In exercise physiology, there is nothing more ‘obvious’ than the existence of lactic acid, ‘known’ for its debilitating effects on exercise performance. That’s been ‘known’ since 1922, when the Nobel Prize in Physiology or Medicine was divided equally between Archibald Vivian Hill “for his discovery relating to the production of heat in the muscle” and Otto Fritz Meyerhof “for his discovery of the fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle”. By 1940, the new science of biochemistry was born due to their enormous input, and their elucidation of the biochemistry was so far ahead of its time that it wasn’t even challenged for nearly 50 years, and is still rigidly defended by many physiology researchers to this day. What was worked out in 1940 was taught in every biology class at high school and university level within the next ten years, and has become ‘enshrined’ within the physiology world as a truth. So much so, that these days, ‘everyone’ knows that ‘lactic acid’ is also known as ‘lactate’, too. Most exercise science people know that ‘lactate’ is just another term for ‘lactic acid’, because we can use lactate concentration levels in the blood as an indicator of anaerobic metabolism, can’t we?
The discoveries of the pathways of glycolysis and cellular energy production were considered so obvious that they were not investigated further, especially by anyone wanting to retain their university funding grants. Until the last couple of decades, when Professor George Brooks of Berkeley University started publishing his new theories on the biochemistry and bioenergetics of lactate, no one in the exercise physiology world was taking too much notice.(1)
Certainly, the popular magazines, and even some recent books purportedly written by experts in the field, are almost agnostic when it comes to sharing the new understandings about lactate. That may be because, even amongst peer-reviewed physiologists, the basic chemistry has been largely forgotten or unpursued.
In fact, in a letter to the editor in the December 2017 journal of the American Physiological Society, ‘Physiology’(2),a correspondent claimed that a peer-reviewed article on ‘the role of lactate as a multi-tissue autocrine regulatory molecule’ in the previous November edition was ‘flawed’, with the authors mistakenly confusing ‘lactate’ with ‘lactic acid’ over fifty times in the one peer-reviewed and published paper.This same correspondent further added: ‘there is no such entity as lactic acid in any living cell or physiological system. Indeed, it is impossible, based on the fundamental laws of physics that underpin the disciplines of organic chemistry, metabolic biochemistry, acid-base chemistry, and physiology, for lactic acid to be produced or present in living systems where cellular and tissue pH is regulated to be between 6.0 and 7.45.’
So, as perceived experts actively oppose each other in various published journals, it’s pretty hard for the regular athlete or coach to keep up to speed. Unfortunately, the science of physiology is not as exact as we have been led to believe; it appears that despite a growing body of science that has thrown new light on the inner workings of intercellular lactate transport and metabolism, readily understandable interpretations on concepts like the ‘lactate shuttle’ are very hard to find for people like me, well-educated in the health sciences, but without a specialist degree in that area of biochemistry.
Certainly, what is becoming more understood and accepted these days is that lactate is not a metabolic waste product or toxin, as has been totally accepted for many years, but it is instead an energy-rich fuel source, widely utilized by a number of organs and tissues in an aerobic setting.
The difference between ‘Lactate‘ and ‘Lactic Acid’
Lactate, (C3H5O3-) is not acidic; it acts as a mild alkali, and in chemistry terms, when it becomes ionised and dissociated within the cytoplasmic fluid of the cell, it can be described as the negatively charged conjugate base, or anion, to the positively charged lactic acid, (C3H6O3+), another 3-carbon molecule derived from the 6-carbon glucose molecule by glycolysis.
Lactate is readily produced in target organs or muscles by ‘producer cells’ following increased metabolic demand, from circulating glucose, and is generally cleared from the muscle or target organ straight away, with any excess lactate produced being very rapidly shuttled elsewhere via the local venous drainage network to the portal venous system of the liver to either be resynthesized back to glucose in a form of ‘reverse glycolysis’, from where it can then be stored as glycogen in the liver, or rapidly delivered as glucose molecules to other tissues that require high energy output. The glucose then has to undergo glycolysis again to be transformed into the very high-power and more easily metabolized 3-carbon pyruvate. Why this building up and stripping down of 6-carbon or 3-carbon molecules is required is a question that I can’t answer, but I am not the designer of such an awesome living machine.
