Lactate formation rate and performance – Lactate transport and importance of lactate (Lactate Part2)

In the first part of the three-part series on lactate, the formation of lactate was explained. It was explained that lactate is involved in energy production and maintains carbohydrate utilization even at high energy demand. But lactate can do even more. It is a type of signaling molecule and is transported in the body to a wide variety of tissues. The transport of lactate has a decisive influence on the performance of an athlete.

Lactate utilization and signaling in the body

Lactate is produced in order to ensure energy production from carbohydrates even under high stress. And to keep the process of energy production going, lactate is removed again. Lactate oxidation is quantitatively the most important means of removing lactate – whether in trained or untrained muscle. As explained in Part 1, this process converts lactate into the energy carrier pyruvate, which supports energy production from carbohydrates (mainly from the simple sugar glucose). Furthermore, the resulting pyruvate – in addition to the new production of glucose (via gluconeogenesis, see below) – can also serve aerobic energy production via the mitochondria. It has been shown that in the body, both lactate and pyruvate are exchanged between tissues and transported via the bloodstream, being converted into each other as needed. Oxidation of lactate accounts for the lion’s share of lactate utilization at over 75 percent. The concentration gradient of lactate (lactate gradient) between muscle and blood could be an important factor in determining whether lactate is taken up or released by the muscle, regardless of whether the muscle is active or not.

The second important pathway of lactate utilization is the regeneration of glucose (glyconeogenesis). One fifth of the lactate is used for the regeneration of glucose. The liver is able to convert accumulating lactate, which is released into the blood by the muscles, into glucose by special enzymes and release it back into the blood to be transported back to the working muscle. This process is called the Cori cycle. Under heavy exercise, this process could be impaired and lead to a further increase in blood lactate. Science still has many unanswered questions to answer here. Lactate also plays a role in the recovery phase after training. Glycogen formation in muscle depends primarily on glucose. However, a significant proportion of muscle glycogen formation in fast-twitch muscles appears to occur via lactate, especially immediately after exercise when circulating lactate levels are elevated. That lactate is also used in humans to regenerate glycogen is certain. Thus, virtually all of the newly formed liver glucose is released into the bloodstream and serves as a precursor to glycogen replenishment in cardiac and skeletal muscle. Glycogen depots in the liver are not initially restored and muscle glycogen will not be fully replenished until food is again consumed. During low-intensity exercise, glucose flux and glucose oxidation may actually be decreased by the body while lactate flux and oxidation increase. Lactate can be used as a carbohydrate source and the available glucose can be saved. Presumably, lactate is also converted to glycogen, although the exact process is still unknown. Animal studies have shown that fast-twitch muscle fibers can convert lactate to glycogen very rapidly. Thus, lactate not only plays a role in providing energy. It also acts as a signal molecule, which is why it is also known as the “lactate hormone”. The function of the signal molecule appears to control, among other things, adaptations to exercise. This includes wound healing and vascularization, pseudo-hypoxia, alteration of gene expression of certain stem cells, sympathetic nerve regulation, and neuronal signaling at the cellular level. Again, research is still in its infancy.

Transport of lactate

The pathways through which lactate is transported in the body are the subject of recent investigations. Only a small proportion of the lactate produced is diffused through the muscle membrane. Lactate can be exchanged between the different muscle fibers via a kind of “cell-cell shuttle” without the lactate having to pass into the blood for this purpose. For example, lactate generated in fast-twitch muscle fibers (net source) can thus be rapidly transported to oxidative fibers (net sink) for utilization. Measurement of blood lactate is therefore unaffected. The release into the blood and the transport to organs happens with the help of special transport systems. These are certain membrane proteins, the monocarbocylate transporters MCTs, which regulate the transfer from muscle to blood. MCTs are found throughout the body, sometimes differing in type from tissue to tissue. There are more than a dozen such isoforms of MCTs. The forms have different properties. Tissues with numerous MCT1 types favor lactate uptake. These include oxidative fibers. Glycolytic fibers are dominated by the MCT4 form, which forces lactate release. Endurance training has been shown to improve metabolic capacity of lactate utilization and membrane transport by increasing the number of MCT1s in oxidative muscle. MCTs not only affect blood lactate levels, but also have an effect on performance. Transport by the MCTs can have some saturation and can also be impeded. Analyses have shown that lactate and hydrogen ions H+ are always transported together in a 1:1 ratio. Thus, the transporters are also called lactate/H+ cotransporters, through which hydrogen is always removed from the muscle along with the lactate. This is important for the pH value of the tissue. Lactate is also used to remove metabolic “waste” and coordinate the functions of the various tissues during exercise. Especially under short, intense exercise, the transporters play a crucial role here. Recent studies even found MCT transporters (mMCTs) for lactate transport into mitochondria. In mitochondria themselves, oxidation of lactate also occurs (an LDH form of mitochondria has been found, the mLDH). MCT density shows to be higher in well-trained athletes than in untrained individuals, not only in the muscles but also in other tissues and cells, such as those of the heart, brain or blood cells. The number and function of the lactate transporters play a central role in the performance of an athlete.

