Combine Creatine With THIS To Fight The Root Cause of Aging | Andrew Salzman

Dave Asprey

May 28, 2026

Episode description

How CD38, PARP, and Leaky Gut Are Destroying Your NAD Levels | Dr. Andrew Salzman

Your NAD is being drained by two hidden enzymes, your gut may be the starting point of every aging process in your body, and creatine does something to your mitochondria that has nothing to do with muscle. This episode rewrites what you thought you knew about longevity, anti-aging biology, and how your body actually produces and delivers energy at the cellular level.

-Watch this episode on YouTube for the full video experience: https://www.youtube.com/@DaveAspreyBPR

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Host Dave Asprey sits down with Dr. Andrew Salzman, a physician, inventor, and biomedical entrepreneur with more than 30 years of experience in drug discovery and development. An alumnus of Harvard Medical School, Yale University, and Columbia University, Dr. Salzman has authored more than 170 scientific publications and holds 50 patents. He invented the original clinical-stage PARP-1 inhibitor, leading to the world's first clinical treatment for raising NAD levels and fighting cancers caused by the BRCA1 and BRCA2 genes. Genentech licensed his breakthrough technology for $600 million. His research into gastrointestinal microbiota, autoimmune disease, oxidative stress, and mitochondrial ATP production now forms the foundation of how millions of patients get treated worldwide.

Dr. Salzman names the two biggest NAD drains in your body, CD38 and PARP, and explains why taking NMN or NR alone is like filling a bathtub with the drain wide open. He breaks down the formulation science behind pairing NAD precursors with CD38 blockers like hydroxytyrosol alongside PARP-reducing antioxidants like ergothioneine, and delivers a paradigm-shifting explanation of creatine as an energy distribution network inside your cells. Rather than a simple muscle supplement, creatine acts as a high-speed ATP shuttle that carries energy from your mitochondria to the precise location and moment your brain, gut, and heart need it most.

You'll Learn:

Why NAD declines with age and which two enzymes are primarily responsible for draining it
How CD38 rises with inflammation rather than NAD levels, and what that means for your supplement strategy
Why creatine is one of the most underrated anti-aging and brain optimization supplements available
How creatine functions as a spatial and temporal energy delivery network for your brain, gut, and heart
Why the gut may be the origin point of the entire aging process and how that cascade unfolds decade by decade
How leaky gut drives systemic infla

Mindsip insights from this episode:

Avoid exercise immediately after meals to protect gut health

Exercising immediately after a meal can steal blood flow from the gut, reducing oxygen and ATP, which can damage the gut lining, especially as you age.

#digestion

#exercise

Avoid energy shortages to prevent irreversible cellular damage

Cellular damage from energy shortages can push a cell past a tipping point into a new, permanently damaged state from which it cannot recover.

#cells

#energy

Combat peroxy nitrite to protect DNA and NAD levels

The highly damaging oxidant peroxy nitrite breaks DNA, activates the PARP enzyme, and depletes NAD, but unlike other oxidants, it has no known beneficial role in the body.

#DNA

#oxidation

Understand inflammation's role in CD38 regulation, not NAD levels

Contrary to some beliefs, the NAD-depleting enzyme CD38 is upregulated by inflammation associated with aging, not by increased levels of NAD itself.

#CD38

#inflammation

Address gut health to combat aging process

The aging process is theorized to originate in the gut as it becomes progressively more porous, allowing bacterial products to cause body-wide inflammation.

#aging

#gut

Boost NAD with Wonderfeel supplement formula

The Wonderfeel supplement combines the NAD precursor NMN with hydroxytyrosol and resveratrol to inhibit the NAD-depleting enzyme CD38, and ergothioneine to reduce PARP activation.

#NAD

#supplement

Prioritize creatine for gut health integrity

Creatine is vital for maintaining the integrity of the gut's tight junctions, as these areas have incredibly high and rapid energy demands that ATP alone cannot meet.

#creatine

#gut

Utilize creatine as an energy delivery system for cells

Creatine functions as a high-speed shuttle, delivering energy from mitochondria to distant parts of the cell where it's needed instantly, like a local power generator.