From supermodels and influencers like Haley Bieber and Kendall Jenner to former NFL athletes like Jay Cutler, the use of NAD+ IV therapy is becoming increasingly popular amongst high-profile celebs, biohackers, and “regular people” alike.
However, while NAD+ IV infusions are thought to support cellular health, energy metabolism, physical performance, and more, the potential downsides are not insignificant. With notoriously unpleasant side effects and hours-long treatment sessions spent stuck in a chair with a needle in your arm, researchers have wondered if there is a better way to get the benefits of intravenous NAD+ without the negatives.
Enter Niagen IV—a new era of NAD+ infusion therapy that uses a pharmaceutical-grade NAD+ precursor called nicotinamide riboside chloride (NRCl). Let’s take a closer look at the differences between NAD+ IV and Niagen IV and why you might want to choose the latter, including the impressive results from the first pilot study comparing the two infusions.
What Is NAD+ IV?
To understand what NAD+ IV is, we must first understand NAD+ itself.
Nicotinamide adenine dinucleotide, or NAD+, is a compound that is fundamental to life as we know it. As an essential coenzyme, NAD+ helps approximately 500 other enzymes to function properly—we can liken NAD+ to the oil in our engines that keeps them functioning in top form and running smoothly. Just as engines cannot perform optimally without oil, neither can our cells. NAD+ is necessary for bodily functions we don’t notice happening internally—like DNA repair and mitochondrial energy production—and those we do, such as your heart beating or muscles contracting as you run.
Every cell in our body needs NAD+—but this vital molecule tends to decline with age due consistent exposure to metabolic stressors that deplete NAD+ by as much as up to 65% between ages 30 and 70. A reduction in NAD+ can result in accelerated aging and signs of age-related physiological decline, making NAD+ maintenance an essential component of healthy aging and longevity.
But boosting NAD+ levels isn’t as simple as popping a capsule of it. Oral supplementation of NAD+ is ineffective, because it cannot cross over cell membranes in its original form—it has to be converted into its components before it could be taken up by the cell and converted to NAD+. Some have turned to NAD+ IV to increase NAD+ levels, however it’s not efficient or ideal.
Let’s take a look at NAD+ IV, which involves high doses of NAD+ delivered intravenously. This direct infusion bypasses the digestive system in the hope of increasing cellular NAD+ levels, however it comes with unpleasant side effects.
Although NAD+ IV clinics were introduced in the early 2000s, NAD+ IVhas been used clinically since the 1960s, when intravenous NAD+ was found to help with alcohol withdrawal. More recently, NAD+ IVs have become more popular than ever in wellness clinics around the world, with increasing use by influencers, celebrities, and athletes—including Justin and Hailey Bieber, Kendall Jenner, Bella Hadid, Kate Upton, Gweneth Paltrow, Joe Rogan, and Jay Cutler.
While there are promising studies showing that boosting cellular NAD+ levels can support energy metabolism and aspects of healthy aging, there’s minimal clinical evidence for the efficacy of NAD+ IV therapy. One reason is that supplementing with NAD+ (either oral or intravenous) is, paradoxically, not the best way to elevate blood NAD+ levels—which brings us to NAD+ precursors like Niagen® IV.
What Is Niagen IV?
Niagen IV is a first-of-its-kind pharmaceutical-grade intravenous therapy of nicotinamide riboside chloride (NRCl).
Orally supplemented nicotinamide riboside (NR) can boost cellular levels of NAD+, and it is one of the most well-known compounds that act as an NAD+ precursor. Research has shown that NR effectively and safely raises blood NAD+ levels without significant side effects.
Clinical trials with oral NR supplementation have suggested that the NAD+ precursor supports heart health, cognitive function, healthy body composition, and metabolic rate.
Oral Niagen has been used in several clinical studies to elevate NAD+ levels in the blood or skeletal muscle (including in overweight adults, healthy middle-aged and older adults, and men in their 70s), a new pilot study shows the intravenous formulation supports a fasterand more efficient delivery of Niagen.
Intravenous NR has shown promise in preclinical studies with animals. The first, published in 2022, found that rats receiving IV NR had significant improvements in aspects of cardiovascular health and physical activity. The second preclinical study found that intravenous NR chronically elevated skeletal muscle NAD+ levels in mice consuming a Western diet.
Now, a new pilot study with middle-aged adults from this year has added to the evidence base of how intravenous NR impacts NAD+ levels—keep reading for more details on this groundbreaking study.
What’s the Difference Between NAD+ IV and Niagen IV?
The first and obvious difference between NAD+ IV and Niagen IV is what’s in the intravenous solution. While NAD+ IV solutions should clearly contain NAD+, the batches may be unreliable since many companies produce NAD+ solutions for IV use, they all may not adhere to the same quality standards.
Conversely, Niagen IV consists of pharmaceutical-grade Niagen® (nicotinamide riboside chloride or NRCl), which is reconstituted with sterile water then mixed with saline for intravenous administration. Intravenous treatments are always administered by qualified and licensed experts.
While the difference between NAD+ IV and Niagen IV may seem minor, they have been shown to produce vastly divergent effects—both in how it works and how you feel.
