Nicotinamide Riboside Lowers Systolic Blood Pressure and Improves Vascular Endothelial Function in Midlife/Older Adults with Above-Normal Systolic Blood Pressure

Background: The majority of midlife and older adults have above-normal systolic blood pressure (SBP), i.e., SBP ≥120 mmHg, placing them at an increased risk for cardiovascular diseases, cognitive dysfunction, chronic kidney disease, and other chronic conditions of aging. Above-normal SBP is associated with vascular endothelial dysfunction, an independent cardiovascular disease risk factor. Age-related reductions in nicotinamide adenine dinucleotide (NAD + ) are thought to contribute to cardiovascular dysfunction, making dietary supplementation with NAD + -boosting compounds, such as nicotinamide riboside, a potential therapeutic approach for improving cardiovascular function with aging. However, whether dietary supplementation with nicotinamide riboside improves cardiovascular function in midlife and older adults remains to be tested in a larger clinical trial with a clinically relevant treatment duration. Purpose: To test the hypothesis that dietary supplementation with nicotinamide riboside would boost NAD + bioavailability, lower casual systolic blood pressure and improve vascular endothelial function in midlife/older adults with above-normal SBP at baseline. Methods: Fifty-two midlife and older (age ≥50 years) men and postmenopausal women with casual SBP ≥120 mmHg underwent 3 months of dietary supplementation with nicotinamide riboside (1000 mg/day, Niagen®, ChromaDex Inc.; n=26, 18F/8M, age: 65 ± 7 years) or placebo (n=26, 13F/13M, age: 68 ± 7 years) in a randomized, double-blind clinical trial. Subjects underwent testing for whole-blood NAD + bioavailability (liquid chromatography mass spectrometry), casual SBP and vascular endothelial function (brachial artery flow-mediated dilation [FMD BA ]) before and after the intervention. Results: NAD + levels increased with nicotinamide riboside supplementation (pre: 20 ± 2 µM, post: 42 ± 6 µM, p=0.001), but not with placebo (pre: 22 ± 1 µM, post: 25 ± 3 µM, p=0.342). Casual SBP was decreased after nicotinamide riboside supplementation (pre: 130 ± 2 mmHg, post: 126 ± 2 mmHg, p=0.016), but not with placebo (pre: 134 ± 2 mmHg, post: 135 ± 3 mmHg, p=0.699). FMD BA was increased after nicotinamide riboside supplementation (pre: 4.2 ± 2.4 Δ%, post: 5.4 ± 3.4 Δ%, p=0.044) but not with placebo (pre: 3.7 ± 2.2 Δ%, post: 3.7 ± 2.3 Δ%, p=0.978). Dietary supplementation with nicotinamide riboside was not associated with any serious adverse events. Conclusions: Dietary supplementation with nicotinamide riboside increases NAD + bioavailability, lowers casual SBP and improves vascular endothelial function in midlife and older adults with above-normal SBP at baseline. R01AG061514, K01HL153326, F31HL154782, Niagen® provided by ChromaDex Inc. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.