A large portion of the population, including athletes and coaches in this current era still believes that the limitations of exercise performance is due to lactic acid build up causing fatigue. It is a stubborn myth that stood through the test of time. This is a relatively old school of thought that has its roots in the work of Fletcher K . Lactic acid was regarded as an end metabolite of glycolysis and elevates as an exercise intensify where oxygen availability decreases.
It was Brooks GA that started the ‘Lactate revolution’. He presented the lactate shuttle hypothesis in his work in 1986. It was due to this hypothesis that scientists, even in present day, question the mechanisms of lactate or lactic acid in the body and its involvement in fatigue.
This report will delve into studies within the recent decade, touching on conflicting ideas pertaining to lactic acid and its involvement in fatigue. I will further break down lactic acid into its biochemical components, lactate and hydrogen ion, and discuss studies which have contradicting beliefs on these component’s implication with fatigue. Finally, I will highlight on recent articles that has even challenged the underlying mechanism behind fatigue.
Lactic Acid as a whole?
Lactic acid was considered a metabolic waste. It is a by-product of glycolysis in the conversion of glucose to pyruvate. It was blamed for the burning sensation felt during and after performing a high intensity exercise which would then finally cause fatigue.
However, the idea of lactic acid causing muscle fatigue has been challenged since the 1980s. For example, human deficient in the enzyme myophosphorylase showed faster muscle fatigue eventhough they are incapable of breaking down glycogen and accumulate lactic acid. Studies on single muscle fibres showed constant rate of fatigue eventhough its pH was intentionally lowered. It is seen today that many studies have challenged one another’s idea. It is important to consider all options before finally cementing a theory.
Firstly, it would be unfair to blame lactic acid as a whole when it literally does not exist in this neutral construct[6, 7]. It expresses as hydrogen ions (H+) and lactate ions in the body [7, 8]. Several studies have and should continue separating these 2 entities and experimented on them separately to find its link with fatigue as either one, both or none of them could be the cause of fatigue.
So is lactate the real culprit?
It was long written in literature that lactate is known as a metabolic waste product. However, lactate is far from being a useless product. There has been growing number of evidence of the beneficial properties of lactate and this has tested the universality of the hypothesis linking muscular fatigue with lactate production.
Lactate, being produced when glucose breaks down to pyruvate , allows continuation of glycolysis by generating the NAD+ needed in glycolysis thus preserving exercise performance and delaying fatigue.
With the presence of oxygen, lactate can be converted to pyruvate which could be converted to glucose. This process is called Cori cycle. It can then be utilized or stored as glycogen, according to the body’s need at that point of time. This makes lactate a good source of energy.
Lactate could be cleared by oxidation in the muscle fibre it was produced. Oxidation of that particular lactate could also happen in other muscle fibres as the lactate is being transported. Those lactate not oxidized will diffuse into the blood veins and transported to the liver.Lactate is favoured by the brain and used extensively as a source of fuel.
Lactate was known to contribute to fatigue. Many studies nowadays shows otherwise, in fact, it has been studied that lactate may delay the onset of acidosis mainly via H+ reduction. In this review and study by Robergs R.A (supported by S.E Allen), H+ were found to be carried out from cells by transporters and also be consumed by lactate. However, this statement has been challenged by Lindinger M.I., stating that Roberg ignored that lactate is an anion. Its increase would therefore reduce Na anions and thus increase H+ to maintain electroneutrality. Although Lindinger might be correct, there are more studies supporting the opposite notion.
A solid ground breaking revolution should occur when lactate is being administered to athletes via energy drinks, however many are still in the dark in recognizing lactates true potential. A study showed that lactate is utilized more efficiently with a greater extent compared to glucose or fructose and also enhances high intensity performance. To further add value to lactate, it is found that performance decrement has no correlation with lactate production.
It is clear from the whole list of resources in literature that lactate is not a bad metabolic waste product and is actually beneficial in more ways than one, especially in delaying the onset of fatigue. Therefore, accusing lactic acid to be the culprit of fatigue would indirectly blame lactate, which is not acceptable when it is a beneficial component in exercise performance.
So it must be Acidosis!
It is clear among literature that acidosis has been under the limelight for causing fatigue. The lowering of pH in the muscle has been accused of causing the burning sensation and the decreasing muscle efficiency that comes with fatigue. In 2003 a review by L. B. Gladden  states that RH Fitts has evidence of a whole list of experiments suggesting that acidosis can have negative detrimental effects on muscle function by “1-reducing the transition of the cross-bridge from the low- to the high-force state, 2-inhibiting maximal shortening velocity, 3-inhibiting myofibrillar ATPase, 4-inhibiting glycolytic rate, 5-reducing crossbridge activation by competitively inhibiting Ca2+ binding to troponin C, and 6-reducing Ca2+ re-uptake by inhibiting the sarcoplasmic ATPase (leading to subsequent reduction of Ca2+ release).”
