Dr. Peter Attia: Supplements for Longevity & Their Efficacy

Peter Attia emphasizes the importance of NAD and its role in the body's cellular processes, particularly as they relate to aging and longevity.

NAD is a ubiquitous molecule involved in energy production and DNA repair in every cell except red blood cells

NAD, one of the most ubiquitous molecules in the body, is involved in hundreds of pathways. Primary among its functions, NAD serves as an electron shuttle. However, as we age, NAD levels decline in most tissues—the decline is most prevalent in the skin, with an average 60% reduction over a person's lifetime.

Studies indicate that in whole blood, NAD levels decrease by about 10 to 20% over four decades. This drop is accompanied by an increase in NADH levels, alluding to a change in redox potential which is associated with mitochondrial function diminishments with age. Peter Attia suggests that this declining redox potential might be linked to the energy decrease experienced as we age.

The NAD pathway has been proposed as a potential target for improving lifespan and healthspan

NAD is a cofactor for sirtuins, which are involved in processes like mitochondrial biogenesis, DNA repair, and senescent cell suppression

The NAD pathway has become a focal point for research into lifespan and healthspan enhancement. Attia discusses cellular pathways including NAD that are of interest for longevity research. He highlights components such as NR, NMN, and NAD itself as integral to sirtuin function and roles in mitochondrial biogenesis, DNA repair, and the suppression of senescence-associated secretory phenotype (SASP).

Sirtuins consume a small fraction of NAD in the process of DNA repair. Attia references research indicating that sirtuins, activated by NAD, can improve mitochondrial biogenesis, increase DNA repair, and reduce SASPs.

Studies in yeast and a transgenic mouse model have shown that increasing sirtuin activity can extend lifespan, but the connection between sirtuins and caloric restriction is not clear

Matt Kaeberlein's experiment with yeast, which lived longer when overexpressing Sirtu, indicates a role for sirtuins in lifespan extension. Furthermore, research shows that overexpressing sirtuins in yeast can extend lifespan, suggesting that sirtuins play a role in longevity, although the connection of sirtuins to caloric restriction remains unclear.

Andrew Huberman discusses the idea that increased NAD could potentially slow aging by reducing reactive oxygen species and improving mitochondrial function. He acknowledges the complexity of the assumption that higher NAD levels directly correlate ...

Dr. Peter Attia and various experts dive into the research and clinical trials surrounding NAD supplementation, discussing the outcomes and implications for healthspan and lifespan.

While NAD levels decline with age, there is no clear evidence that increasing NAD levels through supplementation leads to improved lifespan or healthspan

Through a systematic review of research literature and clinical trials, Attia implies that despite significant announcements and ongoing developments, there is skepticism regarding the effectiveness of NAD supplementation to slow aging. This idea is not as straightforward as once assumed.

The Interventions Testing Program (ITP), a rigorous longevity research program, has not found any lifespan or healthspan benefits from administering NAD precursors like NR to mice

Peter Attia highlights that the Interventions Testing Program (ITP), funded by the National Institute on Aging, has not found any benefits for lifespan or healthspan from administering NAD precursors like NR to mice. The ITP conducts experiments across three independent labs in triplicate, ensuring the robustness of results. Attia specifies that NR was tested at a potent dose and did not result in life extension or healthspan improvement. Ultimately, the ITP found that megadose NR had the same result as placebo.

The available human studies on NAD precursor supplements like NR and NMN have shown small, clinically insignificant effects, such as modest improvements in glucose disposal or reduction in fatty liver disease

A study on a product containing NR and pterostilbene saw no significant difference in various health metrics compared to placebo, though a sub-analysis found a modest reduction in hepatic fat that was statistically — but not clinically — significant. Other human studies involving NMN supplementation showed only minor, clinically insignificant effects on glucose metabolism and nonsignificant reductions in hepatic fat. Attia notes that the overall human study results showed only a small change in LDL cholesterol and slight improvements in other non-essential metrics.

The claims about the benefits of NAD supplementation appear to be based more on mechanist ...

Andrew Huberman and Peter Attia engage in a discussion about various approaches to boosting NAD levels in the body, including through supplements like NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide), as well as direct intravenous infusions. They explore the mechanisms by which these supplements enter cells, their potential effects on health, and considerations regarding cost, dosage, and commercial interests in the marketplace.

NR can directly enter cells and increase NAD levels, while NMN requires the removal of a phosphate group before it can be utilized

Huberman states that NR can cross cell membranes directly, implying it can increase NAD levels without further transformation. In contrast, NMN must have a phosphate group removed before the body can use it, turning it into NR post-ingestion. This suggests that more NMN may be needed compared to NR to achieve the same increase in NAD levels. Despite this, Attia mentioned that after the phosphate group is cleaved off NMN, you're essentially left with NR, suggesting a similar end result.

Huberman refers to claims from developers of NR supplements that NR is 25% more effective than NMN at raising whole blood NAD levels on a milligram-per-milligram basis.

The practical differences between taking NR versus NMN are mainly related to cost and dosage, as the two supplements appear to be comparable in terms of their effects

Huberman mentions the cost considerations and that he has opted for sublingual NMN based on this. The dosage can be adjusted to account for the differences in bioavailability between the two, as discussed by Attia, who suggests that there is not much of a practical difference in outcomes between intravenous NAD, NR, or NMN, since all increase NAD levels.

Attia notes that the only observed effect from taking these supplements is accelerated hair growth, suggesting a comparable effect between NR and NMN. They also discuss that cost and dosage are more of a commerc ...