# Nicotinamide riboside supplementation for treating elevated systolic blood pressure and arterial stiffness in middle-aged and older adults

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2020 · $571,966

## Abstract

PROJECT SUMMARY/ABSTRACT
 The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 that causes Coronavirus Disease 2019
(COVID-19) disproportionately affects older adults such that individuals 60 years and older have markedly
increased risk of infection, severity of morbidity, and mortality. This increased vulnerability with aging is due in
part to greater systemic inflammation and oxidative stress, impaired nitric oxide (NO)-mediated endothelial
dysfunction, and nicotinamide adenine dinucleotide (NAD+) deficiency both at baseline and post-infection. As
such, novel “geroprotective strategies” that: 1) improve baseline risk factor profile for COVID-19; and 2)
restore NAD+ levels, inhibit inflammation and oxidative stress, and improve NO bioavailability/endothelial
dysfunction induced during infection, are essential for reducing severity/lethality of COVID-19 in older adults.
 We recently showed that chronic supplementation (6 weeks) with nicotinamide riboside, a natural dietary
compound, boosts NAD+ bioavailability in older adults. We then translated the results of this pilot study into
an NIA-funded (R01 AG061514) phase IIa randomized clinical trial assessing the efficacy of 3 months of
nicotinamide riboside treatment for lowering systolic blood pressure (SBP) and aortic stiffness in older adults
with baseline SBP in the elevated to stage 1 hypertension range. This 5-year clinical trial is currently in year 2.
 The pathogenesis of COVID-19 includes NAD+ deficiency, hyper-inflammation, excessive reactive oxygen
species (ROS) bioactivity, and pulmonary and systemic NO-mediated endothelial dysfunction. Our preliminary
results in older adults suggest that nicotinamide riboside reduces pro-inflammatory cytokine production in
peripheral blood mononuclear cells (PBMC), decreases endothelial ROS bioactivity, increases endothelial NO
production, and improves in vivo systemic vascular endothelial function. However, these promising initial
findings must be confirmed in a larger cohort to establish the potential efficacy of nicotinamide riboside
supplementation as a geroprotective strategy for prevention and treatment of COVID-19 in older adults.
 The purpose of this administrative supplement is to address a major research objective for the NIA
Division of Geriatrics and Clinical Gerontology in NOT-AG-20-022: The evaluation of pharmacological
interventions that may prevent or mitigate morbidity and/or improve post-infection health in older adults
exposed to SARS-CoV-2. This will be accomplished by: 1) assessing PBMC inflammatory cytokine production
before/after nicotinamide riboside treatment and incubation with specific NAD+-pathway metabolites; 2)
evaluating ex vivo endothelial function in human pulmonary artery endothelial cells bathed in subject serum
with/without COVID-19-like inflammatory and oxidative stress ± protective NAD+ metabolites; and 3) assessing
in vivo systemic endothelial function with nicotinamide riboside treatment. The expected re...

## Key facts

- **NIH application ID:** 10159516
- **Project number:** 3R01AG061514-02S2
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** DOUGLAS R SEALS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $571,966
- **Award type:** 3
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159516

## Citation

> US National Institutes of Health, RePORTER application 10159516, Nicotinamide riboside supplementation for treating elevated systolic blood pressure and arterial stiffness in middle-aged and older adults (3R01AG061514-02S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10159516. Licensed CC0.

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