Gwyneth Paltrow has tried it. So have Kendall Jenner and Hailey Bieber. And lest you think this product is just for women, know that influencers such as Andrew Huberman, Bryan Johnson and Gary Brecka have all endorsed its use, too.
Nicotinamide adenine dinucleotide, or N.A.D.+, has been among the hottest anti-aging supplements for several years. It’s sold by trendy supplement companies as well as retail giants like Walgreens and Walmart.
The molecule is critical for cellular metabolism and other fundamental biological processes, and scientists and supplement companies alike have asserted that its levels drop with age. The idea that taking an N.A.D.+ supplement could help with healthy aging took off, despite the fact that evidence showing a benefit in humans is slim.
And new research suggests that part of the thinking that helped to fuel the booming market for these supplements may be wrong. A study published this month in Nature Metabolism showed that blood levels of N.A.D.+ don’t actually fall with age. Another recent study, which was published as a preprint paper in February and has not yet been peer reviewed, had the same conclusion.
“It did sort of become dogma that N.A.D.+ levels decline with age universally and that that’s contributing to age-related functional declines,” said Matt Kaeberlein, an affiliate professor at the University of Washington who has studied N.A.D.+ but was not involved in the new research. “This should cause people to question how much of that is reality.”
In the latest study, the researchers analyzed blood samples from seven data sets, comprising more than 300 people total. Some of the data compared younger and older adults; other data came from frail individuals and elite athletes. The study did show that supplementation could increase N.A.D.+ levels, but found no evidence that they decline with age.
Riekelt Houtkooper, a professor of translational metabolism at Amsterdam University Medical Center who led the research, said his team initially conducted the study because they hoped to develop a biomarker test to help people decide whether they should take an N.A.D.+ supplement. He said they were “very disappointed with the results.”
Not everyone is discouraged by the findings. Joseph Baur, a professor of physiology at the University of Pennsylvania who was not involved in the research, said that while it was valuable to know what happens with N.A.D.+ blood levels, when it comes to the fundamental theory about N.A.D.+ and aging, “I don’t think it changes things in a major way.”
That’s because a handful of other studies in humans have found that N.A.D.+ levels do drop in certain tissues, including muscle and brain, Dr. Baur said. (Dr. Houtkooper published one such study in 2022.) Dr. Baur acknowledged, though, that this research is still “preliminary.”
According to Dr. Baur, a bigger question is whether the age-related decline that occurs in tissues is enough to cause impairment. Experts know that extremely low levels of N.A.D.+ results in serious health problems. But normal aging is linked to a much smaller drop — by some estimates about 30 percent. And a study published last year that was conducted in mice found that reducing N.A.D.+ levels in muscle by as much as 85 percent didn’t appear to affect their functioning.
Andrew Shao, the senior vice president of global regulatory and scientific affairs at Niagen Bioscience, which sells N.A.D.+ supplements, said that, for him, the new study “changes very little.” Like Dr. Baur, he thinks the research showing that N.A.D.+ declines in tissue is more important.
The theory that N.A.D.+ declines with age emerged roughly 20 years ago, Dr. Kaeberlein said, stemming from studies in yeast, worms and mice that showed that increasing levels of the molecule could improve longevity. But scientists weren’t able to study whether a decline occurs in humans until more recently because testing blood levels of N.A.D.+ is technically very tricky, he added.
However, the theory took off and “outpaced the actual data,” Dr. Kaeberlein said. “You get high-profile people writing review articles, talking at conferences, nowadays going on podcasts stating what I would say are early stage models as if they are proven fact.”
“And as soon as it got into the supplement space,” he continued, “the need for data kind of went out the window, and it all became a marketing exercise.”
Dr. Shao acknowledged that “the message to the consumers and messages spread by influencers out there has probably been oversimplified.” He added: “When we say N.A.D.+ levels are declining with age, we probably need to do some education” to clarify that what the evidence shows is that’s happening in tissue, not blood.
Dr. Houtkooper hasn’t given up on the therapeutic potential of N.A.D.+, though he said he didn’t think there was any reason for normal, healthy individuals to take it as a supplement. Rather than focusing on general aging, he is investigating whether it could be beneficial for people with rare genetic conditions that affect cellular metabolism.
“There’s a lot of possibility still in the field of N.A.D.+,” Dr. Houtkooper said. But, he added, “I think over the past 15 years or so it has been incredibly hyped.”
Dana G. Smith is a Times reporter covering personal health, particularly aging and brain health.
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