholesterol, interleukin 6, tumor necrosis factor-alpha, alanine aminotransferase, and uric acid (all P < 0.05). Moreover, serum metabolomics analysis identified several significantly altered metabolites and metabolic pathways, including pyruvic acid, alpha-ketoisovaleric acid, ammonia recycling, and glutamate metabolism.
CONCLUSION
A modified 5:2 IF dietary intervention significantly reduced the body weight in Chinese adults who were overweight or obese.
Trial Registration
ClinicalTrials.gov Identifier: NCT06552403
Keywords: Intermittent fasting, weight loss, adults, clinical trial
INTRODUCTION
Obesity has become the most prevalent chronic condition and is one of the gravest public health challenges on a global scale [1]. In recent decades, rapid economic development and lifestyle transformations have led to a significant surge in the prevalence of overweight and obesity in China. According to the latest national nutrition and health surveillance data from 2015–2019, the overweight and obesity rates among Chinese adults reached 34.3% and 16.4%, respectively [2]. This alarming trend reflects the changes in dietary habits and physical activity patterns, posing a substantial threat to the overall health of the population.
Overweight and obesity are major risk factors for a plethora of non-communicable diseases, such as coronary artery disease and stroke [3], due to factors such as dyslipidemia, hypertension, and insulin resistance. Similarly, obesity is a well-recognized precursor to type 2 diabetes [4] because an adipose tissue dysfunction disrupts the normal glucose metabolism. Mounting evidence links obesity to an increased risk of various cancers, including breast cancer and liver cancer [5]. These associations underscore the critical importance of effective weight loss and long-term weight management strategies in promoting human health and alleviating the burden of chronic diseases.
Among the various weight loss approaches, daily energy restriction (DER) has long been considered the cornerstone method [6]. DER aims to create a negative energy balance, facilitating weight loss by consistently reducing daily caloric intake. Nevertheless, its effectiveness is often undermined by poor long-term adherence. Prolonged calorie restriction can lead to feelings of hunger, fatigue, and decreased quality of life, causing many individuals to abandon the diet over time [7].
In recent years, intermittent fasting (IF) has emerged as a promising alternative to DER, attracting significant interest from the scientific community and the general public [8,9]. Unlike DER, IF does not require continuous calorie restriction. Instead, it cycles between periods of restricted eating and normal food intake, offering a more flexible and sustainable approach to weight management. One of the key strengths of IF lies in its relatively lenient structure, which helps to alleviate the psychological and physical burdens associated with traditional diets. This flexibility in meal scheduling reduces dietary constraints, potentially leading to higher adherence rates. A recent review [10] showed that IF can alleviate the psychological stress associated with dieting, making it more sustainable in the long run.
The 5:2 IF diet, a popular form of IF, involves consuming a very low-calorie diet on 2 non-consecutive days per week while maintaining normal energy intake on the remaining 5 days [11]. Multiple studies have revealed the efficacy of short- and long-term IF dietary interventions in promoting weight loss among individuals with obesity [12,13,14]. For example, Carter et al. [15] conducted a 12-mon randomized controlled trial comparing the 5:2 IF diet with a continuous energy-restricted diet in patients with type 2 diabetes. The 5:2 IF group experienced significant weight loss and had a more pronounced reduction in the hemoglobin A1c (HbA1c) levels, indicating better glycemic control.
Despite these promising findings, most research on IF has been conducted on Western populations. Considering the notable differences in obesity prevalence, body fat distribution patterns, dietary habits, and metabolic profiles between Chinese and European populations, the generalizability of these results to the Chinese context is unclear. Moreover, no study has specifically examined the impact of dietary interventions, particularly IF, on Chinese individuals with obesity. Understanding how the 5:2 IF dietary intervention affects the Chinese population who are overweight or obese is crucial for developing personalized and effective weight management strategies tailored to this specific demographic. Therefore, this self-controlled clinical trial was designed to systematically explore the effects of a modified 5:2 IF dietary intervention on Chinese adults who were overweight or obese, with the ultimate goal of providing evidence-based recommendations for weight management in this population.
