A 2026 Review Says Blood NAD+ Does Not Fall With Healthy Aging. The First Properly Powered Trial Is About Kidneys.

Almost everything said about NAD+ outside the laboratory rests on one claim: that NAD+ falls as people age, and that topping it back up should therefore help. A narrative review published in Frontiers in Aging on 10 September 2026 reports that the first half of that claim does not survive contact with large human datasets.

The premise

NAD+ — nicotinamide adenine dinucleotide — is a coenzyme involved in cellular metabolism, mitochondrial function, DNA repair and stress-response signalling. It is not a peptide, though it is handled in the same freeze-dried vial format, which is part of why it circulates in the same conversations.

The review, from a group at Evercare and Prince Sultan Military Medical City in Riyadh with co-authors at KAUST and Shaqra University, covered literature from January 2018 to March 2026. Its opening observation is the one worth sitting with: age-associated decline in NAD+ has driven the interest in augmenting it, but recent large-scale human data indicate that whole-blood NAD+ concentrations do not decline with healthy aging.

That is a statement about healthy aging and about whole-blood concentrations, and those qualifiers matter. It does not say NAD+ biology is irrelevant to disease. It says the specific premise most often used to justify topping it up is not supported by the population data.

What the human evidence actually consists of

The review's summary of the clinical literature is blunt. Available human evidence is sparse and consists primarily of small uncontrolled studies, observational investigations and isolated case reports.

What those studies show: short-term intravenous NAD+ or NMN administration has been associated with transient increases in circulating NAD+ levels, and with changes in selected biomarkers related to oxidative stress, inflammation and cellular metabolism. Limited exploratory reports have described self-reported improvements in sleep-related outcomes and neurologic symptoms.

What the reviewers say about those findings: their clinical significance remains uncertain, because of small sample sizes, absence of placebo controls, heterogeneous methodologies and short follow-up.

On harm, the review records nausea, cramping, flushing and chest discomfort among reported adverse effects, and states that long-term safety data are lacking.

Its conclusion is that current evidence is preliminary and insufficient to support routine clinical or wellness use, and that larger randomised controlled trials with standardised protocols and clinically meaningful endpoints are required first.

The trial that is actually built to answer something

Which brings us to the second paper. In July 2026, Kidney International Reports published the protocol for the NAD Augmentation in Diabetic Kidney Disease trial, run from Brigham and Women's Hospital with Boston Medical Center.

It is a phase 2a randomised, multicentre, double-blind, placebo-controlled, parallel-group study. 156 participants aged 30 or older, with diabetes, a urinary albumin-to-creatinine ratio at or above 100 mg/g, and an estimated glomerular filtration rate above 25. They receive either oral pharmaceutical-grade microcrystalline β-NMN — a formulation designated MIB-626 — or placebo, twice daily for 24 weeks, followed by 12 weeks of post-intervention follow-up. Randomisation was stratified by biological sex, age band and enrolling site.

The primary endpoint is the change in urinary albumin-to-creatinine ratio from baseline to 24 weeks. Secondary outcomes include serum creatinine, cystatin C, estimated glomerular filtration rate, biomarkers of kidney injury, glycaemic control, measures of muscle performance and physical function, and the circulating NAD metabolome.

Look at what the endpoint is

This is the part that distinguishes it from almost everything else written about NAD+.

The primary endpoint is albuminuria — protein in urine, measured in a laboratory, with a known relationship to kidney outcomes. Not "biological age." Not energy. Not how a participant reports feeling. A number that goes up or down, in a population with a defined diagnosis, against a placebo arm, with the comparison specified in advance.

It is also, notably, not a trial about aging, even though it carries circulating markers of aging and physical function among its secondary outcomes. The question it was built to answer is narrow, which is exactly why it can be answered.

The registry, and our standing caveat

The trial is registered as NCT05759468. It is listed as recruiting, sponsored by Brigham and Women's Hospital with Boston Medical Center as collaborator, with a start date of 13 April 2023, a primary completion date of 30 November 2026 and a completion date of March 2027. No results have been posted.

Our standing position holds: a registry entry is a filing, not a verified study, and nothing here reports an outcome. What makes this one worth naming is that the protocol is published and peer-reviewed, the investigators are named at identifiable institutions, the endpoint is pre-specified, and there is a placebo arm. Those are the things that make a future result interpretable.

What has not been established

• No adequately powered, placebo-controlled trial of NAD+ or NMN has yet reported a clinical outcome in any indication.
• Whether raising circulating NAD+ changes anything a person would notice is untested.
• Long-term safety of intravenous NAD+ is uncharacterised; the review found no data of that kind.
• The review's own finding about whole-blood concentrations concerns healthy aging, and does not address NAD+ in diagnosed disease.

What to watch

The 30 November primary completion date, three weeks away. Note that a primary completion date is when the last participant finishes the primary measurement, not when results appear — publication typically follows by many months, and the registry's own completion date runs to March 2027.

The number to look for when it does arrive is a simple one: did the albumin-to-creatinine ratio fall further in the NMN arm than in the placebo arm? That single comparison will say more than the whole of the preceding literature.

Sources

1. Alangari A, Arif J, Al Qureshah F, Alkhodairy F. Narrative review of intravenous NAD+ and NAD+ precursors in wellness and translational medicine. Front Aging (2026)
2. Chandra MS, Gagliano-Jucá T, Shekhar S, et al. Nicotinamide Adenine Dinucleotide Augmentation in Diabetic Kidney Disease: Randomized Trial Study Protocol. Kidney Int Rep (2026)
3. ClinicalTrials.gov NCT05759468 — NAD Augmentation in Diabetes Kidney Disease (Brigham and Women's Hospital)

Compounds in this article

NAD+