Intramuscular NAD⁺ Therapy and Neuroenergetic Symptom Modulation: An Exploratory Retrospective Human Pilot Study

Authors

• Zachary J. Dickey DO, HCA Florida Aventura Transitional Year Residency ProgramFollow
• Kirtan Patel BS, Edward Via College of Osteopathic Medicine – Louisiana CampusFollow
• Randy Aldret EdD, CSCS, ATC, Edward Via College of Osteopathic Medicine – Louisiana CampusFollow
• Navneet Sharma MD, Edward Via College of Osteopathic Medicine – Louisiana CampusFollow
• Glenn Goodwin DO, HCA Florida Aventura Transitonal Year Residency ProgramFollow

Abstract

Abstract

Background: Nicotinamide adenine dinucleotide (NAD⁺) is a central regulator of neuronal energy metabolism, mitochondrial function, and axonal integrity. Following mild traumatic brain injury (mTBI) and repetitive subconcussive exposure, neurons undergo a neurometabolic crisis characterized by impaired oxidative phosphorylation, increased ATP demand, and depletion of intracellular NAD⁺ pools. Pre clinical models demonstrate that NAD⁺ depletion contributes to central energy dysregulation, cognitive dysfunction, and axonal and neuronal degeneration through disruption of NAD⁺-dependent pathways including SIRT1-mediated mitochondrial resilience, PARP1-driven NAD⁺ consumption, and SARM1-associated axonal breakdown. Despite growing preclinical evidence supporting NAD⁺based neuroprotection, human clinical data remains absent.

Methods: A real-world clinical pilot study evaluating subjective neurocognitive and functional outcomes following intramuscular (IM) NAD⁺ therapy was performed. Five adult participants received IM NAD⁺ injections (0.33–1.0 cc, gluteal administration) administered every third day over a 3–6 month period as part of routine clinical care. A standardized post-treatment questionnaire assessed over 20 functional domains, including fatigue, concentration, motivation, sleep quality, mood, memory, pain perception, and movement. Responses were coded dichotomously (improvement: yes/no), and outcomes were expressed as the percentage of participants reporting improvement within each domain. Safety outcomes included injection-site discomfort and systemic adverse effects.

Results: All participants (5/5) reported improvement in at least one symptom domain following IM NAD⁺ therapy. The highest response rates were observed in fatigue, motivation, concentration, and reading recall (100%). Improvements were also reported in sleep quality, memory, and movement (60%). When grouped by functional category, average improvement rates were greatest in cognitive domains (68%), followed by physical (50%), behavioral (≈46%), and sensory domains (20%). IM NAD⁺ therapy was well tolerated, with no systemic adverse effects reported; one participant experienced mild, self-limited injection-site soreness.

Conclusion: In this human pilot study, IM NAD⁺ therapy was associated with consistent subjective improvements in neurofatigue and cognitive symptom domains. These findings align with established neuroenergetic models implicating NAD⁺ depletion in neuronal vulnerability following sports-related brain injury. While limited by small sample size and reliance on patient-reported outcomes, this study provides early translational support for prospective investigation of NAD⁺-based interventions in sports concussion and mTBI.

Recommended Citation

Dickey, Zachary J. DO; Patel, Kirtan BS; Aldret, Randy EdD, CSCS, ATC; Sharma, Navneet MD; and Goodwin, Glenn DO (2026) "Intramuscular NAD⁺ Therapy and Neuroenergetic Symptom Modulation: An Exploratory Retrospective Human Pilot Study," Journal for Sports Neuroscience: Vol. 2: Iss. 1, Article 9.
Available at: https://nsuworks.nova.edu/neurosports/vol2/iss1/9