A new study in GeroScience reports that older adults with frailty had lower NAD+ in their blood. It is easy to read that as "NAD+ boosters might prevent frailty." The data do not support that reading. This is what the study found, where it falls short, and what it means if you are weighing NMN or NR.
What the researchers did
Shida and colleagues analyzed 529 community-dwelling adults aged 65 and older from the 2025 wave of the Itabashi Longitudinal Study on Aging in Japan. About 54% were women. They measured whole-blood NAD+ and assessed frailty with the revised Japanese Cardiovascular Health Study criteria.
Only 32 participants (6.0%) met the criteria for frailty. That small group matters for everything below.
The headline numbers
- Median whole-blood NAD+ was 24.00 µmol/L in frail participants versus 25.00 µmol/L in non-frail participants (P = 0.007).
- After adjusting for age, sex, and fasting time, each 1 µmol/L higher NAD+ was associated with lower odds of frailty (OR 0.871; 95% CI 0.780-0.970). That is roughly 13% lower odds per unit.
- Spline analysis found no clear evidence of nonlinearity, so the relationship looked roughly linear across the range studied.
- A Firth penalized-likelihood regression, which suits small event counts and used broader covariate adjustment, gave a similar result (OR 0.880; 95% CI 0.782-0.986).
The catch: hematocrit
When the authors additionally adjusted for hematocrit, the share of blood volume taken up by red blood cells, the association weakened. The odds ratio moved to 0.911, and the confidence interval (0.800-1.034) now includes 1, meaning no association can't be ruled out.
This fits a plausible alternative explanation. Whole-blood NAD+ is heavily influenced by red blood cells, so it may partly reflect blood cell composition, including anemia or other conditions common in frailty, rather than NAD+ status in muscle, brain, or other tissues. The authors say as much: blood cell composition "may partly explain" the association, and cell- and tissue-specific measurements are needed.
Why this doesn't show NAD boosters prevent frailty
It is cross-sectional. Blood NAD+ and frailty were measured at one time point. The study cannot say whether low NAD+ contributes to frailty, frailty lowers NAD+, or something else drives both. Frail people may eat less, move less, be more inflamed, have more chronic disease, or have lower hemoglobin. Any of these could shift blood NAD+.
The difference is small. A one-unit gap in medians (24 vs. 25 µmol/L) is statistically detectable in 529 people. It is far from a clinically obvious biomarker gap, and nobody can tell an individual's frailty risk from it.
The frail group is tiny. With 32 cases, estimates are imprecise. The wide confidence intervals reflect that, and the upper bounds sit close to no effect.
Whole blood is not muscle. Frailty involves muscle, mobility, energy, and weight loss. Circulating NAD+ is a distant proxy for what happens in skeletal muscle or the nervous system.
An association is not an intervention. Even if low NAD+ were causally involved, that would not show raising it with a supplement would reverse frailty. Whether a precursor reaches the relevant tissue is a separate question.
What is known about NAD precursors
NAD+ is central to energy metabolism, redox reactions, and cell signaling, and the idea that it declines with age is a major driver of interest in nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Here is a fair summary of the human evidence, in general terms:
- Raising blood NAD+ is well documented. Human trials with NR and NMN have repeatedly shown increases in circulating NAD+ or its metabolites.
- Functional benefits are less consistent. Some small trials have reported modest changes in measures such as insulin sensitivity in muscle or physical performance. Others found little effect on outcomes like body composition or mitochondrial function. Samples have generally been small and short, and populations vary.
- No trial has shown that NAD precursors prevent or reverse clinical frailty. The Itabashi study does not change that.
This gap between biomarker change and meaningful outcomes is the central unresolved issue in the field.
Practical takeaways
- Don't treat this paper as a reason to start a supplement. It is a hypothesis-generating observation, not evidence of benefit.
- Be wary of consumer NAD+ blood tests. This study suggests whole-blood levels are tangled up with blood cell composition, which complicates interpretation.
- Address established frailty levers first. Resistance training, adequate protein, treating anemia and other medical conditions, and reviewing medications have far stronger evidence than any NAD precursor.
- If you do consider NMN or NR, discuss it with a clinician, especially if you take medications or have a chronic condition or cancer history. Choose products with third-party testing, and note that the regulatory status of NMN as a supplement has shifted in some markets, so check current rules where you live.
- Watch for better studies. The useful next steps are longitudinal cohorts that track NAD+ over time, tissue-specific measurements, and randomized trials with functional frailty endpoints.
The bottom line
The study adds a modest, carefully reported data point: in this Japanese cohort, older adults with frailty had slightly lower whole-blood NAD+. The signal weakened once red blood cell volume was accounted for, the frail group was small, and the design cannot establish cause. It supports further investigation of NAD+ metabolism in aging. It does not show that NAD boosters protect against frailty.
