VO2 max

From WikiProjectMed
Jump to navigation Jump to search

V̇O2 max (also maximal oxygen consumption, maximal oxygen uptake or maximal aerobic capacity) is the maximum rate of oxygen consumption attainable during physical exertion.[1][2] The name is derived from three abbreviations: "V̇" for volume (the dot over the V indicates "per unit of time" in Newton's notation), "O2" for oxygen, and "max" for maximum and usually normalized per kilogram of body mass. A similar measure is V̇O2 peak (peak oxygen consumption), which is the measurable value from a session of physical exercise, be it incremental or otherwise. It could match or underestimate the actual V̇O2 max. Confusion between the values in older and popular fitness literature is common.[3] The capacity of the lung to exchange oxygen and carbon dioxide is constrained by the rate of blood oxygen transport to active tissue.

The measurement of V̇O2 max in the laboratory provides a quantitative value of endurance fitness for comparison of individual training effects and between people in endurance training. Maximal oxygen consumption reflects cardiorespiratory fitness and endurance capacity in exercise performance. Elite athletes, such as competitive distance runners, racing cyclists or Olympic cross-country skiers, can achieve V̇O2 max values exceeding 90 mL/(kg·min), while some endurance animals, such as Alaskan huskies, have V̇O2 max values exceeding 200 mL/(kg·min).

In physical training, especially in its academic literature, V̇O2 max is often used as a reference level to quantify exertion levels, such as 65% V̇O2 max as a threshold for sustainable exercise, which is generally regarded as more rigorous than heart rate, but is more elaborate to measure.

Normalization per body mass

V̇O2 max is expressed either as an absolute rate in (for example) litres of oxygen per minute (L/min) or as a relative rate in (for example) millilitres of oxygen per kilogram of the body mass per minute (e.g., mL/(kg·min)). The latter expression is often used to compare the performance of endurance sports athletes. However, V̇O2 max generally does not vary linearly with body mass, either among individuals within a species or among species, so comparisons of the performance capacities of individuals or species that differ in body size must be done with appropriate statistical procedures, such as analysis of covariance.[2]

Measurement and calculation

Measurement

VO2 max measurement using instruments on a metabolic cart during a graded treadmill exercise test
Gas exchange of VO2 and VCO2 during max test. Begin for 3 minutes at 60 watts and add 35 watts every 3 mins until exhaustion.

Accurately measuring V̇O2 max involves a physical effort sufficient in duration and intensity to fully tax the aerobic energy system. In general clinical and athletic testing, this usually involves a graded exercise test in which exercise intensity is progressively increased while measuring:

  • ventilation and
  • oxygen and carbon dioxide concentration of the inhaled and exhaled air.

V̇O2 max is measured during a cardiopulmonary exercise test (CPX test). The test is done on a treadmill or cycle ergometer. In untrained subjects, V̇O2 max is 10% to 20% lower when using a cycle ergometer compared with a treadmill.[4] However, trained cyclists' results on the cycle ergometer are equal to or even higher than those obtained on the treadmill.[5][6][7]

The classic V̇O2 max, in the sense of Hill and Lupton (1923), is reached when oxygen consumption remains at a steady state ("plateau") despite an increase in workload. The occurrence of a plateau is not guaranteed and may vary by person and sampling interval, leading to modified protocols with varied results.[3]

Calculation: the Fick equation

V̇O2 may also be calculated by the Fick equation: , when these values are obtained during exertion at a maximal effort. Here Q is the cardiac output of the heart, CaO2 is the arterial oxygen content, and CvO2 is the venous oxygen content. (CaO2CvO2) is also known as the arteriovenous oxygen difference.

The Fick equation may be used to measure V̇O2 in critically ill patients, but its usefulness is low even in non-exerted cases.[8] Using a breath-based VO2 to estimate cardiac output, on the other hand, seems to be reliable enough.[9]

Estimation using submaximal exercise testing

The necessity for a subject to exert maximum effort in order to accurately measure V̇O2 max can be dangerous in those with compromised respiratory or cardiovascular systems; thus, sub-maximal tests for estimating V̇O2 max have been developed.