This may sound contradicting as there are resources saying that acidosis do not cause fatigue. However, it is important to know that the experiments explained by RH Fitts, are done in vitro and when the experiments are redone at temperature closer to those experienced physiologically, the said negative effect of acidosis diminishes.
In the recent years, experiments have been showing that acidosis has been far from being the cause of fatigue. Neilsen explained that muscle contraction causes acidosis, loss of intracellular K+ and extracellular K+ build up. High extracellular K+ leads to loss of contraction force therefore fatigue. It was found that acidification nullify the effects of the extracellular K+ that are linked with fatigue. This is further supported by other studies[24-26] on the fact that acidosis has protective capabilities against muscle fatigue.
Gathering all the resources, it would be safe and logical to say that since acidosis delays fatigue, alkalosis (the opposite of acidosis) should have an opposite effect thus cause fatigue faster. However, this was proven wrong in many studies [27-30]. Taking time to look at the whole picture of the studies, studies regarding alkalosis were done as a whole body model experiment (in vivo). Looking back, the experiments done on acidosis were not done as a whole-body experiment. Instead, it was done on single muscle fibre in in vitro situations. Studies from the past showed that acidosis can contribute to fatigue in intact human body or animal [31-33]. To integrate the studies from isolated muscle model with accordance to whole-body exercise, Cairns hypothesised that acidosis may improve performance in isolated muscle, high blood plasma acidosis may cause a reduction in central nervous system’s drive to the muscle thus causing fatigue.
Another limitation that may affect experiments is that fast twitch muscles are more susceptible to acidosis therefore experiments on a single muscle fibre as seen in a lot of studies regarding acidosis, might not give an accurate holistic overview of the reaction of a whole muscular body. Also H+ might interact with other unknown cellular changes in the body therefore slightly discrediting isolated muscle fibre experiments with comparison to whole body experiments.
Overall, acidosis has been thought to be the main contributor to fatigue. However, recent studies in the last decade have been trying to contest the statement. In my opinion, it is rather early to disregard acidosis as the cause of fatigue, as in vitro studies are only suggestive. Future studies should take into account acidosis as a whole body experiment (in vivo) where hormonal and other physiological interactions are possible.
If there are claims of acidosis not causing fatigue, then what does cause fatigue?
So in substitution of the uprising hypothesis that elevated H+ is not the main cause of fatigue, there have been many competitors to claim its place. Supported by a study, Westerblad have been claiming that inorganic phosphate has the main role in fatigue. Inorganic phosphate increases as muscle is being contracted and creatine phosphate is being broken down.
However, a book by Fitts challenged Westerblad’s idea, highlighting several limitations concerning the inorganic phosphate hypothesis. He stated that the studies did not assess the holistic combination of the resultant effect of an elevated inorganic phosphate with low pH and low calcium ion release. Also the effects of acidosis on peak power were not evaluated.
Even Westerblad agreed that the study was done on a single muscle fibre and the result might be different when done with a whole model. He pointed out that studying on a single muscle fibre provides the most direct physiological responds when questioning the cellular mechanisms of fatigue. Also, claiming that the “The differences that inevitably must exist appear to be mainly of a quantitative nature”.
I believe that it is still early to refute the idea of acidosis not causing to fatigue.
In the case of studies on inorganic phosphate, its role in fatigue is still in an early stage and should not be dismissed as of yet. Several questions have yet to be answered. However, creatine phosphate is after all only involved in the first 10 seconds of an intense exercise therefore queries of its role extending within these 10 seconds are questionable.
Other than phosphates, there have been a large number of studies[22, 23] claiming potassium ions to be the main cause of fatigue. In this particular study by Cairns, he states “We hypothesize that during high-intensity exercise a rundown of the transsarcolemmal K+ gradient is the dominant cellular process around which interactions with other ions and metabolites occur, thereby contributing to fatigue”. The raised extracellular K+ causes a sarcolemmal depolarization, therefore disrupting the excitability of the muscle thus resulting in fatigue.
This is however contradictory to a previous study being done on rats. In the study, it suggests that extracellular K+ is overhyped in previous studies on isolated muscles and that it is of less importance for fatigue.
Overall, it is still hard to cement a theory as long as insufficient studies are done on whole intact animal models. This is however, being a case of isolated muscle studies versus in vivo studies. In my opinion applying Occam’s razor, acidosis should stay as the cause of fatigue unless proven otherwise with solid in vivo studies.
So to go back to the age old question, does lactic acid cause fatigue?
It is important to remember that lactic acid disassociates to lactate and H+ ions, each with its own characteristics and interactions with the body therefore it needs to be addressed separately. Taking lactic acid as a whole and blaming it would be unjust and inaccurate. As of recent time, it will take time and effort to disprove acidosis as the cause of fatigue as many studies were done in vitro and results only suggest possible mechanism in the human body. I do however believe that there is no one main mechanism causing fatigue, it is however a collective effort of different mechanisms, few of which are possibly phosphate and extracellular K+, that contribute to fatigue.
As of now, lactate is a good byproduct and acidosis still remains the main cause of fatigue.
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