I am quite confused regarding what limits the VO2 max, options are (1) number of mitochondria or (2) the ability of the cardiovascular system to deliver oxygen to tissues.

I believe it should be the # of mitochondria, as O2 is the last electron acceptor in the ETC, so if for example one had few mitochondria, then his maximal oxygen consumption ought to be way lower than another person with greater # of mitochondria.

My textbook (Guyton and Hall Textbook of Medical Physiology, 13e) says (though with no direct consideration of mitochondria):

"During maximal exercise, both the heart rate and stroke volume are increased to about 95 percent of their maximal levels. Because the cardiac output is equal to stroke volume times heart rate, one finds that the cardiac output is about 90 percent of the maximum that the person can achieve, which is in contrast to about 65 percent of maximum for pulmonary ventilation. Therefore, one can readily see that the cardiovascular system is normally much more limiting on V􏰃 O max than is the respiratory system, because oxygen 2 utilization by the body can never be more than the rate at which the cardiovascular system can transport oxygen to the tissues."

Your help is appreciated.

  • 1
    Why would having more mitochondria help if you were already using all the oxygen that the cardiovascular system can deliver?
    – Bryan Krause
    Jan 22 at 14:37
  • @BryanKrause good point, my point is: how would it help if the cardiovascular system was delivering oxygen more than what the mitochondrias can use (in other words, the mitochondria can also be a limiting factor) do you see my point? Jan 22 at 15:40
  • The original question (I assume this is for a homework/exam/similar?) is not asking you theoretically which could be the limiting factor (obviously, either could be), it's asking you practically which is the limiting factor. If that question is based on the textbook you're reading, and the textbook isn't mentioning mitochondria, what do you think makes sense?
    – Bryan Krause
    Jan 22 at 15:47
  • This question was asked by our professor during the lecture, and he said try to find the answers yourselves, and it might come in the exam. Knowing my professor, he looks at things in a very abstract and objective way. So thought I'd seek a definite answer, if you have any. Jan 22 at 16:58

1 Answer 1


I found a paper the relevance of which you can see by its very title: Central cardiovascular system limits to aerobic capacity:

According to this paper, the main limiting factor indeed is cardiac output, more specifically stroke volume:

[T]he primary physiological determinant of V˙O2max in most humans under most circumstances is cardiac output. Indeed there is a tight (r > 0.9) linear correlation between peak cardiac output and V˙O2max (expressed in l min−1) across a wide range of values. Because maximum heart rate is reasonably similar across most young humans, stroke volume (the amount of blood pumped per heart beat) is perhaps the most critical physiological or structural component of V˙O2max in humans (Lundby, Montero, & Joyner, 2017). (bolded mine)

Yet, there is another critical variable (one which most doping techniques and more or less dubious training methods work on): haemoglobin.

In addition to cardiac output, red blood cell mass (or total body haemoglobin) is an important co-determinant of V˙O2max (Astrand, 1952). Because red cells together with haemoglobin carry oxygen, these factors operate in concert to generate a high arterial O2 content that can deliver oxygen to the contracting skeletal muscles.

Last but not least, and I am positively surprised that the study discusses this, it is also important where and how the oxygen is used:

In addition to absolute cardiac output, it is also important to consider the relative distribution of blood flow. Specifically, early studies demonstrated that leg blood flow decreased when arm exercise was superimposed on cycling exercise (Secher, Clausen, Klausen, Noer, & Trap-Jensen, 1977). This competitive nature between vascular beds was conclusively demonstrated with simultaneous upper and lower limb blood flow measures in highly trained skiers (Calbet et al., 2004). In addition to working locomotor muscle, the metabolic needs of the respiratory muscles also needs to be considered. Specifically, the respiratory muscles have been shown to influence blood flow distribution, which can impact performance (Harms, Wetter, St Croix, Pegelow, & Dempsey, 2000).

One direct consequence is that the breathing technique makes a lot of difference since, as every runner should know, using a lot of upper thoracic respiratory muscles (intercostal, neck) is much more burdensome for the body than deep abdominal breathing and may at some point be a limiting factor as breathing itself starts to take up a significant part of oxygen consumption.

On how numbers of mitochondria and VO2Max correlate

The paper has a brilliant paragraph on this, too, and the take-away message is: not at all, really:

A hallmark of endurance exercise training, as first shown by John Hollsozy, is an increase in the mitochondrial content of the skeletal muscles that are subject to training (Holloszy, 1967). In response to prolonged and intense training, mitochondrial content can double. When observations of mitochondrial adaptations to training were first made, it was argued that they contributed to the increase in V˙O2max seen with training. However, highly trained individuals can have similar mitochondrial adaptations in their trained muscles, yet their V˙O2max values can vary by 1.5- to 2-fold (Holloszy & Coyle, 1984; Lundby & Jacobs, 2016). Additionally, in a brilliant series of studies in rats, Davies and colleagues used dietary iron deficiency to limit mitochondrial function in skeletal muscles in conjunction with blood transfusion to normalize red blood cell parameters. With that experimental paradigm, they showed that V˙O2max could be dissociated from mitochondrial function (Davies et al., 1984; Davies, Maguire, Brooks, Dallman, & Packer, 1982).


Scientific sources seem to agree that while number of mitochondria may influence the max power (as in work/time, which is at about 30% max strength and aerobic) of a specific muscle, the systemic max sustainable output (of which VO2Max is a measurement) is determined predominantly by cardiovascular variables.

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