Nicotinamide Adenine Dinucleotide Does Not Improve Anesthetic Recovery in Rodents

Nicotinamide Adenine Dinucleotide (NAD⁺) is implicated in bioenergetics, DNA repair, and senescence. Depletion of NAD⁺ is associated with aging and neurodegenerative disease, prompting a growing interest in NAD⁺ supplementation. With rising over-the-counter use of NAD, understanding their impact on perioperative recovery becomes essential. This study investigates the effect of NADH, a common NAD⁺ precursor, on anesthesia in rodents. Baseline and post-anesthesia (1.5% isoflurane) open field and Y-maze activity were recorded in adult male and female C57/BL6 mice (n = 8-10/group). NADH (150 mg/kg, intraperitoneal) or vehicle (0.9% normal saline) were given at baseline or during anesthesia. The NADH-treated group exhibited a significant decrease in open-field activity relative to vehicle-treated. This diminished activity was reflected in reduced distance travelled and average velocity after emergence from anesthesia in the NADH-treated group. NADH treatment did not improve Y-maze performance after anesthesia as the number of visits to the novel arm was significantly decreased. This study demonstrates a potentially adverse impact of NADH on recovery from anesthesia. We revealed a depression in open-field activity and Y-maze performance with NADH supplementation, an indicator of cognitive recovery in rodents. The broad implications of NAD⁺ in aging are likely to shape supplementation trends, highlighting the importance of understanding the potential influence of administering NAD⁺ on anesthetic sensitivity and recovery.