Grip Strength as a Transdiagnostic Biomarker: Bridging Metabolic Syndrome, Vascular Health, and Longevity (2025 Review)

Geoffrey. O. Mosota¹
¹Native Inspire Africa, Nairobi, Kenya

Abstract
Grip strength (GS) is increasingly recognized as a vital sign of aging and health status, transcending its role as a musculoskeletal measure. Emerging research indicates GS’s relevance in metabolic syndrome (MetS), cardiovascular health, cognitive function, and mortality risk. This review synthesizes evidence across domains to support the proposition that GS is a transdiagnostic biomarker—accessible, non-invasive, and mechanistically informative. Mechanistic insights into mitochondrial health, inflammation, hormonal regulation, and neuromuscular integrity are discussed alongside intervention protocols and clinical implications.

1. Introduction
   In clinical and public health settings, there is growing interest in biomarkers that reflect systemic health efficiently. Grip strength (GS), a simple measure traditionally used in geriatric and musculoskeletal evaluations, is gaining traction as a predictor of adverse outcomes across a wide range of conditions, from metabolic syndrome (MetS) and cardiovascular disease (CVD) to cognitive decline and frailty (Leong et al., 2015). Unlike single organ biomarkers, GS appears to integrate multiple physiological systems—muscle mass, neuromuscular coordination, mitochondrial energy production, and inflammatory status—into one readout. This review evaluates the transdiagnostic utility of GS, mechanistic links to metabolic health, and evidence from intervention trials.
2. Grip Strength and Metabolic Syndrome (MetS)
   Metabolic syndrome—a constellation of abdominal obesity, dyslipidemia, hypertension, and insulin resistance—is a major driver of global morbidity. Lower GS is consistently associated with a higher risk of MetS across populations, independent of physical activity levels or BMI (Tian et al., 2023). A systematic review by Kim et al. (2022) confirmed that low GS correlates with all MetS components, including fasting glucose, waist circumference, and triglyceride levels.

Mechanistically, muscle strength reflects mitochondrial quality, insulin sensitivity, and protein turnover—factors central to MetS (Distefano & Goodpaster, 2018). Sarcopenia, the progressive loss of muscle mass and function, shares overlapping pathways with insulin resistance and inflammation, suggesting GS as a proxy for metabolic resilience (Wolfe, 2006).

3. GS and Vascular/Cognitive Health
   Low GS is independently associated with increased arterial stiffness, poor endothelial function, and higher carotid intima-media thickness (Satake et al., 2022). GS also predicts stroke risk and post-stroke functional outcomes (Celis-Morales et al., 2018).

Neurocognitively, GS has been associated with hippocampal volume and executive function, implicating shared neural circuits and mitochondrial integrity (Buchman et al., 2007). The neurovascular coupling hypothesis suggests that better GS reflects intact neuromuscular pathways and cerebral perfusion.

4. Mitochondrial and Inflammatory Pathways
   Mitochondrial dysfunction is a hallmark of both MetS and sarcopenia. Grip strength inversely correlates with markers of oxidative stress, mitochondrial DNA damage, and low-grade inflammation (Fabbri et al., 2015). IL-6, TNF-alpha, and CRP—classic inflammatory markers—are elevated in individuals with low GS and are central to MetS pathogenesis (Rodrigues et al., 2021).
5. Clinical and Intervention Implications
   Resistance training and structured exercise improve GS while simultaneously reducing MetS components (Strasser et al., 2012). GS gains are also linked to improved insulin sensitivity, lipid profiles, and reduced visceral fat (Westcott, 2012). Grip strength monitoring is now recommended in clinical frailty assessments, and it may be used as a low-cost screen for cardiometabolic risk (Cruz-Jentoft & Sayer, 2019).

Protocols like progressive resistance training, high-protein diets, and creatine supplementation enhance GS and may serve as adjuncts in MetS management (Devries & Phillips, 2014).

6. Future Directions and Gaps
   Longitudinal studies are needed to clarify causality between declining GS and disease onset. There is also a need for population-specific GS cutoffs to guide interventions. Digital handgrip devices and integration with electronic health records can enable routine use in primary care.
7. Conclusion
   Grip strength reflects far more than musculoskeletal integrity—it integrates mitochondrial, vascular, neural, and metabolic health. As a transdiagnostic biomarker, GS offers a practical, scalable tool for early risk detection and intervention across chronic diseases.

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