EP233: Born Free: Rethinking Chronic Illness Through Systems Biology - Part 1 - Joshua Leisk

Name: EP233: Born Free: Rethinking Chronic Illness Through Systems Biology - Part 1 - Joshua Leisk
Uploaded: 2026-05-18T14:58:04.000Z
Duration: 2 h 5 min 22 s
Channel: BetterHealthGuy

BetterHealthGuyMay 18, 20262h 5m

Topics74

Podcast Introduction and Disclaimer0:01 Episode 233 Overview0:35 Discussion Topics Overview2:35 Joshua Leisk's Personal Journey3:34 How Chronic Illness Became Joshua's Passion4:02 Discovering Patterns in Clients5:02 The Meaning Behind "Born Free"6:05 Conditions Addressed by the Born Free Protocol6:32 Common Cascade and Individual Variables7:05 Data-Driven Approach to Conditions8:33 Alzheimer's and NAD Redox9:32 Microbiome and Nervous System Connection10:35 Acetaldehyde, CMPK, and Fermentation11:05 Common Features Across Conditions12:00 Protocol Focus13:10 Impact of COVID on Chronic Illness13:34 Post-COVID Health Decline15:34 Immune System and Microbial Burden16:31 Factors Driving Complex Chronic Conditions17:30 Nervous System Dysregulation19:30 Nervous System as Bridge20:03 Metabolic Alarms and Nervous System Programming22:01 Cell Danger Response and Purinergic Signaling23:17 Energy Storage and Systemic Reliance25:06 Methylation, Glutathione, and Mitochondrial Cooling26:01 Heavy Metals, Redox Impairment, and Downstream Effects28:04 Safety, Viral Reactivation, and Mitochondrial Dysfunction29:34 Oxalate Production and Mitochondrial Signaling32:35 Genetics, Epigenetics, and Environmental Factors36:02 Mineral Depletion and Soil Quality40:01 Microbiome Assessment and Acetaldehyde-Producing Species41:01 Butyrate Restoration and pH-Tolerant Probiotics45:47 Microbiomes Beyond the Gut47:01 Nasal Microbiome and Nervous System Signaling48:01 Host-Microbe Signaling Cycles and Barrier Dysfunction49:31 Testing the Sinus Microbiome52:11 Physical Drivers of Sympathetic Dominance53:33 Addressing Acetaldehyde and Aldehyde Clearance55:00 Tools for Acetaldehyde Management58:00 Microbiome Remediation Strategy1:00:07 Chronic Infections, Parasites, and Fungi1:03:07 Cholesterol and NAD Redox Proxies1:03:36 Environmental Factors and Fungal Colonization1:08:23 Organic Acids Testing Overview1:09:31 Interpreting Metabolites with Cofactors1:11:00 Key Alarm Bells in OAT Results1:12:07 Microbiome Contributions to NAD Redox Issues1:16:03 Neurotransmitter and Kynurenine Pathways1:16:33 Clinical Application of Metabolic Pathway Overlays1:19:04 Aerobic vs. Anaerobic Glycolysis and Lactic Acidemia1:19:33 Post-Exertional Malaise and Connective Tissue Links1:22:32 Mitochondrial Testing and Electron Transport Feeders1:24:31 Environmental Toxicity and Detoxification Dynamics1:27:03 Environmental Assessment and Remediation1:29:31 Environmental Mold and Healing1:30:16 Personal Carriage of Mold1:31:00 Blood Testing and LDH Isoenzymes1:32:34 Micronutrient Deficiencies and B Vitamins1:36:30 Minerals as Metalloenzymes1:40:33 Iron Regulation and Hepcidin1:42:31 Lactoferrin and Protocol Support1:49:00 Hepcidin as Acute Infection Response1:49:37 Diet, Glycogen, and Microbial Fuel1:50:31 Oxalates, Glucose, and Microbial Biofilms1:53:01 Metabolic Syndrome and Glucose Management1:53:33 Histamine Dysregulation and Nervous System Influence1:54:03 Oxalates as Metabolic Regulators1:55:02 Food, Microbiome, and Dietary Spirals1:56:02 Carnivore Diets and Microbial Diversity1:57:01 GLP-1 Agonists and Metabolic Function1:58:34 Endotoxins, Lipopolysaccharides, and Barrier Function2:00:30 Endogenous versus Exogenous Endotoxins2:02:33 Genetic Factors and Metabolic Context2:03:01 Episode Conclusion2:04:31

