Background Nicotinamide riboside (NR) is a promising compound for augmenting the intracellular NAD+ pool, potentially mitigating age-related decline and associated conditions. While oral NR supplementation has demonstrated safety and bioavailability in multiple animal and human studies, the effects of intravenous NR (NR IV) are far less understood. Until now, pharmaceutical grade NR was not available for injection research.

Objectives Given that intravenous administration may offer advantages in certain conditions and contexts, a systematic investigation of the clinical effects of NR IV is warranted.

Methods The present randomized, double-blinded, placebo-controlled, pilot clinical study was initiated with the primary aim of investigating the safety, tolerability, and the blood NAD+-boosting efficacy of an acute, single dose of NR IV (500 mg, test), NAD+ IV (500 mg, active comparator), oral NR (500 mg, bridge), and saline IV (placebo control) in generally healthy adult participants. The study consisted of two parts; data from 37 and 16 participants in the first and second phases, respectively, were analyzed.

Results No significant differences in vital signs were detected across groups. In comparison to NAD+ IV, NR IV was associated with fewer and less severe adverse experiences during the infusion; no attributable adverse events were reported through the 14-day follow-up period for any treatment groups. Further, the mean tolerable infusion time for NR IV was 75% less than that of NAD+ IV. No clinically meaningful changes in blood chemistry markers were described in the NR IV condition, whereas an increase in white blood cell counts and neutrophils was observed in the NAD+ IV condition, suggesting the presence of an inflammatory response. Finally, NR IV appeared to promote the most robust increases in NAD+ concentration as measured by dried blood spot analyses, with peak NAD+ levels increasing by 20.7% relative to baseline, and acutely outperforming NAD+ IV (p <0.01) and oral NR (p<0.01) at the 3-hr timepoint.

Conclusion This is the first study to clinically evaluate NR IV. Overall, acute intravenous infusions of 500 mg NR were safe in the study participants with no attributable adverse events and only minor and transient infusion-related experiences. In comparison to NAD+ IV, NR IV had a faster infusion time with superior tolerability. At 3 hours post-infusion, blood NAD+ levels were significantly higher in the NR IV group compared to the NAD+ IV group. Future studies in larger populations are needed to validate these results.

RI, JK, AS, and YNE are employees of ChromaDex, Inc. Niagen and Niagen+ are proprietary ingredients of ChromaDex. Niagen is the active ingredient in the commercially available product, TruNiagen. JH and Nutraceuticals Research Institute, LLC were contracted by ChromaDex to conduct this study.

NCT06382688

This study was sponsored by Franklin Health Research and funded by ChromaDex, Inc.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Sterling IRB gave ethical approval for this work.

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All data produced in the present study may be made available upon reasonable request sent to cerpchromadex.com.