Introduction and Objective: Prolonged fasting induces a metabolic switch from glucose to ketone utilization, which may influence cognitive function and metabolic health. However, data on cognitive effects of prolonged fasting (≥24 h), ketone-confirmed metabolic switching, and sex-specific responses remain limited.Methods: In a randomized, within-subject crossover pilot study, healthy adults (18-55 years) completed a control condition (habitual diet) and a prolonged fast (up to 72 hours or β-hydroxybutyrate ≥1.5 mmol/L). Ketosis was monitored daily via fingerstick measurements by the Ketomojo meter. CNS Vital Signs assessed cognition at baseline, control, and fasting states. Primary outcomes included Composite Memory (CM), Neurocognitive Index (NCI), and Reaction Time (RT). Paired and independent t-tests evaluated fasting effects and sex differences in change scores; Hedges’ g estimated effect sizes.Results: Nine participants (5 males and 4 females) completed cognitive assessments. CM scores were significantly higher during fasting compared with the control condition (p = 0.042), with no significant changes in NCI or RT. Change-score analyses demonstrated a significant sex difference in CM response, with females exhibiting greater fasting-related improvement than males (p = 0.009). The magnitude of this sex difference was large (Hedges’ g = 2.13, 95% CI [0.49, 3.69]). No significant sex differences were observed for NCI or RT.Conclusion: These preliminary findings suggest that prolonged fasting may enhance memory performance, with observed sex-specific improvements in females. While limited by sample size, these results suggest that the metabolic switch to ketone utilization may differentially impact cognitive domains by sex, warranting further investigation in larger cohorts.
R. Taneja: None. A. Munshi: None. C. Moreno: None. J. Shubrook: Advisory Panel; Current; Abbott Diabetes. Other – Doc Care Deputy EditorConsensus panel-liver health, screening early stage T1d, Technology in primary care; Current; American Diabetes Association. Advisory Panel; Current; Bayer AG, Boehringer Ingelheim International GmbH. Consultant; Ended; Corcept Therapeutics. Advisory Panel; Ended; Idorsia Pharmaceuticals Ltd. Advisory Panel; Current; Insulet Corporation. Advisory Panel; Ended; Madrigal Pharmaceuticals, Inc. Consultant; Current; Novo Nordisk, Sanofi. G.G. Gayer: None.
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