VO₂ max: The Limiting Factors of Maximum Oxygen Uptake

VO₂ max, commonly known as maximum oxygen uptake, is defined as the highest rate that oxygen can be inspired and utilized in the body during severe exercise at sea level. Consequently, VO₂ max represents the maximal rate of aerobic respiration in the mitochondria and is a measure of an individual's maximal capacity to work aerobically. When exercising at work rates above VO₂ max the energy for this additional work is met entirely through anaerobic metabolism i.e. anaerobic glycolysis. Its current concept originated with the work of Hill et al. in 1923, hypothesising that¹:

•           An upper limit to oxygen uptake exists.
•           There are inter individual differences in VO₂ max.
•           A high VO₂ max is a prerequisite for success in middle- and long-distance running.
•           VO₂ max is limited by the ability of the cardiorespiratory system to transport O₂.

Although there are various inherent physiological limitations to VO₂ max, which will be discussed in turn later in this article, there are other mediums by which VO₂ is also influenced by. The first of which is the fitness level of the individual in question, typically the highest VO₂ max values are seen in athletes which participant in whole body endurance activities such cross-country skiing or long distance running. Another consideration is age, after the age of 25 VO₂ max tends to decline by 1% each year with muscle sarcopenia (the degenerative loss of skeletal muscle mass) accounting for much of the major decrease in values observed at old age. Lastly, gender contributes to a great deal of variation seen in VO₂ max values. Males possess greater amounts of muscle mass along with a larger heart and lungs, all of which allow for superior oxygen transportation. On the other hand, women vary in body composition by increased fat percentage, less muscle mass and smaller heart/lungs.

Perhaps the principal rule to consider when discussing the maximum oxygen uptake is the Fick equation, which is as follows:  

·         VO₂ = CO x a-v O₂ difference
So, VO₂ max = Maximal CO x max a-v O₂ difference.

In this equation, CO represents the cardiac output – in other words central oxygen delivery. On the other hand, a-v O₂ difference relates to the peripheral oxygen utilization - the difference in the oxygen content of the blood between the arterial blood and the venous blood.  Ultimately, maximal utilization of oxygen at the tissues requires an effective O₂ transport cascade and it is the limitations of this pathway which will determine VO₂ max:

Air    -    Alveolar    -    Arterial    -    Capillary    -    Myoglobin    -    Mitochondria.

The first of the limiting physiological factors to maximum oxygen uptake is the pulmonary system, this includes the lungs and the muscles of breathing and is responsible for the delivery of oxygen/removal of carbon dioxide from the blood. Surprisingly, with regards to this system it has been seen in highly trained athletes that arterial O₂ desaturation during maximal work occurs². Although trained individuals have a far superior maximal cardiac output than their sedentary counterparts, this leads to decreased transit time of the red blood cell in the pulmonary capillary. Consequently, there is not sufficient time to saturate the blood with oxygen before it exits the pulmonary capillary, thus significantly reducing the potential quantity of oxygen available to the working skeletal muscle.

In the field of sports science we know that the normal range of VO₂ max values among sedentary and untrained individuals is mainly due to variation in maximal stroke volume, since considerably less variation exists in maximum heart rate and systemic oxygen extraction. Throughout maximal exercise almost all of the available oxygen is extracted from the blood that circulates the active muscles³, the approximate oxygen content of arterial blood is 200mL O₂∙L⁻¹ and in venous blood draining maximally this falls to about 20-30mL O₂∙L⁻¹. Showing there is little oxygen remaining for extraction during severe exercise. As a result the principal method for increasing the VO₂ max with relevant training must be an increase in blood flow, it is estimated that 70-85% of maximum oxygen uptake is linked to maximal cardiac output.⁴
A variety of longitudinal studies have displayed the notion that a training induced VO₂ max increase results from a greater cardiac output, as opposed to a widening of the a-vO₂ difference.⁵  

Within the active skeletal muscle fibres, the mitochondria act as the site where oxygen is consumed in the final step of the electron transport chain during aerobic respiration. It would be reasonable to suggest that an increase in the number of mitochondria would result in a higher maximum oxygen uptake. However, one study observed a modest 20-40% increase in VO₂ max despite a 2.2 fold increase in mitochondrial enzymes⁶. This finding is constant with the view that maximal oxygen uptake during a bout of whole body exercise is limited by oxygen delivery, not it’s utilization at the skeletal muscle.  

1985 saw the definitive research experiment showing that maximal oxygen uptake is limited by oxygen delivery due to restricted blood flow. Saltin et al⁷ observed the effects of maximal exercise using only a small amount of muscle mass, allowing a great amount of cardiac output to be directed onto a concentrated area. Under such conditions the measure oxygen uptake at the quadriceps was 2-3 times than in the same area during a whole body maximal bout of activity. It was therefore concluded that skeletal muscle has a remarkable capacity for blood flow and thus VO₂, however this simply cannot be matched by maximal cardiac output of the heart during whole body exercise. Proving that VO₂ max is bound by the delivery of oxygen and not by the ability of the mitochondria to utilize oxygen.

From the wide range of studies and research discussed throughout this article, it is clear that each step in the pathway of oxygen transport contributes to the determination of VO₂ max. A reduction in this transportation network will predictably result in a lower maximal oxygen uptake. The evidence also demonstrates that it is primarily the ability of the cardiorespiratory system to transport oxygen to the skeletal muscle and not the muscle mitochondria’s ability to consume it that limits and athlete’s VO₂ max value.

References

1.  Hill, D.K. and Lupton, H. (1923) Muscular exercise, lactic acid and the supply and utilisation of oxygen. Quarterly Journal of Medicine. 16: 135-171.
2.    Dempsey, J.A., Hanson, P.G., and Henderson, K.S. (1984). Exercise-induced arterial hypoxaemia in healthy human subjects at sea level. Journal of Physiology. 355: 161-175
3.   Shephard, R. (1977) Endurance Fitness. Toronto and Buffalo: Univ. of Toronto Press. 2:64–103.
4.  Cerretelli P, Di Prampero PE. (1987). Gas exchange in exercise. Handbook of Physiology. The Respiratory System. 4: 297–339.
5.   Ekblom, B., Åstrand, P.O., Saltin, B., Stenburg, J., and Wallstrom, B. (1968) Effect of training on circulatory response to exercise. Journal of Applied Physiology. 24:518–528
6.  Saltin, B., Henriksson, J., Nygaard, E. and Andersen, P. (1977) Fiber types and metabolic potentials of skeletal muscles in sedentary man and endurance runners. Annals of the New York Academy of Sciences. 301:3–29.
7.  Saltin, B. (1985) Hemodynamic adaptations to exercise. American Journal of Cardiology. 55:42-47