Abstract

Nicotinamide adenine dinucleotide (NAD+) serves important roles in hydrogen transfer and as the cosubstrate for poly(ADP-ribose) polymerase (PARPs), the sirtuin (SIRT1-7) family of enzymes, and CD38 glycohydrolases. Recently, intravenous (IV) NAD+ therapy has been used as a holistic approach to treat withdrawal from addiction, overcome anxiety and depression, and improve overall quality of life with minimal symptoms between 3-7 days of treatment. We evaluated repeat dose IV NAD+ (1000 mg) for 6 days in a population of 8 healthy adults between the ages of 70 and 80 years. Our data is the first to show that IV NAD+ increases the blood NAD+ metabolome in elderly humans. We found increased concentrations of glutathione peroxidase -3 and paraoxonase-1, anddecreased concentrations of 8-iso-prostaglandin F2α, advanced oxidative protein products, protein carbonyl, C-reactive protein and interleukin 6. We report significant increases in mRNA expression and activity of SIRT1, and Forkhead box O1, and reduced acetylated p53 in peripheral blood mononuclear cells isolated from these subjects. No major adverse effects were reported in this study. The study shows that repeat IV dose of NAD+ is a safe and efficient way to slow down age-related decline in NAD+.

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