Nicotinamide riboside (NR), a form of vitamin B3, was found to lower blood pressure and reduce arterial stiffness in certain patients, according to a small clinical study published in Nature Communications. The supplement appears to mimic caloric restriction in its ability to improve cardiovascular and other functions of physiological aging.
“This was the first ever study to give this novel compound to humans over a period of time,” said senior author Douglas Seals, PhD, professor, Department of Integrative Physiology, University of Colorado (UC) Boulder, Boulder, CO. “We found that it is well tolerated and appears to activate some of the same key biological pathways that calorie restriction does.”
Previous studies have shown that chronic caloric restriction can fend off some of the hallmarks of aging, such as arterial dysfunction, high blood pressure, and arterial stiffness. Caloric restriction also increases nicotinamide adenine dinucleotide (NAD+), an essential substrate for sirtuins—a class of enzymes that is believed to mediate several of the beneficial effects of caloric restriction.
As humans age, the cellular bioavailability of NAD+ declines and subsequently reduces sirtuin levels, which appears to contribute to physiological aging, the researchers explained.
In animal studies, oral NR supplements increased levels of NAD+ and improved multiple physiological functions.
For this double-blind, placebo-controlled, crossover trial, researchers included 24 lean and healthy men and women aged 55 to 79. Half were given a placebo for 6 weeks, followed by 1,000 mg of nicotinamide riboside chloride (Niagen®, ChromaDex) for 6 weeks. The other group received NR for the first 6 weeks, followed by placebo for the remaining 6 weeks of the trial.
By the end of the study period, oral NR supplementation had elevated NAD+ levels by about 60% compared with placebo, researchers found.
“The idea is that by supplementing older adults with NR, we are not only restoring something that is lost with aging (NAD+), but we could potentially be ramping up the activity of enzymes responsible for helping protect our bodies from stress,” said lead author Christopher Martens, PhD, who was a postdoctoral research fellow at UC Boulder at the time of the study.
NR tended to lower systolic blood pressure and aortic stiffness in the group overall, although not to a statistically significant degree.
However, 13 participants with elevated systolic blood pressure (120-139/80-89 mm Hg) had about a 10-point reduction in systolic blood pressure after supplementation. A drop of that magnitude could translate to a 25% reduction in cardiovascular events, the researchers predicted.
“If this magnitude of systolic blood pressure reduction with NR supplementation is confirmed in a larger clinical trial, such an effect could have broad biomedical implications,” they wrote.
Likewise, NR supplementation tended to lower aortic stiffness more in participants with higher baseline blood pressure.
NR didn’t change total energy expenditure, aerobic exercise capacity, or motor function in this lean and healthy patient population. Future studies should investigate NR supplementation in patients with impaired mobility and reduced cardiovascular fitness, the researchers suggested.
“We are not able to make any definitive claims that this compound is safe or is going to be effective for specific segments of the population,” said Dr. Martens, now an assistant professor at the University of Delaware, Newark, DE. “What this paper provides us with is a really good stepping stone for future work.”
Currently, Drs. Martens and Seals anticipate a larger clinical trial that would look specifically at the impact of NR supplementation on blood pressure and arterial health. Dr. Martens is also launching a separate trial to study the impact of NR on older adults with mild cognitive impairment, a precursor to Alzheimer’s disease.
Still early yet
“This is a very early look into what this new supplement might do,” commented Naveed Sattar, MD, PhD, professor, Metabolic Medicine, University of Glasgow, Scotland. “I would not get too excited at the moment but rather be keen to see bigger and better designed trials to really test whether this novel supplement improves blood pressure and other health markers in patients who are overweight or have hypertension.”
Dr. Sattar added, “We have had many results from such small studies in the past which have not been replicated—so, it’s interesting, but very early.”
The study was partially funded by grants from the National Institutes of Health and the American Federation for Aging Research. ChromaDex, the maker of Niagen®, provided supplements and some financial support.