{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:11:16Z","timestamp":1789031476626,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Nicotinamide adenine dinucleotide (NAD\n                      <jats:sup>+<\/jats:sup>\n                      ) is a major coenzyme critically involved in cellular metabolism, mitochondrial function, DNA repair, and stress-response signaling. Age-associated decline in NAD\n                      <jats:sup>+<\/jats:sup>\n                      levels has generated interest in NAD\n                      <jats:sup>+<\/jats:sup>\n                      -augmenting strategies; however, recent large-scale human data indicate that whole-blood NAD\n                      <jats:sup>+<\/jats:sup>\n                      concentrations do not decline with healthy aging\n                      <jats:italic>per se<\/jats:italic>\n                      . Despite increasing commercial use of IV NAD\n                      <jats:sup>+<\/jats:sup>\n                      therapy in wellness settings, the clinical evidence supporting its efficacy and long-term safety remains limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Literature published between January 2018 and March 2026 was identified\n                      <jats:italic>via<\/jats:italic>\n                      PubMed and Google Scholar searches. Search terms were applied symmetrically across all target compounds and administration routes. Studies were included if they reported human clinical data on IV NAD\n                      <jats:sup>+<\/jats:sup>\n                      or IV NAD\n                      <jats:sup>+<\/jats:sup>\n                      precursor administration, or if they provided directly relevant mechanistic or safety evidence. Mechanistic and foundational studies published before 2018 were selectively incorporated\n                      <jats:italic>via<\/jats:italic>\n                      citation tracking of key included articles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Available human evidence is sparse and consists primarily of small uncontrolled studies, observational investigations, and isolated case reports. Short-term IV NAD\n                      <jats:sup>+<\/jats:sup>\n                      or NMN administration has been associated with transient increases in circulating NAD\n                      <jats:sup>+<\/jats:sup>\n                      levels and changes in selected biomarkers related to oxidative stress, inflammation, and cellular metabolism. Limited exploratory reports have also described self-reported improvements in sleep-related outcomes and neurologic symptoms. However, the clinical significance of these findings remains uncertain due to small sample sizes, lack of placebo controls, heterogeneous methodologies, and short follow-up durations. Reported adverse effects include nausea, cramping, flushing, and chest discomfort, while long-term safety data are lacking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Current evidence regarding IV NAD\n                      <jats:sup>+<\/jats:sup>\n                      therapy remains preliminary and insufficient to support routine clinical or wellness use. Although mechanistic and translational studies provide biological rationale for NAD\n                      <jats:sup>+<\/jats:sup>\n                      augmentation, robust conclusions regarding efficacy, durability of benefit, optimal dosing, and long-term safety cannot currently be established. Larger randomized controlled trials with standardized protocols and clinically meaningful endpoints are required before IV NAD\n                      <jats:sup>+<\/jats:sup>\n                      therapy can be considered evidence-based clinical practice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fragi.2026.1887175","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:00:42Z","timestamp":1789030842000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Narrative review of intravenous NAD+ and NAD+ precursors in wellness and translational medicine"],"prefix":"10.3389","volume":"7","author":[{"given":"Abdulrahman","family":"Alangari","sequence":"first","affiliation":[{"name":"Department of Research & Development, Evercare","place":["Riyadh, Saudi Arabia"]},{"name":"Department of Gastroenterology and Hepatology, Prince Sultan Military Medical City","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Arif","sequence":"additional","affiliation":[{"name":"College of Medicine, Shaqra University","place":["Shaqra, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahd","family":"Al Qureshah","sequence":"additional","affiliation":[{"name":"Bioscience Program, King Abdullah University of Science and Technology (KAUST)","place":["Thuwal, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad","family":"Alkhodairy","sequence":"additional","affiliation":[{"name":"Department of Research & Development, Evercare","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.3390\/metabo14060341","article-title":"Nicotinamide mononucleotide supplementation: understanding metabolic variability and clinical implications","volume":"14","author":"Benjamin","year":"2024","journal-title":"Metabolites"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3812","DOI":"10.3390\/cells11233812","article-title":"Role of liver CD38 in the regulation of metabolic pathways during cold-induced thermogenesis in mice","volume":"11","author":"Benzi","year":"2022","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","first-page":"779","DOI":"10.37212\/JCNOS.610084","article-title":"Intravenous NAD+ effectively increased the NAD metabolome, reduced oxidative stress and inflammation, and increased expression of longevity genes safely in elderly humans","volume":"10","author":"Braidy","year":"2018","journal-title":"J. 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