Dyslipidemia, or abnormally high levels of fats and cholesterol in the blood, can lead to one of several lifestyle-related illnesses due to overconsumption of unhealthy foods. These illnesses continue to be the leading cause of disease and death in developed countries, and therefore, significant resources have been dedicated to understanding and treating the underlying causes. One area of growing interest is the use of Nicotinamide riboside (NR), a form of vitamin B3 that is a precursor to nicotinamide adenine dinucleotide (NAD+). NAD+ is a co-enzyme found in all living cells and is involved in redox reactions during metabolism, and as such, can play a potential role in a wide variety of cellular processes and disease states. However, biomedical studies have honed in on clines in NAD+ levels as an important step in tissues during aging and overnutrition. NR has been demonstrated to increase levels NAD+ and in certain model organisms (e.g. yeast and mice) to help extend life and improve outcomes of metabolic disease. However, in order to take advantage of NR technologies to improve treatments in humans, knowledge of in vivo pharmacokinetics and bioavailability are required.

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In a recent Nature Communications article (Nat. Commun. 10, 12948; 2016) Charles Brenner and colleagues at the Carver College of Medicine, University of Iowa (Iowa City, IA), studied the oral bioavailability of NR and its utilization in different tissues using data from humans and mice. As a pilot-study, the team began by analyzing NAD+ metabolomics of blood and urine from a healthy 52-year-old man given a 1,000 mg dose of NR daily for 7 days. They found that NAD+ levels rose 2.7 fold in the blood after a single dose, and surprisingly that NA adenine dinucleotide (NAAD) increased 45-fold. Follow-up experiments in mice further showed that NR boosts NAD+ greater than NA, and that NR is a direct precursor of NAAD. A validation clinical study in 12 healthy human subjects confirmed that NR can safely boost NAD+ levels, and also that NAAD levels serve as a sensitive biomarker of increased levels of NAD+. This unique combination of pre-clinical and clinical science demonstrates the oral bioavailability of NR, and helps establish criteria for further translation of NR treatment for human disease.