L-Malic acid (MA)

L-Malic acid is a naturally occurring dicarboxylic acid and a fundamental intermediate in the tricarboxylic acid (TCA) cycle, where it is oxidized to oxaloacetate by malate dehydrogenase to generate NADH for the electron transport chain. Beyond its central role in energy metabolism, it serves as a multifunctional metabolite and signaling molecule involved in maintaining redox balance and host-microbiota crosstalk. Clinically, malic acid is widely utilized as a sialagogue to treat xerostomia (dry mouth), as its acidic properties stimulate salivary gland secretion to neutralize the oral environment. It is also commonly administered as a dietary supplement, often in combination with magnesium, for patients with fibromyalgia and chronic fatigue syndrome to support ATP production and reduce muscle fatigue. In the pharmaceutical industry, malic acid is frequently employed as a counter-ion to form stable malate salts of therapeutic agents, such as sunitinib and cabozantinib, enhancing their solubility and oral bioavailability. While malic acid itself is a metabolite rather than a protein target, its associated metabolic enzymes, such as Malic Enzyme 2 (ME2), are emerging as significant therapeutic targets in oncology.

Other names

2-hydroxybutanedioic acidHydroxybutanedioic acidApple acidL-MalateE296

As a sialagogue, malic acid dissociates hydrogen ions (H+) which stimulate salivary glands to secrete saliva as a neutralizing response; in energy metabolism, it acts as a metabolic substrate that facilitates the citric acid cycle to increase ATP production and promote the clearance of lactic acid in muscle tissue.