Fasting-based interventions in experimental acquired brain injury: A systematic review and Meta-analysis stratified by intervention timing.

BACKGROUND

Fasting-based interventions may influence neurological recovery after brain injury through metabolic and neuroprotective mechanisms. We evaluated their association with neurological functional recovery in preclinical acquired brain injury.

METHODS

PubMed, Web of Science, Embase, and Scopus were searched for animal studies published from May 2000 through 25 August 2026 evaluating fasting-based interventions in experimental ischemic stroke, intracerebral hemorrhage, or traumatic brain injury. One representative functional outcome was selected per independent cohort. Postinjury fasting formed the primary therapeutic analysis using REML with modified Knapp-Hartung inference, whereas preinjury fasting was analyzed separately as metabolic preconditioning using a three-level random-effects model with study-clustered small-sample inference.

RESULTS

Thirteen studies were included qualitatively; 12 contributed 17 independent-cohort effects and 316 animals to quantitative synthesis. Four postinjury studies involving 70 animals showed a positive association with neurological recovery (Hedges' g = 1.39, 95% CI 0.54-2.24; P = 0.014; 95% prediction interval 0.24-2.54). Eight preinjury studies contributed 13 effects and 246 animals and also showed a positive association (Hedges' g = 1.89, 95% CI 0.92-2.86; P = 0.002), although the prediction interval crossed the null (-0.85 to 4.64). Early and longer-term assessments yielded positive descriptive estimates. Small-study-effect tests were underpowered and could not exclude publication bias.

CONCLUSIONS

Postinjury fasting was associated with improved neurological outcomes in experimental acquired brain injury, but the evidence was limited to four small animal studies. Preinjury fasting also showed a positive association but represents metabolic preconditioning rather than treatment. These findings do not establish clinical effectiveness or safety and require rigorous prospective preclinical validation.