The use of Nicotinamide Adenine Dinucleotide (NADH) supplementation has gained significant attention due to its touted benefits for brain health, especially as it relates to aging and neurodegenerative diseases. A recent study conducted by researchers at Stanford University, and published on April 1, 2025, sheds new light on this popular supplement, particularly its effects on recovery from anesthesia.
This investigation focuses on the extent to which NADH, a common over-the-counter NAD+ precursor, influences cognitive and locomotor recovery following anesthesia. The findings reveal not only the ineffectiveness of NADH supplementation but unsettlingly highlight its potential to decrease rodent activity post-anesthesia, challenging some assumptions about its benefits.
Using both open field activity and Y-maze tests, the researchers employed adult male and female C57BL/6 mice, administering either NADH or saline as the vehicle. The aim was straightforward yet significant: to ascertain whether administering NADH could expedite recovery from general anesthesia, using isoflurane as the anesthetic agent.
Interestingly, the results demonstrated no benefits from NADH supplementation. Mice treated with NADH showed significantly less activity during open-field tests compared to their saline-treated counterparts, manifesting as decreased distance traveled and reduced average velocity. Following anesthesia, the NADH cohort exhibited diminished activity levels, emphasizing the negative impact of this supplement.
One of the standout findings of the study was observed using the Y-maze test, which assesses spatial memory. The NADH-treated group significantly decreased both the number of visits to novel arms and total entries, signaling impaired cognitive recovery. Contrary to what might be expected, these results place NADH supplementation under scrutiny, particularly for its application amid concerns surrounding postoperative delirium, which can severely impact recovery trajectories.
The authors explained, "NADH decreased both the number of novel arm visits and total arm entries in a post-anesthesia Y-maze trial compared to baseline." Such outcomes led the researchers to propose, "The findings indicate acute NADH administration decreases rodent activity and has no effect on spatial memory performance following general anesthesia." These insights provoke questions about the actual efficacy of NADH, particularly for those considering it for cognitive enhancement and recovery post-surgery.
Historically, the connection between NAD+ and health has been rooted deeply within the framework of energy metabolism and cellular repair mechanisms. NAD+ is known as a pivotal coenzyme, participating actively in metabolic pathways and serving as a vehicle for cellular regeneration. Its depletion has been concomitant with the processes associated with normal aging and neurodegeneration.
Despite the enthusiasm surrounding NAD+ precursors, this study brings sobering news about the acute administration of NADH—one of the most accessible forms. This research suggests caution, particularly for populations susceptible to cognitive decline or those recovering from surgery. The seemingly innocuous act of supplementing NADH could have pivotal consequences on behavior and recovery, as underscored by the observed decline in activity.
Researchers have expressed the necessity for more extensive studies to clarify whether these behaviors translate to clinical settings, especially considering age and health factors. They proposed, "Future studies on the brain redox state with acute administration of NADH... may shed light on the acute effects of NAD supplementation, with and without exposure to anesthetics."
The results echo the need for balanced dialogue around dietary supplements like NADH. Given the potential ramifications of meddling with fundamental processes related to recovery from anesthesia, future users must weigh the benefits against the data trends revealed through this recent study.
Finally, this study serves as a gateway for future investigations, noting the necessity of examining potential changes in mitochondrial function and other pathways to validate the mechanisms behind NADH's effects and its role—or lack thereof—in facilitating post-anesthesia recovery.