Here's What You Need to Know about IV NAD+ vs. NR

NAD+ is having a serious moment. You've probably heard of it from a biohacker, a wellness clinic (like Restore Hyper Wellness), or even your favorite podcast host. And while NAD+ is fascinating, and possibly one of the most intriguing areas in aging research (in my humble opinion), we should really level set on the state of the science compared to the outrageous number of claims that are being made about it.

I’m a supplement researcher. I’ve previously looked at Vitamin D and CBD for performance and healthy aging. Over the past year I’ve also been studying intravenous (IV) NAD+ and nicotinamide riboside (NR) in a controlled setting at Restore Labs (and just presented the first human comparison data to a global panel of scientists). So, I want to walk you through the science: what we do know, what we don’t know, and what you should be thinking about if you’re considering a supplement or infusion.

Here’s what to know about NAD+

Let’s take a trip back in time to ninth grade biology. Nicotinamide adenine dinucleotide (NAD⁺) is one of the most fundamental molecules for life. It’s a coenzyme in metabolism and is essential for turning food into energy (ATP) in your mitochondria (remember the Krebs Cycle and Electron Transport Chain?). It also plays a central role in DNA repair, gene expression, and immune function.

NAD+ levels decline as we age.

As we age, our NAD⁺ levels naturally decline, and this drop has been linked to everything from fatigue and poor sleep to neurodegeneration, metabolic dysfunction, and even cancer. Understandably, there’s growing interest in ways to restore NAD⁺ levels, particularly through supplementation. But as more products—especially intravenous (IV) infusions—flood the wellness market, there’s a lot of confusion (and a fair amount of hype) about what actually works.

NAD lives inside the cell.

Let’s start with the molecules themselves. NAD⁺ lives inside the cell and is made from precursors—nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nicotinic acid (NA)—which are all part of the vitamin B3 (niacin) family. Your body can make NAD⁺ from these precursors through different biochemical pathways.

Is it better to take NAD+ and NR orally or through an IV?

Oral NR and NMN are the most heavily studied in the context of aging and mitochondrial health, with NR having the most human data to date. NA, the form of B3 found in many multivitamins, can also be used to make NAD⁺. These molecules also occur naturally in small amounts in foods like milk, fish, mushrooms, and whole grains. However, the quantities in food are generally not enough to significantly raise NAD⁺ levels the way targeted supplementation can—though diet absolutely plays a role in supporting the overall NAD⁺ pool.

It’s likely that NAD⁺ itself can’t be taken orally and absorbed intact; the molecule is too large and unstable to survive the gut and cross into cells. In fact, there isn’t a transporter for NAD+ into the cells themselves. NAD+ needs to be converted into NR or NMN before it can be absorbed from the bloodstream, which is incredibly inefficient. So most oral NAD⁺ supplements on the market are unlikely to raise your NAD⁺ levels significantly. Instead, your body needs to make NAD⁺ inside the cell from the smaller precursors that can easily be transported.

Oral NR, in particular, has the most robust data in humans. We know that taking 300–1,000 mg daily for just a week can significantly raise NAD⁺ levels in blood and tissues. It’s well absorbed, peaks in about eight hours, and is safe and well tolerated. NMN is also promising, though data in humans is still emerging. Importantly, both NR and NMN are absorbed through specific transporters in your gut and cells, meaning they can get to where they need to go to be converted into NAD⁺. NAD⁺ itself, however, cannot do that.

This brings us to IV NAD⁺, which has seen a surge in popularity at wellness and longevity clinics. On the surface, this seems like a clever workaround: bypass the gut and get NAD⁺ straight into your bloodstream. But there’s a catch. NAD⁺ in the extracellular space acts a bit like a distress signal in the body (remember, NAD+ is supposed to be inside the cell, not in the blood!). In fact, when cells are injured, they release NAD⁺ as a way to alert the immune system. So when we flood the bloodstream with supraphysiologic concentrations of NAD⁺ through an IV, it actually triggers a mild pro-inflammatory response. Clinically, this is often felt as nausea, flushing, stomach cramps, chest pain and even instantaneous diarrhea. This is why IV NAD⁺ infusions are usually done slowly over two to six hours to avoid these side effects. It’s not necessarily dangerous, but it can be uncomfortable.

The literature is lacking on NAD+ and NR.

This is the part that really gets me going: there is only ONE study on IV NAD+ in the literature. And this study was a safety study to understand the kinetics of NAD+ infusion (i.e. how much gets into the bloodstream, how much gets absorbed by the cell, and how much gets peed out). As of right now, there are no published data on outcomes of NAD+ infusion.

And this is the reason we launched our Restore Labs study. Not only is there only one IV NAD+ study, but no one has ever directly compared IV NAD⁺ to IV NR in humans. Ours is the first trial to look at not just safety and tolerability, but also how these infusions affect metabolic markers, body composition, and potential biomarkers of aging. At the time of this writing, I’m currently analyzing the data and writing the manuscript, so stay tuned on outcomes! My hope is that they will be published toward the end of the year.

Given the lack of data, what’s the bottom line for you, the wellness-minded individual trying to decide between these products?

If you’re generally healthy and interested in supporting cellular energy, metabolism, or healthy aging, oral NR has the best data. Although, remember, most of the work is done in older adults and often those with chronic disease.

If you’re considering IV infusions, NAD⁺ and its precursors may still hold promise, especially for individuals dealing with fatigue, recovery from illness, or cognitive decline. IV NR may eventually prove to be a more efficient and comfortable alternative, but the data are just beginning to emerge.

Overall, I’m intrigued by NAD+ and enhancing intracellular concentrations, especially as we age. Honestly, to me, it seems to be on a similar trajectory to the creatine data we are seeing emerge (I wrote about that here). I believe we are entering an exciting chapter in the science of aging and that NAD⁺ and its precursors will be front and center in this story. BUT, we have to respect the complexity of human physiology and the pace of scientific discovery. The hype is REAL and we are seriously lacking in human data.

For now, the major piece of advice I can give is that oral NAD+ is probably a total waste of your money (although I’m willing to be proven wrong as formulations emerge). I would suggest either an NR or NMN precursor, either oral or IV. And, as always, as we continue to uncover what works and what doesn’t, I’m grounded in data and focused on real-world health, and I’ll be here to help you sort fact from fiction.