Scientists carrying out research on the compound nicotinamide adenine dinucleotide — or simply NAD+ — are running into an unusual problem these days: A little too much publicity around their subject of study.
Enthusiasm for NAD+ boosting supplements, injectables and IV infusions has overtaken the wellness and longevity world, attracting A-list celebrities and biohackers — and sparking all manner of claims about its ability to boost energy, combat aging and enhance recovery.
"Initially it was exciting," says Christopher Martens, director of the Delaware Center for Cognitive Aging Research who is leading research in this field. "I think now the cart may be well ahead of the horse."
In fact, the market for NAD+ products is booming. This optimism has roots in legitimate science. But does the evidence really support dishing out hundreds or thousands of dollars to pump your body full of this molecule?
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The claim
NAD+ is often billed as a kind of cure-all — a potent substance that can reverse aging, deliver flawless skin and produce "clean energy." Others tout its benefits for sleep, mental clarity and recovery.
Wellness clinics that market NAD+ therapies are apt to describe it as a "fountain of youth" that works on a cellular level to enliven mitochondria — the energy-producing factories of the cell — and repair our damaged DNA.
The evidence
NAD+ is a crucial molecule that has many functions in the body. It's deeply involved in how our mitochondria produce energy and helps our cells survive and stay healthy, including by repairing our DNA.
The field of longevity research has homed in on NAD+ as a potential therapy because of evidence that our levels decline as we get older, which may also contribute to the risks of age-related diseases, says Dr. Shalender Bhasin, who directs the Boston Pepper Aging Research Center at Brigham and Women's Hospital.
"As a hypothesis, as an idea, it's very attractive," says Bhasin. "But we are still in the early stages of human studies and the health benefits of augmenting NAD+ are yet to be established in large human studies."
Much of the excitement around NAD+ stems from studies done in animal models. This preclinical work shows improvements in mitochondrial health, increased strength and exercise performance, decreased metabolic abnormalities and inflammation, and other benefits.
"In rodents and mice — not in humans — NAD+ is miraculous," says Dr. Samuel Klein, director of the Center for Human Nutrition at Washington University School of Medicine in St. Louis.
Now, there isn't just one source of NAD+. Our cells are constantly using and recycling it, and our body is also making more of it from precursors in our diet, namely vitamin B3 and the amino acid tryptophan. The disease pellagra — which was an epidemic in the early 1900s — stems from a diet deficient in vitamin B3, which subsequently leads to dangerously low levels of NAD+.
The trials that have been done in humans have mostly studied these precursors, using oral supplements containing NR and NMN — short for nicotinamide riboside and nicotinamide mononucleotide. Though mostly small, these studies have yielded some promising data for specific-populations — for example in women with prediabetes, newly-diagnosed patients with Parkinson's disease, or those with peripheral artery disease.
Other trials — including ones that have focused on metabolic health — have not turned up the same impressive findings seen in animals, though.
"The data in humans are pretty iffy right now that it actually has significant benefits," says Klein.
Martens and others have shown that you can meaningfully and safely boost NAD+ levels in the blood after a few weeks of taking these supplements, but he says all of this data remain preliminary, until it's replicated in large human trials.
"It's not uncommon for things to work really well in mice and then not translate to humans," he says.
The marketplace
The landscape of products can be dizzying — and much of it doesn't reflect what's actually been studied in clinical trials.
For example, NAD+ oral supplements are available, even though researchers say the molecule gets degraded in the gut and isn't absorbed well. That's why the scientists are studying NR and NMN precursor pills instead.
"There's an influencer culture that's really promoting the use of NAD+ that is now interfering, a little bit, with our ability to do rigorous science," Marten says.
You can spend anywhere from $30 to more than $80 on pills.
The price tag can rise to several hundred dollars if you opt for the NAD+ shots, which are being marketed widely (These haven't been studied at all).
In addition, many wellness clinics now offer IV infusions to boost your NAD+ levels, which can run anywhere from $200 to upwards of $1,000 for one drip session. Here, too, there's almost no published data.
Rachel Pojednic works at the intersection of academia and the wellness marketplace, serving as the chief science officer for Restore Hyper Wellness — a national chain offering NAD+ infusions — and as a biochemist on the faculty at Stanford University.
She agrees with other researchers that "we are in the early days of clinical trials," but argues NAD+ should not be dismissed as just another example of the "wild wild west of the longevity wellness space."
"When you look at the wide breadth of data in the NAD+ sciences, it's vast and being done by some of the best scientists, truly in the world," she says. "Real people are reporting that it seems to be helping them. And we do need to think about how we follow that kind of signal. This is not going to go away."
Pojednic, whose lab at Restore is doing research in this area, says preliminary findings from a pilot study in humans suggest that NAD+ infusions are actually "very inefficient" at increasing levels in the cell.
The problem, she explains, is that NAD+ has "no easy door" to enter the cell from the bloodstream. In contrast, she says IV infusions done with a precursor — also offered by her company — are much more effective.
The risks
Bahsin and other researchers say NAD+ precursor supplements like NR and NMN appear to be safe, based on what's seen in the clinical trials.
"I think all the studies are showing remarkable safety," he says.
Some mouse models have raised concerns that elevating NAD+ could possibly encourage tumor growth, though Martens says that has not been seen widely in animal research or at all in human studies.
Until there are multi-year trials, this and other long-term risks won't be clear.
Independent testing of supplements on the market suggests there's considerable variability in the quality and what's on the label doesn't necessarily match what's in the product.
Klein says he's personally not convinced these supplements — even if the labels are accurate — have been studied adequately enough in humans to show " the benefits outweigh any harm."
As for the IV infusions, Pojednic points to data from her lab — consisting of 14 people in total — and another, similarly small study that they appears to be "quite safe," though NAD+ infusions did elicit a quite unpleasant experience, with "moderate to severe abdominal cramping, diarrhea, nausea, vomiting," according to her study.
Bottom line
There's good reason that leading researchers and major institutions are undertaking major studies on the potential for NAD+ to improve longevity and combat age-related disease. But for now, the NAD+ products on the market aren't proven to do the average person much good.
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