Dynamics of blood NAD and glutathione in health, disease, aging, and under NAD+-booster treatment

Abstract Nicotinamide adenine dinucleotide (NAD) and glutathione are vital molecules that control redox-state, enzyme functions and metabolic flux in hundreds of cellular metabolic reactions. High NAD + level occurs in fasting and has been associated with health outcomes in model systems, while low NAD + /NADH ratio occurs in specific diseases. Still, the normal, booster-treated or disease-related levels of NADs or glutathiones are not well known in humans. Here, we present a standardized technology for high-throughput quantitative measurement of NAD + , NADH, NADP + , NADPH, GSH and GSSG from a single whole-blood sample. In healthy population (n=299;18-70 year-olds) redox metabolites follow normal distribution in blood and remain unchanged during aging. NAD-boosting increased 4-6 fold the blood NAD + depending on individual, pointing to need of personalized dose adjustment in treatment trials. In patients with cancer, diabetes or neurodegeneration, NADs and glutathiones showed disease-dependent “redox fingerprints”. The evidence highlights the potential of redox profiling as an indicator of metabolic pathology and as a measure of treatment response.