Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models.
Publication/Presentation Date
4-12-2025
Abstract
Disruption of nicotinamide adenine dinucleotide (NAD) biosynthesis and function during infection may impair host defenses and aggravate inflammatory and oxidative organ injury. Increasingly, studies are investigating whether niacin or NAD metabolite treatment is beneficial in infection and sepsis animal models. We examined whether this preclinical experience supports clinical trials. A systematic review of three data bases was conducted through 2/29/2024 and a meta-analysis was performed comparing niacin or NAD metabolite treatment to control in adult animal models employing microbial challenges. Fifty-six studies met inclusion criteria, with 24 published after 2019. Most studies employed mouse (n = 40 studies) or rat (n = 12) models and administered either a bacterial toxin (n = 28) or bacterial (n = 19) challenge. Four and three studies employed viral or fungal challenges respectively. Studies investigated an NAD metabolite alone (n = 44), niacin alone (n = 9), or both (n = 3), usually administered before or within 24h after challenge (n = 50). Only three and four studies included standard antimicrobial support or started treatment > 24h after challenge respectively. In similar patterns with differing animal types (p ≥ 0.06), compared to control across those studies investigating the parameter, niacin or NAD treatment decreased the odds ratio of mortality [95% confidence interval (CI)] [0.28 (0.17, 0.49)] and in blood or tissue increased antioxidant levels [standardized mean differences (95%CI)] (SMD) [3.61 (2.20,5.02)] and decreased levels of microbes [- 2.44 (- 3.34, - 1.55)], histologic and permeability organ injury scoring [- 1.62 (- 2.27, - 0.98) and - 1.31(- 1.77, - 0.86) respectively], levels of TNFα, IL-6 and IL-1β [- 2.47 (- 3.30, - 1.64), - 3.17 (- 4.74, - 1.60) and - 8.44 (- 12.4, - 4.5) respectively] and myeloperoxidase (MPO) [- 1.60 (- 2.06, - 1.14)], although with significant, primarily quantitative heterogeneity for each (I
Volume
15
Issue
1
First Page
12621
Last Page
12621
ISSN
2045-2322
Published In/Presented At
Curran, C. S., Cui, X., Li, Y., Gamble, T., Sun, J., Minkove, S., Livinski, A. A., Eichacker, P. Q., & Torabi-Parizi, P. (2025). Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models. Scientific reports, 15(1), 12621. https://doi.org/10.1038/s41598-025-95735-y
Disciplines
Medicine and Health Sciences
PubMedID
40221506
Department(s)
Department of Medicine
Document Type
Article