2457-P: The Effect of Prolonged Fasting and Nutritional Ketosis on Cognition

Introduction and Objective: During prolonged fasting, liver glycogen stores are depleted, and ketones are produced from adipose tissue fatty acids. This switch to using ketones is intended to be a “metabolic switch.” Previous studies have examined the effects of fasting on weight loss and on molecular changes. However, the impact of fasting on cognition remains unclear. This pilot study aimed to determine whether fasting and the resulting elevation in ketone levels are associated with changes in cognition, as measured by the CNS Vital Signs Cognitive Battery. The ketone level measurements collected by the Ketomojo meter ensured that participants reached nutritional ketosis (defined as ketone levels ≥1.5 mmol/L). Methods: Healthy adults were randomly assigned to either a control or a fasting-first regimen. The control group maintained an ad lib diet, while the ketosis group fasted (or used a ketogenic run-in diet) until they reached nutritional ketosis (>1.5 mmol/L) (or once 72 hours had elapsed). All participants took the cognitive tests four times: at baseline, during a peak ketosis test, during a peak control test, and during a post-control or fasting test. Tests included the Verbal Memory Test, Visual Memory Test, Finger Tapping Test, Symbol Digit Coding, Stroop Test, Shifting Attention Test, and the Continuous Performance Test. Results: Ten participants have enrolled to date, and seven completed the protocol. Four participants achieved nutritional ketosis. The cognitive results showed that nutritional ketosis impacted cognition. Changes were pronounced in complex attention, cognitive flexibility, and executive function, with an average increase of 2.5, 5.167, and 5 points, respectively, during nutritional ketosis, as measured by the Stroop Test and Shifting Attention Test. Conclusion: To date, results from this pilot study show that prolonged fasting to achieve nutritional ketosis leads to marked improvements in cognitive functioning. Recruitment is ongoing. Disclosure C. Moreno: None. R. Taneja: None. A. Munshi: 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. Funding Touro University California College of Osteopathic Medicine