Key Points:
- According to Dr. Peter Attia, taking oral NAD+ precursors like NMN and NR is the most effective method for replenishing NAD+ levels.
- Dr. Attia believes that the hype around NAD+ is mostly “noise,” stating that its ties to increased longevity are still unclear.
Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme present in every living cell, crucial for protecting our genetic blueprints (DNA), enhancing energy production, and boosting metabolism. Without NAD+, human life would cease to exist. Over the last decade, NAD+ has become a focal point of aging and longevity research, but the lack of human trials has left many questions about its efficacy and safety unanswered. In a recent podcast with Peter Attia, MD, the popular practicing physician shared his thoughts on the current state of NAD+ research, NAD+ precursors, and whether NAD+ can actually contribute to prolonged longevity.
Dr. Attia begins by clarifying that when discussing NAD+, he generally refers to NAD+ precursors, which are compounds that are converted to NAD+ once inside the body. Since NAD+ cannot directly enter cells, these precursors provide a more effective means of increasing NAD+ levels within cells. He mentions that NAD+ can also be taken intravenously but points out that nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are the two most well-established precursors shown to replenish NAD+.
The Hype Around NAD+ and Hypotheses on Its Decline
Dr. Attia explains how much of the excitement surrounding NAD+ stems from its relationship to sirtuins – a family of guardian proteins involved in several cellular survival processes ranging from DNA repair, mitochondrial maintenance, and cellular stress responses. Accordingly, sirtuins require NAD+ to carry out these essential functions; however, NAD+ levels diminish with age, leaving less NAD+ for sirtuins. With this in mind, researchers have scrambled to elucidate the reason for NAD+ decline along with the most effective methods to replenish NAD+.
Dr. Attia proceeded to highlight what researchers think is the reason for NAD+ levels plummeting with age. It is widely known that DNA damage increases with age and is tied to the progression of several age-related health conditions. As more DNA damage occurs, the demand for NAD+ to facilitate repair also increases, leading researchers to postulate that this heightened demand results in a reduced availability of NAD+.
Notably, Dr. Attia points to the possibility that NAD+’s decline with age could be entirely unrelated to elevated DNA damage. Whatever the case may be, he notes that many scientists believe that finding a way to restore NAD+ could potentially offset the detrimental effects of DNA damage.
That being said, Peter Attia says, “I think it’s safe to say we don’t yet know the answer to that. But nevertheless, I think a cottage industry around NAD+ has come up, which says look, we know the answer to this or at least we’re going to postulate that the answer is of course NAD+ is going down with age, and whether or not that’s causal or not, giving more NAD+ is going to be a better thing.”
The Current State of NAD+ Research
At the moment, Dr. Attia believes that the hype around NAD+ is mostly “noise,” highlighting how surprisingly little human data there is. Nevertheless, he acknowledges a few studies with somewhat promising data, though he emphasizes that the small sample sizes of these studies warrant further investigation before drawing any definitive conclusions.
One trial he mentions examined the protective effects of the NAD+ precursor NMN combined with the polyphenol pterostilbene on ALS (amyotrophic lateral sclerosis)symptoms. Notably, the study found that the combined treatment successfully delayed the progression of ALS systems and did not induce adverse effects in patients, demonstrating both its safety and tolerability.
Another phase 1 trial Dr. Attia sheds light on explored the effects of NR on Parkinson’s disease in 20 subjects. Uniquely, NR therapy was linked to a clinical improvement in total MDS-UPDRS scores, which is a comprehensive tool used to assess the severity and progression of Parkinson’s disease. However, he notes that the patients who saw the most improvement had a shorter interval since their last dose of levodopa – a medication that is quite effective in the early stages of Parkinson’s. Given the trial’s flaw, Dr. Attia urges for more testing in this setting.
“I think that the evidence that NAD+ and its precursors is geroprotective, meaning we’re going to take a bunch of people who don’t have disease and we’re going to make them live longer, is very very low probability but not zero,” states Dr. Attia. “ I don’t take these compounds. I don’t take NAD infusions. I don’t take NR. I don’t take NMN, and it’s certainly not because there isn’t an abundance of those things out there. But I guess that tells you my level of confidence in this.”
What NAD+ Can Do in Animals
Despite Dr. Attia’s skepticism about the geroprotective effects of NAD+, several longevity enthusiasts, such as Dr. David Sinclair, tout the importance of replenishing NAD+ for enhanced longevity. Although human trials investigating NAD+’s effects are limited, there are several promising findings from preclinical studies demonstrating the potential benefits of NAD+ precursors:
- Enhances DNA repair
- Improves brain function
- Boosts exercise performance in older adults
- Promotes organ health
- Exerts neuroprotection
- Improves insulin sensitivity
- Increases length of telomeres
- Improves metabolism
It is too early to tell whether these findings will translate to humans. Be that as it may, NAD-boosting technologies are becoming increasingly popular in the longevity space.
In fact, some companies have developed products, such as Seragon’s RESTORIN, combining NAD+ enhancers with other longevity-boosting technologies like senolytics – compounds that target and extinguish dysfunctional (senescent) cells linked to aging. However, as Peter Attia stresses, conducting more robust preclinical studies and clinical trials is paramount to continue the advancement of aging interventions.
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