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Nicotinamide riboside and NAD+ injections show preliminary safety in healthy participantsNicotinamide Riboside Injections Are Safe But Cause Mild Pain

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Key Takeaway
Consider this preliminary safety data from small trials before clinical use of nicotinamide riboside or NAD+ injections.

This Phase 1 randomized controlled trial evaluated bolus injections of nicotinamide riboside or NAD+ in healthy participants across two pilot clinical trials. The sample sizes were Trial 1: n=45 and Trial 2: n=39. Interventions were once-daily injections for three days via intramuscular, intravenous, or subcutaneous routes, compared to placebo injections.

The primary outcome was safety assessment. Participant retention was 100% for both studies with no discontinuations. Pain more than two minutes after injection was reported by 45.9% of participants in Trial 2, and muscle soreness and tightness were reported by 43.2% of participants in Trial 2, regardless of route or dose. Systolic blood pressure reductions were observed in both trials, and within-group hsCRP reductions were seen in NR subcutaneous arms.

Safety findings showed no attributable unexpected adverse events or experiences. Serious adverse events were not reported. The interventions were associated with some discomfort but were well tolerated with no concerning safety signals.

Key limitations include small sample sizes, baseline imbalance in hsCRP analysis, and findings being hypothesis-generating only. Larger, properly powered studies are needed. Practice relevance suggests continuing comprehensive metabolic and inflammatory panels in future studies to assess patterns in larger populations.

Nicotinamide Riboside Injections Are Safe But Cause Mild Pain

Imagine waking up with stiff muscles after a workout. Now picture having to take a shot just to feel better. This is the reality for many people seeking new ways to support their health. Recent research offers fresh hope for those who cannot use daily pills.

Doctors have long known that our bodies need a specific molecule called NAD+ to function well. This molecule helps cells produce energy and repair damage. As we age, our natural NAD+ levels drop significantly. This decline is linked to many age-related health problems.

For years, scientists have studied a substance called Nicotinamide Riboside. This substance helps boost NAD+ levels in the body. Oral pills work well for many people. But some patients cannot swallow pills or need faster results. This is where injections come into play.

Two small pilot studies recently tested these injections. Researchers wanted to know if they were safe. They also wanted to see how people felt after receiving the shots. The results provide important information for patients and doctors alike.

A New Way To Deliver The Drug

The first study looked at three different ways to give the drug. Doctors tested shots into the muscle, veins, and under the skin. They also compared the drug to a placebo and a different molecule.

The second study focused on two doses. Participants received either a lower or higher amount of the drug. Some got shots in the clinic while others learned to do it themselves at home.

Both studies involved healthy adults. Participants received the injections for three days. Then they had a week off before the next phase. Everyone completed the study without dropping out.

Safety was the main focus of these trials. Doctors monitored heart rate, blood pressure, and blood chemistry. They also watched for any unexpected side effects. The good news is that no serious problems occurred.

Vital signs stayed stable throughout the trials. Blood tests showed no dangerous patterns. The drug did not cause heart issues or liver damage. This is a major step forward for patients who need reliable treatment options.

However, the experience of getting the shot was not perfect. Many participants felt pain shortly after the needle went in. Muscle soreness was also very common. About 46 percent of people felt pain lasting more than two minutes.

Muscle tightness affected about 43 percent of participants. These feelings happened regardless of the dose or injection site. The discomfort was mild but noticeable. Most people could still function normally despite these feelings.

Understanding The Side Effects

Why did so many people feel sore? The body reacts to any injection. The needle itself causes some irritation. The drug solution can also cause local inflammation. This is a normal reaction to introducing a new substance into the tissue.

The pain usually fades within a few hours. It does not last for days like some other treatments might. Patients can manage this discomfort with rest or simple pain relief if needed. The benefits of raising NAD+ levels likely outweigh these temporary feelings.

This research suggests that injections are a viable option for some patients. People who struggle with pills might find this route helpful. It could also help those who need quick results for a specific condition.

You should talk to your doctor before trying this. They can explain if it fits your health needs. Not everyone needs injections. Daily pills remain the standard choice for most people.

Doctors recommend continuing to monitor blood markers. Larger studies will help confirm these early findings. We need more data to understand long-term effects. This will help guide future treatment decisions.

These trials were small and short. They were designed to check safety first. Now researchers will look at effectiveness in larger groups. Future studies will involve more participants and longer timeframes.

We do not know exactly when this treatment will become widely available. Regulatory approval takes time and more testing. Scientists are already planning the next steps in this research path.

The journey from lab to clinic is never fast. But every step brings us closer to better options. Patients deserve safe and effective choices for their health. This research moves us forward in that goal.

Study Details

Study typeRct
Sample sizen = 5
EvidenceLevel 2
PublishedApr 2026
View Original Abstract ↓
Nicotinamide riboside (NR), an endogenous precursor to the essential coenzyme nicotinamide adenine dinucleotide (NAD+), is characterized as safe and effective at longitudinally elevating NAD+ in blood and tissues, when administered orally. Preclinical research on NR as an augmenter of NAD+ has demonstrated great promise in support of healthy aging, metabolic health, and several diseases, though clinical translation of these findings has been limited. Interest in alternative routes of administration of NR has increased in recent years and led to the development of pharmaceutical-grade NR for intravenous and injectable administration. Two separate Phase 1 pilot clinical trials were conducted evaluating NR via bolus injections. While the designs of the two studies are different, the similarities warrant combined presentation to note the similarities, particularly with regards to safety-related outcomes. Trial 1 involved 45 participants that were randomized to a 3x3 design, accounting for three interventions, placebo, NR, and NAD+ and three routes of administration, intramuscular (IM), intravenous (IV), and subcutaneous (SC), resulting in a 9-arm study (placebo IM, n=5; placebo IV, n=5; placebo SC, n=5; NR IM, n=6; NR IV, n=5; NR SC, n=4; NAD+ IM, n=4; NAD+ IV, n=5; and NAD+ SC, n=6). Participants were administered NR once daily for three days, followed by a 7-day washout period. In Trial 2 (n=39), the 2x2 study design incorporated 4-arms for phase 1, where the participants were randomized to 50 or 100 mg of NR, administered either IM or SC in-clinic for 3 consecutive days, followed by a 7-day washout (50 mg IM, n=7; IM, 100 mg IM, n=11; 50 mg SC, n=11; and 100 mg SC, n=10). Phase 2 of Trial 2 involved participants self-administering either 50 or 100 mg of NR subcutaneously. Safety assessments for both trials included vitals, blood biomarkers, participant reported outcomes regarding the experience, and adverse event monitoring. Participant retention for both studies was 100%, and the injections did not result in any attributable unexpected adverse events or experiences. The experiences described by the participants regarding the actual injection varied. In Trial 2, pain more than two minutes after the injection and muscle soreness and tightness were reported by 45.9 and 43.2% of the participants, respectively, regardless of the route of administration or dose. Vitals remained generally consistent throughout both trials, and reductions in systolic blood pressure observed in both trials should be evaluated in larger, properly powered studies. Blood chemistry biomarkers for both trials did not elicit treatment-related patterns. Both trials presented within-group reductions in hsCRP in the NR SC arms, however, given baseline imbalance and small samples size, this finding should be considered hypothesis-generating, only. Overall, in both trials, the interventions, regardless of route of administration were associated with some discomfort but were well tolerated and did not produce any concerning safety signals. It is recommended that comprehensive metabolic and inflammatory panels should continue to be employed in future studies and clinical settings to assess whether consistent patterns emerge in larger populations.
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