The heart rate ratio method

An estimate of V̇O2 max is based on maximum and resting heart rates. In the Uth et al. (2004) formulation, it is given by:[10]

This equation uses the ratio of maximum heart rate (HRmax) to resting heart rate (HRrest) to predict V̇O2 max. The researchers cautioned that the conversion rule was based on measurements on well-trained men aged 21 to 51 only, and may not be reliable when applied to other sub-groups. They also advised that the formula is most reliable when based on actual measurement of maximum heart rate, rather than an age-related estimate.

The Uth constant factor of 15.3 is given for well-trained men.[10] Later studies have revised the constant factor for different populations. According to Voutilainen et al. 2020, the constant factor should be 14 in around 40-year-old normal weight never-smoking men with no cardiovascular diseases, bronchial asthma, or cancer.[11] Every 10 years of age reduces the coefficient by one, as well as does the change in body weight from normal weight to obese or the change from never-smoker to current smoker. Consequently, V̇O2 max of 60-year-old obese current smoker men should be estimated by multiplying the HRmax to HRrest ratio by 10.

Cooper test

Kenneth H. Cooper conducted a study for the United States Air Force in the late 1960s. One of the results of this was the Cooper test in which the distance covered running in 12 minutes is measured. Based on the measured distance, an estimate of V̇O2 max [in mL/(kg·min)] is:[citation needed]

where d12 is the distance (in metres) covered in 12 minutes.

An alternative equation is:

where d12 is distance (in miles) covered in 12 minutes.

Multi-stage fitness test

There are several other reliable tests and V̇O2 max calculators to estimate V̇O2 max, most notably the multi-stage fitness test (or beep test).[12]

Rockport fitness walking test

Estimation of V̇O2 max from a timed one-mile track walk in decimal minutes (t, e.g.: 20:35 would be specified as 20.58), gender, age in years, body weight in pounds (BW, lbs), and 60-second heart rate in beats-per-minute (HR, bpm) at the end of the mile.[13] The constant x is 6.3150 for males, 0 for females.

Reference values

Men have a V̇O2 max that is 26% higher (6.6 mL/(kg·min)) than women for treadmill and 37.9% higher (7.6 mL/(kg·min)) than women for cycle ergometer on average.[14] V̇O2 max is on average 22% higher (4.5 mL/(kg·min)) when measured using a cycle ergometer compared with a treadmill.[14]

V̇O2 percentiles by age group for treadmill and cycle ergometer cardiopulmonary exercise, in mL/(kg·min)[14]
Percentile Age group, in years
Men Women
20–29 30–39 40–49 50–59 60–69 70–79 80–89 20–29 30–39 40–49 50–59 60–69 70–79 80–89
Treadmill
90 58.6 55.5 50.8 43.4 37.1 29.4 22.8 49.0 42.1 37.8 32.4 27.3 22.8 20.8
80 54.5 50.0 45.2 38.3 32.0 25.9 21.4 44.8 37.0 33.0 28.4 24.3 20.8 18.4
70 51.9 46.4 40.9 34.3 28.7 23.8 20.0 41.8 33.6 30.0 26.3 22.4 19.6 17.3
60 49.0 43.4 37.9 31.8 26.5 22.2 18.4 39.0 31.0 27.7 24.6 20.9 18.3 16.0
50 46.5 39.7 35.3 29.2 24.6 20.6 17.6 36.6 28.3 25.7 22.9 19.6 17.2 15.4
40 43.6 37.0 32.4 26.9 22.8 19.1 16.6 34.0 26.4 23.9 21.5 18.3 16.2 14.7
30 40.0 33.5 29.7 24.5 20.7 17.3 16.1 30.8 24.2 21.8 20.1 17.0 15.2 13.7
20 35.2 29.8 26.7 22.2 18.5 15.9 14.8 27.2 21.9 19.7 18.5 15.4 14.0 12.6
10 28.6 24.9 22.1 18.6 15.8 13.6 12.9 22.5 18.6 17.2 16.5 13.4 12.3 11.4
Cycle ergometer
90 62.2 50.5 41.9 37.1 31.4 26.2 18.7 46.0 32.0 27.3 22.4 20.3 18.0 18.1
80 57.0 39.0 35.1 31.6 27.0 22.6 17.3 40.9 27.0 23.5 20.4 18.5 16.8 14.3
70 52.8 35.5 31.4 28.4 24.5 20.6 16.2 37.5 24.5 21.8 18.9 17.4 15.9 12.9
60 48.3 31.6 29.0 26.3 23.3 19.4 14.6 34.3 22.9 20.3 17.8 16.4 15.0 11.3
50 44.0 30.2 27.4 24.5 21.7 18.3 13.2 31.6 21.6 18.8 16.9 15.7 14.5 10.9
40 40.8 27.9 25.4 23.1 20.7 17.1 12.2 28.9 19.9 17.9 16.1 15.0 13.6 10.1
30 37.4 25.7 23.8 22.0 19.1 16.0 11.1 25.6 18.6 16.6 15.2 14.2 12.9 9.4
20 34.5 22.6 21.9 20.2 17.5 14.7 9.7 21.9 17.0 15.4 14.3 13.4 12.0 8.7
10 28.8 19.1 19.8 17.2 14.7 11.0 8.4 18.8 15.0 13.7 13.0 12.2 10.7 7.8

