Do Longevity Supplements Work and Are They Safe?

Aches and pains. A growing waistline. Diminishing eyesight, hearing loss, memory lapses. These are the woes of growing older for some people, once considered inevitable. But recent, exciting discoveries in the fast-growing field of longevity science have some doctors and researchers pronouncing that these "symptoms" of aging may one day be treatable with pharmaceuticals, gene therapies or other yet-to-be-discovered medical technologies.

Credit: Adobe

Many people haven't been content to wait, though. Dozens of commercial producers are selling hundreds of so-called longevity supplements right now, and sales data suggest an awful lot of people are trying them. But do they work? Are they even safe?

To find out, we scoured the latest research and interviewed two top scientists in the field. What we learned suggests that you may want to hold off on ordering a supply, or at least do your research very carefully.  

There is a solid handful of compounds that look very promising in the scientific quest to slow the aging process. One of the most exciting is nicotinamide adenine dinucleotide, or NAD, which has been shown to extend both the lifespans and youthful function of yeast and animals in clinical trials. Human trials are ongoing, with only a handful published to date. 

NAD (also often written as NAD+) is a substance found in every cell in your body, which controls all kinds of metabolic processes, including the regulation of sirtuins, the so-called "longevity genes." As you age, your NAD+ levels decline, and scientists think it is perhaps this decline that leads to all sorts of other age-related declines.

The working theory, then, is that if we can boost our NAD+ levels as we age, we can slow our decline tremendously. Lab studies on yeast and rodents lend strong support to that theory. The most recent studies have primarily involved the administration of either nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), which is then converted into NAD in the body.

To learn more about NAD, Next Avenue talked to Dr. Shin-Ichiro Imai, professor of developmental biology at the Washington University School of Medicine in St. Louis. Along with Leonard Guarente, Imai discovered the link between NAD and sirtuin control in 1999. He's been studying the molecule ever since. 

"There have been ten human clinical trials using NR, most at very high dose, with no safety issues," Imai said. Most of those trials, however, lasted for a duration of weeks or months at most.

Is it safe to take NAD-boosting supplements continuously, for years? 

"NMN and NR have already been available in Japan and the U.S. since 2015, and some people have been taking it since then," Imai noted. "Anecdotally, I haven't heard of any side effects from the taking of these supplements."      

Some trials, however, have recorded mild side effects including headaches, nausea, diarrhea and skin flushing.

More troubling, however, is the conclusion of a 2019 study that showed a possible link between elevated levels of NAD and tumor growth in isolated cells and animals. Rugang Zhang, deputy director at the nonprofit Wistar Institute Cancer Center in Philadelphia, was the lead researcher on that study. The study, published in the UK journal "Nature Cell Biology," did not find that NAD causes cancer, rather that elevated levels appeared to accelerate oncogenesis (tumor formation) already in motion.

"We don't want to oversell the results of our study," Zhang said. "Lots of studies in the literature have clearly demonstrated that as normal cells age, there is lower NAD. So, supplementing NAD could be beneficial. It's possible that NAD boosters could help people live longer and healthier. We're not saying that if people take NAD boosters they will get cancer. This was a very early study on mouse models, and more study is needed." 

He suggests a course of action grounded in a deep preponderance of evidence: "At the end of the day, we just need more knowledge, through more research. We need the scientific community to come to a consensus. The risk to potential benefit remains to be seen."

Mucking up the risk/benefit ratio further is the fact that supplements are only very lightly regulated by the U.S. Food and Drug Administration, with the testing, evaluation and labeling of such products left up to manufacturers. This presents another dilemma for those considering longevity supplements: there's no sure way of knowing exactly what you're getting.

The results of the few published human clinical trials to date unequivocally show that taking NR boosts levels of NAD in the body. But apparently, more NAD doesn't translate to more youthful function.

"Unfortunately, those studies have not yet shown any significant efficacy," Imai said.

And that's when the substance administered is of lab-grade purity. So what about the typical supplements available online?      

"There are so many products out there," Imai lamented, "particularly for NMN, but I'm concerned about the quality."

Indeed, a 2020 meta-analysis of NAD trials surmised: "it seems likely that side effects linked to interventions that target NAD metabolism more likely arise from impurities rather than the supplements themselves, since this industry generally operates without rigorous control of quality and standardization."

Imai's lab has evaluated a number of commercially available NAD-boosting supplements, but found only two of lab-grade purity. Imai wouldn't disclose the names of the products (both Japanese-made), as he doesn't endorse supplements. But he did note that "they are extremely expensive."

Finally, we asked someone who'd taken an NAD-booster to share her experience. Kim Oberdorfer, an air traffic controller in Oakland, Calif., wasn't impressed.

"I took [a popular NR supplement] for about two months and it just gave me these dull headaches. I was having hot flashes last February, and when I told my sister — I'm forty-seven, she's fifty-three — about how horrified I was to be having them so young, she goes, 'Are you sure it's not just a reaction to an NAD supplement?" said Oberdorfer. "At the time I wasn't really working out much, but my sleep schedule was really messed up and I heard it was good for that as well. I didn't think it helped at all." 

Rashelle Brown is a long-time fitness professional and freelance writer with hundreds of bylines in print and online. She is a regular contributor for NextAvenue and the Active Network, and is the author of Reboot Your Body: Unlocking the Genetic Secrets to Permanent Weight Loss (Turner Publishing). Connect with her on Twitter and Instagram @RashelleBrownMN. Read More