Lactate formation rate

In training theory, the term “lactate formation rate” is often used at present. In order to increase endurance capacity, a low lactate formation rate should be aimed for, which is caused, among other things, by better fat burning and less use of glucose. For athletes with competition goals that require short high-intensity efforts, the lactate formation rate should not be too low, because otherwise high-intensity performances can no longer be achieved because the body would presumably have lost the ability to form sufficient lactate. The lactate formation rate is derived from blood lactate measurements. The level of blood lactate and its increase with increasing load are noted or analyzed for this purpose. The often quoted and used “lactate formation rate” therefore refers to the measured values in the blood and not necessarily to the real rate of lactate formation! It is true that an increased rate of glycolysis is accompanied by an increase in blood lactate concentration with increasing exercise, and that fast-twitch muscle fibers – especially during short and intense exercise – have a higher rate of lactate formation. Nevertheless, well-trained athletes tend to have lower blood lactate concentrations because, among other reasons, they are better able to utilize lactate and not because they would exclusively produce less lactate. In a 1992 study published in the Journal of Applied Physiology (see below), the lower blood lactate levels of athletes compared to low-trained subjects at low intensities were explained by lower production. At higher intensities, where the lactate production of the trained had higher or nearly equal values compared to the less trained subjects, the lower blood lactate values of the trained athletes came from better lactate utilization. Thus, improved aerobic metabolism contributes to better lactate elimination (lactate clearance). In the blood, the lactate is measured that has been formed in the muscle and has passed into the bloodstream. It is not possible to show how much lactate is eliminated in the muscle and how much lactate is immediately removed from the blood (e.g. between measurements) via the requirements of the heart, brain, etc. The blood is then used to measure the anaerobic performance of the athlete. In order to be able to estimate the anaerobic capacity of an athlete, the maximum lactate formation rate VLamax is determined in performance tests. The idea behind this is that anaerobic lactic performance is limited by the maximum rate of glycolysis and the enzymes required for this, which in turn is influenced by lactate formation due to the H+ ions produced. In the test, the content and the temporal change of blood lactate, which is largely produced by the fast-twitch muscle fibers, is determined during short high-intensity exertions (usually second sprints). Since – as described above – the content of blood lactate is not only influenced by the glycolysis rate but also, for example, by the lactate transport capacity, these factors could also have an influence on the determined maximum lactate formation rate (VLamax) and possibly affect the results. How lactate measurement is used in performance diagnostics and what pitfalls exist will be discussed in the third and final part.

According to current research, lactate fulfills at least three important roles in the body by commuting between producer and consumer cells. 1. Lactate is an important energy source for energy production in the mitochondria (mitochondrial respiration). 2. lactate is the most important precursor for the regeneration of glucose by gluconeogenesis. 3. lactate acts as a signaling molecule.

Literature on the subject:

McDermott JC, Bonen A. Glyconeogenic and oxidative lactate utilization in skeletal muscle. Can J Physiol Pharmacol. 1992 Jan;70(1):142-9. doi: 10.1139/y92-021. PMID: 1581848.

Brooks GA. The lactate shuttle during exercise and recovery. Med Sci Sports Exerc. 1986 Jun;18(3):360-8. doi: 10.1249/00005768-198606000-00019. PMID: 3523107.

Yang WH, Park H, Grau M, Heine O. Decreased Blood Glucose and Lactate: Is a Useful Indicator of Recovery Ability in Athletes? Int J Environ Res Public Health. 2020 Jul 29;17(15):5470. doi: 10.3390/ijerph17155470. PMID: 32751226; PMCID: PMC7432299.

Hashimoto T, Brooks GA. Mitochondrial lactate oxidation complex and an adaptive role for lactate production. Med Sci Sports Exerc. 2008 Mar;40(3):486-94. doi: 10.1249/MSS.0b013e31815fcb04. PMID: 18379211.

McLane JA, Holloszy JO. Glycogen synthesis from lactate in the three types of skeletal muscle. J Biol Chem. 1979 Jul 25;254(14):6548-53. PMID: 447733.

Wahl P. et al.. Moderne Betrachtungsweisen des Laktats: Laktat ein überschätztes und zugleich unterschätztes Molekül. Schweizerische Zeitschrift für «Sportmedizin und Sporttraumatologie» 57 (3), 100–107, 2009

Gladden LB. Muscle as a consumer of lactate. Med Sci Sports Exerc. 2000 Apr;32(4):764-71. doi: 10.1097/00005768-200004000-00008. PMID: 10776895.

MacRae HS, Dennis SC, Bosch AN, Noakes TD. Effects of training on lactate production and removal during progressive exercise in humans. J Appl Physiol (1985). 1992 May;72(5):1649-56. doi: 10.1152/jappl.1992.72.5.1649. PMID: 1601768.

Brooks, G., Brooks, T., & Brooks, S. (2008). Laktat als metabolisches Signal der Genexpression. Deutsche Zeitschrift für Sportmedizin, 59(12), 280–286.

Heck, H., & Schulz, H. (2002). Methoden der anaeroben Leistungsdiagnostik. Deutsche Zeitschrift für Sportmedizin, 53(7), 8.

Rabinowitz JD, Enerbäck S. Lactate: the ugly duckling of energy metabolism. Nat Metab. 2020 Jul;2(7):566-571. doi: 10.1038/s42255-020-0243-4. Epub 2020 Jul 20. PMID: 32694798; PMCID: PMC7983055.

Brooks GA. Lactate as a fulcrum of metabolism. Redox Biol. 2020 Aug;35:101454. doi: 10.1016/j.redox.2020.101454. Epub 2020 Feb 9. PMID: 32113910; PMCID: PMC7284908.

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