Article: Nicotinamide Riboside Injections: What Two New Pilot Studies Reveal About Safety

Nicotinamide Riboside Injections: What Two New Pilot Studies Reveal About Safety
Key Takeaways
- Two new pilot clinical studies—the first of their kind—evaluated the safety of nicotinamide riboside (NR) administered via subcutaneous (sub-q) and intramuscular (IM) injection in humans.
- Across both studies, NR injections were generally well-tolerated, with no serious treatment-related adverse events, other than typical injection-site discomfort.
- Preliminary signals around reductions in systolic blood pressure, inflammation, and blood glucose were observed, but are too early to draw conclusions from and require larger, placebo-controlled studies to validate.
- At-home subcutaneous self-injection was shown to be feasible under protocol-defined conditions—a notable finding for the field.
- Pharmaceutical-grade quality and sterility remain non-negotiable for any injectable NAD+ product.
If you’ve been following the NAD+ space, the proliferation of new delivery methods is hard to ignore, especially as injectable wellness has gone mainstream. Intravenous (IV) drips at wellness clinics, subcutaneous shots marketed alongside GLP-1 medications, biohackers self-injecting peptides at home—the culture has shifted dramatically, and NAD+ has been swept along with it.
Yet until now, enthusiasm for injectable NAD+ has outpaced the evidence. Despite the growing popularity, no published clinical data have demonstrated its safety, efficacy, or clinical benefit when delivered subcutaneously or intramuscularly. However, a newly published clinical preprint by Nkrumah-Elie et al. has begun to fill that gap by evaluating both NAD+ itself and nicotinamide riboside (NR), one of its key precursors.¹ The early findings are cautiously encouraging, though important caveats remain.
A Quick Primer on Injection Routes
Because the studies evaluate different ways of delivering NR (and NAD+), it is important to understand what each injection route is and how it differs.
- Subcutaneous injections deliver a compound into the layer of fat just beneath the skin. This is the same general approach used for medications like insulin and many GLP-1 therapies (e.g., Ozempic). Because absorption occurs gradually through fatty tissue, effects tend to be slower and more sustained, and the method is often considered the most practical for self-administration in at-home protocols.
- Intramuscular injections, by contrast, deliver compounds deeper into muscle tissue. Muscle is more vascularized than fat, which generally allows for faster absorption and, in some cases, greater uptake. These injections are more commonly administered in clinical settings, although they can also be performed at home with proper training.
- IV delivery bypasses tissue absorption entirely by infusing compounds directly into the bloodstream. This results in immediate and complete bioavailability, but it also requires clinical supervision, specialized equipment, and significantly more time.
These differences in delivery, such as speed, convenience, and tolerability, are central to why researchers are now exploring subcutaneous and intramuscular injections more closely as a middle ground between oral supplements and IV infusions.
New Pilot Clinical Research: Injectable Nicotinamide Riboside Safety
Conducted by researchers at ChromaDex, a Niagen Bioscience Company, in collaboration with the Nutraceuticals Research Institute and Impact Health Medical, this is the first published clinical research to directly evaluate the safety of subcutaneous (sub-q) and intramuscular NAD+ and NR injections in humans.¹
Study 1 was a randomized, double-blind, placebo-controlled study comparing NR, NAD+, and placebo across multiple delivery routes, including IV, subcutaneous, and intramuscular, in overweight or obese adults with mild-to-moderate fatigue. Participants received one infusion or injection per day for three consecutive days, followed by a seven-day washout, then a follow-up visit.
Study 2 was a randomized, open-label study focused specifically on NR delivery via intramuscular and subcutaneous routes, comparing two doses (50 mg and 100 mg). After an initial three-day in-clinic phase, participants transitioned to self-administering subcutaneous injections at home three times per week for 90 days. This at-home phase is among the first clinical data of its kind and is particularly notable for the field. Full study details are summarized in Table 1.
Table 1. Injectable NR Clinical Studies at a Glance: Study Design and Protocol Details
|
Study Design |
Age Range |
Routes of Administration Tested |
Dose & Interventions |
Injection Protocol |
|
|
Study #1: Absorption and Tolerability of Injectable Administration of Niagen®+, as Compared to NAD+ |
Randomized, double-blind, placebo-controlled, parallel assignment study in 45 overweight or obese adults with mild-to-moderate self-reported fatigue |
40-64 |
Intravenous* Subcutaneous* Intramuscular* *Clinician-administered |
100 mg NR or NAD+* *Dissolved in 2 mL bacteriostatic water |
Injection once daily for three consecutive days |
|
Study #2 Randomized, Open-label, Safety Study of Subcutaneous and Intramuscular Injections of Niagen® Plus |
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 Studies
Clinical Safety Assessments
Across both trials, NR injections were generally well-tolerated, and no serious treatment-related adverse events were reported. Vital signs stayed within normal ranges throughout. Blood chemistry, such as liver enzymes, kidney markers, and blood counts, showed statistically significant fluctuations at isolated timepoints, but a third-party clinician reviewed the data and confirmed none were clinically meaningful or consistent enough to indicate a treatment effect.
