Illustration by Andrea Chronopoulos

The Life Extension Death Match

Nobel laureates and billionaires fight to sell you what they hope is a longevity pill.

“Live healthier for longer through extraordinary science.”

That’s the promise offered by a supplement company called Elysium Health, whose advertisements commonly pop up in social media feeds and in science-related publications. Its founder is an MIT professor and its advisory board includes seven Nobel Prize winners. Do an Internet search for the key ingredients in Elysium’s sole product, Basis, and you’ll come up with reams of scientific research. Customers shell out $40 to $60 a month for a bottle.

But there’s a lot here that isn’t what it seems.

First, the science is still in mice. There’s no evidence that Basis has helped a person live healthier for longer. At least not yet.

Second, Elysium doesn’t make what it sells. Like many supplement marketers, Elysium gets its product from a supplier.

Elysium used to buy its ingredients from an 18-year-old natural products company called ChromaDex. But earlier this year, ChromaDex began to focus on reaching consumers itself. It sold off part of its business and accepted cash infusions totaling nearly $50 million to market its own version of one of the two active ingredients in Basis. The ingredient is nicotinamide riboside, which ChromaDex sells to suppliers as Niagen and to consumers as Tru Niagen, at $45 a bottle or $33.75 a month for an annual subscription. The business opportunity is huge, says ChromaDex president Robert Fried, who calls nicotinamide riboside, or NR, a “once-in-two-lifetimes ingredient.”

Then this fall, ChromaDex sued Elysium for $200 million, essentially accusing its former customer of trying to reap the benefit of its years of work.

Now both companies are fighting to be the dominant provider of NR — and betting that the science behind it will continue to get more compelling.

To your corners

Nearly three years ago, when Elysium began selling Basis, few in the general public had heard of NR, a form of vitamin B3 that is naturally found in milk.

But the scientific world was buzzing about the life-extending potential of a molecule called NAD, which is involved in basic cellular activities like energy production and DNA repair. Harvard anti-aging researcher David Sinclair had shown in mice that reversing the natural decline in NAD that comes with aging can improve metabolism and overall health, and essentially slow the hands of time. Other research showed that NR could boost the levels of NAD in the body.

ChromaDex’s CEO says he had been following work on NAD since 2006, and beginning in 2011, licensed patents from Dartmouth, Cornell, and Washington universities, covering the manufacturing, composition, and use of NR. Around the time Sinclair’s paper was published, ChromaDex developed a reliable way of making NR and began selling it to several supplement providers.

Elysium launched the following year and started selling Basis subscriptions online in early 2015. In Basis, it combined NR with pterostilbene, a compound from grapes and berries that resembles resveratrol, the red wine component that has been shown to turn on genes believed to be involved with longevity.

The company, co-founded by Leonard Guarente, who runs a center on the biology of aging at MIT, promised to upend the supplement industry. Instead of selling questionable products sourced from even-more-questionable suppliers, Guarente pledged that Elysium’s ingredients would be well vetted and pure. The company would plow a large portion of its profits into top-notch scientific research, the kind rarely seen in the world of nutritional supplements.

His vision for a new type of supplement company intrigued prominent scientists, many of whom were frustrated that companies could legally make essentially empty promises, encouraging people to spend billions on products that had no scientific support. Elysium attracted seven Nobel laureates to its scientific advisory board along with over a dozen more researchers, although most of them have expertise in areas other than the biology of aging.

Elysium is a private company, so it’s not clear how well Basis has been selling. But it was enough for Elysium to put in an order in June 2016 that was three times bigger than normal, eventually agreeing to pay nearly $3 million for it, according to ChromaDex’s lawsuit against Elysium. ChromaDex also agreed to stop selling the combination of NR and pterostilbene to anyone other than Elysium.

Then, both sides say, the relationship soured. Two top ChromaDex executives, the vice president of sales and director of scientific affairs, both quit and went to work for Elysium. And Elysium refused to pay for the ingredients it ordered that June, accusing ChromaDex of violating the terms of their contract.

In the first half of this year, ChromaDex stopped supplying Elysium with ingredients. Elysium has since found another supplier, which it has not disclosed.

But the battle over NR rages on. In August ChromaDex filed what’s known as a citizen’s petition with the Food and Drug Administration, claiming it tested Basis made by Elysium’s new supplier and found that it had been “contaminated with toluene.” The petition, signed by ChromaDex’s CEO, called for Basis to be removed from the market until its safety can be checked.

Elysium responded that ChromaDex was abusing the citizen’s petition process, pointing out to the FDA that toluene is commonly used in pharmaceutical processing—including in ChromaDex’s own manufacturing specifications—and that ChromaDex allegedly found it at levels far below what would be dangerous for human health. “ChromaDex’s sole purpose for submitting the petition to FDA was not to raise any safety issue, which does not exist, but to harm Elysium, with which it is engaged in litigation and against whom it is preparing to compete,” the company said in a statement to Elysium is suing ChromaDex over the petition.

And overall, Elysium says, its new version of NR is better than ever, thanks to a new supply chain that “has allowed us to take an exceptional product and make it even purer,” the company’s statement said.

The two companies have been ordered into mediation, but the parties haven’t met yet, and it’s too soon to know whether that will resolve the battle.

(Courtesy of ChromaDex and Elysium Health)

The big prize

Clearly, a lot of people think there’s money to be made on nicotinamide riboside.

ChromaDex in April announced a $25 million investment led by Hong Kong billionaire La Ka-Shing, who owns a chain of health and beauty stores, mainly in China. The company recently raised another $23 million, including $7 million from ICONIQ Capital, a California investment group that has invested for Mark Zuckerberg, Sheryl Sandberg, and other wealthy people in Silicon Valley. Pharmaceutical entrepreneur Phillip Frost owns a chunk of the company as well.

