# Nitrite Supplementation to Mitigate Fatigability and Increase Function in Long COVID Patients

> **NIH VA I21** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

Prevalence of long COVID is surging among Veterans, and Veterans afflicted with this disease typically incur
progressive declines in function, diminished quality of life and increased disability. Skeletal muscle
pathophysiology has been implicated as a significant determinant of long COVID pathophysiology and clinical
declines. Dr. Forman is a cardiologist and geriatrician who is currently engaged in research studying benefits of
nitrite supplementation with investigational new drug (IND) nitrite capsule supplements in older adults with
sedentariness and/or heart failure. In that work, he is focusing primarily on the utility of nitrites to increase
skeletal muscle mitochondrial respiration. Secondarily, he is exploring if mitochondrial respiration changes
correlate to changes in physical function. In particular, he is studying if increased serum and skeletal muscle
nitrite elevations correlate to improvements in cardiorespiratory fitness (i.e., peak oxygen utilization [VO2]), and
to decreased fatigability (i.e., rating of perceived exertion [RPE] during steady-state submaximal [1.5 miles per
hour] walking). In this SPiRE application, Dr. Forman proposes to redirect his expertise in nitrite therapeutics to
Veterans with long COVID. Nitrites will be administered as nitrate-rich beetroot juice versus nitrate-poor
placebo. When beetroot juice is ingested, nitrates are metabolized to nitrite. Compared to IND nitrite capsules,
beetroot juice is relatively easier to administer, less expensive, and hemodynamically safer. Whereas serum
nitrite levels have not been consistently high in studies of beetroot juice interventions as compared to nitrite
capsules, this proposal aims to optimize nitrite levels using 210 ml per day of Beet-It nitrate beverage (James
White Drinks Ltd., Ipswich, UK) to provide 16 mmol of nitrate/day for 14 days versus a 210 ml of nitrate-
depleted placebo. All participants will also undergo physical therapy. Endpoints in this SPiRE study are
oriented principally to physical function. Endpoints (measured pre- and post- the 2-week intervention) include
fatigability as well as walking efficiency (VO2/kg) during steady-state walking. Furthermore, traditional
functional indices of peak VO2, VO2 at anaerobic threshold, 6-minute walk distance, short physical
performance battery, and pulmonary function tests will also be assessed. Nitrite levels (both serologically and
in the skeletal muscle itself) will be measured to best ascertain the relationship of nitrite and putative clinical
changes. In addition, analyses of skeletal muscle will clarify if nitrite-mediated changes in physical function
correlate to changes in skeletal muscle respiration. Overall, this proposal aligns with the Veteran’s Affairs
Office of Research and Development’s commitment to research that helps Veterans affected by COVID-19,
and it also aligns with the Rehabilitation Research and Development’s mission to maximize Veterans’
functional independence, quality of life an...

## Key facts

- **NIH application ID:** 10784599
- **Project number:** 5I21RX004409-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Daniel E. Forman
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-03-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10784599

## Citation

> US National Institutes of Health, RePORTER application 10784599, Nitrite Supplementation to Mitigate Fatigability and Increase Function in Long COVID Patients (5I21RX004409-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10784599. Licensed CC0.

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