Insulin resistance as central lever

Metabolic health is often simplified to a matter of blood sugar, but at its root, it is a complex system of energy substrate signaling. While many view chronic disease as an inevitable part of aging, a systems-thinking approach reveals that maintaining high "flux"—the capacity to efficiently move and clear energy through the body—is the primary lever for longevity. Without the stimulus of regular movement, even the most optimized diet can fail to prevent the accumulation of metabolic waste that leads to insulin resistance and heart disease.

In this episode, we sit down with Greg Mushen, a technologist who turned his engineering mind toward his own biology after conventional medicine failed to address his chronic health issues. Mushen breaks down his "Theory of Flux" and why he believes the key to disease resistance lies in meeting our body's "clearance burden". From studying the activity levels of hunter-gatherer populations to debunking myths about walking and V2 max, Mushen provides a data-driven framework for optimizing health through the lens of evolutionary biology and systems engineering.

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In this episode, we cover:

• The Theory of Flux: Understanding health as the dynamic capacity to move nutrients and fuel through the system rather than a static set of markers.
• Insulin Resistance Reimagined: Why blood sugar is a symptom, not the root cause, and how fat accumulation in the liver and muscle disrupts signaling.
• The Power of PAL: Why a Physical Activity Level (PAL) of 2.0 is the "golden ratio" observed in disease-free subsistence populations.
• Walking vs. HIT: De-bunking the idea that you need high intensity to improve V2 max and why the "area under the curve" for oxygen consumption is what matters.
• The Saturated Fat Paradox: Comparing the Messiah and Chimané populations to understand how high activity levels can mitigate the risks of high-fat diets.
• Fiber as a Sensor: Why fiber is more than just "throughput" and acts as a critical environmental sensor for metabolic signaling.
• The "Walking Grifter" Philosophy: Why walking is the most under-leveraged tool for increasing metabolic flux with the lowest recovery cost.

🎙 What Greg Mushen & Josh Clemente discuss:

• [00:53] — Greg’s transition from tech engineering to "debugging" his own biology.
• [06:55] — The mold exposure and chronic fatigue that sparked a deep dive into primary literature.
• [11:36] — How correcting a copper deficiency became a "point of light" for understanding micronutrients.
• [20:53] — Lessons from the Messiah: High saturated fat intake paired with extreme physical activity.
• [25:26] — Defining Flux: The capacity to clear substrate and prevent metabolic accumulation.
• [30:26] — The PAL 2.0 threshold: Why doubling your basal metabolic rate is the key to warding off chronic disease.
• [51:10] — Lipid Kinetics: Using the "sink and drain" analogy to understand LDL residence time.
• [01:00:19] — The Integral of Oxygen: Why walking 15,000 steps can be as effective for V2 max as short bursts of HIT.
• [01:17:16] — Why Greg changed his mind on plant-based vs. animal protein.
• [01:28:24] — Greg's personal stack: From 15k steps and resistance training to PD5 inhibitors and custom fiber blends.

Levels helps you see how food affects your health, empowering you with the tools needed to achieve health goals and improve healthspan. Levels Members gain access to the Levels app and continuous glucose monitors (CGMs), providing real-time feedback on how diet and lifestyle choices impact your metabolic health.

Look for new shows every month on A Whole New Level, where we have in-depth conversations with thought leaders about metabolic health.

🔗 Helpful links

Watch the conversation: https://youtu.be/A1KSG2qyVww⁠

Find us on YouTube: ⁠⁠⁠⁠⁠⁠https://youtube.com/levelshealth?sub_confirmation=1⁠⁠⁠⁠⁠⁠

📲 Connect

Connect with Greg Mushen on LinkedIn:

https://www.linkedin.com/in/gregmushen