A 28-day study to evaluate the physiologic effects of beta-nicotinamide mononucleotide on hepatic fat, insulin sensitivity, muscle bioenergetics and performance, and other NAD+-dependent physiologic processes in middle-aged and older men and women

• Grant number: 19/14938-7
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): January 15, 2020
• Effective date (End): January 14, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal researcher: Antonio Carlos Pereira-Barretto
• Grantee: Marcelo Rodrigues dos Santos
• Supervisor abroad: Shalender Bhasin
• Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Research place: Harvard University, Boston, United States
• Associated to the scholarship: 16/24306-0 - The effect of NEPRIlysin (LCZ696) on EXercise TOLerance, muscle vasodilatation, muscle strength and body composition in patients with Heart Failure - NEPRIExTol-HF Trial, BP.PD

Abstract

Nicotinamide mononucleotide (NMN) is a nutraceutical which is sold over the counter as a dietary supplement. The overall objective of this project is to evaluate the safety and tolerability of NMN administration twice a day for 28 days, and to determine whether NMN administration for 28 days raises NAD+ levels in the blood. An additional aim is to determine the physiologic effects of raising intracellular NAD+ on bioenergetics, mitochondrial function, muscle performance and physical function, liver fat, and metabolism. Towards this long-term goal, we propose to conduct a 28-day phase Ib study to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of NMN administered daily for 28 days in community-dwelling, overweight or obese, older male and female volunteers, 45 years or older. This 28-day phase Ib trial will be conducted in community-dwelling overweight or obese male and female participants, 45 years or older. The selection of the NMN dose was guided by the pharmacokinetic and safety data from phase IA and 1B trials conducted by the study investigators at the Brigham and Women's Hospital. An IND is not required for the proposed investigation of this supplement compound because: 1. the clinical investigation is intended only to evaluate the physiologic effect of NMN on bioenergetics, mitochondrial function, muscle performance, and metabolism in healthy volunteers, and 2. The investigation does not intend to evaluate the nutritional supplement's ability to diagnose, cure, mitigate, treat, or prevent a disease.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS SANTOS, MARCELO RODRIGUES; NUNES ALVES, MARIA-JANIEIRE DE NAZARE; JORDAO, CAMILA PAIXAO; NOVAES PINTO, CAIO EDUARDO; SOUZA CORREA, KELLY THAYANE; DE SOUZA, FRANCIS RIBEIRO; PEIXOTO DA FONSECA, GUILHERME WESLEY; TOMAZ FILHO, JOAQUIM; COSTA, MARCEL; RODRIGUES PEREIRA, ROSA MARIA; et al. Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study. AMERICAN HEART JOURNAL, v. 239, p. 1-10, SEP 2021. (16/24833-0, 16/24306-0, 19/14938-7)

DE SOUZA, FRANCIS RIBEIRO; MOTTA-SANTOS, DAISY; SOARES, DOUGLAS DOS SANTOS; DE LIMA, JULIANA BEUST; CARDOZO, GUSTAVO GONCALVES; PINTO GUIMARAES, LUCIANO SANTOS; NEGRAO, CARLOS EDUARDO; DOS SANTOS, MARCELO RODRIGUES. ssociation of physical activity levels and the prevalence of COVID-19-associated hospitalizatio. JOURNAL OF SCIENCE AND MEDICINE IN SPORT, v. 24, n. 9, p. 913-918, SEP 2021. (16/24306-0, 19/14938-7)