Nutraceutical Intervention Preserves Red Blood Cell Function and Neuroendocrine Balance in Fibromyalgia‐Induced Systemic Stress

ABSTRACT Fibromyalgia (FM) is a complex chronic disorder characterized by widespread pain, fatigue, and cognitive disturbances, with evidence pointing to systemic involvement beyond musculoskeletal symptoms. This study used a validated rodent model to investigate FM's multi‐systemic effects and the therapeutic potential of Boswellia (BS) supplementation. FM was experimentally induced in a rat model and a comprehensive set of physiological markers was evaluated, including food intake, body weight, HPA axis hormones (ACTH, corticosterone), oxidative stress indicators (GSH, GSH‐Px, MDA), inflammatory cytokines (IL‐1β, IL‐6, TNF‐α, IL‐10), metabolic profile, liver and kidney function, and red blood cell (RBC) parameters. Particular focus was given to RBC oxidative status and anion exchange via the band 3 protein (AE1), critical for erythrocyte function. FM led to decreased food intake and weight, HPA axis hyperactivation, elevated oxidative stress, inflammation, and metabolic and organ dysfunction. RBC physiology and AE1 activity was also disrupted. Daily oral BS administration significantly countered these effects, restoring redox balance, reducing inflammation, stabilizing HPA function, and protecting metabolic and organ systems while preserving RBC integrity. These findings highlight the systemic impact of FM and suggest BS as a possible nutraceutical, offering broad benefits through antioxidant, anti‐inflammatory, and organ‐protective mechanisms.