At maximal exercise, the primary factor limiting VO2max in healthy, untrained individuals is:

• A Pulmonary diffusing capacity; alveolar-arterial O2 difference widens at maximum exercise due to diffusion limitation
• B Skeletal muscle mitochondrial density; oxidative phosphorylation capacity is the rate-limiting step in untrained individuals
• C Central cardiac output (O2 delivery); maximal heart rate and stroke volume define the upper limit of O2 delivery to muscles ✓
• D Ventilatory capacity; minute ventilation is the first system to reach maximum during graded exercise testing

Explanation

In untrained healthy individuals, VO2max is primarily limited by central cardiovascular O2 delivery (cardiac output = HR × SV). Evidence includes: (1) VO2max improves proportionally with endurance training-induced increases in stroke volume (ventricular remodelling, increased blood volume); (2) acute increases in cardiac output (blood transfusion, EPO) directly increase VO2max; (3) the Fick equation — VO2 = CO × (CaO2 - CvO2) — shows that at maximal exercise, skeletal muscle O2 extraction is near-maximal, making CO the variable that drives VO2max. In elite athletes, pulmonary diffusion can become limiting. Muscle mitochondria are the peripheral limiter in sedentary individuals, but even then, the muscle can utilise more O2 if delivery were higher.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.