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Nicotinamide riboside boosts vascular health, cognitive function in adults with peripheral artery disease
A four-week pilot trial that evaluated the effects of nicotinamide riboside, a form of vitamin B3, in older adults with peripheral artery disease (PAD) resulted in improvements in aspects of vascular health and cognitive function. Peripheral artery disease occurs when plaque deposits cause narrowing of the arteries of the arms and/or legs.
Nicotinamide riboside is a precursor of NAD+, a molecule that occurs in all living cells. “One of the hallmarks of aging is the decline in NAD+ levels, an essential cofactor for cellular metabolism, energy production, and survival,” Zsofia Szarvas, MD, and colleagues wrote in the July 2025 issue of The Journal of Pharmacology and Experimental Therapeutics.1
They concluded that the study’s findings suggest that nicotinamide riboside could improve cognitive outcomes in older individuals with PAD, potentially through decreased oxidative stress and improved health of the endothelium, the inner lining of the blood vessels.
The trial included eight men and women between the ages of 57 and 82 years who received 1000 milligrams nicotinamide riboside, daily, for four weeks. Peripheral and microvascular endothelial function, brain vascular responses, cognitive performance, blood values and other factors were evaluated at the beginning and end of the study.
Nicotinamide riboside showed a trend towards improvement in peripheral endothelial function (as measured by flow-mediated dilation) and microvascular endothelial function. Brain vascular responses and cognitive performance also improved. Nicotinamide riboside was also associated with decreased oxidative stress and other benefits.
Dr. Szarvas and associates remarked that these preliminary study findings could provide a foundation for future research involving a greater number of participants and a longer trial duration.
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Apply What You've Learned: Peripheral Artery Disease
- Peripheral artery disease (PAD) is a cardiovascular disease that affects the arteries in the body’s periphery, i.e., the legs, arms and/or pelvis. It involves the buildup of atherosclerotic plaque within the arteries, which impairs blood flow. Peripheral artery disease can cause poor circulation, restricted activity levels and even loss of limbs.2
- A symptom of PAD is pain that most often affects the legs (particularly the calves). This pain, known as intermittent claudication, can occur during walking or other forms of exertion and is relieved by rest. Peripheral artery disease may be one manifestation of cardiovascular disease that also occurs in other areas of the body, such as the carotid or coronary arteries.3 Therefore, therapies that help protect against cardiovascular disease can help lower the chances of developing PAD.
- Endothelial dysfunction, oxidative stress and inflammation are contributors to PAD and other forms of cardiovascular disease.4 Endothelial dysfunction refers to impaired function of the blood vessels’ lining (endothelium) and is characterized by an imbalance between arterial constriction and expansion.
- Because oxidative stress is a major contributor to PAD and other cardiovascular diseases, people with PAD should ensure an adequate intake of antioxidant nutrients. Common dietary antioxidants include carotenoids like lycopene and lutein, vitamin C, vitamin E, selenium, zinc, coenzyme Q10, lipoic acid and glutathione and numerous plant compounds. Propionyl-L-carnitine, a derivative of carnitine that is produced in the body or consumed as a nutrient, increased pain-free walking distance by 31% compared with a placebo and improved quality of life in a systematic review of 12 studies that included 1,423 participants with intermittent claudication who were treated orally or intravenously with 1-2 grams daily.5
References
- Szarvas Z, Reyff ZA, Peterfi A, et al. Effects of NAD+ supplementation with oral nicotinamide riboside on vascular health and cognitive function in older adults with peripheral artery disease: Results from a pilot 4-week open-label clinical trial. J Pharmacol Exp Ther. 2025 May 14;392(7):103607. DOI: 10.1016/j.jpet.2025.103607.
- What Is Peripheral Artery Disease? National Heart, Lung and Blood Institute. National Institutes of Health. https://www.nhlbi.nih.gov/health/peripheral-artery-disease. Accessed 2025 Jun 24.
- Allison MA, Armstrong DG, Goodney PP. et al. Health Disparities in peripheral artery disease: a Scientific Statement from the American Heart Association. Circulation. 2023 Jul 18;148(3):286-296. doi: 10.1161/CIR.0000000000001153.
- Higashi Y. Roles of oxidative stress and inflammation in vascular endothelial dysfunction-related disease. Antioxidants (Basel). 2022 Sep 30;11(10):1958. doi: 10.3390/antiox11101958.
- Kamoen V, Sitchele RV, Campens L et al. Propionyl-L-carnitine for intermittent claudication. Cochrane Database Syst Rev. 2021 Dec 26;12(12):CD010117. doi: 10.1002/14651858.CD010117.pub2.
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