Immune thrombocytopenia (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition in which platelet levels fall and bleeding becomes more difficult to stop. Treatment options can be limited for people whose disease responds poorly to corticosteroids. In 2026, Nature Medicine published results from a clinical trial of NMN, or nicotinamide mononucleotide, a compound widely studied in aging research1.
This article reviews what the study established and what remains uncertain, based on the primary paper. In brief, the trial reported a favorable safety profile, while the efficacy findings remain an early signal that requires confirmation in a controlled comparative study.
What You Will Learn
- What ITP is and why it can be difficult to treat
- Why NMN entered ITP research through the relationship between CD38 and NAD+
- The proposed mechanism of platelet destruction and NMN action in animal experiments
- The design and results of the phase 1/2 trial in humans, including safety and platelet response
- The study’s significance, limitations, and points requiring caution
What Is Immune Thrombocytopenia?
ITP is an autoimmune disease in which the immune system mistakenly attacks and destroys the body’s own platelets. Platelets help stop bleeding. When their number falls, bruising, pinpoint bleeding under the skin, and bleeding from the gums or nose become more likely. In Japan, ITP is designated as an intractable disease2.
- Autoimmune disease
- A group of conditions in which the immune system, which normally protects against external threats, mistakenly attacks the body’s own tissues.
Adult ITP does not always resolve quickly. Low platelet counts may persist, or the disease may recur after an initial improvement. Corticosteroids are commonly used as first-line treatment. However, some people have steroid-resistant disease that responds inadequately, while others have steroid-dependent disease that relapses when the dose is reduced. These cases create a need for approaches that do not broadly suppress the entire immune system.
CD38 and NAD+: Why NMN Entered ITP Research
The rationale for studying NMN in ITP involves two molecules: CD38 and NAD+.
The research team had previously reported that a drug known as an anti-CD38 antibody restored platelet counts within three days in refractory ITP. However, the mechanism responsible for this rapid increase was unclear.
CD38 is an enzyme that degrades NAD+, or nicotinamide adenine dinucleotide, a coenzyme essential to cellular energy metabolism3. NAD+ levels also decline with aging4. The relationship between CD38 and NMN is discussed in this article.
- Coenzyme
- A substance that assists an enzyme in carrying out a biochemical reaction.
NMN is a precursor of NAD+. The study began with a hypothesis: If CD38 lowers NAD+, could replenishing NAD+ with NMN alter the disease process?
- Precursor
- A substance used as a starting material to produce another molecule.
Mechanism Identified in Animal Experiments
Evidence that NMN might influence ITP first came from experiments in mice.
In the mouse experiments, CD38 degraded NAD+ and created a state of intracellular NAD+ deficiency. Macrophages then shifted toward a pro-inflammatory M1 phenotype, and the amount of FcγRI, a receptor that binds antibodies, increased on their surfaces. Higher FcγRI expression made it easier for macrophages to engulf antibody-coated platelets, promoting platelet destruction. The researchers proposed this sequence as one contributor to lower platelet counts in ITP.
- Macrophage
- An immune cell that engulfs and processes pathogens, damaged cells, and other material.
When the researchers inhibited CD38 or administered NMN to restore NAD+, the shift toward M1 macrophages weakened and FcγRI expression declined. Macrophage uptake of platelets was consequently reduced, and the fall in platelet count was prevented.
The researchers also stimulated the immune systems of mice with an egg-white protein. NMN administration did not reduce their capacity to produce antibodies against this foreign antigen. This finding suggests that the intervention may reduce platelet destruction while preserving necessary immune functions such as humoral immunity, at least in this animal model. This differs from treatments that broadly suppress immune activity1.
- Humoral immunity
- An immune response in which antibodies are produced to recognize and help eliminate pathogens or other antigens.
[🖼️ Image: Schematic of CD38–NAD+-mediated platelet destruction and its suppression by NMN]
Phase 1/2 Trial in Humans: Design and Outcomes
Based on the animal findings, the researchers conducted an early phase 1/2 clinical trial in people with ITP. The study examined safety and tolerability and looked for an initial signal in platelet counts.
- Phase 1/2 trial
- An early clinical study combining elements of phase 1, which focuses primarily on safety, and phase 2, which explores whether a treatment may have biological or clinical activity in people with the target condition.
Trial Design
This was a single-arm, open-label phase 1/2 trial without a placebo control. All participants received NMN. The trial was registered as NCT06776510 on ClinicalTrials.gov5.
The study included 25 adults with steroid-resistant or steroid-dependent ITP. Participants took 450 mg of oral NMN twice daily, for a total of 900 mg/day, for two weeks.
