Article: Nicotinamide Riboside Injections: Exploratory Findings from a Two-Part Pilot Study
,%20building%20on%20the%20safety%20findings%20examined%20in%20a%20co...){kind=link}
Nicotinamide Riboside Injections: Exploratory Findings from a Two-Part Pilot Study
Key Takeaways
- A two-part pilot study provides the first exploratory human data on the potential benefits of injectable nicotinamide riboside (NR), building on the safety findings examined in a companion blog.
- Repeated NR injections were associated with participant-reported reductions in fatigue and improvements in sleep impairment, quality of life, and skin.
- These self-reported improvements were accompanied by objective biological changes, including favorable shifts in mitochondrial bioenergetics and reductions in several markers of oxidative stress.
- Together, the findings provide a promising foundation for continued research but remain preliminary. Larger, longer-term, placebo-controlled studies are needed to confirm the effects.
As injectable wellness has become more mainstream, interest in NAD+ injections and alternative delivery methods has grown alongside it. While early attention centered largely on intravenous (IV) NAD+ drips, researchers are now exploring intramuscular (IM) and subcutaneous (sub-Q) delivery of NAD+ precursors such as nicotinamide riboside (NR). NR is a form of vitamin B3 that the body uses to produce NAD+. Although it has been studied extensively as an oral supplement, clinical research on NR injections is only beginning.
A companion blog, Nicotinamide Riboside Injections: What Two New Pilot Studies Reveal About Safety, examined the safety findings from two pilot studies in which injectable NR was generally well tolerated. This article takes a closer look at one of those trials, turning from safety to its exploratory findings on potential benefits.
The trial followed the same participants from an initial in-clinic portion¹ into roughly three months of at-home injections.² Together, its two reports examine changes in how participants felt (self-reported measurements), as well as biological measurements related to cellular energy metabolism and oxidative stress. Although preliminary, the findings offer an early look at the potential benefits of injectable NR.
A Closer Look at the Two-Part Pilot Study
The trial was conducted by researchers affiliated with ChromaDex, a Niagen Bioscience Company, in collaboration with Impact Health Medical and Verséa Health.
The randomized, open-label study involved 39 adults and was conducted in two phases. During the initial three-day, in-clinic phase, researchers compared two doses of NR administered via IM or sub-Q injection. In the subsequent 90-day at-home phase, all participants self-administered sub-Q NR, including those who had received IM injections during the first phase.
Findings from this single trial were reported in two separate publications. Part I, published by Nkrumah-Elie et al., examined outcomes from the in-clinic phase,¹ while Part II, published by Russ et al., focused on the 90-day at-home phase.² Notably, Russ et al. measured longer-term changes against the original baseline taken before any injections, so their results reflect change across the full trial rather than the 90-day phase alone. The overall study protocol is summarized in Table 1.
Table 1. Injectable NR Clinical Study at a Glance: Study Design and Protocol Details
|
Study Design |
Age Range |
Routes of Administration Tested |
Dose & Interventions |
Injection Protocol |
|
|
Randomized, Open-label, Safety Study of Subcutaneous and Intramuscular Injections of Niagen® Plus Phase I: Phase II: |
Randomized, open-label, two-phase study in 39 healthy adults with some degree of fatigue |
18+ (average age: 46.7) |
Phase I: Intramuscular & Subcutaneous* Phase II: Subcutaneous** *Clinician-administered **Self-administered; at-home injections |
50 or 100 mg NR* *Reconstituted from sterile powder (500 mg multi-use vial) with bacteriostatic water |
Phase I: Injection once daily for three days Phase II: Injection three times per week for 90 days |
Key Findings from the Trial
Fatigue
Fatigue was evaluated with two validated self-report instruments. The PROMIS Fatigue scale measures the frequency and severity of fatigue over the previous seven days, while the Fatigue Assessment Scale (FAS) measures chronic mental and physical fatigue. Using both allowed the investigators to capture recent as well as longer-standing symptoms.
During the in-clinic phase, participants who received 100 mg of IM or sub-Q NR reported significant reductions in fatigue by Day 10 compared with baseline.¹ The 100 mg sub-Q group also showed a significant improvement on the FAS.
Similarly, in Russ et al., participants in both the 50 mg and 100 mg sub-Q groups reported significant reductions in fatigue that were maintained through the end of the study.² When both dose groups were combined, FAS scores were also significantly lower at Days 40 and 100. However, FAS changes were not statistically significant within either dose group separately.