They’ve been rewarded by ChromaDex’s sales of Tru Niagen to consumers. In the last financial quarter, revenue jumped 55 percent from the year before. The stock price has tripled since April.

Elysium won’t release financial details but says it has seen strong sales growth as well. The company has raised a total of about $26 million in two fundraising series, the last of which was in 2016. Its investors include Gerald Chan, of Morningside Partners, whose family gave a naming donation to the Harvard School of Public Health in 2014 in honor of their father, T.H. Chan.

These big bets on NR seem premature to Jeffrey Flier, the former dean of Harvard Medical School and an expert in cellular metabolism. There is no scientific evidence that NR does what both companies suggest—that it provides more energy, boosts cellular health, and extends life, he said in a recent interview in his office, high above the medical school’s quad.

ChromaDex’s president says NR could be a “once-in-two-lifetimes ingredient.”

Flier said a high-profile Boston businessman whom he declined to name came to see him after he wrote a Boston Globe op-ed in March criticizing Elysium for using prominent researchers and the veneer of science to promote its product. “I don’t have anything against Elysium,” Flier said he told the man. “It’s just that I like good science.” The man kept pushing, Flier said, insisting that Basis had made him feel much better, and leaving a bottle behind for Flier to sample.

Flier, who later threw out the pills, said he told the man that his own experience and the testimonials of others were proof of nothing. Evidence can only be found in the type of large-scale human research that hasn’t yet been done on NR.

To win approval to sell a drug, a company must show that a product safely and effectively fights disease. It’s virtually impossible to prove that a product extends the human lifespan, because such a study would take decades and be prohibitively expensive. Selling a nutritional supplement is easier and cheaper. All a company has to do is avoid making specific claims — like life extension — that it can’t prove. That’s why bottles of Basis offer “cellular health and optimization” rather than longevity. The longevity benefits are instead implied by Elysium’s corporate “vision,” for life that is “healthier and longer through extraordinary science.”

What researchers have shown so far is that taking NR increases NAD in the blood of both mice and humans. In a new placebo-controlled study of 120 healthy older adults, funded by Elysium, people who took the normal dose of Basis for a month saw a 40 percent jump in their NAD blood levels. Those who took a double dose saw a 90 percent boost. The study was published this fall but was conducted in 2016, while ChromaDex was still Elysium’s supplier.

There’s also good evidence that NAD has the potential to affect aging and its related diseases — in mice.

Charles Brenner, ChromaDex’s new chief scientific adviser and a long-time leader in NAD research, said the molecule is a central regulator of metabolism in every type of tissue. “NAD underlies everything that is important,” he told me after giving a talk last month at Harvard. NAD helps convert fuel into energy, power muscles, circulate blood, and repair DNA.

Brenner, now at the University of Iowa, has spent more than a dozen years tracking the pathways the body uses to create NAD — and he discovered that NR offers the most efficient route. “We found a pathway that stressed cells really depend on,” he said. “The more metabolically stressed an animal is, the more it benefits from NR. We think that in the coming months and years, data will emerge from human clinical testing that will strongly justify particular human populations taking it.”

“This is the type of thing that might yield some bad news that will hurt all of us.”

Rudy Tanzi, an Alzheimer’s researcher at Harvard, said he joined ChromaDex’s scientific advisory board this year because he believes that a shortfall in cellular energy plays a key role in Alzheimer’s — and that boosting NAD might jumpstart cellular energy. He’s tried NR on mice bred to have an Alzheimer’s-like condition and saw a benefit. Another researcher reported similar results last week.

“I don’t want to say anybody should take Niagen to prevent Alzheimer’s, but my goal is to investigate: can Niagen help in Alzheimer’s?” Tanzi said. He takes the supplement himself most days, along with his multi-vitamins, even though he says he’s not sure if it’s doing him any good.

The reason Tanzi can’t be sure is that there still isn’t any research showing that the higher levels of NAD in the human body have the benefits that have been seen in mice.

It’s extremely common for promising results in mice to fail to carry over to people. That’s happened countless times in research on aging, cancer, and particularly Alzheimer’s. And even though research might someday show a benefit for people, it’s not clear how much of an NAD boost would be required. The 90 percent increase that apparently comes from a double dose of Basis might not be enough. Or it could be too much.

NAD expert Eric Verdin, who’s not connected to either company but has collaborated with Brenner on research and is a friend of Guarente’s, said he’s also enthusiastic about what he considers early research on NAD. “The loss of NAD that occurs during aging, I predict will end up being a major pathway in our fight to delay aging and the diseases associated with it. The data is really there,” said Verdin, president of the Buck Institute for Research on Aging in Novato, California.

But what’s much less certain, he said, is whether a supplement can correct this age-related decline. “That’s completely unclear, even though a lot of people are buying these supplements. There’s no evidence they are correcting the problem in older people,” he said.

Verdin said he is also worried that boosting NAD levels might in rare cases spur cancer — and that if something does go wrong with the supplement, it could tarnish his whole area of scientific research. “I have some concern about the field of aging jumping ahead of itself and embracing unproven treatments,” he said. “As a physician and scientist in the field of aging, I’m a little worried this is the type of thing that might yield some bad news that will hurt all of us.”

Overall, he added, NAD supplementation has “become a story about money more than about science and medicine.”

This story was updated on December 15, 2017, to clarify that NR is a form of vitamin B3 and that ChromaDex specifies how NR should be manufactured but does not necessarily manufacture it itself.

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