SUBJECTS AND METHODS
Study design and participants
This open-label, self-controlled clinical trial recruited overweight or obese volunteers from January 1, 2022, to December 31, 2023, among permanent residents of Hangzhou, China. This study was approved by the Institutional Review Board of the Tongde Hospital of Zhejiang Province (protocol number: 2021036), and all participants provided written informed consent. This trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/, registration number: NCT06552403). The inclusion criteria of the participants were as follows: (1) participants aged 18 to 60 yrs, (2) participants with a body mass index (BMI) ≥ 24 kg/m2, and (3) participants with a relatively stable body weight who were engaged in light physical labor. Participants who met the following criteria were excluded: (1) participants taking any medication with an effect on body weight in the 3 mon prior to enrollment, (2) participants with liver or kidney dysfunction (liver enzymes ≥ 2 times normal; blood creatinine > the upper limit of normal), (3) participants with a history of cardiovascular disease (e.g., coronary heart disease and stroke), (4) participants with malignant tumors, (5) women during pregnancy or breastfeeding, and (6) participants deemed unsuitable by the investigator to participate in this trial. The criteria for the exclusion or withdrawal of participants during the trial were as follows: (1) participants with sudden serious illness, (2) participants who failed to implement the dietary intervention program and upload diet-related data, and (3) participants who voluntarily requested to withdraw from the trial.
Outcomes
The primary outcomes were changes in the anthropometric measurements, glycolipid metabolism indicators, adipokines, and inflammatory factors before and 24 weeks after the modified 5:2 IF diet intervention. The secondary outcome was the change in metabolic components after the participants received the modified 5:2 IF diet intervention for 24 weeks. The anthropometric measurements included weight, BMI, and waist circumference (WC). All measurements followed standardized procedures. The body weight was measured to the nearest 0.1 kg using a calibrated electronic scale (HNH-318; Omron, Shanghai, China). The participants were instructed to wear light clothing and remove their shoes prior to the measurement. The scale was calibrated regularly according to the manufacturer’s guidelines to ensure accurate readings. The height was measured using an electronic stadiometer (HNH-318; Omron) to the nearest 0.1 cm. During the measurement, the participants were required to stand upright with their heels together and back straight against the stadiometer. The BMI was calculated as the weight (kg) divided by the height (m2). The WC was measured at the midpoint between the iliac crest and the lowest rib using a non-stretch tape to the nearest 0.1 cm. The participants stood upright with relaxed breathing; the measurements were taken twice and averaged.
The glycolipid metabolism indicators contained the fasting C-peptide (FCP), HbA1c, fasting plasma glucose (FPG), fasting plasma insulin (FPI), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), and uric acid. The adipokines included leptin and adiponectin. The inflammatory factors contained tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and high-sensitivity C-reactive protein (hsCRP). The participants’ metabolic components were analyzed by serum metabolomics analysis. These measurements were taken at the baseline and 24 weeks.
Interventions
The traditional 5:2 IF diet consisted of 2 random fasting days during which the energy intake was reduced significantly, with 5 days of habitual intake per week [16]. Compared to the traditional 5:2 IF diet, the modified 5:2 IF diet (defined by the authors) involved 2 non-consecutive fasting days (25%–30% of the total required daily energy intake based on the ideal body weight) and 5 days of habitual intake (limited total energy intake according to the ideal body weight) per week, as well as a 4-week run-in period and a minimum of 6,000 steps of physical activity per day. For the 4-week run-in period, participants consumed 60% of their total energy (based on ideal body weight) on 2 non-consecutive days per week in the first and second weeks, with normal energy intake at other times, and approximately 30% of their total energy on 2 non-consecutive days per week in the third and fourth weeks. The ideal body weight (kg) was calculated as the height (cm) minus 105 [17]. After a 4-week run-in period, all participants received a 24-week modified 5:2 IF dietary intervention. Each participant was informed of their ideal body weight and the energy content of various foods, and individualized recipes were developed.
The dietary intervention in this study was conducted at Tongde Hospital, a tertiary-level hospital in Hangzhou. The study participants were all residents from the urban areas of Hangzhou. The primary dietary education tool was a hospital-developed mobile application (app) that provided personalized dietary plans tailored to each participant’s health status, including age, BMI, and dietary preferences. The app also sent regular push notifications containing dietary knowledge, including information on appropriate food choices, portion control, and meal timing.
