# Nicotinamide riboside as an Enhancer of Exercise Therapy in hypertensive older adults: The NEET Trial

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2020 · $232,983

## Abstract

ABSTRACT
More than 80% of older adults have hypertension, with higher prevalence of high systolic blood pressure (SBP)
putting them at high risk for cardiovascular (CV) disease and death. Because drug therapy that lowers SBP is
associated with side effects such as hypotension, syncope, and kidney dysfunction, there is a great need for
effective lifestyle SBP-lowering interventions for the older population that can replace drug therapy. While
aerobic exercise is a recommended lifestyle intervention for controlling SBP and preventing CV disease
naturally, in older adults it has been shown to be less effective in vascular-tissue remodeling because of
arterial stiffness, resulting in less efficient SBP control. Reduced bioavailability of nicotinamide adenine
dinucleotide (NAD+), a cofactor for the deacetylase sirtuin1 (SIRT1), may contribute to age-related vascular
dysfunction via oxidative stress and reduced nitric oxide (NO). Exercise-induced overexpression of NAD+-
dependent SIRT1 improves the bioavailability of NO. Preclinical evidence suggests that poor vascular-function
improvement in response to exercise in older mice is caused by insufficient NAD+ levels to stimulate SIRT1
activity. Importantly, replenishment of NAD+ levels induced vascular remodeling, improved vascular
function, and reduced SBP in mice. An objective of this study, therefore, is to test a combination of aerobic
exercise and nicotinamide riboside, a compound that replenishes NAD+ levels, to optimize exercise's SBP-
lowering effect in hypertensive older adults. Initial human clinical trials demonstrated that nicotinamide riboside
supplementation (1,000 mg/day) was safe and showed a higher potential to reduce SBP and arterial stiffness
in participants with elevated SBP. As we have preclinical evidence that combining NAD+ replenishment with
exercise is an ideal strategy for improving vascular function, our central hypothesis is that the intervention of
aerobic-exercise training combined with nicotinamide riboside supplementation will reduce SBP in
hypertensive older adults more effectively than will exercise alone. We will enroll 45 participants 65 years and
older into either: (1) 1,000 mg/day of nicotinamide riboside plus 3 days/week of supervised, center-based
walking exercise, or (2) the same exercise program combined with placebo, or (3) 1,000 mg/day of
nicotinamide riboside alone. All participants will undergo daytime continuous SBP and arterial-stiffness
measurements by pulse-wave velocity at baseline and at 6 weeks. Elevated SBP will then be determined as
daytime average above 130 mmHg, measured by the 24-hour blood-pressure device. To our knowledge, this
study will be the first attempt to enhance exercise therapy with nicotinamide riboside in hypertensive older
adults. We believe that nicotinamide riboside is “the missing piece of the puzzle” in improving vascular
remodeling and SBP management in older adults. Preliminary evidence from this pilot study may support a full-...

## Key facts

- **NIH application ID:** 10000000
- **Project number:** 5R21AG064282-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Robert T Mankowski
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $232,983
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000000

## Citation

> US National Institutes of Health, RePORTER application 10000000, Nicotinamide riboside as an Enhancer of Exercise Therapy in hypertensive older adults: The NEET Trial (5R21AG064282-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10000000. Licensed CC0.

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