You can bet that at this moment teams of scientists from around the world are looking for the answers, and that an overall consensus view on the question is some time off, (if possible at all in the world of academia!) although I personally am persuaded by the sheer volume of work in this area of physiology by George Brooks and his team at Berkeley University, and a growing number of researchers exploring the same territory. Brooks et al have published their experimental data consistently since the early 1980s, and Brooks first focused himself on the lactate accumulation question as a postgraduate researcher at Berkeley in the early 1970s. His initial hypothesis seems to have not wavered much from its basic tenets in the 49 years since he started his work, but as more research is done on this formerly ‘hallowed ground’ of biochemistry and physiology, the details of the biochemical and genetic pathways are being fleshed out.
What is undoubtable is that the process, although seemingly unwieldy, is extremely rapid and efficient, with the construction and de-construction of the differing molecules occurring millions of times a second in the various metabolic tissues (whether organ or muscle) of the body. The turnover or transfer of hydrogen protons and electrons as glucose is broken down into 3-carbon molecules, especially at very high work rates, was formerly attributed to the presence of the conjugate acid to lactate, lactic acid, but it seems to be more likely that any acid in the local tissues is due to the pooling of protons accumulated amidst the lactate, which is thought to ‘buffer’ the acid load created by high energy output, as well as serve as an important aerobic fuel in itself. So even though lactic acid may not exist as a defined physiological entity in a living system, the protons that predispose to acidity are there in abundance (3). There still appears to be much discussion going on about where the protons come from, but the main point to understand is that they are always there following intense bouts of exercise, possibly originating from ‘upstream’ in various glycolytic pathways, and these protons are capable of acidifying their local environment, which in itself can detract from performance potential or aid it, depending on other acid-alkali conditions. From what I have read in the literature lately, discussion is very much ongoing, and the science is still in its infancy.
So what can we believe is ‘true’ about lactate, or its conjugate acid, lactic acid, these days? And more importantly, will this ‘new’ knowledge significantly affect how we objectively measure for oxygen uptake, anaerobic threshold intensity(a.k.a ‘lactate turnpoint’), or ‘anaerobic power’ intensity (lactate concentration above 4mmol/L), given that it has turned what we’ve known for so long ‘upside down’?
Despite all of this new material to assimilate, I do not believe that the practice of training or objectively measuring performance data will be impacted much, if at all, from the currently emerging understanding. The onset of the anaerobic threshold is still signaled by an increase in lactate concentration above the normal aerobic level, regardless of whether the lactate is an acidic metabolic waste-product, or an excess accumulation of a useful high-energy substrate in local metabolic tissues, awaiting imminent shuttling to another region of the body that is able to metabolize it.(1,3,5)
Lactate seems to be produced and ‘cleared’ at similar rates until a higher work rate is established where more lactate is produced than can be readily metabolized. Possibly the very diminished ability of the body to produce ATP energy anaerobically is the reason why the lactate accumulation rate spikes as soon as glycolysis proceeds from lower intensity aerobic production of a relatively large amount of ATP per glucose molecule (32 to 38) to the relatively minuscule amount of ATP generated per glucose molecule anaerobically (about 2 ATP). The exercising muscles’ uptake of lactate can’t match the supply, and exercise has to slow to truly aerobic levels again in order to fully clear the accumulated lactate substrate.
There is now some good evidence that lactate is preferentially utilized by muscle or organ tissues at higher metabolic work rates; at lower metabolic intensities glucose is preferred.
- Lactate, not Lactic Acid, is Produced by Cellular Cytosolic Energy Catabolism: Robergs et al, Letters to the Editor,Physiology, Dec 12, 2017: https://journals.physiology.org/doi/full/10.1152/physiol.00033.2017
- The Science and Translation of Lactate Shuttle Theory, George A Brooks, Cell Metabolism, https://www.sciencedirect.com/science/article/pii/S1550413118301864
- Lactic Acid and Exercise Performance : Culprit or Friend? Simeon P Cairns, https://pubmed.ncbi.nlm.nih.gov/16573355
- Glycolysis Paradigm Shift Dictates a Reevaluation of Glucose and Oxygen Metabolic Rates of Activated Neural Tissue, Avital Schurr, Frontiers in Neuroscience, Oct 10 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192285/?fbclid=IwAR21qpPZojyW_c2ABGmHZJG5OlBKsQej1ccdiq3iveC5M9WjH2K1XH-WG3Y
- Biochemistry of exercise-induced metabolic acidosis https://journals.physiology.org/doi/full/10.1152/ajpregu.00114.2004