Effect of training

Non-athletes

The average untrained healthy male has a V̇O2 max of approximately 35–40 mL/(kg·min).[15][16] The average untrained healthy female has a V̇O2 max of approximately 27–31 mL/(kg·min).[15] These scores can improve with training and decrease with age, though the degree of trainability also varies widely.[17]

Athletes

In sports where endurance is an important component in performance, such as road cycling, rowing, cross-country skiing, swimming, and long-distance running, world-class athletes typically have high V̇O2 max values. Elite male runners can consume up to 85 mL/(kg·min), and female elite runners can consume about 77 mL/(kg·min).[18]

High values in absolute terms for humans may be found in rowers, as their greater bulk makes up for a slightly lower V̇O2 max per body weight. Elite oarsmen measured in 1984 had V̇O2 max values of 6.1±0.6 L/min and oarswomen 4.1±0.4 L/min.[19] New Zealand sculler Rob Waddell has one of the highest absolute V̇O2 max levels ever tested.[20]

Animals

V̇O2 max has been measured in other animal species. During loaded swimming, mice had a V̇O2 max of around 140 mL/(kg·min).[21] Thoroughbred horses had a V̇O2 max of around 193 mL/(kg·min) after 18 weeks of high-intensity training.[22] Alaskan huskies running in the Iditarod Trail Sled Dog Race had V̇O2 max values as high as 240 mL/(kg·min).[23] Estimated V̇O2 max for pronghorn antelopes was as high as 300 mL/(kg·min).[24]

Limiting factors

The factors affecting V̇O2 may be separated into supply and demand.[25] Supply is the transport of oxygen from the lungs to the mitochondria (combining pulmonary function, cardiac output, blood volume, and capillary density of the skeletal muscle) while demand is the rate at which the mitochondria can reduce oxygen in the process of oxidative phosphorylation.[25] Of these, the supply factors may be more limiting.[25][26] However, it has also been argued that while trained subjects are probably supply limited, untrained subjects can indeed have a demand limitation.[27]

General characteristics that affect V̇O2 max include age, sex, fitness and training, and altitude. V̇O2 max can be a poor predictor of performance in runners due to variations in running economy and fatigue resistance during prolonged exercise. The body works as a system. If one of these factors is sub-par, then the whole system's normal capacity is reduced.[27]

The drug erythropoietin (EPO) can boost V̇O2 max by a significant amount in both humans and other mammals.[28] This makes EPO attractive to athletes in endurance sports, such as professional cycling. EPO has been banned since the 1990s as an illicit performance-enhancing substance. But by 1998 it had become widespread in cycling and led to the Festina affair[29][30] as well as being mentioned ubiquitously in the USADA 2012 report on the U.S. Postal Service Pro Cycling Team.[31] Greg LeMond has suggested establishing a baseline for riders' V̇O2 max (and other attributes) to detect abnormal performance increases.[32]

Clinical use to assess cardiorespiratory fitness and mortality

V̇O2 max/peak is widely used as an indicator of cardiorespiratory fitness (CRF) in select groups of athletes or, rarely, in people under assessment for disease risk. In 2016, the American Heart Association (AHA) published a scientific statement recommending that CRF – quantifiable as V̇O2 max/peak – be regularly assessed and used as a clinical vital sign; ergometry (exercise wattage measurement) may be used if VO2 is unavailable.[33] This statement was based on evidence that lower fitness levels are associated with a higher risk of cardiovascular disease, all-cause mortality, and mortality rates.[33] In addition to risk assessment, the AHA recommendation cited the value for measuring fitness to validate exercise prescriptions, physical activity counseling, and improve both management and health of people being assessed.[33]

