Nicotinamide riboside improves walking for people with circulation problems

Nicotinamide riboside improved an important measure of physical activity for a cohort of people suffering peripheral artery disease. It’s the first time this effect has been demonstrated for this much-studied ingredient. 

The new research was published in the journal Nature Communications. It was the work of a broad-based team of researchers associated with hospitals and universities in Illinois, California, Kentucky, Florida and Georgia. 

Nicotinamide riboside (NR) is a pyridine-nucleoside and a form of vitamin B3. It functions as a precursor to nicotinamide adenine dinucleotide, or NAD+. The study material was supplied by ChromaDex, which supplies a form of the ingredient patented as Niagen. 

Peripheral artery disease (PAD), also known as peripheral vascular disease, is a condition of poor blood circulation to areas in the body distant from the heart. It particularly affects the lower extremities and is often associated with atherosclerosis. 

According to a 2015 study published in the journal Circulation, lower extremity PAD affects eight million people in the U.S. and more than 200 million worldwide. The authors of that study speculated PAD will become increasingly common as the U.S. population survives longer with chronic disease.  

PAD sufferers exhibit mobility impairments compared to their peers, and they experience other complications such as ulcerations and amputations at a greater rate. 

There are two approved drugs to treat this condition, the authors of the 2015 study noted, but one works only slightly better than placebo while the results from taking the second drug are only slightly better than the first one. 

The new study noted that PAD sufferers exhibit increased oxidative stress and impaired mitochondrial function in addition to gross motor symptoms. NR has been demonstrated to improve mitochondrial function in humans, the authors noted. 

The researchers also included in their trial resveratrol, a noted antioxidant polyphenol isolated from grapes and other natural sources. Supplement manufacturer ReserveAge supplied the resveratrol ingredient. 

The trial was notable for its long duration: six months. For their study cohort, the researchers recruited 90 patients who suffered from PAD and had been treated by several of the authors, as well as new patients coming into the clinic at the Northwestern University School of Medicine. 

That complicated the recruitment of a study cohort, a process which stretched over several years, from December 2018 to September 2022. The average age of the participants was about 70.

The study design also included a run-in phase to determine which of the subjects were most likely to adhere to the supplementation protocol for the full six months. Several subjects, nonetheless, demonstrated less than full compliance. 

The primary measure of the study was the improvement in six-minute walking distance. The 2015 study mentioned above noted that “the six-minute walk test has been validated as an outcome measure and is increasingly recognized as a meaningful outcome measure in patients with PAD.” 

The present study was structured in three arms: an NR-only group, an NR-plus-resveratrol group and a placebo group. The subjects were divided roughly evenly between the groups. 

The NR-only group took two pills daily delivering 500 milligrams (mg) of the ingredient. The group that also took resveratrol consumed a 125-mg daily dose. 

In addition to the primary outcome, the researchers measured outcomes on the Walking Impairment Questionnaire (WIQ) Stair Climbing Score, a standardized measure of mobility impairment for PAD sufferers. They also took biopsies of the gastrocnemius muscle, the calf’s principal muscle. 

The researchers found that the NR group showed a significant improvement in their six-minute walking distance of more than 30 meters versus placebo. The resveratrol-plus-NR group improved but not by as much. 

There was an improvement for the NR group in one of the muscle biopsy measures, which examined the difference in muscle satellite cell density. Muscle satellite cells are defined as “myogenic stem cells responsible for muscle regeneration throughout the lifespan.” 

There was no change between the groups for the other secondary outcomes. That the NR intervention was slightly less effective when combined with resveratrol might have been an artifact of the small sample size, which was reduced even further by the smaller number of subjects in the NR-plus-resveratrol group who completed more than 75% of the specified supplement regimen, according to the researchers. 

“In post-hoc analyses, compared to placebo, NR alone significantly improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters among people with at least 75% adherence to study pills. NR increased satellite cell abundance in gastrocnemius muscle, compared to placebo, meeting the pre-specified criterion for statistical significance, but did not affect muscle fiber type,” the researchers concluded.