Abstract
Background
Altered NAD+ metabolism has been described in rheumatoid arthritis (RA), but intravenous NAD+ has not been clinically evaluated for inflammatory arthritis.
Case presentation
A 49‐year‐old woman with a rheumatologist‐documented diagnosis of RA had progressive polyarthralgia, intermittent swelling, marked morning stiffness, and baseline hand and wrist ultrasonography showing active synovitis. After approximately 4 months of inconsistently taken methotrexate, discontinued because of adverse effects, she received four intravenous NAD+ infusions for aesthetic and antiaging purposes: 250 mg in 500 mL of 0.9% sodium chloride over approximately 1 hour every 2 weeks. She reported rapid pain relief after individual infusions and subsequent improvement in swelling, morning mobility, function, and analgesic use. No infusion‐related adverse events were reported. Nine months later, follow‐up ultrasonography showed no synovitis or Doppler hyperemia. Psychologic support, exercise, and improvement in personal circumstances occurred concurrently.
Conclusion
The symptomatic and ultrasonographic changes were temporally associated with intravenous NAD+, but incomplete diagnostic documentation, previous methotrexate exposure, concurrent psychosocial changes, and the uncontrolled retrospective design preclude causal inference. This case is hypothesis‐generating and supports prospective controlled investigation.
Introduction
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease in which early disease‐modifying antirheumatic treatment is important to limit joint damage and disability. 1 NAD+ regulates cellular energetics, redox homeostasis, and NAD+‐dependent signaling. 2 NAD+ metabolism is altered in RA and has been proposed as a therapeutic target, although intravenous NAD+ has not been clinically evaluated for inflammatory arthritis. 3 , 4 We report symptomatic and ultrasonographic improvement temporally associated with intravenous NAD+ administration.
Case Presentation
The patient, a 49‐year‐old Lebanese woman working as a bank branch manager, developed joint pain beginning in the little finger and progressing to migratory polyarthralgia, intermittent swelling, and marked morning stiffness. She later developed a rash over both legs and feet. Her history was notable only for appendectomy. Symptom onset coincided with substantial occupational and family stress, including caring for a son hospitalized for several months and ongoing marital conflict. Detailed examination findings from the original rheumatology visit were unavailable.
Initial complete blood cell count was reportedly normal; markers of inflammation, rheumatoid factor, anticyclic citrullinated peptide antibodies, and other autoimmune serology were unavailable. In August 2024, bilateral hand and wrist ultrasonography showed marked synovial hypertrophy of both wrists and right metacarpophalangeal joints with Doppler hyperemia consistent with active synovitis, together with articular irregularities and distal osteophytes (Figure 1A–C). A rheumatologist diagnosed RA, but the original consultation notes and diagnostic criteria were unavailable; therefore, fulfillment of the 2010 American College of Rheumatology/EULAR classification criteria could not be independently verified. 5
Figure 1.
Representative musculoskeletal ultrasonography at baseline and follow‐up after intravenous NAD+ therapy. Baseline images demonstrate synovial hypertrophy involving the (A) right second metacarpophalangeal joint, (B) left first metacarpophalangeal joint, and (C) right fourth metacarpophalangeal joint, with Doppler hyperemia visible in panels A and C, consistent with active synovitis. (D–F) Corresponding follow‐up images show no visible synovial hypertrophy or Doppler hyperemia in the displayed views. The baseline and follow‐up examinations were obtained at different time points and with different ultrasonographic settings; therefore, the images provide a qualitative rather than standardized quantitative comparison. MCP, metacarpophalangeal.
Methotrexate with vitamin supplementation was prescribed. Adherence was initially inconsistent, and the patient reported partial improvement during approximately four months of treatment before discontinuing it because of adverse effects.
Approximately 2 months later, she received intravenous NAD+ for aesthetic and antiaging purposes rather than RA treatment. Each session comprised 250 mg NAD+ in 500 mL 0.9% sodium chloride infused over approximately 1 hour every 2 weeks for four sessions, totaling 1,000 mg over 6 weeks. Around the same time, she divorced, began psychologic support, and resumed regular gym exercise.
She reported rapid pain reduction after individual infusions and, by treatment completion, marked improvement in pain, swelling, morning mobility, function, cold tolerance, energy, mood, and analgesic requirements. All four sessions were completed without reported interruption, dose modification, or adverse events. Nine months later, follow‐up bilateral hand ultrasonography showed no synovitis, Doppler hyperemia, tenosynovitis, significant effusion, erosion, or soft‐tissue abnormality; joint spaces were preserved (Figure 1D–F). No validated disease activity measures, serial markers of inflammation, or follow‐up serology were available. The clinical chronology is summarized in Supplementary Figure 1, and the patient's perspective is presented in Box 1. Written informed consent was obtained from the patient for publication of this case report. No data beyond those presented in this article will be shared. Additional patient‐level clinical data are not publicly available because of patient privacy and confidentiality considerations and the scope of the patient's consent for publication.
Box 1. Patient perspective*.