A 2023 meta-analysis of observational cohort studies showed an inverse and independent association between V̇O2 max and all-cause mortality risk.[34] Every one metabolic equivalent increase in estimated cardiorespiratory fitness was associated with an 11% reduction in mortality.[34] The top third of V̇O2 max scores represented a 45% lower mortality in people compared with the lowest third.[34]

As of 2023, V̇O2 max is rarely employed in routine clinical practice to assess cardiorespiratory fitness or mortality due to its considerable demand for resources and costs.[35][36]

History

British physiologist Archibald Hill introduced the concepts of maximal oxygen uptake and oxygen debt in 1922.[37][26] Hill and German physician Otto Meyerhof shared the 1922 Nobel Prize in Physiology or Medicine for their independent work related to muscle energy metabolism.[38] Building on this work, scientists began measuring oxygen consumption during exercise. Key contributions were made by Henry Taylor at the University of Minnesota, Scandinavian scientists Per-Olof Åstrand and Bengt Saltin in the 1950s and 60s, the Harvard Fatigue Laboratory, German universities, and the Copenhagen Muscle Research Centre.[39][40]

See also

References

  1. ^ Clemente C. J.; Withers P. C.; Thompson G. G. (2009). "Metabolic rate and endurance capacity in Australian varanid lizards (Squamata; Varanidae; Varanus)". Biological Journal of the Linnean Society. 97 (3): 664–676. doi:10.1111/j.1095-8312.2009.01207.x.
  2. ^ a b Dlugosz, Elizabeth M.; Chappell, Mark A.; Meek, Thomas H.; Szafrańska, Paulina; Zub, Karol; Konarzewski, Marek; Jones, James H.; Bicudo, Eduardo; Nespolo, Roberto F.; Careau, Vincent; Garland, Theodore (2013). "Phylogenetic analysis of mammalian maximal oxygen consumption during exercise" (PDF). Journal of Experimental Biology. 216 (24): 4712–4721. doi:10.1242/jeb.088914. PMID 24031059. S2CID 15686903.
  3. ^ a b Smirmaul, BP; Bertucci, DR; Teixeira, IP (2013). "Is the VO2max that we measure really maximal?". Frontiers in Physiology. 4: 203. doi:10.3389/fphys.2013.00203. PMC 3733001. PMID 23935584.
  4. ^ Kaminsky, Leonard A.; Imboden, Mary T.; Arena, Ross; Myers, Jonathan (2017). "Reference Standards for Cardiorespiratory Fitness Measured With Cardiopulmonary Exercise Testing Using Cycle Ergometry: Data From the Fitness Registry and the Importance of Exercise National Database (FRIEND) Registry". Mayo Clinic Proceedings. 92 (2): 228–233. doi:10.1016/j.mayocp.2016.10.003. PMID 27938891. S2CID 3465353.
  5. ^ Basset, Fabien A.; Boulay, Marcel R. (1 January 2000). "Specificity of treadmill and cycle ergometer tests in triathletes, runners and cyclists". European Journal of Applied Physiology. 81 (3): 214–221. doi:10.1007/s004210050033. ISSN 1439-6319. PMID 10638380. S2CID 24902705.
  6. ^ Bouckaert, J.; Vrijens, J.; Pannier, J. L. (1990). "Effect of specific test procedures on plasma lactate concentration and peak oxygen uptake in endurance athletes". The Journal of Sports Medicine and Physical Fitness. 30 (1): 13–18. ISSN 0022-4707. PMID 2366529.
  7. ^ Costa, M. M.; Russo, A. K.; Pićarro, I. C.; Barros Neto, T. L.; Silva, A. C.; Tarasantchi, J. (1989). "Oxygen consumption and ventilation during constant-load exercise in runners and cyclists". The Journal of Sports Medicine and Physical Fitness. 29 (1): 36–44. ISSN 0022-4707. PMID 2770266.
