Lactate: Update

By May 1, 2015 May 12th, 2015 Exercise

Until recently, lactate in the blood from lactic acid from the muscles was thought of as a waste product that caused fatigue and muscle soreness. A revolution has occurred in this field in the last few years. With a better understanding of the physiology, we’ve come to know lactate as an important part of our overall fitness and health.

Blood lactate is a normal and important component of our body chemistry. Its metabolism includes simultaneous muscle uptake and release at rest during all intensities of exercise. Specifically, lactate provides an important source of energy, in the form of glucose, that helps replace muscle glycogen stores when they are diminished; it ‘s an important fuel for aerobic metabolism (to help maintain fat-burning); and helps spare blood glucose. These actions occur during all exercise to varying degrees, especially during hard training and competition.

Lactate is also utilized as an energy source for many other tissues throughout the body. It’s used by cardiac muscle, the liver and kidney, red and white blood cells, and the brain. Lactate is also important for wound repair and regeneration. The largest mass of tissue, skeletal muscle, uses considerable amounts of lactate.


The old view that lactate, beginning with the muscle’s production of lactic acid during hard exercise (oxygen debt), is a “dead end” waste product has changed dramatically in recent years. It’s not simply an anaerobic metabolite. This is the case when oxygen availability is low, but lactic acid is also formed aerobically in the presence of sufficient oxygen.

Lactic acid is produced in muscles even at rest. The amount can increase significantly with increased exercise intensity. When lactic acid levels elevate, pH lowers. This is associated with muscle fatigue, but it may not be the cause, which is still unknown. (Other factors, including disruption of calcium and phosphorus metabolism and muscle imbalance may be factors in fatigue.) Lactic acid is ultimately diffused into the blood with more than 99% being converted to lactate.

Lactate plays an important role in providing energy to muscles as a source of carbohydrate. During moderate intensity exercise, for example, lactate may become more important than glucose for muscle energy, which may help spare blood glucose. Aerobic muscles utilize lactate for energy as well, helping to burn fat.

Lactate accomplishes this by returning to the muscle cells from the blood, and converting to glucose. This provides fuel for the muscle directly, and also helps maintain fat burning for energy. (Lactate conversion to glucose also occurs in the liver.)

Like other animals, humans can quickly restore depleted glycogen in aerobic and anaerobic muscle fibers, even in the absence of food. This is an important part of the “fight or flight” mechanism. In addition to lactate, fat and protein serve as important sources of energy to help replace depleted glycogen stores.

Lactate is an immediate (less than 30 minutes) fuel source that helps replenish glycogen following exercise, especially hard training. Food sources can also contribute, if consumed immediately following a workout or race. Complete repletion of glycogen stores during recovery over the next 90 minutes and beyond is more dependent upon the breakdown of fat (from glycerol) and protein (certain amino acids convert to glucose).

Up to half of the total energy for glycogen repletion comes from lactate, and 50% or more from the breakdown of fat and protein. However, new research shows these levels may be conservative and that fat and protein may contribute more significantly to glycogen replacement.

The process of active recovery – the cool down – following exercise is important for a variety of reasons, one of which is glycogen repletion. This occurs quickly in the anaerobic muscle fibers with the contribution of glycogen from the aerobic fibers. Glycogen, lactate, fat and protein all provide significant contributions to this process.

The highest levels of lactate oxidation occur when free fatty acids (FFA) in plasma are low. This is often due to the inhibition of lipolysis by insulin – low FFA uptake and oxidation results in enhanced lactate oxidation. (Pyruvate oxidation is primarily regulated by FFA at the level of acetyl-CoA, where high levels of acetyl-CoA generated from FFA oxidation result in inhibition of carbohydrate oxidation by the pyruvate dehydrogenase complex.)

The Cori cycle helps regulate and recycle lactate (and pyruvate) to glucose for use as energy.

Lactate does not necessarily increase fatigue during racing or long endurance activities. It’s probably a mix of several (or many) structural and chemical factors. And, lactate (or lactic acid) is not directly associated with muscle soreness. Why does max exercise to exhaustion cause an individual to stop exercising? Even at maximum lactate steady state levels (MLSS), no one is certain. Baron, et al. measured more than 10 common parameters from lactate and pyruvate to oxygen uptake and carbon dioxide in trained men on a cycle ergometer to exhaustion (average time about 55 minutes). They concluded, “Exercise termination was not associated with evidence of failure in any physio-logical system during prolonged exercise performed at MLSS.”


In the heart, free fatty acids are the major fuel for cardiac muscle at rest as these muscle fibers are even more oxidative than aerobic skeletal muscle. High levels of free fatty acids can reduce lactate metabolism because the heart muscle can utilize these fats. In this case, more lactate is “backdiffused” – returned back to the blood unchanged.

