PHYSIOLOGY
Lactic Acid The Latest
Performance-Enhancing Drug
David Allen and Hákan Westerblad
The 2004 Athens Olympics will undoubtedly see many records broken.
Improved performances will be attributed to better training, superior
genes, or the use of performance-enhancing drugs, both legal and
illegal. From a physiological perspective, one of the major limits to
improved performance is the decline in muscle function as muscles are
used intensively and repeatedly—a phenomenon called muscle fatigue.
Many of the approaches used by athletes to enhance their performance,
such as creatine supplementation, carbohydrate loading, and training
at high altitude, are targeted at the various pathways that
con-tribute to muscle fatigue. For many athletes, coaches, and sports
commentators, muscle fatigue and the accumulation of lactic acid
(generated from the anaerobic breakdown of glycogen) are more or less
synonymous. However, the importance of lactic acid in muscle fatigue
is now under scrutiny (1): On page 1144 of this issue, Pedersen et al.
(2) present a further challenge to the traditional view with their
demonstration that lactic acid, in fact, has beneficial effects on the
performance of fatigued muscles. They show in rat muscle fiber
preparations that lactic acid influences the activity of chloride ion
(Cl-) channels, which in turn sustains the action potentials that are
necessary for muscle contraction.
It was A. V. Hill in 1929 who proposed that the accumulation of lactic
acid in muscles contributes to muscle fatigue (3). Using preparations
of isolated frog muscle removed from solution and kept in nitrogen,
Hill showed that, following electrical stimulation, mechanical
performance gradually declined as the muscle accumulated large amounts
of lactic acid. However, if the muscle preparation was transferred to
a saline solution equilibrated with nitrogen, which enabled the
lac-tic acid to diffuse away, muscle performance improved. Such
experiments, and their equivalents in mammalian muscle, suggested that
accumulation of intracellular lactic acid
might be a principal cause of muscle fatigue. The theoretical basis
for this idea was provided by Fabiato (4), who showed that increased
intracellular acidification (acidosis) of muscle due to accumulation
of lactic acid blocked force production by the muscle's contractile
proteins.
Doubts about the importance of lactic acid in muscle fatigue, however,
have accrued since these early studies. For in-stance, humans
deficient in the enzyme myophosphorylase are unable to break down
glycogen or accumulate lactic acid, but their muscles fatigue more
rapidly than normal (5). The direct depressant effect of acidosis on
contractile proteins, clearly evident at or below room temperature, is
greatly reduced at body temperature (6). Work on single muscle fibers
has shown that when muscle cells are intentionally rendered acidic,
the rate of fatigue remains unchanged (7).
It was Nielsen and his colleagues who ushered in a new phase in our
understanding of the effects of muscle acidosis (8). They argued that
the accumulation of extracellular potassium ions (K+) is a key
component of muscle fatigue and showed that force in an isolated
muscle declined steeply when the K+ concentration in-creased.
Importantly, if the muscle was rendered acidic, much of the decline in
force was reversed and was accompanied by recovery of action potential
generation.
In the new study, Pedersen et al. (2) take this observation a step
further using a preparation of "skinned" single muscle fibers from the
rat. In their preparation, the surface membrane of the muscle fiber is
removed (mechanical skinning), but the internal network of tubules in
the fiber (T-
tubules) seals over and retains its function-al connection to the
sarcoplasmic reticulum. This intriguing preparation can be activated
in various ways. Crucially for these experiments, electrical
stimulation generates action potentials in the sealed T-tubules and
causes normal release of calcium ions (Caz+) from the sarcoplasmic
reticulum, resulting in muscle contraction.