“During the period when my hand symptoms worsened and I was diagnosed with rheumatoid arthritis, I was under considerable stress in both my professional and personal life. I work as a bank branch manager, which carries significant responsibilities. At home, I was caring for my children and supporting their education, and my son was hospitalized for several months following an accident. At the same time, I was experiencing ongoing marital conflict and felt emotionally unstable and unhappy in my home environment. I felt that the accumulated stress affected my general health and contributed to a significant decline in my physical and psychological well‐being.
After my divorce, I decided to focus more on myself and my health. I sought psychological support, began exercising regularly at the gym, and started intravenous NAD+ therapy. Following these changes, I noticed an overall improvement in my health. I felt that my joint pain decreased rapidly after each NAD+ session, and I also experienced a clear improvement in my mood. With the continued sessions, the pain became much less frequent and eventually resolved from my perspective.”
Discussion
To our knowledge, this is the first peer‐reviewed case report describing RA improvement temporally associated with intravenous NAD+. Human RA research has identified reduced intracellular NAD+, associations with inflammation and disease activity, and improvement of selected inflammatory features after ex vivo NAD+ precursor exposure. 3 However, these findings do not establish that intravenously administered NAD+ reaches relevant intracellular compartments or improves RA. The available human intravenous study assessed metabolite disposition, not rheumatologic efficacy. 4
The temporal sequence and later absence of ultrasonographic inflammation make the observation notable, but causal inference is weak. Alternative explanations include natural disease fluctuation, placebo or expectation effects, retrospective recall, occasional analgesic use, residual effects of methotrexate, and concurrent psychologic, social, and exercise‐related changes. Diagnostic uncertainty, missing baseline serology and disease activity measures, and nonstandardized, nonblinded ultrasonographic comparison further limit interpretation.
This case should therefore be regarded as hypothesis‐generating. Prospective controlled studies should use validated RA outcomes, inflammatory biomarkers, standardized blinded power‐Doppler ultrasonography, NAD+ metabolite measurements, and systematic safety monitoring. Intravenous NAD+ should not be adopted for RA outside research settings.
Conclusion
Symptomatic improvement and the absence of previously documented inflammatory findings on follow‐up ultrasonography were temporally associated with four intravenous NAD+ infusions, but this single retrospective case cannot establish causality or efficacy. Controlled prospective investigation is required.
AUTHOR CONTRIBUTIONS
All authors contributed to at least one of the following manuscript preparation roles: conceptualization AND/OR methodology, software, investigation, formal analysis, data curation, visualization, and validation AND drafting or reviewing/editing the final draft. As corresponding author, Dr Bou Dargham confirms that all authors have provided the final approval of the version to be published and takes responsibility for the affirmations regarding article submission (eg, not under consideration by another journal), the integrity of the data presented, and the statements regarding compliance with institutional review board/Declaration of Helsinki requirements.
Supporting information
Supplementary Figure 1. Clinical timeline of the patient's disease course, interventions, and outcomes. The timeline summarizes symptom onset, rheumatologic evaluation and diagnosis, methotrexate treatment and discontinuation, initiation and completion of intravenous nicotinamide adenine dinucleotide (NAD+) therapy, concurrent psychosocial changes, and subsequent patient‐reported and ultrasonographic outcomes. T0 represents initiation of intravenous NAD+ therapy; negative and positive values indicate months before and after T0, respectively.
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ACKNOWLEDGMENTS
The authors acknowledge the use of ChatGPT (OpenAI) for language refinement and editorial assistance. All scientific content, clinical data, analysis, interpretation, and conclusions were developed independently by the authors. The authors reviewed and approved all AI‐assisted revisions and take full responsibility for the final content of the article.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Dr Bou Dargham acknowledges the training received through the Scholars in HeAlth Research Program (SHARP), which was supported in part by the Fogarty International Center and the Office of Dietary Supplements of the National Institutes of Health under award number D43 TW009118. No grant or external financial support was received for this work. The patient personally paid the full cost of the intravenous nicotinamide adenine dinucleotide treatment. No commercial organization provided the treatment, medication, clinical services, manuscript support, or other assistance free of charge. The authors personally covered the cost of the follow‐up ultrasonographic examination.
1Faculty of Medicine, Beirut Arab University, Beirut, Lebanon; 2Medistic Medical Center, Beirut, Lebanon; 3Department of Radiology, Al‐Jabal Hospital, Qurnayil, Lebanon; 4Department of Anesthesiology, Hammoud Hospital University Medical Center, Saida, Lebanon.
Additional supplementary information cited in this article can be found online in the Supporting Information section (https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.90151).
Author disclosures are available at https://onlinelibrary.wiley.com/doi/10.1002/acr2.90151.
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Associated Data
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Supplementary Materials
Supplementary Figure 1. Clinical timeline of the patient's disease course, interventions, and outcomes. The timeline summarizes symptom onset, rheumatologic evaluation and diagnosis, methotrexate treatment and discontinuation, initiation and completion of intravenous nicotinamide adenine dinucleotide (NAD+) therapy, concurrent psychosocial changes, and subsequent patient‐reported and ultrasonographic outcomes. T0 represents initiation of intravenous NAD+ therapy; negative and positive values indicate months before and after T0, respectively.
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