NAD+ and Cellular Health: What Research Says About IV and Oral Supplementation
Nicotinamide adenine dinucleotide (NAD) is a vital coenzyme involved in cellular energy production, DNA repair, and regulation of aging and disease processes. Interest in NAD supplementation, including intravenous (IV) infusions, has grown due to its potential to counteract age-related NAD decline and support cellular health.
NAD levels naturally decrease with age and in various disease states, contributing to impaired mitochondrial function, increased oxidative stress, and reduced cellular repair capacity. Preclinical studies show that boosting NAD—often via precursors like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN)—can improve metabolic health, protect against neurodegeneration, and extend healthspan in animal models.[1][2][3] Early human trials suggest benefits for metabolic parameters, cardiovascular health, and neuroprotection, but most clinical data focus on oral or intranasal precursors rather than direct IV NAD+ administration.[1][4][5]
IV NAD+ infusions are marketed for rapid NAD repletion, but clinical evidence is limited. A pilot study found that during a 6-hour IV NAD+ infusion, plasma NAD+ levels did not rise until after 2 hours, suggesting rapid cellular uptake or metabolism. Urinary excretion of NAD+ and its metabolites increased, but the clinical significance of these pharmacokinetic findings remains unclear.[6] Systematic reviews indicate that NAD+ and NADH supplementation is generally well tolerated, with mild side effects such as muscle pain, fatigue, and headaches, but robust evidence for disease-specific benefits is lacking.[4][5]
Potential benefits of NAD supplementation—whether oral or IV—include improved energy metabolism, reduced inflammation, enhanced DNA repair, and possible neuroprotective effects. However, the efficacy, optimal dosing, and long-term safety of IV NAD+ infusions are not yet established in large, well-controlled clinical trials.[1][7][5] Most experts recommend further research to clarify which delivery methods and patient populations may benefit most.
In summary, NAD is a promising therapeutic target, but the clinical benefits of IV NAD+ infusions remain speculative and require more rigorous investigation. Oral NAD+ precursors have more established safety and efficacy profiles, while IV NAD+ is still under study.[1][4][5]
References
1. Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns. Bhasin S, Seals D, Migaud M, Musi N, Baur JA. Endocrine Reviews. 2023;44(6):1047-1073. doi:10.1210/endrev/bnad019.
2. Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes. Braidy N, Berg J, Clement J, et al. Antioxidants & Redox Signaling. 2019;30(2):251-294. doi:10.1089/ars.2017.7269.
3. Preclinical and Clinical Evidence of NAD Precursors in Health, Disease, and Ageing. Reiten OK, Wilvang MA, Mitchell SJ, Hu Z, Fang EF. Mechanisms of Ageing and Development. 2021;199:111567. doi:10.1016/j.mad.2021.111567.
4. Evaluation of Safety and Effectiveness of NAD in Different Clinical Conditions: A Systematic Review. Gindri IM, Ferrari G, Pinto LPS, et al. American Journal of Physiology. Endocrinology and Metabolism. 2024;326(4):E417-E427. doi:10.1152/ajpendo.00242.2023.
5. Clinical Evidence for Targeting NAD Therapeutically. Radenkovic D, Reason, Verdin E. Pharmaceuticals (Basel, Switzerland). 2020;13(9):E247. doi:10.3390/ph13090247.
6. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. Grant R, Berg J, Mestayer R, et al. Frontiers in Aging Neuroscience. 2019;11:257. doi:10.3389/fnagi.2019.00257.
7. Regulation of and Challenges in Targeting NAD+ Metabolism. Migaud ME, Ziegler M, Baur JA. Nature Reviews. Molecular Cell Biology. 2024;25(10):822-840. doi:10.1038/s41580-024-00752-w.