The initial dietary education was carried out by endocrinologists who received formal training from the consulting dietitian. Before the intervention, the doctors received unified training on the standardized intervention protocol to ensure the consistency and quality of the dietary education. During the intervention, the investigators interacted with the participants through WeChat. The participants regularly uploaded their diet, exercise, and monthly weight via WeChat, and received real-time guidance and supervision from the investigators. The participants were followed up by telephone every month to ensure their compliance.
Measurements
The participants were required to fast for at least 8 h. Fasting venous blood was collected between 8 a.m. and 9 a.m. at the baseline and 24 weeks, respectively. After centrifugation, the serum samples were analyzed for the FPG, FCP, LDL-C, TG, HDL-C, TC, and uric acid using a fully automated biochemistry analyzer (Roche Cobas 6000 c501; Roche, Mannheim, Germany). The levels of leptin (Catalog number: MM-0084H1; Enzyme Immunoassay Industrial Co., Ltd, Shanghai, China), adiponectin (Catalog number: MM-1535H1; Enzyme Immunoassay Industrial Co., Ltd), hsCRP (Catalog number: BY-EH110433; Enzyme Immunoassay Industrial Co., Ltd), IL-6 (Catalog number: MM-0049H1; Enzyme Immunoassay Industrial Co., Ltd), and TNF-α (Catalog number: MM-0122H1; Enzyme Immunoassay Industrial Co., Ltd) were measured using commercially available ELISA kits.
The homeostasis model assessment of β-cell (HOMA-β) and HOMA of insulin resistance (HOMA-IR) were calculated to assess the islet cell secretory function and insulin resistance status, respectively [18]:
| HOMA-β = [20 × FPI (mU/L)]/[FPG (mmol/L) − 3.5] |
| HOMA-IR = [FPI (mU/L) × FPG (mmoL/L)]/22.5 |
The visceral adipose index (VAI) was calculated to assess visceral fat accumulation [19]:
| VAI-male = [WC (cm)/39.68 + (1.88 × BMI)] × [TG (mmoL/L)/1.03] × [1.31/HDL (mmoL/L)] |
| VAI-female = [WC (cm)/36.58 + 1.89 × (BMI)] × [TG (mmoL/L)/0.81] × [1.52/HDL (mmoL/L)] |
The serum samples were also used for serum metabolomics analysis. Ultra-high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (Agilent 1290; Agilent Technologies, Inc., Santa Clara, CA, USA) was applied to identify the metabolites. Differential compounds in the participants at the baseline and 24 weeks were identified by principal component analysis. Online MetaboAnalyst software (https://www.metaboanalyst.ca/MetaboAnalyst/home.xhtml) was used to conduct the metabolic pathway analysis, and the KEGG database (https://www.kegg.jp) was used to search for metabolic pathways with statistical differences.
Sample size
The sample size was calculated according to the SD of the change in body weight from previous studies [20,21]:
| Sample size, n = [(μα + μβ) × σd/δ]2 |
where the value of α, β, μα, μβ, δ, and σd were 0.05 (2-sided), 0.10, 1.960, 1.281, 4 kg [20], and 6.5 kg [21], respectively, based on previous studies. The minimum and actual sample sizes were 27 and 30 participants, respectively, after considering a 20% loss to follow-up.
Statistical analysis
For an analysis of the participants’ characteristics, the continuous and normally distributed variables are summarized as the mean and SD. The Kolmogorov–Smirnov test was used to assess the normality of the data distribution.-For datasets conforming to a normal distribution, paired t-tests were used to evaluate the differences between the baseline and 24-week measurements. Repeated-measures analysis of variance was conducted to analyze changes across the baseline, 12-week, and 24-week time points, followed by Bonferroni post hoc tests for pairwise comparisons. In contrast, variables were summarized as quartiles when the data deviated from normality (Median, 25th, and 75th percentiles). The Wilcoxon signed-rank test was applied. All statistical analyses and graphical representations were performed using GraphPad Prism software (GraphPad Software, San Diego, CA, USA). Statistical significance was defined as a 2-sided P-value < 0.05.