During exercise, however, lactate serves as a key source of energy for cardiac muscle. Lactate uptake and oxidation in the heart increases proportionally with rising heart rates and increased lactate levels. Lactate may provide 60% of the energy for cardiac muscle contraction during exercise, with other potential energy sources being glucose and, to a lesser extent, pyruvate and ketones.

Poor lactate metabolism is associated with various types of heart disease, and occurs in diabetes. Similar reductions in lactate metabolism in the heart are also seen in so-called normal aging.


In the brain, lactate metabolism is important in supplying glucose to neurons during exercise, when a significant amount of blood is shunted to working muscles. In addition, lactate rather than glucose may be the primary and preferred energy source during neuronal activation at all times. Lactate is produced by the astrocytes for uptake by nearby neurons. Astrocyte metabolism is mostly glycolytic while that of neurons is largely oxidative.

Anatomically, astrocytes appear to be an important intermediary between the capillaries, neurons and the synapses of neurons. In addition, their cycling of glutamate –>glutamine–>glutamate may significantly affect lactate metabolism: increased glutamate uptake is associated with increased lactate production. (Glutamate is the primary excitatory neurotransmitter of the cerebral cortex.)

Lactate also plays a key role in the lactate-alanine cycle, which helps the glutamine-glutamate cycle.

Brain injury associated with lactic acidosis (hyperglycemia-related cerebral ischemic damage) is the process whereby ischemia leading to reduced oxygen causes increased glycolysis and increased lactic acid production to the point of acidosis-related cell damage. The blame has always been on lactic acid, but more recently it’s been shown that both glucose and lactic acid are actually neuroprotective. Newer research shows that the cause of neuronal damage in these brain injuries is thought to be high levels of cortisol.

The Lactate Shuttles

Among the more interesting features of new lactate research are lactate shuttles; these do more than get you to the airport. The first is the peroxisomal lactate shuttle. While about 90% of short- and medium-chain fatty acids are oxidized in the mitochondria (the process of beta oxidation), 10% are oxidized in peroxisomes – tiny enzyme-containing organelles. The purpose of this process is thought to be shortening of longer chain fatty acids for mitochondrial oxidation. This is a significant amount of potential energy. In addition, the acetyl-CoA from peroxisomes provides energy for the synthesis of bile acids, phospholipids, cholesterol and other fatty acids.

The spermatogenic lactate shuttle occurs in mammalian spermatozoa, which uses lactate as an aerobic energy source for motility. Lactate is oxidaized in the motochondria to pyruvate in aerobic pathways. This intracellular lactate shuttle appears to operate in spermatozoa but apparently not in muscles cells.

Lactate and Injury

To this point I’ve discussed lactate in relation to its role in the production of energy. But lactate can stimulate other activities. For example, collagen production can double due to high levels of lactate. Healing wounds not only produces but accumulates high levels of lactate. This mechanism is not impaired by oxygen, an important factor in treating patients with hyperbaric chambers as oxygen has a no or little effect on wound lactate levels. In addition, lactate simulates the production of new blood vessels (angiogenesis) through enhanced vascular endothelial growth factor (VEGF), produced in macrophages. Lactate may also promote healing by increasing the oxygen supply to the area through its pH-mediated vasodilation. Lactate stimulation following injury may be the end result of adrenal gland stimulation. As adrenaline levels rise, there is a corresponding increase in lactate.

The complex physiology of lactic acid and lactate metabolism is still unraveling. In the coming years new research will reveal even more interesting and useful information.

Partial Bibliography

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Fontana P, Boutellier U, Knopfli-Lenzin C (2009). Time to exhaustion at maximal lactate steady state is similar for cycling and running in moderately trained subjects. Eur J Physiol DOI 10.1007/s00421-009-1111-9.

Gertz EW, Wisneski JA, Stanley WC, Neese RA. (1988). Myocardial Substrate Utilization during Exercise in Humans. J Clin Invest;82(6):2017-25.

Gladden LB (2004). Lactate metabolism: a new paradigm for the third millennium. J Physiol 558: 5-30.

Goto K, Ishii N, et al. (2009). Hormonal and metabolic responses to slow movement resistance exercise with different durations of concentric and eccentric actions. Eur J Appl Physiol;106(5):731-9.

Herrero P, Dence CS, et al. (2007). L-3-11C-Lactate as a PET Tracer of Myocardial Lactate Metabolism: A Feasibility Study. J Nucl Med 2007; 48:2046–2055.

Ide K, Schmalbruch IK (2000). Lactate, glucose and O2 uptake in human brain during recovery from maximal exercise. J Physiol; 522: 159-164.

Raja G, Brau L, Palmer TN, Fournier PA (2008). Fiber-specific responses of muscle glycogen repletion in fasted rats physically active during recovery from high-intensity physical exertion. Am J Physiol; 294: R633–R641.

Raja G, Mills S, Palmer TN, Fournier PA (2007). Lactate availability is not the major factor limiting muscle glycogen repletion during recovery from an intense sprint in previously active fasted rats. J Exper Biol 207, 4615-4621.

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