Few things have the ability to provoke a response in the way that fear might, and few things seem to provoke fear in the way death can. Death anxiety seems to be the most discussed topic in all of human history, inspiring work from every time period and culture. Methods for addressing or managing this fear vary wildly, but the most obvious method to remove the fear is to remove death itself. History is full of ill-fated attempts to circumvent death or, even better, rejuvenate the body to a younger state.
We have all heard the stories – Gilgamesh seeks out the secrets of immortality after witnessing the death of his friend Enkidu, Juan Ponce de León’s search for the fountain of youth, and alchemists attempting to produce the elixir vitae. These stories represent the hopes of our ancestors for longer, more youthful lives, and for as long as these hopes have existed, there have been people there to sell the hopeful a variety of treatments for aging. I probably don’t need to mention that none of these treatments were effective.
More recently, scientists have taken an interest in aging as a biological process and have wondered what interventions, if any, could slow, halt, or even reverse the ravages of aging. In the last 30 years, the field of aging research has experienced immense growth, moving from a small fringe of researchers to becoming a mainstay of biological investigations that attracts both NIH and billionaire funding.
Scientists have achieved great success in extending the life span of multiple species in the laboratory, including nematode worms, flies, and mice. These achievements suggested that aging was dynamic, and they enticed scientists to continue looking for an anti-aging treatment for humans. Dozens of interventions have been investigated in the lab, but despite the continued success with animal models, an effective treatment for human aging remains elusive.
Yet, the nuances of scientific research rarely matter to those looking to cash in early on something that seems promising. Fifteen years ago, resveratrol was touted as a potential ally in the fight against old age, and it seemed promising. Studies indicated that it might work as a sirtuin activator, helping to regulate metabolic activity and thereby slow aging, similar to how some have suggested caloric restriction might slow the process. Formulations of resveratrol are still being researched for various potential medical benefits, but more than a decade and a boatload of research funds later, the hype was a bust.
The lack of confirmatory research did not stop profiteers from selling resveratrol as soon as various media outlets gave superficial reporting on the potential of the molecule. Despite the subsequent fifteen years of research showing no benefit to human health or aging, you can still buy a “six months’ supply” for $189.00 from online retailers. Resveratrol has firmly taken its place among other hyped “medicines” that turn a profit but confer no benefit. Resveratrol is not the first molecule or intervention that has had this trajectory, and it is doubtful that it will be the last.
Recently, promotions of NAD precursors among the supplement salesmen have been on the rise. NAD (nicotinamide adenine dinucleotide) is an extremely important metabolic coenzyme, primarily involved in redox reactions, and is found in all cells and is necessary for cellular function. The basic claim that is seen circulating is that natural levels of NAD decrease as we age and, further, the decrease is directly related to various disease states associated with aging. The thought is simple from here: restore more youthful levels of NAD in older individuals, and we will delay the aging process or slow the progression of age-related disease.
The majority of products that claim to boost NAD levels are actually precursors such as NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside). Precursors are used due to their bioavailability compared to NAD itself. Nevertheless, NAD is synthesized from these precursors (among others), and they have been shown to increase NAD levels.
Studies in mice were very promising and included protection from neurodegeneration, improvements in lung function, improvements in immune cell function, reduction of chronic inflammation, and protective effects against photodamage caused by UVB. Humans, however, are not mice, and it has been noted in many studies that trials in animals rarely translate to humans. NAD precursors have undergone some clinical trials, and it is a sure thing that researchers hoped to replicate some of the success seen with lab mice, but the results seem lackluster. Little of the improvements and protective effects observed among the mice were seen in the human clinical trials.
There were some positive results with clinical trials, which included increased insulin sensitivity for prediabetic women, modest improvement in muscle performance, and increased telomere lengths. Further, the doses of administered NMN seemed to be well tolerated and safe. There were, however, no significant positive results for sleep quality, eyesight improvement, cognition improvement, or insulin sensitivity among men.
While these results are indeed interesting, there is a lack of large-scale, long-term clinical trials looking into more indicators of health than are currently available. Safety concerns alone are enough to justify the need for further research. Current trials deem most NAD precursors as ‘safe’, but these studies are done in the short term, while people usually take supplements for a very long time – in this case, likely for the rest of their lives. Further, more research is needed looking into subpopulations. It may be the case that NAD precursors are safe for older individuals but not for younger. It could also be the case that the current clinical trials weren’t large enough to detect adverse effects that would become apparent in the general population.
As of 2020, the NMN market was worth some $250 million worldwide, and it is expected to grow in the upcoming years. It is certainly possible that NMN or NR supplementation will be doctor-recommended and science-approved in the future for various complaints arising from the aging process, it is also certainly possible that it will go the way of resveratrol and turn into another great disappointment in our search to lead longer, healthier lives. Either way, it is too early to tell, and the results of current clinical trials don’t justify the amount of money currently being invested in such products.
We all hope for some magic pill that can keep us younger for longer, but for now, we might have to be content to save our money and wait for the science to do its work.
