ORIGINAL RESEARCH article
Front. Nutr.
Sec. Clinical Nutrition
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1615376
Metabolic Syndrome Worsens Sarcopenia and Reduces Nutritional Therapy Benefits in Advanced Gastric Cancer
Provisionally accepted
- 1Macau University of Science and Technology, Taipa, Macao, SAR China
- 2Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang Province, China
- 3Second Clinical Medical School, Zhejiang Chinese Medical University, Hangzhou, Jiangsu Province, China
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Background: Emerging evidence suggests metabolic syndrome (MetS) exacerbates sarcopenia progression and compromises nutritional interventions, yet its dual role as both etiological driver and therapeutic effect modifier remains uncharacterized. This study investigated MetS-related sarcopenia pathophysiology and assessed its impact on nutritional therapy efficacy in advanced gastric cancer. Patients and Methods: We conducted a dual-phase investigation combining Mendelian randomization (MR) analysis of European-ancestry GWAS data (n=654,783) with retrospective evaluation of 65 sarcopenic gastric cancer patients receiving chemotherapy and enteral nutrition. MR evaluated causal relationships between individual components of MetS and sarcopenia phenotypes, while clinical analyses compared outcomes by MetS status (IDF/AHA criteria). Results: MR analysis of MetS components identified paradoxical causal effects: waist circumference increased appendicular lean mass (OR=1.480, p<0.001) but impaired walking speed (OR=0.864, p<0.001). In the clinical cohort, MetS patients exhibited accelerated nutritional decline with 2.6-fold greater weight loss (-1.70 vs -0.66 kg, p=0.01), attenuated muscle preservation (48.1% vs 73.7% SMI improvement, p=0.066), and reduced median PFS (75.0 vs 84.5 days, p=0.061). Protein trajectories revealed MetS-specific catabolic patterns, particularly transferrin depletion (Δ=-0.26 vs -0.05 g/L, p=0.0004). Conclusion: The integration of genetic and clinical findings shows that MetS components causally contribute to sarcopenia pathogenesis, and that the composite MetS phenotype confers nutritional therapy resistance. This establishes MetS's dual role as a driver of disease and a modifier of treatment efficacy.
Keywords: metabolic syndrome, Sarcopenia, Mendelian randomization, gastric cancer, Nutritional therapy
Received: 22 Apr 2025; Accepted: 26 Sep 2025.
Copyright: © 2025 XU, Zhang, Yao and Wong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wang Yao, yaowang3372@163.com
Vincent Kam Wai Wong, kawwong@must.edu.mo
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