How peripheral metabolism signals the brain

Perlmutter details cytokine signaling, blood-brain barrier dysfunction, and why systemic mitochondrial health affects microglia.

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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.

Watch this episode on YouTube for the full video experience:

https://www.youtube.com/@DaveAspreyBPR

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

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 is the top podcast for people who want to take control of their biology, extend their longevity, and optimize every system in the body and mind. Each episode features cutting edge insights in health, performance, neuroscience, supplements, nutrition, hacking, emotional intelligence, and conscious living.

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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 in health, 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: microglia brain health, brain immune system mitochondria, neuroinflammation podcast, mitochondrial dysfunction brain, david perlmutter podcast, dr david perlmutterneurologist, grain brain author podcast, alzheimers brain metabolism, parkinsons microglia, autism brain inflammation, gut brain immune signaling, short chain fatty acids brain, butyrate propionate brain, glp-1 brain behavior, glp-1 addiction research, red light therapy brain, infrared light mitochondria brain, 40 hz light sound brain, hyperbaric oxygen brain health, lithium microglia brain

Resources:

• Learn More About Dr. Perlmutter at: https://drperlmutter.com/

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