Nitrites, Skeletal Muscle Mitochondrial Bioenergetics, and Physical Activity in Old Age

Phase 2 Completed 64 enrolled Gladwin, Mark, MD National Institute on Aging (NIA) · collab National Institutes of Health (NIH) · collab

RandomizedParallel-groupQuadruple-blindTreatment

Summary

This 2-site randomized double blinded controlled trial is to confirm and more definitively clarify the impact of a 12-week course of nitrite versus placebo on mitochondrial bioenergetics in older sedentary adults. This investigator will take an integrative physiology approach to determine the effect of nitrite therapy on a comprehensive assessment of mitochondrial energetics, skeletal muscle vascular function, and whole body physical function (cardiorespiratory function, exercise endurance, strength, balance, and physical activity) and fatigability.

Timeline

Start: 2021-04-23
Primary completion: 2023-07-14
Completion: 2023-07-14

Outcome

Missed primary endpoint

registry analysis (superiority test); 20 mg Sodium Nitrite TID Arm vs Placebo Control Arm; p = 0.9017; Mean Difference (Net) 0.5; NCT04405180 ↗

paper Nitrite supplementation was not associated with improvements in skeletal muscle mitochondrial respiration PMID 41691463 ↗

Publications

Forman DE, Perera S, Shiva S, Glynn NW, Stakich TS, Ramos SV, Distefano G, Wolf C, Kendi A, Sterczala AJ, Sipula IJ, Bello FM, Jurczak MJ, Sciurba FC, Gladwin MT, Newman AB, Coen PM. Benefits of oral nitrite supplementation on mitochondrial respiration and physical function in older adults. J Gerontol A Biol Sci Med Sci. 2026 Mar 10;81(4):glag034. doi: 10.1093/gerona/glag034.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Sodium Nitrite	Small molecule	20 mg	Oral

Indications

No indication recorded.