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Research Paper|Volume 7, Issue 11|pp 1004—1021

Improved motor and cognitive performance with sodium nitrite supplementation is related to small metabolite signatures: a pilot trial in middle-aged and older adults

Jamie N. Justice1, Lawrence C. Johnson1, Allison E. DeVan1, Charmion Cruickshank-Quinn2, Nichole Reisdorph2, Candace J. Bassett1, Trent D. Evans1, Forrest A. Brooks1, Nathan S. Bryan3, Michel B. Chonchol4, Tony Giordano5, Matthew B. McQueen1, Douglas R. Seals1
  • 1Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA
  • 2Integrated Department of Immunology, University of Colorado Anschutz Medical Campus and National Jewish Hospital, Denver, CO 80045, USA
  • 3Baylor College of Medicine, Houston, TX 77030, USA
  • 4Division of Renal Diseases & Hypertension, University of Colorado Denver, Aurora, CO 80045, USA
  • 5TheraVasc Inc., Cleveland, OH 44106, USA

* * Equal contribution

Received: September 3, 2015Accepted: November 2, 2015Published: November 30, 2015
https://doi.org/10.18632/aging.100842

Copyright: © 2015 Justice et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Advancing age is associated with reductions in nitric oxide bioavailability and changes in metabolic activity, which are implicated in declines in motor and cognitive function. In preclinical models, sodium nitrite supplementation (SN) increases plasma nitrite and improves motor function, whereas other nitric oxide-boosting agents improve cognitive function. This pilot study was designed to translate these findings to middle-aged and older (MA/O) humans to provide proof-of-concept support for larger trials. SN (10 weeks, 80 or 160 mg/day capsules, TheraVasc, Inc.) acutely and chronically increased plasma nitrite and improved performance on measures of motor and cognitive outcomes (all p<0.05 or better) in healthy MA/O adults (62 ± 7 years). Untargeted metabolomics analysis revealed that SN significantly altered 33 (160 mg/day) to 45 (80 mg/day) different metabolites, 13 of which were related to changes in functional outcomes; baseline concentrations of 99 different metabolites predicted functional improvements with SN. This pilot study provides the first evidence that SN improves aspects of motor and cognitive function in healthy MA/O adults, and that these improvements are associated with, and predicted by, the plasma metabolome. Our findings provide the necessary support for larger clinical trials on this promising pharmacological strategy for preserving physiological function with aging.