title: Improved motor and cognitive performance with sodium nitrite supplementation is related to small metabolite signatures: a pilot trial in middle-aged and older adults.
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 to 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.
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Justice
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Johnson
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Allison E
authors.initials: AE
authors.lastname: DeVan
authors.affiliation: Integrated Department of Immunology, University of Colorado Anschutz Medical Campus and National Jewish Hospital, Denver, CO 80045, USA.
authors.forename: Charmion
authors.initials: C
authors.lastname: Cruickshank-Quinn
authors.affiliation: Integrated Department of Immunology, University of Colorado Anschutz Medical Campus and National Jewish Hospital, Denver, CO 80045, USA.
authors.forename: Nichole
authors.initials: N
authors.lastname: Reisdorph
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Candace J
authors.initials: CJ
authors.lastname: Bassett
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Trent D
authors.initials: TD
authors.lastname: Evans
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Forrest A
authors.initials: FA
authors.lastname: Brooks
authors.affiliation: Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Bryan
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Michel B
authors.initials: MB
authors.lastname: Chonchol
authors.affiliation: TheraVasc Inc., Cleveland, OH 44106, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Giordano
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: McQueen
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000368:Aged; D003071:Cognition / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D010865:Pilot Projects; D012977:Sodium Nitrite / Q000008:administration & dosage* / Q000097:blood
chemical_list: D012977:Sodium Nitrite
keywords: aging; metabolomics; neuromuscular; nitrates/nitrites; precision medicine