- Open-label trial
- A study in which both participants and clinicians know which treatment is being administered. This trial had no untreated or placebo control group.
Primary Outcomes
The researchers prespecified two main areas of assessment.
The first was safety and tolerability: whether serious adverse effects occurred and whether participants could continue taking the study intervention.
The second was platelet response. A response was defined as reaching a platelet count of at least 50,000/μL, equivalent to 50 × 10⁹/L, within two weeks and confirming that level in two tests performed at least one day apart. An increase was not counted as an NMN-associated platelet response if it followed the addition or dose escalation of a thrombopoietin receptor agonist or corticosteroid, or the use of emergency rescue treatment.
- Tolerability
- The degree to which a person can continue a treatment despite its adverse effects.
- Thrombopoietin receptor agonist
- A type of ITP medication that stimulates platelet production.
Trial Results: Safety and Platelet Response
The study reported findings on both safety and preliminary efficacy.
Safety
No major safety concern was reported. There were no dose-limiting toxicities requiring NMN reduction or discontinuation and no treatment-related serious adverse events.
Mild treatment-related adverse events were observed in 12% of participants, while mild, grade 1 infections occurred in 8%. Immunoglobulin levels did not change substantially, indicating that antibody-mediated immune function was maintained during the study.
- Dose-limiting toxicity
- An adverse effect severe enough to prevent further dose escalation or continuation at the tested dose.
- Immunoglobulin
- A protein that functions as an antibody.
[🖼️ Image: Changes in platelet counts before and after treatment and the proportion meeting the primary endpoint]
Platelet Response
Five of the 25 participants, or 20%, met the prespecified platelet-response criterion. In other words, platelet counts rose above the defined threshold in a subset of participants after NMN administration.
This result requires cautious interpretation. As exploratory secondary information rather than the primary endpoint, 60% of participants had a platelet count at least 1.5 times their baseline value during treatment, and 52% were reported to maintain a response through week 8. These findings are hypothesis-generating and do not establish efficacy.
The combination of few major safety concerns and platelet-count increases in some participants is the central signal from this small early-phase study1.
Interpreting the Study: Significance and Limitations
The findings do not establish that NMN treats ITP. The trial included only 25 participants and had no control group that did not receive NMN. Both clinicians and participants knew that NMN was being administered. A larger randomized, placebo-controlled trial is required to estimate the magnitude and durability of any effect accurately.
Nevertheless, the research team proposed the CD38–NAD+ axis as a possible new therapeutic target in ITP. Rather than removing immune cells, NMN may alter cellular metabolism in a way that reduces macrophage-mediated platelet destruction. This remains a mechanistic and clinical hypothesis requiring further testing.
For another perspective on how NMN may increase NAD+, see this article.
Summary
- ITP is an autoimmune disease in which immune-mediated platelet destruction causes low platelet counts. Options may be limited when corticosteroids are ineffective or cannot be reduced.
- The proposed mechanism involves CD38-mediated NAD+ depletion, a pro-inflammatory macrophage shift, and increased engulfment of antibody-coated platelets.
- In the phase 1/2 trial, oral NMN showed a favorable safety profile, and 5 of 25 participants, or 20%, met the platelet-response criterion.
- The study was small, single-arm, and open-label. A larger controlled trial is necessary before efficacy can be established.
Important Considerations
This article summarizes medical research. The NMN used in the study was administered under physician supervision as part of a clinical trial. The results do not show that any particular supplement dose treats or prevents ITP.
The dose of 900 mg/day was selected and monitored in a clinical-trial setting. It should not be reproduced through self-directed use of commercial supplements. Anyone seeking treatment for ITP or another medical condition should consult a qualified healthcare professional.
References
- 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 ↩
- 難病情報センター「特発性血小板減少性紫斑病（ITP）」. https://www.nanbyou.or.jp/entry/303 ↩
- Sauve, A. A., Munshi, C., Lee, H. C. & Schramm, V. L. The reaction mechanism for CD38. A single intermediate is responsible for cyclization, hydrolysis, and base-exchange chemistries. Biochemistry 37, 13239–13249 (1998). https://doi.org/10.1021/bi981248s ↩
- Migaud, M. E., Ziegler, M. & Baur, J. A. Regulation of and challenges in targeting NAD+ metabolism. Nat. Rev. Mol. Cell Biol. 25, 822–840 (2024). https://doi.org/10.1038/s41580-024-00752-w ↩
- ClinicalTrials.gov. NCT06776510. https://clinicaltrials.gov/study/NCT06776510 ↩
