Low-dose oral NMN was safe and moved platelet counts in a phase 1/2 ITP trial

A phase 1/2 trial has found that low-dose oral nicotinamide mononucleotide, the NAD+ precursor better known as NMN, was safe and produced a clinically meaningful platelet response in one in five adults with steroid-refractory immune thrombocytopenia, a bleeding disorder in which the immune system destroys its own platelets. The results, published April 29 in Nature Medicine, mark the first time NMN has been tested in a regulated, disease-specific clinical trial. Prior NMN research consists almost entirely of healthy-volunteer longevity studies.

How the trial was designed

The single-arm, open-label trial enrolled 25 patients between January 15 and March 17, 2025, all with ITP that had failed to respond to, or remained dependent on, corticosteroid therapy. Each patient received 450 mg of oral NMN twice daily for two weeks (a total daily dose of 900 mg split across morning and evening). The primary endpoints were safety and tolerability, together with a platelet-count response defined as a platelet level of at least 30 x 10^9 per liter and at least a doubling of baseline count. The trial is registered as NCT06776510.

Five patients (20 percent) met the primary platelet-response endpoint. An exploratory analysis found that 60 percent of patients achieved platelet counts more than 1.5 times their baseline at some point during the two-week treatment window. Fifty-two percent maintained that response through week 8, six weeks after NMN was stopped. No patient required rescue therapy during the treatment period.

What the safety data showed

No dose-limiting toxicities or treatment-related serious adverse events occurred in any of the 25 patients. NMN at 450 mg twice daily was well tolerated. The authors, a 17-person team led by Huiyuan Li and Lei Zhang at the Chinese Academy of Medical Sciences and Peking Union Medical College, also monitored infections as a secondary safety signal. Any therapy that alters macrophage polarization in ITP carries a theoretical risk of tipping immune surveillance toward immunosuppression. No concerning infection signal emerged during the treatment or follow-up periods.

The mechanism: NAD+ and macrophage polarization

The trial tests a specific mechanistic hypothesis the same group had been building toward. In earlier work, they showed that an anti-CD38 monoclonal antibody could rapidly raise platelet counts in refractory ITP. CD38 is a membrane-bound enzyme that degrades NAD+. The team found that CD38-mediated NAD+ depletion in macrophages drives them toward a pro-inflammatory M1-like polarization state. In that state, macrophages upregulate Fc-gamma-RI, a high-affinity receptor that promotes the engulfment and destruction of antibody-coated platelets, the core pathology in ITP. In mouse models of the disease, either blocking CD38 pharmacologically or supplementing with NMN restored intracellular NAD+ levels and reprogrammed macrophages away from the platelet-destroying M1 state, preventing the thrombocytopenia that otherwise developed after platelet transfer.

This is a narrow, immunometabolic hypothesis, not the familiar longevity-adjacent claim about replenishing NAD+ to slow aging. In ITP, NAD+ depletion in macrophages creates a permissive signal for autoantibody-mediated platelet destruction. NMN, by restoring intracellular NAD+, may brake that process, not by boosting platelet production but by dialing down the immune-mediated clearance that defines the disease. The authors describe the CD38-NAD+ axis as an immunometabolic checkpoint in ITP, language that positions the pathway as a druggable node in antibody-mediated autoimmune disease beyond ITP.

Where this fits in the NMN evidence

The dose used, 450 mg twice daily, falls within the range of 300 to 900 mg once-daily doses tested in prior NMN safety trials in healthy adults. The largest of those, a 2023 randomized, multicenter, double-blind, placebo-controlled trial by Yi and colleagues in GeroScience, enrolled 80 healthy middle-aged adults and found NMN safe and well tolerated at doses up to 900 mg daily for 60 days, with dose-dependent increases in blood NAD+ concentrations and improvements in six-minute walk distance and self-reported health scores. That trial, like most NMN research, was oriented toward healthy aging endpoints. The Nature Medicine trial is the first to test whether NMN does anything clinically useful in a defined disease.

Reading the results carefully

A 20 percent response rate in 25 patients means five people improved. That is worth paying attention to, but in an open-label study with no placebo, the number needs a cold read. Both patients and clinicians knew they were getting NMN. ITP platelet counts fluctuate on their own, and some of those five responses may reflect the disease’s natural course rather than the drug. The authors are explicit about this: the next step is a randomized, placebo-controlled phase 2 trial, probably in the range of 60 to 100 patients, designed to separate treatment effect from background noise. Spontaneous remission in chronic ITP is uncommon, but it happens.

What makes the result harder to dismiss outright is the durability. Fifty-two percent of patients held their response through week 8, six weeks after they stopped taking NMN. If the mechanism really involves shifting macrophages from a pro-inflammatory to a regulatory state, a carry-over after the drug clears is at least biologically plausible. Reprogramming takes time to wear off in a way that a direct pharmacologic boost does not. But with 25 patients and no control group, durability is an observation, not evidence. The phase 2 trial will need to test it directly.

What this trial does not say

The trial does not show that NMN treats aging. That sounds obvious, but it is worth stating because the supplement industry has spent years marketing NMN as a longevity molecule. The patients here had a specific autoimmune blood disease. The endpoints were platelet counts, bleeding events, and safety, none of the epigenetic clocks or NAD+ blood level measurements that populate healthy-aging NMN studies.

It also does not mean NMN is ready for the clinic, in ITP or anywhere else. Phase 1/2 exists to establish safety and look for an efficacy signal. Both boxes got a check. But the sample is 25 people, the design was open-label, and the comparison is to baseline platelet counts, not to a control arm. Those are not design flaws, they are what phase 1/2 is. The question is whether the signal holds up when you tighten the controls.

Setting aside the supplement-industry narrative, this trial offers something the NMN field has been missing: a test of the molecule against a defined disease mechanism with a measurable clinical endpoint. For a decade, NMN research orbited healthy aging. The Li et al. paper plants it in a different soil, immunometabolism, macrophage biology, autoimmune disease. Whether or not ITP turns out to be the right disease for this mechanism, the framework shifts the conversation from does NMN slow aging to does NMN do something specific in a disease where NAD+ metabolism is directly implicated. That is a sharper question, and it is testable.

The trial was small and early. The mechanism is plausible. The safety was clean. The response rate was modest but durable. A larger randomized study is the only way to know whether any of it holds. For now, it is a start, not an answer.

References

1. Li H, Xu Y, Chen Y, et al. Low-dose oral nicotinamide mononucleotide for immune thrombocytopenia: a phase 1/2 trial. Nat Med. 2026. https://doi.org/10.1038/s41591-026-04366-x
2. Yi L, Maier AB, Tao R, et al. The efficacy and safety of beta-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience 45(1):29-43. 2023. https://doi.org/10.1007/s11357-022-00705-1