Innovative Dietary Strategies: A novel approach to Obesity management and diseases prevention

Abstract Obesity represents a major global health issue, associated with metabolic syndrome, insulin resistance, and chronic inflammation. Identifying effective and sustainable dietary strategies is essential for improving metabolic efficiency and reducing related comorbidities. Recent evidence highlights the role of Orexin-A, a hypothalamic neuropeptide regulating arousal, appetite, and energy expenditure, as a potential biomarker of neuro-metabolic adaptation. This study aimed to evaluate the effects of three different dietary interventions—low-calorie Mediterranean diet, intermittent fasting (16:8), and alternate-day fasting (5:2)—on body composition, metabolic parameters, inflammatory profile, and plasma Orexin-A levels in obese subjects. Thirty obese participants (15 males and 15 females, aged 20–40 years) were recruited from the Dietetics and Sports Medicine Unit of the University of Campania “Luigi Vanvitelli”. Subjects were divided into three groups (n=10 per group), each following one of the three dietary regimens for 12 months. Anthropometric parameters, lipid and glycemic profiles, and inflammatory cytokines (CRP, TNF-α, IL-6, IL-10) were measured at baseline (T0) and at 3-month intervals (T1, T2, T3). Plasma Orexin-A levels were quantified by ELISA. All dietary regimens improved body composition and metabolic health over time, but with distinct patterns. The 16:8 intermittent fasting protocol produced the most rapid and consistent benefits, including significant reductions in BMI, visceral fat, total cholesterol, and blood glucose, along with a marked increase in Orexin-A levels (p < 0.001). The low-calorie Mediterranean diet induced gradual improvements, becoming significant at T3, while the 5:2 fasting regimen produced modest, non-significant changes. The observed rise in Orexin-A correlated with enhanced metabolic flexibility and reduced inflammation, suggesting a neuroendocrine adaptation to time-restricted feeding. Among the dietary strategies tested, intermittent fasting (16:8) proved to be the most effective in improving metabolic efficiency, reducing inflammation, and increasing Orexin-A levels. These results support its potential as a practical and sustainable therapeutic approach for obesity management.