Thread by @doctorinigo

Muscle acidosis is real and it decreases performance significantly. However, Lactate is NOTthe reason for muscle acidosis.
Free thread depicting the role of lactate during hgh intensity exercise: 🧵😉 👇

During high-intensity exercise, skeletal muscle experiences a significant increase in protons (H⁺) concentration, leading to a decrease in intracellular pH and therefore increasing skeletal muscle acidosis. These protons come mainly from:

1) ATP hydrolysis is the primary source of H⁺during exercise. H⁺build up in the cytosol leading to decreased in muscle pH.
ATP + H₂O → ADP + HPO₄²⁻+ H⁺

2) Lactate formation from pyruvate receives ("buffers") one H⁺ from the oxidation of NADH to NAD+ during glycolysis. This step is the only possible step for the regeneration of NAD+ so that glycolysis can continue and REDOX status can be maintained. Hence, Lactate DOES NOT cause acidosis as it is NOT a source of protons (H⁺). The “acid” simply doesn’t exist.

Therefore, although most people (me included) commonly associate lactate with acidosis (like we still also talk about “anaerobic threshold”), the reality is that lactate is NOT the cause of muscle acidosis. Lactate is a “surrogate” or a “biomarker” of the rate of ATP hydrolysis and glycolysis (aka, exercise intensity). Therefore, when you see high levels of blood lactate it means that there is a high level of metabolic stress caused by a high rate of ATP hydrolysis and glycolytic activity.

Lactate has an amazing amount of autocrine, paracrine and endocrine functions highly and ubiquitously involved in health and disease; it is a “lacthormone”. Furthermore, lactate is also a preferred fuel for most cells in the body.

During exercise, lactate production is KEY for the continuation of glycolysis at high intensities, so it is GOOD. Lactate can only be oxidized back to pyruvate and then Kreb’s cycle via Acetyl-CoA in mitochondria. So, someone with high mitochondrial function will be able to clear lactate very well, taking advantage of a great energy source. If mitochondrial function is reduced, lactate will build up and won’t be able to regenerate NAD+ for the continuation of glycolysis.

Furhtermore, the reduced capacity to buffer H⁺ will cause a further accumulation of cytosolic H⁺ leading to: 1) inhibition of glycolysis by inhibition of the rate-limiting enzyme of glycolysis, phosphofructokinase (PFK) and 2) inhibition of calcium release from sarcoplasmic reticulum decreasing muscle contraction.

Furthermore, as an autocrine signaling molecule, we found that lactate decreases the activity of CPT1/2 which will affect fatty acid transport into mitochondria and that it also decreases the rate of ATP production:
(END)pubmed.ncbi.nlm.nih.gov/35308271/