The goal of this study is to learn about the safety of Niagen®Plus, an injectable form of nicotinamide riboside (NR), and to see how it affects levels of NAD+ in the blood. Niagen®Plus will be given either by subcutaneous (under the skin) or intramuscular (into the muscle) injection at two dose levels (50 mg or 100 mg).

The main questions this study aims to answer are:

Is Niagen®Plus safe and well-tolerated when given by injection several times over 100 days?

How do NAD+ levels in blood change after repeated doses of Niagen®Plus?

What are participants' and clinicians' experiences with the injections?

Researchers will also look at changes in fatigue, sleep, quality of life, inflammation markers, mitochondrial efficiency, and perceived skin appearance.

Participants will:

Receive three injections in clinic on Days 1-3, followed by a Day 10 follow-up visit

Self-inject Niagen®Plus at home three times per week from Days 10-100

Return to the clinic on Days 40 and 100 for safety and laboratory testing

Complete short surveys about fatigue, sleep, and overall well-being throughout the study

The study will include 40 generally healthy adults and will last about 100 days per participant.

This is a single-site, prospective, randomized, open-label, parallel 4-arm pilot trial designed to evaluate the safety and pharmacodynamic effects of Niagen®Plus (nicotinamide riboside chloride, NRCl) when administered by injection. The study includes two phases over approximately 100 days per participant.

In Phase 1, participants receive three consecutive daily injections of Niagen®Plus (50 mg or 100 mg; subcutaneous or intramuscular) administered in clinic on Days 1-3, followed by a Day 10 follow-up visit for safety evaluation and laboratory testing. In Phase 2, participants continue self-administration of subcutaneous Niagen®Plus at home three times per week (Monday, Wednesday, Friday) through Day 100, returning to the clinic on Days 40 and 100 for repeat safety assessments, sample collection, and exploratory analyses.

Primary endpoints assess safety and tolerability through vital signs, comprehensive metabolic and hematologic panels (CMP, CBC, homocysteine), and adverse-event monitoring. Secondary endpoints include changes in whole-blood NAD⁺ concentrations measured by dried-blood-spot analysis and clinician- and participant-reported injection experience. Exploratory endpoints include fatigue, energy, sleep, and quality-of-life assessments; plasma biomarkers of inflammation (C-reactive protein); phenotypic age calculation; oxidative stress testing (in urine); mitochondrial efficiency testing; and subjective evaluations of skin appearance.

The target enrollment is 40 generally healthy adults (10 per arm). The study is not powered for hypothesis testing but will inform the design of subsequent placebo-controlled trials by characterizing safety profiles, pharmacokinetic trends, and feasibility of at-home administration.

Inclusion Criteria:

• Generally healthy adults, aged 18+
• Demonstrated baseline fatigue as determined by a below average score from the FAS (threshold prespecified in SAP).
• NAD+ or NAD+ precursor injection naïve (including intravenous, intramuscular, subcutaneous, or other injection route) (i.e., 8 weeks abstinent)
• Non-anemic
• Willingness to adhere to lifestyle considerations and study procedures.
• Ability to read English, and provide written informed consent.
• Willingness to self-administer the study material, via subcutaneous injection for 90 days (days 10-100 of the study), and complete finger prick blood collections.

Exclusion Criteria:

• One or more uncontrolled chronic illness including but not limited to diabetes, cardiovascular disease, liver, disease, kidney disease, or any form of cancer. An uncontrolled chronic illness, in this case, is defined as any changes to medication or other treatment modalities in the last 90 Days.
• More than one chronic disease diagnosis under active treatment.
• Any chronic disease, as determined by the primary investigator, that increases risk or confounds safety.
• Any acute illness within 14 Days prior to Visit 1 (Day 1).
• Cancer diagnosis within the last 5 years
• Anemia (as defined by hemoglobin levels below 100 g/L, and other blood measures)
• Current pregnancy or lactation; unwilling to use effective contraception if of childbearing potential.
• Use of any NAD+ supplement, NAD+ precursor, or vitamin B3 product, orally, nasally, by patch, or injection within the last 60 Days. NAD+ precursors and related compounds include niacin (NA), nicotinamide (NAM), nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), NAD+, NADH, NAD+3, inositol hexanicotinate, apigenin; etc. The exception is the use of a daily oral multivitamin, that may contain vitamin B3 (niacin/nicotinamide). Such use will need to be documented.
• Hypersensitivity or allergy to NR, niacin, other forms of vitamin B3/NAD+ precursors, bacteriostatic water
• Significant aversion to needles or finger pricks.
• Participation in another clinical intervention study, 90 Days (or 5 half-lives of the intervention, whichever is longer) prior to Visit 1 (Day 1).
• Any other condition rendering the participant unsuitable per investigator.
• Excessive daily use of alcohol, defined as 4 or more drinks on one occasion, or illicit drug use which would prevent adherence to the protocol as determined by the investigator.

Individual participant data (IPD) will not be shared. De-identified aggregate data and summary results will be shared with the sponsor and may be included in publications or presented at scientific meetings.