  8. ^ Thrush, DN (January 1996). "Spirometric versus Fick-derived oxygen consumption: which method is better?". Critical Care Medicine. 24 (1): 91–5. doi:10.1097/00003246-199601000-00016. PMID 8565545.
  9. ^ Fanari, Z; Grove, M; Rajamanickam, A; Hammami, S; Walls, C; Kolm, P; Saltzberg, M; Weintraub, WS; Doorey, AJ (June 2016). "Cardiac output determination using a widely available direct continuous oxygen consumption measuring device: a practical way to get back to the gold standard". Cardiovascular Revascularization Medicine: Including Molecular Interventions. 17 (4): 256–61. doi:10.1016/j.carrev.2016.02.013. PMC 4912455. PMID 26976237.
  10. ^ a b Uth, Niels; Henrik Sørensen; Kristian Overgaard; Preben K. Pedersen (January 2004). "Estimation of VO2max from the ratio between HRmax and HRrest--the Heart Rate Ratio Method" (PDF). Eur J Appl Physiol. 91 (1): 111–5. doi:10.1007/s00421-003-0988-y. PMID 14624296. S2CID 23971067.
  11. ^ Voutilainen, Ari; Mounir Ould Setti; Tomi-Pekka Tuomainen (July 2020). "Estimating Maximal Oxygen Uptake from the Ratio of Heart Rate at Maximal Exercise to Heart Rate at Rest in Middle-Aged Men" (PDF). World J Mens Health. 38 (4): 666–672. doi:10.5534/wjmh.200055. ISSN 2287-4208. PMC 8443998. PMID 32777866.
  12. ^ [Leger, Luc A., and J_ Lambert. "A maximal multistage 20-m shuttle run test to predict\ dot VO2 max." European journal of applied physiology and occupational physiology 49.1 (1982): 1-12.]
  13. ^ Kilne G, et al. (1987). "Estimation of VO2 max from a one mile track walk, gender, age and body weight". Med. Sci. Sports Exerc. 19 (3): 253–259. PMID 3600239.
  14. ^ a b c Kaminsky, Leonard A.; Arena, Ross; Myers, Jonathan; Peterman, James E.; Bonikowske, Amanda R.; Harber, Matthew P.; Medina Inojosa, Jose R.; Lavie, Carl J.; Squires, Ray W. (2022). "Updated Reference Standards for Cardiorespiratory Fitness Measured with Cardiopulmonary Exercise Testing". Mayo Clinic Proceedings. 97 (2): 285–293. doi:10.1016/j.mayocp.2021.08.020. PMID 34809986.
  15. ^ a b Heyward, V (1998). "Advance Fitness Assessment & Exercise Prescription, 3rd Ed". p. 48.
  16. ^ Guyton, A.; Hall, J.E. (2011). "Textbook of Medical Physiology, 12th Ed". pp. 1035–1036.
  17. ^ Williams, Camilla; Williams, Mark; Coombes, Jeff (14 November 2017). "Genes to predict VO2max trainability: a systematic review". BMC Genomics. 18 (Suppl 8): 831. doi:10.1186/s12864-017-4192-6. PMC 5688475. PMID 29143670.
  18. ^ Noakes, Tim (2001). The Lore of Running. (3rd edition) Oxford University Press ISBN 978-0-88011-438-7
  19. ^ Hagerman, FC (July–August 1984). "Applied physiology of rowing". Sports Med. 1 (4): 303–26. doi:10.2165/00007256-198401040-00005. PMID 6390606. S2CID 35619324.
  20. ^ Gough, Martin (17 June 2009). "Monsters wanted". BBC. Archived from the original on 1 November 2010.
  21. ^ Glaser, R. M.; Gross, P. M.; Weiss, H. S. (1972). "Maximal aerobic metabolism of mice during swimming". Experimental Biology and Medicine. 140 (1): 230–233. doi:10.3181/00379727-140-36431. PMID 5033099. S2CID 378983.
  22. ^ Kitaoka, Y.; Masuda, H.; Mukai, K.; Hiraga, A.; Takemasa, T.; Hatta, H. (2011). "Effect of training and detraining on monocarboxylate transporter (MCT) 1 and MCT4 in Thoroughbred horses". Experimental Physiology. 96 (3): 348–55. doi:10.1113/expphysiol.2010.055483. PMID 21148623. S2CID 28298003.
  23. ^ Roger Segelke (9 December 1996). "Winterize Rover for cold-weather fitness, Cornell veterinarian advises". Cornell University Chronicle. Retrieved 7 December 2018.
