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. 2025 Aug:51:206-211.
doi: 10.1016/j.clnu.2025.06.017. Epub 2025 Jun 25.

The association between serum zonulin levels and sarcopenia in older adults: How does intestinal permeability affect sarcopenia?

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The association between serum zonulin levels and sarcopenia in older adults: How does intestinal permeability affect sarcopenia?

Kübra Erdoğan et al. Clin Nutr. 2025 Aug.

Abstract

Background & aims: Sarcopenia, characterized by the progressive loss of muscle mass and function, significantly reduces the quality of life and increases mortality risk in older individuals. Recent evidence highlights the role of intestinal permeability and its associated biomarker, zonulin, in the development of sarcopenia via chronic inflammation pathways. However, the relationship between serum zonulin levels and sarcopenia remains unclear. This study aims to investigate the association between serum zonulin levels and sarcopenia in elderly individuals and to assess the potential of zonulin as a diagnostic biomarker for sarcopenia.

Methods: A total of 93 patients aged ≥60 years were prospectively included. Serum zonulin levels were measured using enzyme-linked immunosorbent assay (ELISA), and sarcopenia diagnosis was established using the International Society of Physical and Rehabilitation Medicine (ISPRM), experts in the special interest group on sarcopenia (ISarcoPRM) algorithm, incorporating handgrip strength, chair stand test (CST), and ultrasonographic measurements of anterior thigh muscle thickness adjusted for body mass index (BMI). Logistic regression and Receiver Operating Characteristic (ROC) curve analyses were conducted to evaluate predictors of sarcopenia and zonulin's diagnostic performance.

Results: Zonulin levels were significantly elevated in sarcopenic patients compared to non-sarcopenic counterparts (24.92 ng/ml [21.01-27.06] vs. 19.52 ng/ml [18.00-22.85]; p < 0.001). Multivariate logistic regression identified zonulin (odds ratio (OR) = 1.204, 95 % confidence interval (CI): 1.043-1.391; p = 0.011) as an independent predictor of sarcopenia. ROC analysis revealed an area under the curve (AUC) of 0.745, with an optimal zonulin cutoff of 23.33 ng/ml (71 % sensitivity, 79 % specificity).

Conclusions: Elevated serum zonulin levels are associated with sarcopenia in elderly individuals, suggesting a potential role of intestinal barrier dysfunction in sarcopenia pathophysiology. Zonulin shows promise as a novel biomarker for sarcopenia diagnosis, warranting further investigation in longitudinal studies to clarify causality and clinical utility.

Keywords: Chronic inflammation; Intestinal permeability; Older people; Sarcopenia; Ultrasound; Zonulin.

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Conflict of interest statement

Conflict of interest The authors declare that they have no competing interests.

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