Am J Physiol Regul Integr Comp Physiol. 2004 Sep;287(3):R502-16
Exercise Science Program, Department of Physical Performance and Development, Johnson Center, Rm. B143, The University of New Mexico, Albuquerque, NM 87131-1258, USA. rrobergs@unm.edu
The development of acidosis during intense exercise has traditionally been explained by
the increased production of lactic acid, causing the release of a proton and the formation
of the acid salt sodium lactate. On the basis of this explanation, if the rate of lactate
production is high enough, the cellular proton buffering capacity can be exceeded,
resulting in a decrease in cellular pH. These biochemical events have been termed lactic
acidosis. The lactic acidosis of exercise has been a classic explanation of the
biochemistry of acidosis for more than 80 years. This belief has led to the
interpretation that lactate production causes acidosis and, in turn, that increased
lactate production is one of the several causes of muscle fatigue during intense
exercise. This review presents clear evidence that there is no biochemical support for
lactate production causing acidosis. Lactate production retards, not causes, acidosis.
Similarly, there is a wealth of research evidence to show that acidosis is caused by
reactions other than lactate production. Every time ATP is broken down to ADP and P(i),
a proton is released. When the ATP demand of muscle contraction is met by mitochondrial
respiration, there is no proton accumulation in the cell, as protons are used by the
mitochondria for oxidative phosphorylation and to maintain the proton gradient in the
intermembranous space. It is only when the exercise intensity increases beyond steady
state that there is a need for greater reliance on ATP regeneration from glycolysis and
the phosphagen system. The ATP that is supplied from these nonmitochondrial sources and
is eventually used to fuel muscle contraction increases proton release and causes the
acidosis of intense exercise. Lactate production increases under these cellular
conditions to prevent pyruvate accumulation and supply the NAD(+) needed for phase 2 of
glycolysis. Thus increased lactate production coincides with cellular acidosis and
remains a good indirect marker for cell metabolic conditions that induce metabolic acidosis.
If muscle did not produce lactate, acidosis and muscle fatigue would
occur more quickly and exercise performance would be severely impaired.