  24. ^ Lindstedt, S. L.; Hokanson, J. F.; Wells, D. J.; Swain, S. D.; Hoppeler, H.; Navarro, V. (1991). "Running energetics in the pronghorn antelope". Nature. 353 (6346): 748–50. Bibcode:1991Natur.353..748L. doi:10.1038/353748a0. PMID 1944533. S2CID 4363282.
  25. ^ a b c Bassett D.R Jr.; Howley E.T. (2000). "Limiting factors for maximum oxygen uptake and determinants of endurance performance". Med Sci Sports Exerc. 32 (1): 70–84. doi:10.1097/00005768-200001000-00012. PMID 10647532.
  26. ^ a b Bassett, David R.; Howley, Edward T. (May 1997). "Maximal oxygen uptake: 'classical' versus 'contemporary' viewpoints". Medicine &amp Science in Sports &amp Exercise. 29 (5): 591–603. doi:10.1097/00005768-199705000-00002. PMID 9140894.
  27. ^ a b Wagner P.D. (2000). "New ideas on limitations to VO2max". Exercise and Sport Sciences Reviews. 28 (1): 10–4. PMID 11131681.
  28. ^ Kolb E. M. (2010). "Erythropoietin elevates V.O2, max but not voluntary wheel running in mice". Journal of Experimental Biology. 213 (3): 510–519. doi:10.1242/jeb.029074. PMID 20086137.
  29. ^ Lundby C.; Robach P.; Boushel R.; Thomsen J. J.; Rasmussen P.; Koskolou M.; Calbet J. A. L. (2008). "Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport?". Journal of Applied Physiology. 105 (2): 581–7. doi:10.1152/japplphysiol.90484.2008. hdl:10553/6534. PMID 18535134.
  30. ^ Lodewijkx Hein F.M.; Brouwer Bram (2011). "Some Empirical Notes on the Epo Epidemic in Professional Cycling". Research Quarterly for Exercise and Sport. 82 (4): 740–754. doi:10.5641/027013611X13275192112069. PMID 22276416.
  31. ^ "U.S. Postal Service Pro Cycling Team Investigation". USADA. October 2012. Retrieved 4 January 2023.
  32. ^ Conal Andrews (28 July 2010). "Greg LeMond's suggestions for a credible future for cycling". velonation.com. Retrieved 4 January 2023.
  33. ^ a b c Ross, Robert; Blair, Steven N.; Arena, Ross; et al. (13 December 2016). "Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart Association". Circulation. 134 (24): e653–e699. doi:10.1161/CIR.0000000000000461. PMID 27881567. S2CID 3372949.
  34. ^ a b c Laukkanen, Jari A.; Isiozor, Nzechukwu M.; Kunutsor, Setor K. (2022). "Objectively Assessed Cardiorespiratory Fitness and All-Cause Mortality Risk" (PDF). Mayo Clinic Proceedings. 97 (6): 1054–1073. doi:10.1016/j.mayocp.2022.02.029. PMID 35562197. S2CID 248737752.
  35. ^ Kaminsky, Leonard A.; Imboden, Mary T.; Ozemek, Cemal (2023). "It's Time to (Again) Recognize the Considerable Clinical and Public Health Significance of Cardiorespiratory Fitness". Journal of the American College of Cardiology. 81 (12): 1148–1150. doi:10.1016/j.jacc.2023.02.004. PMID 36948730. S2CID 257649017.
  36. ^ Lavie, Carl J.; Arena, Ross; Kaminsky, Leonard A. (2022). "Making the Case to Measure and Improve Cardiorespiratory Fitness in Routine Clinical Practice". Mayo Clinic Proceedings. 97 (6): 1038–1040. doi:10.1016/j.mayocp.2022.04.011. PMID 35570068.
  37. ^ Hale, Tudor (15 February 2008). "History of developments in sport and exercise physiology: A. V. Hill, maximal oxygen uptake, and oxygen debt". Journal of Sports Sciences. 26 (4): 365–400. doi:10.1080/02640410701701016. PMID 18228167. S2CID 33768722.
  38. ^ "The Nobel Prize in Physiology or Medicine 1922". Nobel Foundation. Retrieved 11 October 2018.
  39. ^ Seiler, Stephen (2011). "A Brief History of Endurance Testing in Athletes" (PDF). Sportscience. 15 (5).
  40. ^ "History of Exercise Physiology". Human Kinetics Europe. Retrieved 11 October 2018.