Oral MIB‐626 (β Nicotinamide Mononucleotide) Safely Raises Blood Nicotinamide Adenine Dinucleotide Levels in Hospitalized Patients With COVID‐19 and Acute Kidney Injury: A Randomized Controlled Trial

DOI record: { "DOI": "10.1096/fba.2025-00014", "ISSN": [ "2573-9832", "2573-9832" ], "URL": "http://dx.doi.org/10.1096/fba.2025-00014", "abstract": "<jats:title>ABSTRACT</jats:title>\n <jats:p>\n Nicotinamide adenine dinucleotide (NAD\n <jats:sup>+</jats:sup>\n ) plays an important role in the innate immune response and is depleted during SARS‐CoV‐2 infection due to increased turnover. It is unknown whether treatment with NAD\n <jats:sup>+</jats:sup>\n precursors can safely raise NAD\n <jats:sup>+</jats:sup>\n levels in patients with COVID‐19. To determine whether MIB‐626 (\n <jats:italic>β‐</jats:italic>\n nicotinamide mononucleotide), an NAD\n <jats:sup>+</jats:sup>\n precursor, can safely increase blood NAD\n <jats:sup>+</jats:sup>\n levels and attenuate acute kidney injury (AKI) and inflammation in hospitalized patients with COVID‐19, 42 adults, ≥ 18 years, hospitalized with COVID‐19 and AKI, were randomized in a 3:2 ratio to MIB‐626 1.0‐g or placebo tablets twice daily for 14 days. Circulating NAD\n <jats:sup>+</jats:sup>\n and its metabolites, markers of AKI, inflammation, and disease severity, were assessed. MIB‐626 treatment significantly but gradually raised blood NAD\n <jats:sup>+</jats:sup>\n levels to a peak between 5 to 14 days (16.0 ± 6.9, 25.5 ± 12.6, and 42.6 ± 25.6 μg/mL at baseline, days 5 and 14) and raised plasma concentrations of NAD\n <jats:sup>+</jats:sup>\n metabolites 1‐methylnicotinamide, N‐methyl, 2‐pyridone, 4‐carboxamide rapidly to a peak by day 3. Changes in serum creatinine, cystatin‐C, and serum markers of AKI did not differ significantly between groups. Serum CRP, IL‐6, and TNFα and indices of disease severity also did not differ between groups. MIB‐626 treatment of patients with COVID‐19 and AKI safely and substantially raised blood NAD\n <jats:sup>+</jats:sup>\n and plasma concentrations of NAD\n <jats:sup>+</jats:sup>\n metabolites. Markers of AKI, inflammation, and disease severity did not differ between groups, likely due to the slow rise in NAD\n <jats:sup>+</jats:sup>\n levels. Future studies should assess whether a rapid increase in NAD\n <jats:sup>+</jats:sup>\n by parenteral administration can attenuate disease severity and AKI.\n </jats:p>\n <jats:p>\n <jats:bold>Trial Registration:</jats:bold>\n <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"http://clinicaltrials.gov\">ClinicalTrials.gov</jats:ext-link>\n Identifier: NCT05038488\n </jats:p>", "alternative-id": [ "10.1096/fba.2025-00014" ], "article-number": "e70011", "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2025-01-16" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "2025-03-31" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 3, "value": "2025-06-18" } ], "author": [ { "affiliation": [ { "name": "Research Program in Men's Health: Aging and Metabolism Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA" } ], "family": "Pencina", "given": "Karol M.", "sequence": "first" }, { "affiliation": [ { "name": "Division of Renal Medicine Brigham and Women's Hospital Boston Massachusetts USA" } ], "family": "Leaf", "given": "David E.", "sequence": "additional" }, { "affiliation": [ { "name": "Research Program in Men's Health: Aging and Metabolism Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA" } ], "family": "Valderrabano", "given": "Rodrigo J.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medicine, Section of Nephrology Boston Medical Center and Boston University Chobanian &amp; Avedisian School of Medicine Boston Massachusetts USA" } ], "family": "Waikar", "given": "Sushrut S.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Family and Community Medicine University of Alabama Birmingham Alabama USA" } ], "family": "Mehta", "given": "Tapan S.", "sequence": "additional" }, { "affiliation": [ { "name": "Research Program in Men's Health: Aging and Metabolism Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA" } ], "family": "Shang", "given": "Yili Valentine", "sequence": "additional" }, { "affiliation": [ { "name": "Research Program in Men's Health: Aging and Metabolism Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA" } ], "family": "Latham", "given": "Nancy K.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Family and Community Medicine University of Alabama Birmingham Alabama USA" } ], "family": "John", "given": "Tejossy", "sequence": "additional" }, { "affiliation": [ { "name": "University of Texas Medical Branch Galveston Texas USA" } ], "family": "Volpi", "given": "Elena", "sequence": "additional" }, { "affiliation": [ { "name": "Tulane University School of Medicine New Orleans Louisiana USA" } ], "family": "Fusco", "given": "Dahlene", "sequence": "additional" }, { "affiliation": [ { "name": "Research Program in Men's Health: Aging and Metabolism Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA" } ], "family": "Memish‐Beleva", "given": "Yusnie", "sequence": "additional" }, { "affiliation": [ { "name": "Division of Renal Medicine Brigham and Women's Hospital Boston Massachusetts USA" } ], "family": "Krishnamurthy", "given": "Shobana", "sequence": "additional" }, { "affiliation": [ { "name": "Metro International Biotech Worcester Massachusetts USA" } ], "family": "Lavu", "given": "Siva", "sequence": "additional" }, { "affiliation": [ { "name": "Metro International Biotech Worcester Massachusetts USA" } ], "family": "Karmi", "given": "Salma", "sequence": "additional" }, { "affiliation": [ { "name": "Metro International Biotech Worcester Massachusetts USA" } ], "family": "Livingston", "given": "David J.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-3982-6200", "affiliation": [ { "name": "Research Program in Men's Health: Aging and Metabolism Boston Claude D. 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