As organisms age, NAD+ levels drop, which leads to a decrease in mitochondrial health; this in turn leads to age-related health issues. Aging muscles in particular tend to lose mitochondrial content and function, contributing to sarcopenia and frailty. NAD+ levels also can be depleted by lifestyle choices such as overeating and lack of exercise.
Data from 529 participants in the Itabashi Longitudinal Study on Aging indicated that for every small (1 micromole per liter) increase in NAD+ levels, the risk of frailty decreased by 13%.
The findings support NAD+ as an important biomarker of healthy aging and physical resilience, although they note that their data does not prove that increasing NAD+ will reduce frailty.
“Lower whole-blood NAD⁺ concentration was associated with frailty and greater frailty burden among community-dwelling older adults,” wrote the researchers in the journal GeroScience. “Further longitudinal studies incorporating cell- or tissue-specific measurements are needed to clarify the temporal and biological relationships among NAD⁺ metabolism, blood cell composition, and frailty.”
Nicotinamide riboside
Commenting independently on the new findings, Andrew Shao, PhD, SVP of global regulatory and scientific affairs, Niagen Bioscience, said the study is a useful addition to the NAD+ conversation.
“It finds that lower whole-blood NAD+ is associated with frailty in older adults, though the authors are careful to note potential study limitations,” he said. “It reinforces that NAD+ biology in aging should include but go beyond blood to also address tissues. There is more consistent human evidence of age-related NAD+ differences in tissues like skeletal muscle, and the Itabashi authors themselves call for cell- and tissue-specific longitudinal work.
“This is consistent with past findings demonstrating the connection between NAD+ decline and age and reinforces the importance of both tissue-specific and functional outcome analyses, which is where we think the field should focus,” added Dr. Shao.
The approach for Niagen Bioscience has been to raise NAD levels using nicotinamide riboside (NR), a version of niacin (vitamin B3) and a potent precursor to NAD.
A recent study from scientists at Nestlé compared nicotinamide, NR, and NMN and found that both NR and NMN increased circulating NAD+ concentrations after 14 days.
Study details
Data from 529 Japanese community-dwelling adults aged 65 or older revealed that whole-blood NAD+ levels were lower for people with frailty (assessed using the revised Japanese Cardiovascular Health Study Criteria), compared to those without frailty.
However, once the researchers adjusted the data for hematocrit, the percentage of blood that is made up of red blood cells, the association weakened.
“Further studies using cell- and tissue-specific measurements are needed to clarify the relationship between NAD⁺ metabolism and frailty,” concluded the researchers.
Source: GeroScience, 2026, doi: 10.1007/s11357-026-02545-9. “Association between whole-blood NAD+ concentration and frailty in community-dwelling older adults: the Itabashi Longitudinal Study on Aging”. Authors: T. Shida, et al.