The investigators noted that when action potentials stimulated Cat+
release, mild de-polarization of the T-tubules caused a large
reduction in contractile force but, as Neilsen et al. found (8), this
effect could be partially re-versed by acidosis. Their key observation
is that this effect could be eliminated by removing Cl- from the
solution bathing the muscle preparation, suggesting that acidosis
exerts a beneficial effect on Cl- channel activity. A central feature
of the new mechanism is that the accumulation'of extracellular K+
results in action potentials becoming a less effective trigger of Caz+
release in working muscles. Acidosis reduces this effect by decreasing
the contribution of Cl- channels, which act to clamp the membrane
potential near the chloride reversal potential. Because the chloride
reversal potential is near the resting membrane potential, the effect
of Clchannel activity is to increase the amount of sodium ion (Na+)
current necessary to generate an action potential, which then triggers
Cat+ release. This mechanism will only operate under conditions in
which the amplitude of the action potential has be-come a
rate-limiting step for muscle activity. Unfortunately, it is not easy
to establish whether this is the case in different types of muscle
fatigue.
The Pedersen et al. findings add to the complexity of the contribution
of intracellular and extracellular acidosis to muscle performance.
Generated by the anaerobic breakdown of glycogen, lactic acid is, from
the standpoint of active muscle, an inefficient way to produce ATP. An
increase in intracellular acidosis will affect the function of many
intracellular proteins besides contractile proteins, but we do not yet
know which of these are important for muscle contraction. Lactic acid
is ferried out of muscle cells by lactate transporter proteins,
creating an extracellular acidosis, which probably contributes to the
painful sensations of muscle fatigue experienced by athletes. Once in
the circulation, lactate
can be metabolized by other tissues and may be involved in the
regulation of the respiratory and circulatory systems.
Fatigue has many sources that may be present at different sites in
muscle cells. Many constituents of muscle metabolism (lactic acid,
glycogen, phosphocreatine, in-organic phosphate, ATP, Cat+, Na+, K+)
change during fatigue and, for each of these, we need to know which
proteins are affected and how these proteins regulate muscle
contraction. Equally important is the effect of multiple cellular
changes on muscle activity in the intact animal. Athletes and trainers
who keep abreast of these issues may potentially be able to modify
aspects of their training or performance in ways that give them a
competitive edge.
References
1. H. Westerblad et aL, News Physiol Sci. 17, 17 (2002).
2. T. H. Pedersen et at., Science 305, 1144 (2004).
3. A. V. Hill, P. Kupalov, Proc. R. Soc. London Ser. B 105,
313 (1929).
4. A. Fabiato, F. Fabiato, J. Physiol (London) 276, 233 (1978).
5. E. B. Cady et aL, J. Physiol (London) 418, 311 (1989).
6. E. Pate et aL, J. Physiol. (London) 486, 689 (1995).
7. J. D. Bruton et aL, J. Appl. Physiol. 85, 478 (1998).
8. O. B. Nielsen et al, J. PhysioL 536, 161 (2001).
1112-1113 20 AUGUST 2004 VOL 305 SCIENCE www.sciencemag.org
D. Allen is at the Institute of Biomedical Research, University of
Sydney, NSW 2006, Australia. H. Westerblad is at the Karolinska
Institute, S-171 77 Stockholm, Sweden. E-mail: [email hidden].
edu.au, [email hidden]
"Tom DiMauro" <[email hidden]> wrote in message news:<[email hidden]>...
Quoted message said:could you email me the article it the science web site requires a account be
setup.
Thanks,
"Bob Schroedter" <[email hidden]> wrote in message
news:[email hidden]...
Quoted message said:from a post on another newsgroup...