RESULTS
Characteristics of participants
Forty-five participants with overweight or obesity were included in the trial, and 31 participants completed the trial with complete measurement data (Fig. 1). Of these 31 participants, 9 were male and 22 were female. The mean BMI, FPG, and FPI were 30.35 ± 4.25 kg/m2, 5.50 ± 0.71 mmoL/L, and 106.00 ± 55.47 pmoL/L, respectively. The mean age was 30 ± 7 yrs (18–47 yrs).
Fig. 1. Flow diagram describing the processes of participant recruitment.
GLP-1RA, glucagon-like peptide-1 receptor agonist; IF, intermittent fasting.
Effects of the modified 5:2 IF dietary intervention on people who are overweight or obese
Table 1 lists the characteristics of the participants before and 24 weeks after the modified 5:2 IF diet intervention. After 24 weeks of a modified 5:2 IF dietary intervention, the participants experienced significant reductions in BMI, WC, and VAI (P < 0.05) (Fig. 2A, D, and E). Moreover, the changes in BMI and weight among different time points were also compared. The participants’ BMI decreased significantly from the baseline after 12 weeks of intervention (P < 0.05), but the changes in BMI and body weight from weeks 13 to 24 were significantly smaller than those from weeks 0 to 12 (P < 0.05) (Fig. 2B and C).
Table 1. Parameters of the participants before and after the diet intervention.
| Variables | Baseline | 24 weeks | P-value |
|---|---|---|---|
| Weight (kg) | 82.5 ± 13.2 | 76.8 ± 12.5 | 0.0549 |
| Waistline (cm) | 98.8 ± 9.9 | 92.8 ± 8.9 | 0.0069 |
| BMI (kg/m2) | 30.4 ± 4.3 | 28.2 ± 4.0 | 0.0259 |
| FPG (mmoL/L) | 5.5 ± 0.7 | 5.0 ± 0.5 | 0.0015 |
| HbA1c (%) | 5.3 ± 0.5 | 5.1 ± 0.4 | 0.0714 |
| FPI (pmoL/L) | 106.0 ± 55.5 | 78.4 ± 34.3 | 0.0194 |
| FCP (nmoL/L) | 0.8 ± 0.4 | 0.8 ± 0.3 | 0.8161 |
| TG (mmoL/L) | 1.7 (1.2, 2.8) | 1.4 (1.1, 1.8) | < 0.001 |
| TC (mmoL/L) | 5.1 ± 1.0 | 4.6 ± 0.9 | 0.0238 |
| LDL-C (mmoL/L) | 3.3 ± 0.6 | 3.0 ± 0.5 | 0.0074 |
| HDL-C (mmoL/L) | 1.2 ± 0.2 | 1.1 ± 0.2 | 0.6108 |
| Uric acid (umoL/L) | 428.9 ± 107.5 | 385.1 ± 61.5 | 0.0346 |
| ALT (U/L) | 32.8 ± 16.0 | 23.5 ± 10.0 | 0.0042 |
| AST (U/L) | 25.8 ± 6.6 | 23.5 ± 10.0 | 0.3830 |
| Leptin (μg/L) | 13.5 ± 8.3 | 12.8 ± 4.2 | 0.6836 |
| Adiponectin (pg/mL) | 1,693.0 ± 744.1 | 1378.0 ± 464.0 | 0.0578 |
| IL-6 (ng/L) | 30.1 (25.8, 33.5) | 16.5 (13.3, 18.2) | < 0.001 |
| hsCRP (mg/L) | 0.9 (0.3, 1.3) | 0.6 (0.2, 1.2) | 0.8314 |
| TNF-α (ng/L) | 381.4 (281.8, 497.2) | 326.1 (260.7, 369.4) | 0.0341 |
| HOMA-IR | 3.9 ± 2.2 | 2.6 ± 1.3 | 0.0070 |
| VAI | 2.2 ± 1.3 | 1.7 ± 0.5 | 0.0276 |
Values are presented as mean ± SD or mean (Q1, Q3). Differences between baseline and 24-week measurements were analyzed using a paired t-test; a P-value < 0.05 (2-sided) was considered statistically significant. The levels of TG, IL-6, hsCRP, and TNF-α did not follow a normal distribution. Hence, the Wilcoxon test was used in this case.
BMI, body mass index; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; FPI, fasting plasma insulin; FCP, fasting C-peptide; TG, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; IL-6, interleukin 6; hsCRP, high sensitivity C-reactive protein; TNF-α, tumor necrosis factor-alpha; HOMA-IR, homeostasis model assessment of insulin resistance; VAI, visceral adipose index.
