National Institute on Aging (USA) Workshop: Exploring Opportunities and Feasibility of Trials on Effects of Increasing NAD+ Levels in Older Adults*

Nicotinamide Adenine Dinucleotide (NAD) Augmentation to Attenuate the Severity and Improve Outcomes in Older Adults with SARS-CoV-2 Infection

Shalender Bhasin, M.D., Brigham and Women's Hospital, Harvard University — December 9, 2021

Abstract: A majority of people infected with the SARS-CoV-2 remain asymptomatic or suffer from only a mild respiratory illness; however, a subset of patients develop a more severe illness that can progress rapidly to acute respiratory distress syndrome, multi-organ failure, and high risk of death. An unbridled, heightened inflammatory response and the excessive release of cytokines in critically ill patients with COVID-19 pneumonia contributes to the development of acute respiratory distress syndrome and multi-organ failure, similar to that observed in severe cases of other major respiratory viral diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), respiratory syncytial virus, and influenza. The recognition of the important role of aggressive inflammatory response in the pathophysiology of ARDS and multiorgan failure in severe COVID-19 disease has led to the hypothesis that immunomodulatory therapy that can attenuate the inflammatory response could modulate disease severity and improve outcomes.

Nicotinamide adenine dinucleotide (NAD) serves as a co-factor in signaling pathways that regulate innate immunity to respiratory viruses (e.g., the influenza, SARS, MERS, and SARS-CoV-2), inflammation, and cell survival. Older people have low levels of NAD, and SARS-CoV-2 infection further depletes NAD levels by upregulating CD38 and poly-ADP-ribose polymerases (PARPs). Older individuals have lower levels of NAD and are at increased risk for COVID-19 infection, developing a more severe disease, and of dying from the disease. Raising cellular NAD levels by administration of its precursor β nicotinamide mononucleotide, NMN) boosts innate immunity to other coronaviruses and be beneficial in improving outcomes in patients with COVID-19, particularly in patients with at risk co-morbidities which heighten inflammation and also increase susceptibility to negative outcomes of COVID-19. We have shown that oral administration of a crystalline formulation of β nicotinamide mononucleotide substantially raises the intracellular NAD levels. Randomized clinical trials to determine the efficacy of NAD augmentation in reducing the severity of SARS-CoV-2 infection and reduce the length of hospital stay are in progress.

Dr. Shalender Bhasin is a Professor of Medicine at the Harvard Medical School, and Director of the Research Program for Men’s Health and Aging at the Brigham and Women’s Hospital in Boston, MA. He is also the Director of the Boston Claude D. Pepper Aging Research Center. Dr. Bhasin is an internationally recognized expert in Men’s Health and aging. He has published more than 400 original research papers in top tier journals, has led some of the most important randomized trials of the benefits and risks of testosterone and other function promoting therapies in older adults, elucidated the mechanisms of testosterone action, and clarified the role of circulating hormone binding proteins. Dr. Bhasin has been the recipient of numerous teaching and research awards. He was the recipient of the Outstanding Clinical Investigator Award from the Endocrine Society and Frontiers in Science Award from American Association of Clinical Endocrinologists.

*Read all the abstracts of the workshop interventions: