VO2,max: What Do We Know, and What Do We Still Need to Know?

Authors, Journal, Affiliations, Type, DOI

• Author: Benjamin D. Levine
• Affiliation: Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas; University of Texas Southwestern Medical Center, Dallas TX, USA
• Journal: Journal of Physiology, Volume 586.1, pp 25–34 (2008)
• Type: Topical Review (expert narrative review)
• DOI: https://doi.org/10.1113/jphysiol.2007.147629

Overview

This topical review by Levine addresses three key questions about VO2max: whether it exists as a true physiological ceiling, why elite endurance athletes have such large VO2max values, and what limits exercise at VO2max. The Hawkins 2007 study (n=156 paired incremental + supramaximal tests) definitively proves VO2max is a parametric limit — subjects performing >30% extra work anaerobically never substantively exceeded their VO2max. Elite athletes' large VO2max is explained primarily by high cardiac output driven by enhanced LV end-diastolic volume from chamber compliance and pericardial distensibility. Exercise cessation at VO2max results from peripheral muscle fatigue mechanisms (Ca2+ failure, impaired Na/K pump, ROS, cross-bridge slowing) that signal the brain to reduce central motor drive.

Keywords

Maximal oxygen uptake, VO2max, Fick equation, cardiac output, endurance athletes, exercise physiology

Key Takeaways

Classical View: VO2max Is Limited by Convective Oxygen Transport

• VO2max concept originated with A.V. Hill (1923): a finite rate of maximal oxygen transport from environment to mitochondria supports oxidative ATP production for physical work
• Widely used as: measure of exercise performance; marker of population-based fitness and CVD risk; prognostic marker in HF for transplant referral (Weber et al. 1987: peak VO2 <14 mL/kg/min)
• VO2max is easily altered by manipulations that increase (blood transfusion, EPO, altitude acclimatization) or decrease (blood removal, beta-blockade) oxygen delivery without altering arterial PO2
• Maximal vasodilatory capacity of skeletal muscle exceeds the ability of the heart to deliver blood while maintaining adequate arterial perfusion pressure (Secher 1977; Richardson 1999)

Does VO2max Exist? The Hawkins 2007 Proof

• Definitive proof: Hawkins et al. 2007 (Med Sci Sports Exerc, n=156 paired tests in well-trained collegiate middle-distance runners)
• Protocol: incremental exercise test to VO2max, followed next day by supramaximal test (accumulated O2 deficit; Medbo 1988 methodology)
• Result: subjects sustained >30% greater work rates than oxidative capacity would support (via high glycolysis + substrate-level phosphorylation) — yet VO2max was rarely higher and never substantively so compared to the incremental test
• VO2max never approached the oxidative requirements of the higher workload — levelling off was demonstrably real
• Refutes the Central Governor Model (Noakes): subjects clearly could recruit more motor units and exercise at much higher intensities anaerobically — but no myocardial ischaemia occurred either
• Taylor et al. 1955 (n=115): only 7/115 subjects failed to achieve the VO2 plateau criterion — establishing VO2max as a cardiorespiratory performance measure

The Fick Equation and Its Parametric Limits

• VO2max = (LVEDV − LVESV) × HR × (a-v O2 difference)
• Maximum theoretical a-v O2 difference: ~200 mL/L (20 vol%) assuming Hgb 17 g/dL (FIS ski racing upper limit), 100% arterial saturation, lowest reported mixed venous saturation 14% (Operation Everest II — near Everest summit)
• Peak a-v O2 differences in non-athletes are not much below elite athlete values (Sutton 1988; Hagberg 1985) — so the major determinant of elite athlete VO2max is cardiac output
• Mitchell et al. 1958 (half-century confirmation): levelling of VO2 at VO2max is associated with clear levelling of cardiac output

Why Do Elite Athletes Have Large VO2max?

• Elite athletes' distinguishing feature: large stroke volume (not higher maximum heart rate — athletes' HR_max is if anything lower than non-athletes)
• Large stroke volume ← large end-diastolic volume (EDV)
• End-systolic volume is not smaller in athletes — so EDV is the single most important factor
• Mechanism (Levine et al. 1991, direct invasive P-V curves):
  • Enhanced cardiac chamber compliance (both static P-V curves and operational compliance dV/dP)
  • Athletes use Starling mechanism to increase SV markedly
  • Contractility was not different between athletes and non-athletes — all SV difference explained by EDV
  • Largest male athletes: supine EDV ~250 mL during volume infusion → SV ~130–150 mL → at HR 200 → CO ~30 L/min
• Pericardial constraint: Pericardium limits maximal LV filling in normal hearts (Stray-Gundersen 1986 dogs; Hammond 1992 pigs — pericardiectomy increased EDV, CO, and VO2max)
• Elite athletes have compliant hearts AND distensible pericardiums — together enabling extraordinary EDV
• Rapid diastolic relaxation and active suction (Ferguson 2001): Athletes fill more rapidly at high heart rates; remodeled heart (increased equilibrium volume) creates mechanical restoring forces → diastolic suction pulls blood from LA across mitral valve into LV apex even during tachycardia
• Published records: largest CO during exercise 42.3 L/min (world-class orienteer; Ekblom 1968); largest SV 212 mL (world champion cyclist); highest VO2max 7.48 L/min (large elite skier; Saltin 1996)
• Theoretical upper limit of VO2max: ~8 L/min (combining max possible a-v O2 difference with highest reported exercise CO — likely lower in practice due to ventilatory limitations in athletes)

