The Latest on NAD: Hope or Hype?

Healthy Aging

Recent science is popping the NAD bubble

In the Annals of the New York Academy of Sciences, DeVito et al. summarize the outcomes of a symposium on geroscience and geroprotectors (aka aging science and anti-aging therapeutics).  For this series, we’re sharing the latest and greatest thoughts on how to discover holy grail geroprotectors that could meaningfully delay aging to improve our healthspan and longevity.

Young blood molecules

Last week, we talked about ‘young blood’ studies, which  showed that older mice infused with young mouse blood get, well, younger. The question is why? This week, we are covering a molecule in blood that declines with age and has been extensively studied for anti-aging properties. It’s called nicotinamide adenine dinucleotide, or NAD.

What is NAD?

NAD is an important cellular helper. It helps our mitochondria generate energy. It helps other enzymes express genes and repair DNA. It also helps proteins, called sirtuins, regulate inflammation, natural day-night cycles, and cell growth. As described by Radenkovic et al., NAD’s ability to help improve mitochondrial function, repair DNA, and calm inflammation, have made it an anti-aging candidate.

So, how do we raise our NAD levels?

Our bodies use dietary vitamin B3 (aka, niacin) or tryptophan to naturally make NAD. While NAD itself is not orally bioavailable, a precursor called NR (nicotinamide riboside) can be absorbed as a supplement and effectively used to increase NAD.

While NMN can also be used to raise NAD levels, the FDA just made NMN supplements illegal to sell in the U.S. because it does not meet the criteria of dietary supplements.

What are the health benefits of NAD precursor supplements?

In their review, Rajman et al. cover the many benefits of NAD demonstrated in animal models, including improved metabolic, heart, and immune health. In some models, raising NAD levels has even extended lifespan.

In human clinical trials, however, Nielsen et al. show that the excitement around NR supplementation is starting to fade.

While NR supplements have been shown to be safe and can effectively increase NAD levels in humans, Rajman et al. summarize that clinical trials with NR alone had no benefits related to:

• Insulin sensitivity
• Glucose control
• Resting energy expenditure
• Oxidation of lipids
• Body composition

Some effects that have been detected in NR clinical trials include lower inflammatory cytokines and lowered energy metabolism. Most health benefits in humans have come from vitamin B3 itself, which may or may not have to do with NAD.

In summary, despite the promise of NAD+ in animal models, the hype of using NR supplements alone – as holy grail geroprotectors that can meaningfully decrease clinically relevant conditions and help us live longer – has less hope.