TRICARBOXYLIC ACID CYCLE INTERMEDIATES (Specifically: Malic Acid, Citric Acid, and Succinic Acid)

What are tricarboxylic acid intermediates?

The tricarboxylic acid cycle (TCA), also known as the Krebs or citric acid cycle, is a cyclic reaction used by the body to generate energy from the foods we eat. The TCA cycle occurs in the mitochondria, the cell’s energy powerhouse. The TCA cycle has intermediates, including malic acid, citric acid, and succinic acid, which are known to be involved in energy metabolism in the mitochondria.

What do tricarboxylic acid intermediates do in the body?

While these intermediates used to be thought of as byproducts of cellular metabolism to make lipids, nucleotides, and proteins, they are now known as important molecules with many different functions. Metabolites of the TCA cycle may be involved in remodeling the contents of the chromosome, regulating gene expression, modifying proteins, acting on platelets, and performing immune functions [^[1]]. TCA cycle intermediates also regulate the production of reactive oxygen species, a class of free radicals [^[2]].

Evidence suggests these intermediates also play a role in maintaining cellular immunity. When cells are in stress conditions, the membrane enclosing the mitochondria within the cell can become compromised, releasing TCA cycle intermediates into the cytosol or the fluid flowing inside the whole cell, directly influencing cellular immunity through its interactions there [^[2]].

How can tricarboxylic acid intermediates help alleviate certain Long COVID symptoms and pathophysiology? 

Supplementation with TCA cycle intermediates can help boost mitochondrial function and help patients recovering from COVID-19, especially older people. Supplemented along with amino acids, TCA cycle metabolites can play a supporting role in helping prevent mitochondrial damage, oxidative stress, and muscle loss. A combined supplement that includes amino acids and TCA cycle intermediates such as citric, succinic, and malic acids may be relevant to maintaining mitochondrial function. Such a supplement cocktail was studied in a mouse aging model and was found to preserve mitochondrial function, support muscle mass, and preserve physical and cognitive abilities [^[1]]. While more work is needed to elucidate the exact role of TCA cycle intermediates in Long COVID pathophysiology, the research seems promising.