Taken together, these findings provide preliminary signals that injectable NR may reduce fatigue, although the results differed by questionnaire and treatment group.
Mitochondrial Health
The reported improvements in fatigue were accompanied by a measurable shift in cellular energy metabolism. Following repeated NR injections, participants screening showed greater shift toward reliance on mitochondrial energy production relative to glycolysis.²
This was assessed using MeScreen™ mitochondrial profiling, a dried-blood-spot test that estimates ATP production through two major pathways: mitochondrial oxidative phosphorylation and glycolysis. Oxidative phosphorylation generates ATP within the mitochondria, while glycolysis produces ATP by breaking down glucose outside the mitochondria.
After 30 days of at-home injections, the ratio of mitochondrial ATP production to glycolytic ATP production increased by over 41.3%, and this shift was maintained through the end of the study.² The results suggest a greater reliance on mitochondrial energy metabolism and provide a potential biological link to the observed improvements in fatigue.
Oxidative Stress
Oxidative stress occurs when the production of reactive molecules—often called free radicals—exceeds the body’s ability to manage them through its protective defenses. Although these molecules are naturally produced during processes such as energy metabolism and immune activity, excessive or prolonged oxidative stress can damage cellular fats, proteins, and DNA. Oxidized molecules also stimulate the release of inflammatory signals, and are thus implicated in the pathogenesis of chronic low-grade inflammation.³
To determine whether repeated NR injections affected this balance, Russ et al. measured a panel of 16 urinary biomarkers representing several types of oxidative damage.² When both dose groups were combined, 14 of the 16 biomarkers were significantly lower than baseline at one or more follow-up assessments.
By the end of the study, 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, had decreased by more than 50%.² Carboxymethyl lysine (CML), a marker of protein damage associated with aging and metabolic stress, decreased by approximately 57% from baseline. Nitrotyrosine, a modified amino acid that serves as a key biomarker of oxidative and nitrosative (nitrogen-induced) stress, decreased by more than 80%.
However, not all reductions were sustained throughout the study. Several markers of lipid oxidation, including malondialdehyde, decreased significantly after 30 days but rose toward their baseline levels by the final visit. By that point, the changes were no longer statistically significant. Additionally, fewer significant changes were observed when the 50 mg and 100 mg dose groups were analyzed separately. Therefore, the finding that “14 of 16 markers” decreased significantly reflects the combined analysis of both dose groups, not the results for each dose individually.
Taken together, the reductions across multiple biomarkers point to a possible shift in cellular redox balance—the balance between oxidative activity and the body’s antioxidant defenses. These findings are consistent with the established roles of NAD+ in mitochondrial function, cellular antioxidant defense systems, and inflammatory control although the mixed changes warrant further investigation.
Quality of Life
Participants’ overall sense of well-being was measured with the PROMIS Global Health assessment, a validated 10-item questionnaire developed by the National Institutes of Health. It evaluates perceived physical, mental, and social health.
During the in-clinic phase, perceived physical health improved significantly as early as day 10 in the 100 mg sub-Q group, but declined significantly in the 50 mg sub-Q group.¹
During the at-home injection phase, Russ et al., reported significant improvements in both global mental and physical health compared with baseline when the 50 mg and 100 mg sub-Q groups were analyzed together.² However, when the two dose groups were analyzed separately, only the 50 mg group showed a significant improvement in perceived mental health. Neither dose group showed a significant change in perceived physical health. These findings suggest that improvements in overall perceived health were significant when both dose groups were combined, but the results were less consistent when each dose was evaluated separately.
Skin
Skin outcomes were assessed through participant self-report rather than a clinical or instrument-based measure. Reports of perceived facial skin improvement became more frequent during the at-home phase. By the end of the study, nearly 37% of participants reported an improvement in facial appearance.² Some participants also reported improvements noticed by others, while improvements in body skin were reported less commonly.
There is a biological basis for studying the relationship between NAD+ and skin health as NAD+ supports cellular energy metabolism, DNA repair, and sirtuin activity, all of which are relevant to skin function and aging.⁴
Although these results are promising, they are best treated as exploratory and require confirmation using objective dermatologic endpoints.
Sleep
Sleep was assessed using two PROMIS questionnaires, each addressing a distinct aspect. Sleep disturbance concerns sleep itself, including perceived quality, difficulty falling asleep, and restlessness. Sleep-related impairment concerns the effect of sleep problems on daytime alertness, concentration, and functioning.