Fig. 2. Effects of the modified 5:2 intermittent fasting dietary intervention on the BMI of people with overweight or obesity. The variables are summarized as the mean and SD. Differences between the baseline and 24-week measurements were analyzed using a paired t-test. Comparisons across baseline, 12-, and 24-week timepoints were conducted via repeated-measures analysis of variance. A P-value < 0.05 (2-sided) was considered significant.
BMI, body mass index; VAI, visceral adipose index.
*P < 0.05, **P < 0.01, ***P < 0.001.
For the glucose metabolism, the participants’ FPG, FPI, and HOMA-IR levels decreased significantly after 24 weeks of the 5:2 IF diet intervention (P < 0.05) (Fig. 3A, C and E), but no significant changes in the FCP and HbA1c levels were observed (Fig. 3B and D) (P > 0.05) (Fig. 3). Regarding the lipid metabolism, the participants’ TG, TC, and LDL-C levels decreased significantly after 24 weeks of dietary intervention (P < 0.05) (Fig. 4A, B, and D), whereas the HDL-C level did not change significantly (P > 0.05) (Fig. 4C). Moreover, the participants’ ALT and uric acid levels also decreased significantly after 24 weeks of the 5:2 IF diet intervention (P < 0.05) (Supplementary Fig. 1).
Fig. 3. Effects of the modified 5:2 intermittent fasting dietary intervention on blood glucose. The variables were summarized as the mean and SD. The differences between the baseline and 24-week measurements were analyzed using a paired t-test. A P-value < 0.05 (2-sided) was considered significant.
FPG, fasting plasma glucose; FCP, fasting C-peptide; FPI, fasting plasma insulin; HbA1c, hemoglobin A1c; HOMA-IR, the homeostasis model assessment of insulin resistance.
*P < 0.05, **P < 0.01.
Fig. 4. Effects of the modified 5:2 intermittent fasting dietary intervention on lipid metabolism. The normally distributed variables are summarized as the mean and SD. The differences between the baseline and 24-week measurements were analyzed using a paired t-test. A P-value < 0.05 (2-sided) was considered significant. The TG level did not follow a normal distribution. Hence, the Wilcoxon test was used in this case.
TG, triglycerides; TC, total cholesterol; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol.
*P < 0.05, **P < 0.01.
In terms of adipokines and inflammatory factors, the 24-week 5:2 IF dietary intervention significantly reduced the IL-6 and TNF-α levels (P < 0.05) (Fig. 5A and C), but did not affect the levels of leptin, adiponectin, and hsCRP (P > 0.05) (Fig. 5B, D and E).
Fig. 5. Effects of the modified 5:2 intermittent fasting dietary intervention on adipokines and inflammatory factors. Differences between baseline and 24-week measurements were analyzed using a paired t-test. A P-value < 0.05 (2-sided) was considered significant. The levels of IL-6, hsCRP, and TNF-α did not follow a normal distribution. Hence, the Wilcoxon test was used in this case.
IL-6, interleukin 6; hsCRP, high sensitivity C-reactive protein; TNF-α, tumor necrosis factor-alpha.
*P < 0.05, **P < 0.01.
Principal component analysis showed significant differences in the participants’ serum metabolites after 24 weeks of the 5:2 IF dietary intervention (Fig. 6). Nine compounds showed the most significant changes in the participants’ metabolite levels after the 24-week dietary intervention: pyruvic acid, alpha-ketoisovaleric acid, ketoleucine, 3-methyl-2-oxopentanoic acid, alpha-tocopherol, glutamic acid, glutamine, methionine, and methionine sulfoxide (Fig. 7). Metabolic pathway analysis revealed the following major pathways involved in the differential metabolites following the dietary intervention: ammonia recycling; glutamate metabolism; Warburg effect; glucose-alanine cycle; valine, leucine, and isoleucine degradation; transfer of acetyl groups into mitochondria; and pyruvaldehyde degradation.
Fig. 6. PC analysis for participants’ serum metabolites after 24 weeks of the 5:2 intermittent fasting dietary intervention.
PC, principal component.
