{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:58:37Z","timestamp":1785445117586,"version":"3.56.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Declines in nicotinamide adenine dinucleotide (NAD+) are linked to metabolic stress accompanying aging and disease. While precursor-based approaches elevate systemic NAD, their clinical translation can be constrained by biosynthetic bottlenecks and first-pass metabolism. RENEWAL-NAD+ (ClinicalTrials.gov NCT07336836; retrospectively registered 01\/04\/2026) was a double-blind, randomized, placebo-controlled Phase 0\/1b trial in healthy adults aged 45\u201375\u00a0years (60 randomized; primary analysis\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200950) evaluating 5\u00a0days of oral LathMized\u00ae NAD+ (LNAD+), a physicochemically modulated formulation that alters the supramolecular organization and solution behavior of NAD+ while preserving its native molecular structure. The primary endpoints were change in intracellular NAD (icNAD), measured in whole blood, and circulating NAD (cirNAD), measured in separated plasma, relative to baseline. LNAD+ produced a rapid and pronounced increase in icNAD, with a 53% elevation versus placebo at Day 6 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20095.48e\n                    <jats:sup>\u221214<\/jats:sup>\n                    ; Hedges\u2019\n                    <jats:italic>g<\/jats:italic>\n                    \u2009=\u20093.66), while cirNAD was unchanged (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.60), demonstrating compartment-selective augmentation. Plasma NAD catabolites increased substantially (1-methyl-nicotinamide, MeNAM\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20095.39e\n                    <jats:sup>\u221213<\/jats:sup>\n                    ; N1-methyl-2-pyridone-5-carboxamide, 2PY\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20092.95e\n                    <jats:sup>\u221216<\/jats:sup>\n                    ), consistent with downstream engagement of NAD metabolic flux. Exploratory analyses identified non-overlapping correlates for the two compartments (cirNAD tracking inflammatory and metabolic markers, icNAD tracking red blood cell indices and NAM). Treatment was very well tolerated: symptom incidence was comparable between groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.68), only one mild adverse event (nausea, Grade 1) occurred in the LNAD+ arm, and no secondary clinical, vital-sign, wellbeing, or wearable-derived endpoint survived multiplicity correction. These data demonstrate rapid intracellular NAD augmentation after oral LNAD+ dosing with pharmacodynamic evidence of downstream metabolism, compartment-specific physiological signatures, and a favorable short-term safety profile, with exploratory multi-omic analyses ongoing.\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02399-1","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T07:30:30Z","timestamp":1785396630000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-110X","authenticated-orcid":false,"given":"Sergey A.","family":"Kornilov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0875-2568","authenticated-orcid":false,"given":"Waylon J.","family":"Hastings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne Fahey","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Leitz-Langan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0576-677X","authenticated-orcid":false,"given":"Andrew T.","family":"Magis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve M.","family":"Coppess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Komac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"issue":"1","key":"2399_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.tibs.2006.11.006","volume":"32","author":"P Belenky","year":"2007","unstructured":"Belenky P, Bogan KL, Brenner C. 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Federal Register Vol. 46, No.\u00a017, January 27, 1981, part 56) and the Office for Protection from Research Risks Reports: Protection of Human Subjects (Code of Federal Regulations 45 CFR 46). IRB Tracking Number 20215675. The study was conducted per IRB-approved protocol (10\/13\/2021, Version 1) with study code ISBA-101 and study number 1320748. The study was conducted according to the ethical principles of the Declaration of Helsinki and current Good Clinical Practice guidelines, and in compliance with federal, state, and local regulatory requirements, including 21 CFR 312, 21 CFR 50, and 21 CFR 56.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from each participant in an electronic format (e-consent) at enrollment following pre-screening and pending confirmation with the Study Coordinator. The Study Coordinator and\/or the PI of the study described the study and answered questions about the study goals and the protocol, as needed. The principles of informed consent followed are described by Federal Regulatory Guidelines (Federal Register Vol. 46, No.\u00a017, January 27, 1981, part 50) and the Office for Protection from Research Risks Reports: Protection of Human Subjects (Code of Federal Regulations 45 CFR 46). The Informed Consent Form was reviewed and approved by Western IRB (now known as WCG IRB) as part of the protocol submission.","order":2,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"At the time the study was initiated, statistical analysis plan was signed, and throughout the study duration no personnel at Institute for Systems Biology or ISB BioAnalytica held personal or financial relationships that could be viewed as conflict of interest (see Supporting Material). At the time of the study, SK was an employee of Institute for Systems Biology, and upon completion of the study and their departure from Institute for Systems Biology was contracted by BioNADRx as a research consultant and holds stock options. WJH holds stock options in BioNADRx and received consultancy fees during the preparation of this manuscript. WK is the CEO of BioNADRx and holds stock options and shares. LFM holds stock options in BioNADRx and is a Company Advisor. SMC and ATM are founders of ISB BioAnalytica Inc. Following completion of the study and their departure from ISB BioAnalytica, SMC participated in seed-round investing and holds shares in BioNADRx. ML is an investor in BioNADRx and holds stock options and shares.","order":3,"name":"Ethics","label":"Disclosures","group":{"name":"EthicsHeading","label":"Declarations"}}]}}