Alternatives to Resveratrol: The Anti-Aging NAD Trend

Ever wonder why children are bursting with boundless energy all day long?  The answer is: young Mitochondria.

Mitochondria fuel our cells, providing them with energy originated from bacteria that colonized other cells about 2 billion years, they become fickle as we age. A prominent hypothesis regarding aging states that decaying of Mitochondria is a major expediter of aging. While it’s not clear why our Mitochondria diminish as we age, data implies that it can cause everything from heart failure to neurodegeneration, in addition to a noticeable decrease in energy.

Current research states it may be possible to reverse mitochondrial decay with dietary supplements that boost cellular levels of a molecule called NAD (Nicotinamide Adenine Dinucleotide). But caution is advised: While there’s promising test-tube data and animal research about NAD boosters, no human clinical trial results have been published yet.

NAD is a pillar of energy metabolism, among other roles, and its dwindling level with age has been linked to mitochondrial deterioration. Supplements containing Nicotinamide Riboside, or NR, a precursor to NAD that’s found in trace amounts in milk, could help improve NAD levels. In support of that idea, half a dozen Nobel Laureates and other renowned scientists are collaborating with two small companies offering NR supplements.

The NAD trend gained popularity at end of 2013 with a high-profile paper by Harvard’s David Sinclair and colleagues. Remember, Sinclair achieved fame in the mid-2000s for research on yeast and mice that implied the red wine ingredient Resveratrol mimics anti-aging effects of calorie restriction. This time his lab made headlines by reporting that the Mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (Nicotinamide Mononucleotide), a molecule that naturally occurs in cells and, like NR, increases levels of NAD.

Of note: Muscle strength did not increase in the NMN-treated mice—the researchers hypothesized that one week of treatment wasn’t enough to accomplish that in spite of signs that their age-related mitochondrial deterioration was reversed.

NMN isn’t available as a consumer product. But Sinclair’s report generated enthusiasm about NR, which was already on the market as a supplement called Niagen. Niagen’s manufacturer, ChromaDex, a publicly traded Irvine, Calif., company, sells it to various retailers, which market it under their own brand names. In the wake of Sinclair’s paper, Niagen was praised by the media as a possible chartbuster.

In early February, Elysium Health, a startup cofounded by Sinclair’s former mentor, MIT Biologist Lenny Guarente, joined the NAD game by debuting another supplement with NR. Christened Basis, it’s only offered online by the company. Elysium is taking precautions with regards to scientific credibility. Its website boasts a dream team of advising scientists, including five Nobel Laureates and other big names such as the Mayo Clinic’s Jim Kirkland, a leader in Geroscience, and Biotech pioneer Lee Hood. Currently, there isn’t a startup with more stars on its roster.

Shortly thereafter, ChromaDex reaffirmed its first-comer status in the NAD game by revealing that it had conducted a clinical trial validating that “a single dose of NR resulted in statistically significant increases” in NAD in humans—the first evidence that supplements could truly boost NAD levels in human beings. Details of the study won’t be out until it’s reported in a peer-reviewed journal, the company said. (ChromaDex also brandishes Nobel credentials: Roger Kornberg, a Stanford professor who won the Chemistry prize in 2006, chairs its scientific advisory board. He’s the son of Nobel Laureate Arthur Kornberg, who, ChromaDex proudly notes, was among the first scientists to study NR some 60 years ago.)

The NAD results merge into a related story about enzymes called Sirtuins, which Guarente, Sinclair and other researchers have implicated as key players in conferring the longevity and health benefits of calorie restriction. Resveratrol, the wine ingredient, is thought to stimulate one of the Sirtuins, SIRT1, which appears to help protect mice on high doses of Resveratrol from the negative effects of high-fat diets. An abundance of other health benefits have been attributed to SIRT1 activation in hundreds of studies, including several small human trials.

This is the NAD correlation: In 2000, Guarente’s lab reported that NAD fuels the activity of Sirtuins, including SIRT1—the more NAD there is in cells, the more SIRT1 does beneficial things. One of those things is to induce formation of new Mitochondria. NAD can also activate another Sirtuin, SIRT3, which is believed to keep Mitochondria functioning properly.

The Sinclair group’s NAD paper garnered attention in part because it demonstrated a unique way that NAD and Sirtuins work together. The researchers discovered that cells’ nuclei send signals to Mitochondria that are needed to maintain their normal operation. SIRT1 helps insure the signals get through. When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

NAD boosters might work collaboratively with supplements like Resveratrol to help revitalize Mitochondria and stave off diseases of aging. Elysium is banking on this potential synergy—its NR-containing supplement includes a Resveratrol-like substance called Pterostilbene (pronounced tero-STILL-bean), which is found in blueberries and grapes.

Why choose Pterostilbene in lieu of Resveratrol?

While Resveratrol has dominated the anti-aging spotlight over the past decade, nameless researchers in places like Oxford, Miss., have quietly shown that Pterostilbene is a kind of extra-robust variant of Resveratrol. The Pterostilbene molecule is virtually identical to Resveratrol’s, with the exception of a few variances that make it more “bioavailable” (animal studies indicate that about four times as much ingested Pterostilbene gets into the bloodstream as Resveratrol). Test-tube and rodent studies also suggest that Pterostilbene is more powerful than Resveratrol when it comes to enhancing brain function, staving off various kinds of cancer and preventing heart disease.

Elysium isn’t the only Pterostilbene merchant. As a matter of fact, ChromaDex also provides Pterostilbene for supplements separately from Niagen.

Prior to Sinclair’s paper, researchers had shown in 2012 that when given doses of NR, mice on high-fat diets gained 60% less weight than they did on the same diets without NR. Furthermore, none of the mice on NR exhibited signs of diabetes, and their energy levels improved. The scientists reportedly characterized NR’s effects on metabolism as “nothing short of astonishing.”

The dearth of human data is cause for hesitation.  Despite Nobel Laureates involvement, it’s advisable to wait until more is known before rushing out to purchase some NR.  There’s a good chance more data will be revealed, based on the mounting excitement about NAD.