Injection Tolerability
The injections were well-tolerated, but they were not painless. In Study 2, roughly 46% of participants reported pain lasting more than two minutes after injection, and 43% reported muscle soreness or tightness. These reactions broke down predictably by route: intramuscular injections were more likely to cause muscle soreness, while subcutaneous injections were more associated with local skin reactions like redness and itching, affecting around half of the participants. These are fairly typical injection-site reactions, though worth factoring in if you're considering this approach.
Notably, IV-delivered NR generated fewer subjective complaints than IV NAD+, which aligns with prior clinical findings, and is consistent with the mechanistic premise that IV NAD+ raises extracellular NAD+ levels, which can trigger an immune-signaling response, potentially explaining why IV NAD+ infusions sometimes cause pain and muscle tightness.
Early Signals From Injectable NR: Blood Pressure, Glucose, and Inflammation
A few findings were interesting enough to flag, while being too preliminary to draw conclusions from:
- Blood pressure: Both studies observed modest reductions in systolic blood pressure in certain groups—roughly 10-12 mmHg acutely in the NR IV group (Study 1) and the 50 mg subcutaneous group (Study 2). However, these effects were not consistent across all groups or timepoints, leading the authors to appropriately characterize the findings as hypothesis-generating rather than a confirmed benefit. Similar reductions in blood pressure have also been reported in prior studies of oral NR supplementation.²'³
- Inflammation (hsCRP): In Study 1, the subcutaneous NR group entered with elevated inflammation markers at baseline and saw reductions over the injection period—a pattern that mirrors findings with oral NR in other studies. However, the baseline differences between groups make it difficult to attribute the change cleanly to NR.
- Blood glucose: Three of the four groups in Study 2 showed acute drops in fasting glucose after the first injection, with values remaining within normal ranges. The directional consistency across groups is interesting—possibly hinting at some effect on glucose metabolism or insulin sensitivity—but is far from conclusive.
While these results are promising, as with any pilot research, these findings come with important context. Both trials were small by design, intended to generate preliminary safety data rather than definitive conclusions. Additionally, Study 2 lacked a placebo group, so within-group changes should be interpreted as descriptive rather than causal. Lastly, there are no published long-term repeat-dose toxicology studies yet, so it is not yet known what organs might be affected by sustained injectable NR use over months or years.
A Promising First Step—And a Warning About the Injectable NAD+ Products Already on the Market
This research represents a meaningful step forward. This is the first published clinical evidence on the safety of injecting NR subcutaneously or intramuscularly in humans, and the short-term safety picture is encouraging for generally healthy adults. At-home self-administration also appears feasible under carefully defined conditions.
What this research is not is a clinical endorsement of the injectable NAD+ products currently flooding the wellness market. Sterility and pharmaceutical-grade quality are non-negotiable—the United States Food and Drug Administration (FDA) has issued recalls of injectable NAD+ products due to contamination concerns, and injections that bypass your gut also bypass your body’s natural defense systems (e.g., the digestive system), making it that much more important to avoid contaminated products.
If you are curious about injectable NR, the authors’ own advice is the right starting point: consult a healthcare provider, use only pharmaceutical-grade products from compliant compounding pharmacies, and request documentation of sterility and potency testing before using anything. This research is a promising first step, and the field now has its first published human safety data. What it still needs is the larger, controlled research to tell us what injectable NR can actually do.
This post is for informational purposes only and does not constitute medical advice. The study discussed is a preprint and has not yet been peer-reviewed.
References
- Nkrumah-Elie, Y., Kwon, J., Simpson, S., Idoine, R., Mavoyan, J., Russ, A., Cavanaugh, J., Fuller, K., Hawkins, E., Jaeger, J., & Shao, A. (2026). Preliminary Safety Analysis of Two Pilot Clinical Trials Involving Injections of Niagen®, Nicotinamide Riboside Chloride. https://doi.org/10.64898/2026.04.28.26352007
- Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., Chonchol, M., & Seals, D. R. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9(1), 1286. https://doi.org/10.1038/s41467-018-03421-7
- Lin, Y., Zeidan, R. S., Lapierre-Nguyen, S., Costello, H. M., Anton, S. D., Buford, T. W., Christou, D. D., Gumz, M. L., Leeuwenburgh, C., Martens, C. R., McDermott, M. M., Migaud, M. E., Sandesara, B., Seals, D. R., Qiu, P., Wang, Y., & Mankowski, R. T. (2025). Nicotinamide riboside combined with exercise to treat hypertension in middle-aged and older adults: a pilot randomized clinical trial. GeroScience, 1–14. https://doi.org/10.1007/s11357-025-01815-2