Introduction: Sarcopenia is a condition characterized by muscle mass loss. Some investigations have demonstrated the role of brain-derived neurotrophic factor (BDNF) as a protector against the presence of sarcopenia in patients with chronic kidney disease. We aimed to explore the role of circulating BDNF in the development of sarcopenia among individuals with disease-related malnutrition (DRM). Materials and Methods: A total of 160 patients diagnosed with DRM according to the Global Leadership Initiative on Malnutrition (GLIM) criteria were enrolled. Anthropometric data, muscle mass assessed via ultrasound at the rectus femoris quadriceps (RFQ) level, bioelectrical impedance analysis (skeletal muscle mass [SMM], appendicular skeletal muscle mass [aSMM], and appendicular skeletal muscle mass index [aSMMI]), handgrip strength, biochemical parameters, dietary intake, and circulating levels of BDNF were measured. Results: A total of 55 patients (34.4%) were classified as sarcopenic, while 105 patients (65.6%) were classified as non-sarcopenic. Phase angle (−0.6 ± 0.2°; p = 0.01), reactance (−5.8 ± 2.1 Ohms; p = 0.03), SMM (−3.3 ± 0.2 kg; p = 0.04), aSMM (−2.1 ± 0.3 kg; p = 0.03), aSMMI (−0.8 ± 0.2 kg; p = 0.03), dominant muscle area (−0.7 ± 0.2 cm2; p = 0.04), and dominant Y-axis thickness (−0.4 ± 0.1 cm; p = 0.03) were worse in patients with sarcopenia. Muscle strength was higher in non-sarcopenic patients (8.5 ± 1.2 kg; p = 0.01). Circulating BDNF levels were significantly higher in non-sarcopenic patients compared to sarcopenic patients (94.7 ± 3.9 ng/mL; p = 0.01). Logistic regression analysis indicated a reduced risk of sarcopenia (OR = 0.16, 95% CI = 0.11–0.43; p = 0.03) in patients with higher BDNF levels, after adjusting for body mass index, gender, energy intake, and age. Conclusion: Our study identified an association between low serum BDNF levels and sarcopenia in patients with DRM.

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