More on the Supposed Youth Pill

A new study helps the case for a supplement known as NR, but it’s not yet a slam dunk.

There hasn’t been much evidence that taking a form of vitamin B known as NR, or nicotinamide riboside, makes you healthier. NR boosts the levels of a molecule called NAD, which plays a key role in cellular health, but it’s been unclear exactly what higher levels of NAD will do for you — and not just for a mouse.

Even so, NR is popular, and sales have been growing. People shell out $40 to $60 a month for supplies of NR pills that go by such brand names as Tru Niagen and Basis. Two companies that have both a rich scientific pedigree and the backing of billionaires, ChromaDex and Elysium Health, have been brawling in court over rights to sell the supposed wonder supplement. Both companies imply it’s an anti-aging pill; ChromaDex’s president calls NR a “once-in-two-lifetimes ingredient.”

That might prove to be true someday, but research published Thursday doesn’t make NR look revolutionary yet.

The study, published in Nature Communications, found that NR is safe to take in high doses for six weeks. It also helped reduce systolic blood pressure — the higher of the two numbers in a reading — by 10 points among participants who had somewhat elevated levels. It did not lower blood pressure for people who already had normal readings.

But the study was small — only 24 people completed it—in addition to being brief. So the finding did not reach statistical significance.

Nonetheless, both ChromaDex’s chief scientific officer and the lead scientist on the study say the new research confirms the supplement’s promise. “It’s very exciting,” says Charles Brenner, the company’s chief scientific adviser, who conducted early research on NR but was not directly involved in this study.

The 24 study participants took 1,000 milligrams a day of Niagen, four times what’s recommended on the bottle. “It’s like taking a bottle per week rather than per month,” Brenner says. But he adds that many customers are already taking more than what’s recommended. “Almost certainly, therapeutic doses will be higher than 250 milligrams per day,” he said in a follow-up email.

Although sometimes in medicine less is more, the dose used in the study was based on amounts shown most effective in lab mice, says Christopher Martens, who led the research at the University of Colorado.

Stress test

In the body, NR is converted into nicotinamide adenine dinucleotide (NAD), which Brenner describes as “the central regulator of metabolism.”

NAD levels fall naturally with age, and many other factors can knock your NAD levels out of whack, including heart failure, brain diseases, alcohol, and even changing time zones, says Brenner, who is also the head of biochemistry and co-director of the Obesity Research and Education Initiative at the University of Iowa.

In his lab research, Brenner has found that NR reverses those negative effects in mice. “If you can give the animal that’s under this metabolic stress nicotinamide riboside, it’s going to allow the stressed tissues to restore their NAD level and improve their function,” he says.

The new study was the third published analysis of NR in people. Together the studies show that the supplement increases levels of NAD in the body. The link that’s yet to be confirmed is whether that extra NAD does anything good, and for whom.

“It’s pointing in the right direction, but here it’s not significant so we can’t draw any conclusions as good scientists,” says David Sinclair, a Harvard Medical School geneticist who works on similar research and has ties to Elysium.

“We need to conduct much larger-scale studies before I can recommend it to the masses.”

Sinclair, who also co-directs the Paul F. Glenn Center for the Biology of Aging at Harvard, published his own research last week in the journal Cell, showing that he could reverse the aging of blood vessels in mice. The loss of a protein called sirtuin 1, which can be triggered by the age-related decline of NAD, damages the vessels, the study found. Sinclair and his colleagues used an NAD precursor called nicotinamide mononucleotide, or NMN, to spur the reversal. (One of Martens’ co-authors has also studied supplementation with NMN and found similar benefits in mice.)

Martens, now an assistant professor at the University of Delaware, says caloric restriction, which is known to extend life span in animals, works the same way — boosting NAD levels to improve cellular health and extend life. But caloric restriction is also known to trigger bone loss and reduce immune function. Martens, Brenner, and Sinclair all say that boosting NAD seems to have fewer side effects than restricting calories.

“Our study provides very promising evidence that NR may have some physiological benefits, but I don’t think that by themselves our data are the definitive measure of safety by any means,” says Martens. He received supplies of Niagen and some funding from ChromaDex for the recent study, but he developed the research plan and protocol independent of the company.

He says the suggestion from his study that Niagen might reduce blood pressure and blood vessel stiffness should be used to direct future research, rather than as evidence of Niagen’s effectiveness. There are 10 active clinical trials involving nicotinamide riboside, looking at whether the supplement affects brain function, muscle metabolism, kidney injuries, metabolic health, the immune system, and the heart.

“We need to conduct much larger-scale studies in hundreds of people to confirm its safety,” Martens says, “before I can recommend it to the masses.”

This story was updated on March 31, 2018, to correct that Brenner is ChromaDex’s chief scientific adviser, not chief scientific officer, and to clarify the description of the study’s findings in people with normal blood pressure.