• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

muscle fatigue and lactic acid (lactates)


Senior Member
scientists used to think not so long ago that muscle pain/fatigue after exercise was du to lactic acid building up under anaerobic circumstancies.

It seems that it is not so simple, and that lactic acid may be even protective for the muscle.

Here some lights about it coming from wikipedia:

Metabolites are the substances (generally waste products) produced as a result of muscular contraction. They include chloride, potassium, lactic acid, ADP, magnesium (Mg2+), reactive oxygen species, and inorganic phosphate.
Accumulation of metabolites can directly or indirectly produce metabolic fatigue within muscle fibers through interference with the release of calcium (Ca2+) from the sarcoplasmic reticulum or reduction of the sensitivity of contractile molecules actin and myosin to calcium.

Intracellular chloride partially inhibits the contraction of muscles. Namely, it prevents muscles from contracting due to "false alarms", small stimuli which may cause them to contract (akin to myoclonus). This natural brake helps muscles respond solely to the conscious control or spinal reflexes[citation needed] but also has the effect of reducing the force of conscious contractions.

High concentrations of potassium (K+) also causes the muscle cells to decrease in efficiency, causing cramping and fatigue. Potassium builds up in the t-tubule system and around the muscle fiber as a result of action potentials. The shift in K+ changes the membrane potential around the muscle fiber. The change in membrane potential causes a decrease in the release of calcium (Ca2+) from the sarcoplasmic reticulum.[1]

Lactic acid
It was once believed that lactic acid build-up was the cause of muscle fatigue.[2] The assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to contract. The impact of lactic acid on performance is now uncertain, it may assist or hinder muscle fatigue.

Produced as a by-product of fermentation, lactic acid can increase intracellular acidity of muscles.
This can lower the sensitivity of contractile apparatus to Ca2+ but also has the effect of increasing cytoplasmic Ca2+ concentration through an inhibition of the chemical pump that actively transports calcium out of the cell.
This counters inhibiting effects of potassium on muscular action potentials. Lactic acid also has a negating effect on the chloride ions in the muscles, reducing their inhibition of contraction and leaving potassium ions as the only restricting influence on muscle contractions, though the effects of potassium are much less than if there were no lactic acid to remove the chloride ions. Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca2+.

Lactic acid is now used as a measure of endurance training effectiveness and VO2 max.[3]

Molecular mechanisms
Muscle fatigue may be due to precise molecular changes that occur in vivo with sustained exercise.
It has been found that the ryanodine receptor present in skeletal muscle undergoes a conformational change during exercise, resulting in "leaky" channels that are deficient in calcium release. These "leaky" channels may be a contributor to muscle fatigue and decreased exercise capacity.[4]"

Interestingly many ME patients could have a "chloride brake" dysfunction that would explain the myoclonus in their symptoms.

About Ryanodine Receptors:

"Ryanodine receptors (RyRs) are high conductance intracellular cation channels that release calcium ions from stores such as the endoplasmic reticulum and sarcoplasmic reticulum.
Although RyRs are expressed in many cell types, their roles have only been extensively characterised in tissues in which they are abundant: RyR1 is essential for excitation–contraction coupling in skeletal muscle; whereas RyR2 is required for the analogous signal transduction pathway in heart. Defects in RyR1 cause malignant hyperthermia and a spectrum of myopathies in skeletal muscle; whereas RyR2 dysregulation can result in fatal cardiac arrhythmias and is involved in heart failure. Altered RyR gating has been implicated in a range of other diseases, including epilepsy, neurodegeneration, pain and cancer."
Last edited:


Senior Member
Logan, Queensland, Australia
Its been known for decades that lactic acid neither produces fatigue (in the short term) nor causes muscle pain. Its associated with these things, but they are due to other causes. It takes a lot of lactic acid to create burning, and other acids are more likely to be responsible, especially carbonic acid. Lactic acid actually assists energy production in the short term, though in periods of longer than several days it can have the opposite affect due to pH changes to an enzyme needed for oxygen storage and release.

So in the short term lactic acid itself is indirectly good for energy, and a sign that the body is using its alternative energy pathway. Its the long term that is the problem, as well as whatever in ME is forcing lactate production rather than aerobic metabolism.
Thank you for this clear summary, pattismith.

I came across this thread as I was looking for something on Ca-actin binding and calcium. Recently I read something about research into metabolites but didn't understand it. This seems to be an exciting field of research. As I'm not a scienist I find it difficult to follow, but look forward to hearing more and potentially what might help or hinder recevery or day to day maintenance of energy production. I live in the UK but have had mitochondrial tests done by Dr. John McLaren Howard and my last showed no TL blocking but Ca-actin binding (moderate). I have to pay for consultations and tests as they are not available on NHS and no private health insurance. Consequently try to do all I can to understand the cellular processes and what might help.