Objective: Metabolic syndrome (MetS) represents a growing and significant public health burden worldwide. The evidence regarding whether skipping breakfast affects the development of MetS and its components remains inconsistent and uncertain. This study aimed to synthesize the best available evidence regarding the association between skipping breakfast and the risk of MetS and its components. Methods: This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines. We systematically searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception until May 2025. Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed the risk of bias. This review included cross-sectional and cohort studies on the association between breakfast skipping and the risk of MetS and its components. Results: Nine studies were included after quality evaluation by NOS. Pooled results from the meta-analysis revealed that skipping breakfast was significantly associated with an increased risk of MetS (OR: 1.10, 95% CI: 1.04–1.17) and its components—namely abdominal obesity (OR = 1.17, 95% CI 1.01–1.34), hypertension (OR: 1.21, 95% CI: 1.10–1.32), hyperlipidemia (OR: 1.13, 95% CI: 1.04–1.23), and hyperglycemia (OR = 1.26, 95% CI: 1.16–1.37). Conclusions: The meta-analysis demonstrated that skipping breakfast was significantly associated with an increased risk of MetS and its key components—abdominal obesity, hypertension, hyperlipidemia, and hyperglycemia. These findings highlight regular breakfast consumption as a potential modifiable factor for preventing and managing MetS and related cardiometabolic diseases.

Background: Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30–44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results: Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups. Notably, subgroup analyses revealed comparable physiological responses between TRF and intermittent energy restriction modalities. Cardiometabolic adaptations were highly age-dependent. Young adults exhibited significant reductions in fasting insulin and HOMA-IR, alongside a robust reduction in fat mass. However, a significant loss of fat-free mass (FFM) was observed in both young and older cohorts. While middle-aged and older adults experienced the most pronounced improvements in triglycerides, systolic blood pressure, and insulin sensitivity, our conservative sensitivity analysis unmasked a significant elevation in low-density lipoprotein cholesterol (LDL-C) in this group, mirroring the robust LDL-C increase observed in young adults. Early middle-aged adults exhibited highly variable responses with no significant overall improvements in cardiometabolic parameters. Conclusions: IF is an effective weight-management tool, but elicits distinct, age-specific metabolic trajectories. While middle-aged and older adults derive pronounced cardiometabolic benefits, they face critical risks of lean mass depletion, necessitating a combined “IF+” strategy (adequate protein and resistance training). Crucially, the age-specific risk of LDL-C elevation dictates a mandate for vigilant lipid monitoring. Given that the certainty of evidence was rated as low to very low per GRADE criteria, these age-specific patterns should be interpreted as hypothesis-generating, warranting validation in future large-scale trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a peril to public health. Xanthine oxidoreductase (XOR) is implicated in oxidative stress and lipid metabolism, which constitute the pathological basis of MASLD. As a specific XOR inhibitor, febuxostat therefore exhibits considerable potential for mitigating MASLD. However, the efficacy and underlying mechanisms of febuxostat in this context remain to be elucidated. Against this background, the present study aimed to observe the effect of febuxostat on the physiological changes of male MASLD rats and explore the related mechanisms. All rats were assigned to three groups: control, high-fat diet (HF), and high-fat diet with febuxostat (HF + F). After euthanasia, biosamples were immediately harvested to conduct an extensive suite of experiments, encompassing histological examination, assessment of biochemical and oxidative stress markers, serum non-targeted metabolomics, and Western blot analysis. Histological examination showed marked reductions in hepatic lipid accumulation and hepatocellular degeneration in the HF + F group relative to the HF group. Consistently, compared to the HF group, the HF + F group showed significant reductions in the elevated levels of plasma/hepatic lipids, and plasma oxidative stress markers (p < 0.05). Serum metabolomics revealed distinct metabolic profiles among groups, with 51 differential metabolites between HF + F and HF groups, with pathways such as taurine and hypotaurine metabolism and starch and sucrose metabolism being significantly altered (p < 0.05). Western blot analysis showed reduced p-JNK and increased NRF2 and HO-1 expression in the HF + F group (p < 0.05). In summary, we found that inhibiting XOR with febuxostat improved hepatic steatosis, serum metabolic dysregulation and systemic oxidative stress status, and it accompanied by JNK/NRF2/HO-1 pathway key molecule protein alterations in male MASLD rats.

Cardiometabolic multimorbidity (CMM), defined as the co-occurrence of two or more of the following: diabetes, ischemic heart disease, stroke, and other cardiovascular diseases, is a leading cause of global mortality. Although vitamins and fatty acid are known to influence cardiometabolic diseases through lipid metabolism, the mediating role of lipid metabolites in linking dietary vitamins and fatty acid intake to CMM remains unclear. We conducted a case–control study based on the Ningxia cohort, including 200 patients with CMM and 200 age- and sex-matched controls. Dietary intake was assessed using a semi-quantitative food frequency questionnaire, and plasma lipid profiles were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. We assessed associations between dietary nutrients and CMM using logistic regression and their relationships with lipid metabolites via Pearson correlation. Mediation analysis identified lipid metabolites that link vitamin and fatty acid intake to CMM, and these mediators were incorporated into a predictive model. We found that higher intake of vitamin E (VE), total fatty acids (FA), polyunsaturated fatty acids (PUFA), and monounsaturated fatty acids (MUFA) was significantly associated with lower CMM risk (OR < 1, FDR ≤ 0.05). Lipid profiling identified 349 differentially abundant metabolites, primarily triglycerides and diglycerides, elevated in CMM patients. Mediation analysis revealed 292 significant pathways: dietary intake VE and PUFA was linked to lower CMM risk via modulation of glycerolipid metabolites, while dietary intake FA and MUFA was linked to lower risk through regulation of glycerophospholipids. A predictive model incorporating age, sex, dietary factors, and key mediating lipids achieved good discrimination (AUC: 0.765–0.812). These findings suggest that dietary intake of VE, FA, PUFA, and MUFA is associated with reduced CMM risk through modulation of plasma lipid metabolism, with specific lipid metabolites potentially acting as key mediators.