# 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 · $502,464

## Abstract

Project Summary
 More than 90% of cardiovascular diseases (CVD) and cognitive impairment/dementia occur in men and
women >50 years of age. Changes in age demographics in the U.S. predict progressive increases in these
disorders without effective, evidence-based interventions. The age-related increase in systolic blood
pressure (SBP) is a major factor driving the increased risk of these disorders in later middle-aged and older
(MA/O) adults. This increase in SBP is due primarily to stiffening of the large elastic arteries, as indicated by
increased carotid-femoral pulse wave velocity (CFPWV), which reflects stiffening of the aorta. Aortic
stiffening with aging is mediated by structural and functional (increased vascular smooth muscle tone)
changes in the arterial wall stimulated by oxidative stress and chronic low-grade inflammation.
 New BP guidelines describe a casual (resting) SBP of 120-129 mmHg as “elevated” and SBP of 130-139
mmHg as “stage 1 hypertension”, as these levels account for much of the increased risk of CVD and other
BP-influenced disorders of aging. Importantly, ~50% of adults age >50 have SBP within these ranges. The
first-line treatment for lowering SBP in these ranges is lifestyle-based therapy. In this context, we have shown
that caloric restriction (CR) reduces SBP and CFPWV in older mice and in overweight/obese MA/O humans,
but adherence is poor and CR reduces muscle and bone mass. As a result, we have since shown that
boosting NAD+ bioavailability to stimulate SIRT-1, a “CR mimetic” approach, reduces CFPWV and oxidative
stress in old mice, and we recently took the first step in translating these findings in a small pilot study of MA/O
adults (n=24). We found that supplementation with nicotinamide riboside, a natural, commercially available
precursor of NAD+ and novel CR mimetic, was well-tolerated and increased NAD+ bioavailability in the overall
group, and reduced SBP (-8 mmHg) and CFPWV in a subgroup (n=13) with baseline SBP of 120-139 mmHg.
 Here we propose a randomized, placebo controlled, double-blind, single-site phase IIa clinical trial to
assess the safety and efficacy of oral nicotinamide riboside (500 mg capsules 2x/day; NIAGEN®; ChromaDex
Inc.) for 3 months vs. placebo (n=59/group) for decreasing SBP and aortic stiffness in MA/O men and women
(50-79 years) with SBP in the elevated/stage 1 hypertension (120-139 mmHg) range. We hypothesize that
treatment will be safe and well-tolerated, and will reduce SBP and CFPWV, as related to increases in systemic
NAD+ bioavailability and reductions in vasoconstrictor factors, oxidative stress and inflammation.
Aim 1: To measure casual SBP (primary outcome) before/after nicotinamide riboside vs. placebo treatment;
Aim 2: To measure 24-hour ambulatory SBP and CFPWV (secondary outcomes) before and after treatment;
Aim 3: To determine the safety and tolerability of treatment with nicotinamide riboside vs. placebo;
Aim 4: To measure systemic NAD+ and NAD+–related metabolite conce...

## Key facts

- **NIH application ID:** 9852565
- **Project number:** 5R01AG061514-02
- **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:** $502,464
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852565

## Citation

> US National Institutes of Health, RePORTER application 9852565, Nicotinamide riboside supplementation for treating elevated systolic blood pressure and arterial stiffness in middle-aged and older adults (5R01AG061514-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852565. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*