VO2max vs. Performance

• VO2max is NOT equivalent to sport performance (time to cover a distance)
• It is a major determinant of endurance performance, particularly over longer distances
• An elite athlete with VO2max 80 mL/kg/min can clearly outperform a recreational athlete with 40 mL/kg/min
• Other determinants of endurance performance: sport-specific economy; anaerobic capacity; fuel utilization; speed at maximal lactate steady state (Joyner 1991; Joyner & Coyle 2007)
• Athletes can perform briefly above VO2max (sprinters) — anaerobic contributions

Altitude and VO2max

• VO2max decreases with altitude — mechanism is pulmonary diffusion limitation (exaggerated in athletes due to high pulmonary blood flows)
• Endurance athletes may develop exercise-induced arterial hypoxaemia (EIAH) even at sea level
• Proof that altitude VO2max reduction is oxygen transport, not motor recruitment (Wehrlin & Hallen 2006):
  • Supramaximal running tests at constant speed (107% normoxic VO2max velocity) at altitudes 300–2800 m
  • VO2max reduced linearly 0.6% per 100 m altitude in direct proportion to SpO2 reduction
  • Performance reduced 1.4% per 100 m in direct proportion to VO2max decrease
  • Motor recruitment (running speed) was constant — refuting central governor explanation for altitude VO2max reduction
• At extreme altitude (3500 m, Medbo 1988): 100% of performance reduction was due to reduced accumulated O2 uptake; anaerobic capacity (O2 deficit) was unchanged

Why Do Athletes Stop at VO2max?

• Local skeletal muscle fatigue — oxygen-dependent mechanisms:
  • Failure of sarcoplasmic reticulum calcium release (Allen 2007)
  • Impaired Na/K pump activity — K+ accumulation (McKenna 2007)
  • Slowed cross-bridge cycling due to ROS and metabolic mediators (Fitts 2008; Ferriera & Reid 2008)
• These muscle factors activate afferent neural pathways → reduced central motor drive and neural activation (Todd 2007; Amann & Calbet 2007)
• Under severe acute hypoxia: central fatigue may be prominent and limit exercise before peripheral fatigue develops (Amann 2007)
• Key point: Multiple redundant mechanisms; factors may be more or less prominent in different circumstances

Genetic Factors and Phenotypic Plasticity

• VO2max is partially heritable (HERITAGE Family Study, Bouchard 1998): familial resemblance in sedentary state
• ACE gene (angiotensin-converting enzyme I/D polymorphism): early enthusiasm not confirmed — many successful endurance athletes lack the "endurance genotype" (multiple studies in Kenyans, cyclists, swimmers, orienteers)
• Training-induced cardiac adaptation: 1 year of training can achieve the same LV mass as elite endurance athletes (Morrow/Levine 1997, 1998)
• However, LV EDV and compliance remain much lower than in cross-sectional studies of elite athletes — suggesting:
  • Pericardial constraint requires more than 1 year to dilate/remodel
  • Optimal cardiac size and compliance may require training during growth and development (Saltin 1995)

Limitations of the Document

• Narrative topical review — no systematic methodology; reference selection reflects expert opinion
• Published 2008 — some specific genetic findings have evolved (GWAS era has superseded ACE gene focus)
• Hawkins 2007 study was in well-trained collegiate middle-distance runners — may not generalise to untrained populations or patients with cardiac disease
• Quantitative figures (largest published CO, SV, VO2max) are anecdotal high watermarks, not population estimates

Key Concepts Mentioned

• concepts/VO2max — primary topic; Fick equation; parametric limits; athlete determinants; altitude; fatigue mechanisms
• concepts/Athletes-Heart — LV compliance; EDV; pericardial constraint; diastolic suction; Starling mechanism
• concepts/Cardiopulmonary-Exercise-Testing — peak VO2 as prognostic marker; VO2max measurement methodology

Key Entities Mentioned

• No new entity pages required

Wiki Pages Updated

• wiki/sources/vo2max-jphysiol-2008 — created
• wiki/wikiindex.md — updated
• wiki/sourceindex.md — updated
• concepts/VO2max — new concept page created
• concepts/Athletes-Heart — new concept page created
• concepts/Cardiopulmonary-Exercise-Testing — updated with VO2max physiological basis