Boosting Post-Stroke Recovery: The Role of Nutritional Supplementation in Reducing Fatigue—A Single-Blind Randomized Controlled Trial

Post-stroke fatigue (PSF) remains a debilitating barrier to recovery. Chronic inflammation and oxidative stress often create physiological plateaus that standard rehabilitation alone cannot resolve. This single-blind randomized controlled trial (RCT) evaluated the efficacy of Food for Special Medical Purposes formulated with iron and other vitamins and minerals in Sucrosomial® form, allowing improved absorption, bioavailability, and tolerability, as an adjunct to neurorehabilitation. One hundred and twenty stroke patients were randomized into an experimental group (Sid-G) receiving the specific nutraceutical compound or a control group (CG) receiving standard care. Longitudinal assessments from baseline (T0) through 16 weeks (T3) measured clinical outcomes (including fatigue, motor/cognitive function) and physiological markers, specifically phase angle (PhA) derived from Bioimpedance Analysis, and key inflammatory and oxidative stress biomarkers (IL-6 and MPO). The Sid-G cohort demonstrated superior, sustained improvements in fatigue, motor, and cognitive function (p < 0.05). These clinical gains were reflected in the following physiological observations: the time × group interaction for cellular integrity (SPhA) was not significant, though within-group improvements were observed in Sid-G (p = 0.009); at the group level, significant time × group interactions were detected for key inflammatory and oxidative stress markers (IL-6, p = 0.001; MPO, p = 0.026). Correlational analysis revealed a significant association between changes in inflammatory markers and clinical recovery outcomes in Sid-G, a pattern absent in the CG. Adjunctive supplementation may support recovery by helping patients to overcome physiological plateaus. These findings support further evaluation of an integrated, metabolically focused approach to neurorehabilitation.