Most brain decline, mood instability, and impulsive behavior start with a breakdown in how the brain’s immune cells produce and use energy. This episode shows how mitochondrial health inside microglia influences cognition, emotion, and long-term brain resilience, and how everyday inputs quietly push those systems toward damage or repair.
Host Dave Asprey is joined by Dr. David Perlmutter, a board-certified neurologist and six-time New York Times bestselling author whose work focuses on the intersection of neurology, nutrition, metabolism, and brain health. A Fellow of the American College of Nutrition and member of the Editorial Board of the Journal of Alzheimer’s Disease, Dr. Perlmutter brings decades of clinical and research experience to this conversation on how inflammation and mitochondrial function shape the brain across the lifespan.
Together, they explore how microglial cells shift their behavior based on metabolic conditions, and how those shifts influence neurodegeneration, emotional regulation, impulse control, and cognitive performance. The discussion covers real-world inputs that shape these systems, including sleep optimization, fasting, ketosis, glucose regulation, gut signaling, environmental toxins, and tools referenced in the episode such as red and infrared light, 40 Hz light and sound, hyperbaric oxygen, lithium, nicotine, supplements, nootropics, GLP-1 agonists, and dietary approaches like carnivore and ketosis. The conversation connects brain biology to lived experience, showing how metabolism influences behavior, decision making, and long-term human performance through a Smarter Not Harder lens.
You’ll Learn:
• How microglia shift between supportive and destructive states and why metabolism drives that change
• How mitochondrial function inside immune cells influences inflammation and brain resilience
• How inflammation affects the prefrontal cortex, impulse control, and reward-driven behavior
• What the episode says about GLP-1 agonists and behavior changes like reduced cravings and gambling
• How gut-derived signaling and short-chain fatty acid balance (butyrate vs propionate) relates to brain function
• How tools like red and infrared light, hyperbaric oxygen, and 40 Hz light and sound connect to microglia
• The lifestyle levers discussed in the episode: sleep optimization, fasting, ketosis, glucose control, and toxin reduction
• The compounds mentioned, including lithium, nicotine, urolithin A, CoQ10, rosmarinic acid, and dihydromyricetin
Thank you to our sponsors!
-KILLSwitch | If you’re ready for the best sleep of your life, order now at https://www.switchsupplements.com/ and use code DAVE for 20% off.
-BodyGuardz | Visit https://www.bodyguardz.com/ and use code DAVE for 25% off.
-Our Place | Stop cooking with toxic cookware and upgrade to Our Place today. With a 100-day risk-free trial, plus free shipping and returns, you can experience this game-changing cookware with zero risk. Visit: fromourplace.com/DAVE Use code: DAVE for 10% off sitewide
-Pique | Establish a powerful foundation for sustained wellness with Pique. Unlock 20% off: piquelife.com/DAVE
Timestamps:
0:00 – Introduction
1:45 – Autism Spectrum
4:38 – Alzheimer’s & Beta Amyloid
7:02 – Brain Immune Cells
8:06 – GLP-1 & Parkinson’s
10:44 – M1 vs M2 Microglia
13:08 – Pharmaceutical Microdosing
15:51 – Gene Therapy
19:09 – Mold & Toxins
21:58 – Environmental Pollution
26:05 – MPTP Discovery
29:07 – Healing Interventions
31:39 – Light & Sound Therapy
36:35 – Mitochondrial Function
44:57 – Inflammation & Prefrontal Cortex
48:00 – GLP-1 Global Impact
52:11 – Mitochondrial Community
56:05 – Consciousness & The Field
1:00:00 – Psychedelics
1:06:35 – Death & Knowing
1:09:06 – Heart-Brain Connection
1:11:06 – Closing Thoughts
Resources:
• Learn More About Dr. Perlmutter at: https://drperlmutter.com/
• Get My 2026 Biohacking Trends Report: https://daveasprey.com/2026-biohacking-trends-report/
• Join My Low-Oxalate 30-Day Challenge: https://daveasprey.com/2026-low-ox-reset/
• Dave Asprey’s Latest News | Go to https://daveasprey.com/ to join Inside Track today.
Website: https://daveasprey.com
TikTok: https://www.tiktok.com/@daveaspreyofficial
Instagram: https://www.instagram.com/dave.asprey/
Facebook: https://www.facebook.com/Daveaspreyofficial/
X: https://x.com/daveasprey
YouTube: https://www.youtube.com/c/daveaspreybpr
The Human Upgrade Podcast: https://www.instagram.com/TheHumanUpgradePodcast/ https://m.facebook.com/Thehumanupgrade/
Danger Coffee: https://dangercoffee.com/DAVE15
Dave Asprey’s BEYOND Conference: https://beyondconference.com/
Dave Asprey’s New Book – Heavily Meditated: https://daveasprey.com/heavily-meditated/
Dave’s favorite supplements: https://www.shopsuppgradelabs.com/discount/DAVE15
Upgrade Collective: https://www.ourupgradecollective.com
Upgrade Labs: https://upgradelabs.com
40 Years of Zen: https://40yearsofzen.com