In a Nutshell

Joshua Leisk's Born Free model frames complex chronic illness as a self-reinforcing cycle of mitochondrial dysfunction, sympathetic overdrive, impaired glycogen storage, and progressive mineral depletion that leaves the system unable to restore homeostasis. Core drivers include lactic acidemia from prolyl hydroxylase inhibition, acetaldehyde-producing microbial overgrowth, barrier breakdown, and heavy metal accumulation that further impairs glutathione redox and NAD balance. Recovery requires a sequenced approach: restore resources (glycogen, minerals, glutathione), reduce burdens (microbial load, environmental toxins), and reestablish parasympathetic signaling before addressing downstream issues like aldehydes or biofilms.

AI-Generated Notes

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Welcome to the Better Health Guy podcast, where we take a deep dive into complex chronic conditions and explore ways to build resilience, improve vitality, and achieve better health. The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing discussed on this podcast should be considered medical advice. As always, please discuss any health-related decisions with your own personal medical authority.

Welcome to episode 233 of the Better Health Guy podcast. Today, we explore Born Free: Rethinking Chronic Illness Through the Lens of Systems Biology. My guest today is Joshua Leisk. Joshua is a biological engineer and independent researcher focused on complex chronic illness. He's the creator of Born Free, a patient-led community research project that develops models and potential interventions for conditions such as heart disease. His work takes a systems biology, reverse engineering approach, exploring how disruptions in metabolism, mitochondrial function, and cellular signaling may contribute to chronic disease. He is known for developing detailed, evolving models that aim to explain how illness begins, progresses, and may potentially be reversed. Joshua collaborates with a global community of patients, practitioners, and researchers. Joshua is a professor at the University of Michigan's Center for Sharing Pathway Diagrams, Hypotheses, and Research intended to advance the understanding of complex chronic conditions. He is a founder of the Collaborative Sciences Institute, which provides systems biology education for clinicians treating complex chronic disease. He's also involved with Renegade Research, a 501c3 nonprofit, bringing together patients, caregivers, scientists, and clinicians to drive innovation in healthcare.

In part one of our discussion here in episode 233, we talk about the many factors that drive these complex conditions. We talk about sympathetic overdrive, the microbiome, testing, and diet. In part two of our discussion in episode 234, we'll talk about the immune system, structural issues, hypoxia, oxidative stress, and inflammation, the mitochondria, cell activation syndrome, and the Born Free Protocol.

When I was diagnosed with chronic fatigue syndrome, before we even called it ME-CFS, very little was understood about the mechanisms that underlie the condition. Today's guest has deeply explored those mechanisms and put together a really detailed model for recovering from ME-CFS and many other complex chronic conditions. If you've looked into his work, you've probably seen his detailed pathway diagrams. Our goal today is really to try to explore the higher level concepts of his model and view chronic illness in a different way.

I had severe ME-CFS, not that it was called that back in my teens. I was bedbound. My worst rolling over in bed was enough to knock me out again for another day. People would carry me to the bathroom, that kind of thing. It was not a pleasant time. I recovered from that. That was a very slow grind and then ultimately had a successful career. I sold up the IT business back when I was 38. And at that point, I wasn't quite sure what to do with life. I'd put my feet up for a little while. I traveled a little. Focused on doing some metabolic coaching and fitness. And that was kind of a passion for a little while.

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EP233: Born Free: Rethinking Chronic Illness Through Systems Biology - Part 1 - Joshua Leisk

Podcast Introduction and Disclaimer00:01

Episode 233 Overview00:35

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