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. 

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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 inflammation, crashes NAD, and accelerates biological aging throughout the body 
• What controls tight junction integrity and how ATP, butyrate, creatine, and fasting all play a role 
• Why most creatine supplements fail to absorb properly and what to look for in a high-quality source 
• How to rebuild your microbiome in three to four weeks through diet alone, without antibiotics 
• Why walking immediately after a meal may be doing more harm than good to your gut lining 

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Dave Asprey is a four-time New York Times bestselling author, founder of Bulletproof Coffee, and the father of biohacking. With over 1,000 interviews and 1 million monthly listeners, The Human Upgrade brings you the knowledge to take control of your biology, extend your longevity, and optimize every system in your body and mind. Each episode delivers cutting-edge insights inhealth, performance, neuroscience, supplements, nutrition, biohacking, emotional intelligence, and conscious living. 

New episodes are released every Tuesday, Thursday, Friday, and Sunday (BONUS). Dave asks the questions no one else will and gives you real tools to become stronger, smarter, and more resilient. 

Keywords: Dr. Andrew Salzman, NAD depletion, CD38 inhibition, PARP inhibition, NMN supplements, creatine ATP shuttle, leaky gut aging, tight junction integrity, inflammaging, lipopolysaccharide gut, flagellin toxin, butyrate gut healing, ergothioneine, hydroxytyrosol, peroxynitrite, superoxide mitochondria, creatine energy distribution, gut origin of aging, NAD bathtub analogy, BRCA PARP inhibitor, Wonderfeel, creatine monohydrate, intestinal permeability, microbiome butyrate, selective digestive decontamination, TMAO nitric oxide 

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Timestamps:  

00:00 – Trailer 

01:12 – Introduction & BRCA Background 

02:19 – DNA Damage & PARP 

04:38 – Free Radicals & Oxidative Stress 

11:37 – NAD & Antioxidant Defense 

12:34 – CD38 & NAD Depletion 

23:31 – The Gut-Aging Hypothesis 

30:05 – ATP, Creatine & Energy Distribution 

36:41 – Creatine as Energy Shuttle 

51:09 – Microbiome & Gut Repair 

59:21 – TMAO & Nitric Oxide Interference 

1:03:52 – Flagellin & Gut Inflammation Research 

1:09:45 – FDA & Pharmaceutical Incentives 

1:16:05 – Closing 

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