Full Text : Allen and Westerblad, PHYSIOLOGY: Enhanced: Lactic Acid--The
Latest Performance-Enhancing Drug, Science 2004 305: 1112-1113
http://www.sciencemag.org/cgi/content/full/305/5687/1112
----- Original Message -----
From: "Larry Weisenthal" <[email hidden]>
Newsgroups: rec.sport.swimming
Sent: Saturday, August 21, 2004 4:57 AM
Subject: Lactic Acid Paradigm Shift
Quoted message said:On NPR Friday there was an in depth science story which was of
monumental
Quoted message said:Quoted message said:importance to exercise physiology. Published in Science. I haven't
read
it
Quoted message said:Quoted message said:yet, but basically, it goes like this:
Conventional thinking is that lactic acid is something bad...which
degrades
Quoted message said:Quoted message said:muscle performance. Lactic acid forms when there is so much sugar
metabolism
Quoted message said:Quoted message said:that the mitochondria of the cells can't handle it. Glucose is degraded
to
Quoted message said:Quoted message said:pyruvate to make ATP to power the muscle contraction. The pyruvate then
enters
Quoted message said:Quoted message said:the mitochondria to go into the Krebs cycle to make still more ATP. But
when
Quoted message said:Quoted message said:pyruvate is produced so fast that it can't be processed by the
mitochondria, it
Quoted message said:Quoted message said:gets converted to lactic acid, which is either stored in the muscle cell
or
Quoted message said:Quoted message said:washed away into the blood stream. Lactic acid is a temporary storage
form of
Quoted message said:Quoted message said:potential energy. Once the mitochondria have caught up, lactic acid can
be
Quoted message said:Quoted message said:metabolized in the mitochondria to produce ATP to power muscles. In
fact,
the
Quoted message said:Quoted message said:preferred energy source for cardiac muscle is lactic acid, although all
muscles
Quoted message said:Quoted message said:can "burn" it to produce ATP.
But the "problem" is that lactic acid lowers the pH of the muscle cells.
Conventional wisdom is that this is bad and that the falling pH is
responsible
Quoted message said:Quoted message said:for "poisoning" muscle contraction. So this has led to all sorts of
theories
Quoted message said:Quoted message said:about training improving the "buffer capacity" of muscle cells (you can
read
Quoted message said:Quoted message said:about this everywhere, including in Maglischo). And it has led to all
sorts of
Quoted message said:Quoted message said:nutritional supplements to imrpove buffering to reduce the fall in pH,
notably
Quoted message said:Quoted message said:sodium bicarbonate.
Turns out this is all wrong. Lactic acid and the lower pH actually
helps
keep
Quoted message said:Quoted message said:the muscles working during periods of fatigue. The real culprits in
causing
Quoted message said:Quoted message said:fatiguing muscle to stop working are potassium and phosphate. The lower
pH
Quoted message said:Quoted message said:helps the muscle cells continue to work in the presence of the altered
potassium and phosphate concentrations.
This actually makes sense, teleologically speaking. Generally, when the
body
Quoted message said:Quoted message said:does something, it does it for a purpose. Why should humans evolve to
produce
Quoted message said:Quoted message said:a toxin which causes muscle to shut down? It makes much more sense that
lactic
Quoted message said:Quoted message said:acid helps the muscle fibers to compensate for ionic imbalances which
occur
Quoted message said:Quoted message said:during extreme exercise. So, actually, the athlete would be, at least
in
Quoted message said:Quoted message said:theory, better served by INCREASING lactate concentration, rather than
decreasing it. Yogurt is a very good source of lactic acid. I'm going
to
Quoted message said:Quoted message said:start experimenting with "yogurt loading" right before I swim (I'm
really
good
Quoted message said:Quoted message said:at exercising with food in my stomach).
The lactic acid may still be the culprit in one thing...that being the
muscle
Quoted message said:Quoted message said:"burn." The lactic acid, when it leaks out of the local muscle cells in
high
Quoted message said:Quoted message said:concentrations, my activate sensory nerve receptors which are sensitive
to
Quoted message said:Quoted message said:changes in pH. Again, it makes teleological sense for the body to have
an
Quoted message said:Quoted message said:"early warning" system for work overload. The lactic acid "burn" is a
signal
Quoted message said:Quoted message said:to slow down.
So lactic acid is not a villain, but rather a hero. Triple threat.
Storage
Quoted message said:Quoted message said:form of energy. Lowers pH to allow muscle cells to continue to function
with
Quoted message said:Quoted message said:altered potassium and phosphate levels. Warns body that there is
impending
Quoted message said:Quoted message said:overload.
There's probably a commercial opportunity in this. From "Power Yogurt"
to
"I
Quoted message said:Quoted message said:[heart] lactate" T shirts.
- Larry