Some of the leading drawbacks of NAD+ IV drips are the uncomfortable and often painful side effects they produce during the infusion, including headaches, nausea, vomiting, dizziness, lightheadedness, diarrhea, and flushing.
These adverse effects typically arise because the large dose of extracellular NAD+ (that occurs with IV administration) is interpreted by the body as the presence of damaged or dead cells. NAD+ IV therefore may lead to the perception of trauma within the body, leading to an immune response, and potentially causing inflammation. Which may cause NAD+unpleasant symptoms.
NAD+ IVs can take a long time—sometimes up to 4 to 6 hours due to the unpleasant side effects (certainly not how most people want to spend half a day).
Conversely, Niagen IV is made of NR—which is already broken down into the correct compound needed to enter cells—leading to faster infusion times, fewer side effects, and NAD+ levels that rise more rapidly.
Why Is Niagen IV Better Than NAD+ IV?
In a randomized, double-blinded, placebo-controlled, preprint pilot clinical study, researchers compared the effects of acute, one-time doses of 500mg of either Niagen IV, NAD+ IV, oral NR, or a placebo in a group of 37 healthy adults with an average age of 40.
The results were striking.
Compared to the NAD+ IV, people who received the Niagen IV experienced significantly fewer adverse effects, superior tolerability, up to a 75% shorter infusion time, more rapid blood NAD+ elevations at 3 hours post-infusion, and fewer markers suggestive of an inflammatory immune response.
Let’s take a closer look at the specifics of how Niagen IV outperformed NAD+ IV in this pilot study.
Niagen IV Has a Faster Infusion Time
As time is our most precious commodity, reducing the overall infusion time by up to 75% compared to NAD+ IV is one of the leading benefits of using Niagen IV instead.
In the first arm of this pilot study, the infusion was started slowly, and the speed was increased or decreased in response to the participants’ requests based on their comfort and tolerability.
The Niagen IV was much faster—indicating that they were more comfortable with quicker infusion—taking an average of 2 hours and 7 minutes, while the NAD+ IV ran for 3 hours and 3 minutes. The maximum infusion time was much greater in the NAD+ IV, reaching over 4.5 hours, compared to just over 3 hours in the Niagen IV group.
In a second arm of the trial, a smaller group of men were randomized to get either NAD+ or Niagen IVs, with all IV lines beginning in their fully open flow state. However, the participants could still increase or decrease the infusion based on their comfort.
The Niagen IV infusions ranged from 10 minutes to three hours, while the NAD+ IV took 20 minutes to just over three hours, equating to a 75% reduction in the total time needed to complete the Niagen IV.
Niagen IV Has Fewer Side Effects
Tolerability and side effects are also a significant component of getting an IV drip—if you are in pain and discomfort for four-plus hours, you might think twice about going back for another infusion.
This pilot study showed that people on the Niagen IV had significantly fewer side effects, with the most commonly reported sensation being tingling in the mouth and extremities. Others reported feelings of congestion or “runny nose,” as well as pressure in the head and ears.
Comparatively, people in the NAD+ IV group experienced anxiety, headaches, nausea, chest tightness, feeling woozy, hot flashes, stomach cramping, diarrhea, and sudden urges to have a bowel movement (which half of them had to do during the treatment session).
Niagen IV Elevates NAD+ Quickly
It’s all well and good if there are fewer side effects and less time in the chair—but does it actually work to elevate NAD+ levels in the body?
The answer is yes: people who received the Niagen IV had increased NAD+ by an average of 20% three hours after the infusion compared to their baseline levels. Blood levels of NAD+ peaked at 3 hours post-infusion, which remained elevated at 16% higher 24 hours later and 8.1% higher one week later.
Conversely, NAD+ IV did not elevate blood NAD+ until 24 hours later, with only a 2% average increase compared to baseline during this time. The NAD+ elevation reached its peak at 14 days post-infusion, with an average of 15.1% increase compared to baseline levels.
Niagen IV Does Not Promote Inflammation
Lastly, this pilot clinical study demonstrated that those receiving NAD+ IV experienced an elevated white blood cell count, which may indicate an inflammatory response. Alternately, those who received Niagen IV did not experience changes to their white blood cell count.
Extracellular NAD+ in the bloodstream (which occurs with IV administration) is interpreted by the body as the presence of damaged or dead cells. NAD+ IV administration may lead to the perception of trauma within the body, leading to an immune response, and potentially causing inflammation.
Conversely, Niagen IV safely increases intracellular NAD+ levels without triggering an inflammatory immune response.
A second study investigating Niagen injection which is currently underway, will hopefully provide more insight into this mechanism.
Where Can I Get Niagen IV?
If you’re sold on the benefits of Niagen IV and are jumping to try your first infusion, check out this Niagen+ Store Locator to find a clinic that offers it near you.
Some of the premium wellness clinics offering Niagen IV include Drip Hydration, Next Health, Pure Vitality, Restore Hyper Wellness, REVIV, Vessel Longevity + IV Bar, and more.
Key Takeaways
With one-quarter of the time needed for infusions, markedly better toleration with mild and expected side effects, and more rapid elevation of NAD+, Niagen IV is a superior NAD+ solution with highly bioavailable ingredients.
Since there is only one pilot study, larger studies are needed in different populations to verify these results.
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