Fig. 7. Box plots of the metabolites with more significant changes in concentration before and after the modified 5:2 intermittent fasting dietary intervention.
CTRL, control.
DISCUSSION
This study examined the effects of the modified 5:2 IF dietary intervention on Chinese adults who were overweight or obese after 24 weeks. The 24-week modified 5:2 IF dietary intervention significantly reduced the BMI, WC, and the levels of FPG, FPI, TC, LDL-C, ALT, uric acid, IL-6, and TNF-α in individuals who were overweight or obese. Serum metabolomics analysis revealed significant changes in certain metabolites before and after the dietary intervention.
IF is an important dietary intervention for weight loss. When fasting for 8 to 12 h, the body does not have access to its typical source of energy (glucose), and the liver will begin to break down fatty acids to produce ketone bodies, which will be used as an alternative energy source to maintain the metabolism of the vital organs and tissues [22]. Some studies have reported that when calorie-restricted diets result in weight loss, approximately 75% and 25% of the weight lost can be attributed to fat and muscle, respectively [23,24]. Many studies have reported that the 5:2 IF is an effective dietary intervention for weight loss, and that IF may cause a decrease in the cholesterol, TG, glucose, and insulin levels [16,25,26]. Nevertheless, these studies have focused mainly on European or American populations, whereas there are differences in the obesity levels and dietary patterns among various populations. In addition, the effects of 5:2 IF dietary interventions on Chinese populations have received less attention.
This study assessed the effects of a modified 5:2 IF dietary intervention on the Chinese population who were overweight or obese using a self-controlled clinical trial. The modified 5:2 IF was implemented to overcome the drawbacks of the traditional format, with non-consecutive fasting days playing a significant role. Spacing out the 2 fasting days helps avoid prolonged, continuous energy restriction, reducing the likelihood of severe hunger, fatigue, and low productivity. This also allows for seamless integration into daily life, enabling individuals to attend social events or work commitments without conflict. The flexibility of non-consecutive fasting days enables the participants to adjust their schedules according to personal preferences, boosting adherence. Customizing energy intake on fasting days according to the ideal body weight ensures a personalized and scientifically grounded calorie-restriction program. A 4-week run-in period eases participants into the dietary changes, while the daily 6,000-step requirement complements the diet, enhancing weight management and metabolic health. This holistic approach, combining diet and exercise, offers a more effective strategy for improving health.
These results suggest that the 24-week modified 5:2 IF dietary intervention significantly reduced the BMI, WC, and levels of FPG, FPI, TC, LDL-C, ALT, uric acid, IL-6, and TNF-α in people who are overweight or obese. The body weight change showed a non-significant result (P = 0.0549), while the BMI showed a significant decrease (P = 0.0259). This difference was because the BMI, calculated from the weight and height, reflects the body composition more comprehensively. In addition, the statistical outcomes are affected by the sample size, data variability, and test sensitivity. The P-value for the change in body weight was close to the significance threshold, but it did not meet the standard, unlike the significant decrease in BMI.
Previous trials have shown that IF significantly reduces the participants’ LDL-C levels compared to the baseline levels [15,27], but the HDL-C levels usually remain unchanged or decrease slightly [15,21]. Several studies have found that the participants’ FPG levels generally remained constant during the IF diet [28,29], while the FPI levels were reduced significantly from the baseline [29,30]. Most studies have shown that IF has little effect on the HbA1c level in non-diabetic patients [31,32]. Moreover, IF has been reported to have no significant effect on the key indicators of inflammation, such as the TNF, IL-6, and C-reactive protein levels [13,33]. The modified 5:2 IF dietary intervention used in this study, which included at least 6,000 steps of physical activity per day, may explain why the changes in the FPG, IL-6, and TNF-α levels in this study differed from those in previous studies. In addition, the participants in the present study underwent a 4-week dietary run-in period before receiving the formal 24-week modified 5:2 IF dietary intervention, which allowed these results to reflect the impact of the dietary intervention more accurately.
