Original episode & show notes | Raw transcript
This document explores the physiological components that determine an individual’s maximal oxygen uptake, or VO2 max. We will dissect the science presented in the podcast, moving from the overarching formulas to the microscopic interactions within your muscles, to understand what truly limits this critical aspect of endurance performance.
To understand VO2 max, we must first look at its constituent parts. The cornerstone for this is the Fick Equation, a simple yet powerful formula developed by 19th-century physiologist Adolf Fick. It describes the relationship between oxygen consumption, blood flow, and oxygen utilization.
The primary Fick equation is:
VO2=Q×(a−v)O2 difference
Let’s break this down:
VO2: This is the volume of oxygen consumed by the body. When we talk about VO2 max, we are referring to the maximum rate at which this can occur.
Q: This represents cardiac output, which is the total volume of blood the heart pumps per minute. Cardiac output itself has two components:
Heart Rate (HR): The number of times your heart beats per minute.
Stroke Volume (SV): The volume of blood pumped from the left ventricle per beat.
Therefore, Q=HR×SV.
(a−v)O2 difference: This is the arteriovenous oxygen difference. It measures how much oxygen is extracted from the blood by the tissues. It’s the difference between the oxygen content of arterial blood (blood flowing to the muscles) and venous blood (blood flowing away from the muscles). This is the “utilization” part of the equation.
So, the expanded Fick equation for VO2 max looks like this:
VO2max=(Max HR×Max SV)×Max (a−v)O2 difference
A common misconception, born from the deceptive simplicity of this multiplicative formula, is that all three components—heart rate, stroke volume, and A-VO2 difference—are equally important limiters of VO2 max. The central question the podcast explores is whether this is true. Can you increase your VO2 max just as effectively by training your muscles to utilize more oxygen as you can by training your heart to deliver more?
Let’s focus on the utilization side of the equation first: the A-VO2 difference. This represents the work done by the muscles. For your VO2 to be anything other than zero, your muscles must actively extract oxygen from the blood.
The Magic Trick: How Oxygen “Disappears”
The entire process of oxygen moving from the atmosphere into your mitochondria is passive. It requires no direct energy input (ATP). This movement is governed by gradients in partial pressure, a concept from basic physics and chemistry. Gas flows from an area of high pressure to an area of low pressure.
Atmosphere to Lungs: The partial pressure of oxygen (PO2) in the air is high.
Lungs to Blood: The PO2 in the alveoli of your lungs is lower, so oxygen diffuses into the blood, where it binds to hemoglobin.
Blood to Muscle Cell: In the capillaries surrounding your muscles, the blood has a high PO2.
Muscle Cell to Mitochondria: Inside a working muscle cell, the mitochondria are constantly consuming oxygen to produce ATP, turning it into water. This creates a near-zero pressure zone for oxygen.
This final step is the engine driving the entire process. The “disappearance” of oxygen in the mitochondria creates a powerful pressure gradient that pulls oxygen out of the blood, through the muscle cell, and into the mitochondria. Your body doesn’t “push” or “stuff” oxygen into cells; it creates a vacuum that oxygen passively fills.
The Role of Myoglobin
Inside the muscle cell, a protein called myoglobin plays a crucial role. Like its cousin hemoglobin in the blood, myoglobin binds to oxygen. It has a very high affinity for oxygen, meaning it holds onto it tightly.
Function 1: Storage: It acts as a small, localized oxygen reserve within the muscle.
Function 2: Diffusion Facilitation: It helps shuttle oxygen from the cell membrane to the mitochondria, smoothing out the diffusion process.
Crucially, myoglobin does not act like a “bucket brigade,” actively passing oxygen along. It simply exists in the cell, and as the mitochondrial “vacuum” lowers the local PO2, myoglobin releases its bound oxygen, which then continues its passive journey down the pressure gradient.
The podcast highlights key studies that investigate whether training the “utilization” side of the Fick equation can increase overall VO2 max.
Study 1: Capillaries, Fiber Size, and Fractional Utilization
Finding: The study “Determinants of Endurance in Well-Trained Cyclists” compared two groups of cyclists with similar VO2 max values but different FTPs (as a percentage of VO2 max). The group with a higher FTP (better fractional utilization) had:
Smaller muscle fibers.
The same number of capillaries per fiber.
This resulted in a higher capillary density (more capillaries per square millimeter of muscle).
Interpretation: Having more capillaries packed into a smaller area reduces the distance oxygen has to diffuse from the blood to the mitochondria. According to Fick’s Law of Diffusion, a shorter distance means a faster rate of flux. This improves endurance and how much of your VO2 max you can sustain (your FTP), but the study showed it did not correlate with a higher absolute VO2 max. The VO2 max values were the same between groups.
Study 2: The One-Legged Cycling Experiment
This is the critical study for understanding the primary limiter of VO2 max.
Setup: Subjects trained one leg extensively for seven weeks while the other leg remained untrained (but maintained its base fitness).
Results for the Trained Leg:
Citrate synthase activity (a marker for mitochondrial density) increased by 30%.
Blood flow to the leg increased by 16%.
A-VO2 difference (utilization) increased by a small but significant 4.2%.
The one-legged VO2 max of the trained leg increased by 8.1%.
The Crucial Finding: When the subjects performed a standard, two-legged cycling test, their overall VO2 max was completely unchanged.
Interpretation: The trained leg developed a superior ability to utilize oxygen. However, when both legs were working, the system’s ability to deliver oxygen (i.e., the central cardiac output) became the bottleneck. The trained leg’s enhanced utilization potential could not be realized because the heart couldn’t pump enough blood to satisfy both legs at that higher rate. The muscles were ready and willing to use more oxygen, but the delivery service couldn’t keep up.
This is further evidenced by the fact that the one-legged VO2 max (around 3.2 L/min) was over 80% of the two-legged VO2 max (3.9 L/min). If delivery wasn’t the limiter, you would expect the one-legged value to be closer to 50% of the two-legged value. The fact that a single leg can demand almost as much oxygen as the entire system can provide proves that the system’s delivery capacity is the main constraint.
The evidence presented leads to a clear conclusion: The components of the Fick equation are not created equal.
While utilization (A-VO2 difference) is essential—without it, there is no oxygen uptake—it is not the primary limiter of VO2 max in a whole-body exercise context. Your muscles, with their vast potential for mitochondrial and capillary adaptation, are more than capable of using all the oxygen your heart can deliver.
The true bottleneck is cardiac output (Max Heart Rate × Max Stroke Volume).
The plateau we see in a VO2 max test occurs because the heart has reached its maximum capacity to pump oxygenated blood. Your muscles could use more, but the supply has been maxed out. This is why the podcast host critiques statements like “we’re putting more oxygen to the muscle than it knows what to do with.” The reality is the exact opposite: the muscles are starved for oxygen, and the heart simply can’t deliver any more.