EP 1369
1369. This Brain Trick Feels Like Cheating (Do THIS)
In this episode of The Human Upgrade, Host Dave Asprey sits down with Dr. David Perlmutter, board-certified neurologist and six-time New York Times bestselling author, for a deep conversation on how brain health, behavior, and neurodegeneration are driven by metabolism inside the brain’s immune system. They explore how microglial cells shift between supportive and destructive states based on mitochondrial function, why inflammation cuts off access to the prefrontal cortex and locks the brain into impulsive survival behavior, and how these mechanisms show up across Alzheimer’s, Parkinson’s, autism spectrum traits, addiction, and mood regulation. The discussion spans sleep optimization, fasting, ketosis, gut-derived signaling, environmental toxins, and real-world interventions including red and infrared light, 40 Hertz light and sound, hyperbaric oxygen, lithium, nicotine, GLP-1 agonists, supplements, and nootropics. Together, they connect cutting-edge neuroscience with lived experience, showing how restoring metabolic balance in the brain’s immune system supports cognition, emotional regulation, resilience, and long-term brain optimization.
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In this Episode of The Human Upgrade™...
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
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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: cell danger response podcast, mitochondria aging, mitochondrial dysfunction aging, health optimization medicine, dr ted achacoso, boomer anderson, troscriptions, troscriptions methylene blue, methylene blue mitochondria, methylene blue biohacking, cellular aging podcast, anti aging mitochondria, metabolic stress aging, fasting ketosis metabolism, mitochondrial energy production, neuroplasticity mitochondria, sleep optimization aging, functional medicine mitochondria, smarter not harder biohacking, dave asprey mitochondria
Resources:
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“Globally, we are keeping people away from their prefrontal cortex and locking them into amygdala-based behavior, and a big driver of that is inflammation.”
David Perlmutter
0:00 – Introduction
Opening discussion on how brain immune cells shift toward destructive behavior when their mitochondria become dysfunctional, and why neurodegenerative conditions trace back to brain immune system imbalance.
1:45 – Autism Spectrum
Autism framed as a cluster of manifestations influenced by genetics, epigenetics, toxicity, microbiome changes, and the balance of short-chain fatty acids like butyrate and propionate.
4:38 – Alzheimer’s & Beta Amyloid
Why focusing on beta amyloid removal misses the upstream immune dysfunction that leads to amyloid accumulation, and how drug approvals have centered on surrogate markers rather than cognition.
7:02 – Brain Immune Cells
How microglial cells act as protectors or aggressors depending on their mitochondrial metabolism, and why targeting metabolism matters more than treating downstream symptoms.
8:06 – GLP-1 & Parkinson’s
Discussion of the April 2024 New England Journal study where GLP-1 agonists arrested Parkinson’s progression by modifying microglial metabolism, highlighting the power of metabolic intervention.
10:44 – M1 vs M2 Microglia
Understanding the shift from supportive M2 microglia to destructive M1 states, how this transition is reversible, and how similar immune polarization occurs throughout the body.
13:08 – Pharmaceutical Microdosing
Exploration of drugs that influence immune cell metabolism, including PPAR gamma agonists, metformin, rapamycin, and GLP-1 agonists, through an integrative medicine lens.
15:51 – Gene Therapy
Dave shares personal experiences with folistatin and VEGF gene therapies, alongside discussion of different gene delivery vectors and their longevity and safety considerations.
19:09 – Mold & Toxins
Genetic susceptibility to mold, increased environmental aggressiveness of modern mold, and Dave’s personal history with toxic mold and Bartonella exposure.
21:58 – Environmental Pollution
Florida sugarcane practices, paraquat use, air pollution impacts on migrant communities, and toxic blue-green algae linked to neurodegenerative disease risk.
26:05 – MPTP Discovery
The landmark 1982 discovery showing how a mitochondrial toxin triggered permanent Parkinson’s through sustained microglial activation.
29:07 – Healing Interventions
Key lifestyle levers and targeted interventions discussed, including ketogenic diet, hyperbaric oxygen, mitochondrial nutrients, lithium orotate, nicotine, and immune receptor signaling.
31:39 – Light & Sound Therapy
MIT research using 40 Hertz light and sound to shift microglia back to supportive states, alongside Dave’s early infrared light experiments affecting brain function.
36:35 – Mitochondrial Function
Viewing neurodegenerative diseases as acquired mitochondropathies and why mitochondrial health underpins immune balance and brain resilience.
44:57 – Inflammation & Prefrontal Cortex
How inflammation disrupts the anterior cingulate pathway, locks behavior into the amygdala, and fuels impulsivity and global social polarization.
48:00 – GLP-1 Global Impact
Observations on GLP-1 drugs reducing cravings beyond food, including gambling and shopping, and their potential economic and behavioral impact worldwide.
52:11 – Mitochondrial Community
Mitochondria described as a communicating network using cytokines, biophotons, vibration, and possible quantum effects across the body.
56:05 – Consciousness & The Field
Reflections on health as alignment with a universal field, inspired by natural patterns, Fibonacci geometry, and lived experience.
1:00:00 – Psychedelics
Discussion of ibogaine research for addiction, safety considerations, and the importance of proper clinical settings and experienced facilitators.
1:01:59 – Love & Judgment
Exploring unconditional love, early life programming, self-acceptance, and how judgment reinforces ego-driven behavior.
1:06:35 – Death & Knowing
How clinicians sense when death is near, the concept of a human biofield, and the body’s innate awareness beyond measurement.
1:09:06 – Heart-Brain Connection
Recognizing shared energy fields across systems, the convergence of disease frameworks, and moving beyond purely mechanical models of health.
1:11:06 – Closing Thoughts
Stories about intuition, interconnectedness, and the importance of stepping out of fight-or-flight to recognize inherent goodness and shared humanity.
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