What is the physiological importance of lactate?

September 29, 2025 •

3 min read

For decades, lactate was mistakenly viewed as a metabolic dead-end causing fatigue during exercise. This perspective has been radically revised, as modern research shows what is the physiological importance of lactate: it is a dynamic and essential molecule continuously produced and used under both aerobic and anaerobic conditions.

Quick Summary

Lactate is a versatile molecule serving as a vital energy substrate for the heart and brain, a key precursor for glucose production through gluconeogenesis, and a powerful signaling molecule that coordinates whole-body metabolism via intercellular communication.

Key Points

Energy Substrate: Lactate is a major fuel source for high-demand organs like the heart and brain, especially during exercise or stress.
Gluconeogenic Precursor: It serves as the primary precursor for glucose synthesis in the liver and kidneys, a process known as gluconeogenesis or the Cori Cycle.
Signaling Molecule: Acting as a "lactormone," lactate binds to the HCAR1 receptor, regulating various biological processes, including inflammation and lipid metabolism.
Epigenetic Regulator: The process of lactylation, a newly discovered post-translational modification, allows lactate to alter gene expression and cellular function.
Clinical Marker: Elevated lactate is a critical biomarker in clinical settings, indicating a complex stress response and helping to predict patient outcomes in conditions like sepsis and trauma.
Metabolic Flexibility: The lactate shuttle enables tissues to produce or consume lactate based on metabolic needs, acting as a dynamic regulator of energy substrate partitioning.

From Misunderstood Waste to Metabolic Hero

For centuries, lactate, often misidentified as "lactic acid," was blamed for causing muscle fatigue and soreness after intense exercise. This misconception stemmed from early, limited experiments, leading to the incorrect conclusion that lactate was merely a waste product of oxygen-deprived metabolism. The paradigm shifted significantly with the development of the "Lactate Shuttle Theory" in the 1980s, redefining lactate as a vital, continuously produced metabolite and signaling molecule. This theory revolutionized our understanding of metabolic regulation. Lactate is now understood as an energetic currency, shuttled between cells and tissues to optimize energy utilization and coordinate metabolic responses.

The Lactate Shuttle: An Intercellular Highway

The lactate shuttle describes the movement of lactate between different cells and cellular compartments, facilitated by monocarboxylate transporters (MCTs).

A Preferred Fuel for High-Demand Organs

Many oxidative tissues prefer lactate over glucose as a fuel source, especially during periods of high energy demand. During strenuous exercise, the heart muscle can derive over 60% of its oxidative energy from blood lactate. The brain, while primarily fueled by glucose, readily takes up and oxidizes lactate when levels rise during exercise or after injury, potentially supplying a significant portion of its energy needs. The astrocyte-neuron lactate shuttle (ANLS) supports this by transferring lactate from astrocytes to neurons.

Major Player in Gluconeogenesis

Lactate is the most important precursor for gluconeogenesis, the synthesis of glucose from non-carbohydrate sources. The Cori Cycle describes lactate from muscles being transported to the liver, converted back into glucose, and released into circulation.

Lactate as a Powerful Signaling Molecule

Lactate acts as a versatile signaling molecule, or "lactormone," mediating various physiological processes. Lactate binds to the HCAR1 receptor, mainly in adipose tissue, inhibiting fat breakdown and linking carbohydrate and lipid metabolism. It also influences the immune response by modulating macrophage polarization and T-cell function, exhibiting both pro- and anti-inflammatory effects. In wound healing, high local lactate promotes new blood vessel formation by signaling the release of growth factors like VEGF.

The Rise of Lactylation: Epigenetic Regulation

A recent discovery reveals lactate's role in epigenetics through lactylation. Lactate converts to lactyl-CoA, which modifies lysine residues on histones and other proteins. This histone lactylation influences chromatin structure and regulates the expression of hundreds of genes, directly linking cellular metabolism to gene transcription and supporting adaptations like mitochondrial biogenesis in response to exercise.

Clinical Significance of Lactate

Lactate levels are an important clinical biomarker. Elevated lactate is a prognostic indicator in critically ill patients. While previously linked solely to tissue hypoxia, it's now understood that hyperlactatemia often reflects a complex stress response and altered clearance, making it a marker of disease severity. Lactate supplementation may benefit TBI patients as the injured brain uses it for energy, potentially reducing swelling and providing neuroprotection. In heart failure, lactate can support myocardial metabolism as the heart uses it for fuel.

Lactate Metabolism: A Tale of Two Eras

A table contrasting the old and modern understanding of lactate metabolism is available. The old view considered lactate a waste product produced only under anaerobic conditions, causing fatigue and acidosis. The modern understanding recognizes it as a continuously produced vital energy source, gluconeogenic precursor, and signaling molecule under both aerobic and anaerobic conditions, actively shuttled and regulated via transporters and receptors. For a detailed table, refer to {Link: ScienceDirect https://www.sciencedirect.com/science/article/pii/S2213231720300422}.

Conclusion: Beyond a Simple Metabolite

The misconception of lactate as a mere waste product has given way to a sophisticated understanding of its pivotal role in regulating whole-body metabolism. Through the lactate shuttles, it acts as a primary energy source, a crucial gluconeogenic precursor, and a powerful signaling molecule. Its involvement in epigenetic regulation via lactylation further solidifies its status as a master regulator of metabolic adaptation. From optimizing athletic performance to serving as a clinical biomarker and therapeutic target, the physiological importance of lactate is undeniable and continues to be a frontier of medical and physiological research. A detailed discussion can be found in {Link: ScienceDirect https://www.sciencedirect.com/science/article/pii/S2213231720300422}.

Frequently Asked Questions

No, this is a long-standing myth based on outdated science. While lactate levels rise during intense exercise, fatigue is primarily caused by other factors like the buildup of hydrogen ions, which cause muscle acidity. Lactate, in fact, helps to buffer this acidity.

The lactate shuttle theory explains how lactate is constantly produced and transported between different cells and organs. It describes lactate as an energy currency, moving from producing tissues (like glycolytic muscle fibers) to consuming tissues (like oxidative muscle fibers, heart, or brain) to be used as fuel.

The brain can efficiently use lactate for energy, particularly during heightened activity or low glucose availability. Astrocytes produce lactate and shuttle it to neurons, supporting neuronal function and plasticity. Lactate has also been explored as a neuroprotective agent in conditions like traumatic brain injury.

Lactate is the primary precursor for gluconeogenesis, the process by which the liver and kidneys synthesize new glucose. This occurs via the Cori Cycle, which helps maintain stable blood sugar levels, especially during fasting or prolonged exercise, by recycling lactate back into glucose.

Lactylation is a type of epigenetic modification where a lactate molecule is attached to a protein, typically a histone. This process can alter gene expression, providing a mechanism for metabolic changes to directly influence genetic programming and cellular function.

Lactate is measured clinically to assess tissue perfusion and predict patient prognosis, particularly in critical illnesses like sepsis, trauma, and shock. Persistently high lactate levels can signal severe stress or impaired metabolic clearance, helping guide treatment decisions.

Yes, lactate and lactic acid are not the same. In the body's physiological pH, "lactic acid" dissociates into a lactate anion and a hydrogen ion. The anion lactate is what is produced and utilized by the body, and it actually helps neutralize the hydrogen ions that contribute to acidosis.