During the in-clinic phase, all treatment groups showed reductions in sleep disturbance, but the decrease was statistically significant only in the 100 mg IM group.¹ Sleep-related impairment decreased significantly only in the 100 mg sub-Q group.
Russ et al. reported sleep-related impairment was significantly lower after approximately 90 days of injections than at baseline, when both 50 mg and 100 mg groups were analyzed together.² When examined separately, the reduction was significant in the 100 mg group, while the 50 mg group showed numerical reductions that did not reach statistical significance.
Overall, the sleep findings were mixed. Selected measures improved following the in-clinic injections, while the significant longer-term finding concerned reduced sleep-related daytime impairment rather than less sleep disturbance.
These findings are biologically relevant because NAD+ metabolism is closely connected to the body’s circadian system, which coordinates daily patterns in sleep, activity, metabolism, and other biological processes.⁵ NAD+ levels fluctuate throughout the day under the influence of the cellular clock, while NAD+-dependent enzymes can, in turn, help regulate circadian activity.⁶
A Promising Foundation for Injectable Nicotinamide Riboside Research
Together, this two-part trial represents an important first step in the clinical investigation of injectable NR, providing initial human data on its safety, biological activity, and potential benefits. Its two reports describe different portions of the same investigation, ranging from short-term clinician-administered IM and sub-Q dosing to approximately 90 days of at-home sub-Q use.
By the final assessment, participants reported improvements in fatigue, sleep-related impairment, and perceived mental and physical health. These self-reported changes were accompanied by favorable shifts in mitochondrial bioenergetics and several markers of oxidative stress. However, the findings were not consistent across every measurement, dose group, or timepoint.
The combination of participant-reported improvements and objective biological changes makes the overall pattern noteworthy and identifies several promising areas for continued research. As a pilot study, however, the trial was designed primarily to evaluate safety and identify potential signals rather than establish clinical efficacy. Its small sample, open-label design, and absence of a placebo group limit the conclusions that can be drawn.
The next step is to evaluate injectable NR in adequately powered, randomized, placebo-controlled, and longer-term trials. Such studies will be essential to determine whether the initial findings can be replicated, whether the observed biological changes translate into meaningful health benefits, how injectable NR performs over time, and which dosing approaches are most effective. For now, this two-part investigation provides an early clinical foundation and a clear rationale for further investigation of injectable NR.
This post is for informational purposes only and does not constitute medical advice. The publications discussed in this article are currently published as preprints and have not yet been peer-reviewed.
References
- Nkrumah-Elie, Y., Kwon, J., Russ, A., Simpson, S., Hailu, F., Allen, T., Chen, H., & Shao, A. (2026). Part 1 of a 2-part, open-label clinical trial evaluating repeated nicotinamide riboside parenteral administration: 3 consecutive days of intramuscular and subcutaneous injections. https://doi.org/10.64898/2026.10.12.26365345
- Russ, A., Nkrumah-Elie, Y., Hailu, F., Kwon, J., Allen, T., Shao, A., & Chen, H. (2026). Part 2 of a 2-part open-label clinical trial evaluating repeated nicotinamide riboside parenteral administration: 90 days of at-home subcutaneous injections. https://doi.org/10.64898/2026.10.13.26365470
- Hussain, T., Tan, B., Yin, Y., Blachier, F., Tossou, M. C. B., & Rahu, N. (2016). Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxidative Medicine and Cellular Longevity, 2016(1), 7432797. https://doi.org/10.1155/2016/7432797
- Conlon, N. J. (2022). The Role of NAD+ in Regenerative Medicine. Plastic and Reconstructive Surgery, 150(4 Suppl), 41S-48S. https://doi.org/10.1097/prs.0000000000009673
- Huang, W., Ramsey, K. M., Marcheva, B., & Bass, J. (2011). Circadian rhythms, sleep, and metabolism. Journal of Clinical Investigation, 121(6), 2133–2141. https://doi.org/10.1172/jci46043
- Ramsey, K. M., Yoshino, J., Brace, C. S., Abrassart, D., Kobayashi, Y., Marcheva, B., Hong, H.-K., Chong, J. L., Buhr, E. D., Lee, C., Takahashi, J. S., Imai, S., & Bass, J. (2009). Circadian Clock Feedback Cycle Through NAMPT-Mediated NAD+ Biosynthesis. Science, 324(5927), 651–654. https://doi.org/10.1126/science.1171641