The mechanisms through which IF affects the metabolism are unclear. Moreover, the IF-caused weight loss may be related to the changes in the gut microbiota and appetite. Ravussin et al. [34] attributed the IF-induced weight loss primarily to decreased appetite and increased fat oxidation, rather than increased energy expenditure. IF alters the metabolism. During early fasting, endogenous glucose serves as the fuel for glycolysis and mitochondrial oxidative phosphorylation. As fasting continues and glycogenolysis slows, however, the body’s energy source is converted from glucose energy from the liver to fatty acids from fat and glycerol from lipolysis [35,36]. Obesity promotes adipose inflammation. Moreover, the pro-inflammatory effects of adipose tissue immune cells perpetuate local inflammation and can disrupt insulin signaling, which in turn promotes the development of local and systemic insulin resistance [37,38]. IF alters the energy metabolism of adipocytes and adipose tissue immune cells, reduces the pro-inflammatory effects of immune cells, and reduces inflammatory cytokines associated with insulin resistance [39]. In addition, IF alters the gut microbiota, leading to changes in immunity and metabolism [35,40]. This study analyzed the differences in serum metabolites in the participants before and after 24 weeks of 5:2 IF dietary intervention and explored the potential metabolic pathways for these metabolites. These results showed that after 24 weeks of dietary intervention, the serum metabolite levels that exhibited the most significant changes were pyruvic acid, alpha-ketoisovaleric acid, ketoleucine, 3-methyl-2-oxopentanoic acid, alpha-tocopherol, glutamic acid, glutamine, methionine, and methionine sulfoxide. In addition, the major pathways for these metabolites included the following: ammonia recycling; glutamate metabolism; Warburg effect; glucose-alanine cycle; valine, leucine and isoleucine degradation; transfer of acetyl groups into the mitochondria; and pyruvaldehyde degradation. These results may provide additional references to the mechanisms of the effects of IF dietary interventions on people with overweight or obesity.
The present study assessed the effects of a modified 5:2 IF dietary intervention for 24 weeks on the body weight, WC, glycolipid metabolism indicators, adipokines, and inflammatory factors in Chinese adults who were overweight or obese, and analyzed the possible pathways involved in the metabolites that were significantly different after the dietary intervention using serum metabolomics. This study may provide a reference for the effects of a modified 5:2 IF dietary intervention in overweight or obese adults in China. Nevertheless, several limitations should be noted when interpreting the results. First, this study used a self-controlled study design, in which part of the observed effect of the dietary intervention may be attributed to the phenomenon of “regression toward the mean” and the difficulty of controlling for the confounding effect of non-experimental factors on the results. Second, the sample size of this study was small. Therefore, future studies need randomized controlled trials with larger sample sizes to confirm the effects of a modified 5:2 IF dietary intervention on overweight and obese adults in China.
The 24-week modified 5:2 IF dietary intervention significantly reduced the BMI, WC, and levels of FPG, FPI, TC, LDL-C, ALT, uric acid, IL-6, and TNF-α in overweight or obese Chinese adults. Future studies will require larger sample sizes of randomized controlled trials to confirm the effects of a modified 5:2 IF dietary intervention in Chinese overweight and obese adults.
ACKNOWLEDGMENTS
The authors wish to extend their sincere gratitude to Ms. Weiwei Jin, a registered dietitian from the Nutrition Department of Tongde Hospital of Zhejiang Province, for her invaluable consultation and dedicated personnel training throughout the development and implementation of this project.
Footnotes
Funding: This study was funded by the Chinese Medical Science and Technology Plan of Zhejiang Province (grant No. 2023ZL027), National Leading Medical Specialty Development Project – Department of Geriatrics, Tongde hospital of Zhejiang Province (grant No. [2024]90662) and the Health Science and Technology Plan of Zhejiang Province (grant No. 2021KY113).
Data Availability Statement: The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
Conflict of Interest: The authors declare no potential conflicts of interests.
- Conceptualization:Wang X, Xun Y;
- Data curation:Gao Q, Xun Y, Wang Y, Mao S;
- Formal analysis:Gao Q, Xun Y, Wang Y, Mao S;
- Investigation:Gao Q, Xun Y, Wang Y, Mao S;
- Writing - original draft:Wang X;
- Writing - review & editing:Wang X.
SUPPLEMENTARY MATERIAL
Effects of the modified 5:2 intermittent fasting dietary intervention on liver function and blood uric acid.
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Associated Data
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Supplementary Materials
Effects of the modified 5:2 intermittent fasting dietary intervention on liver function and blood uric acid.