Alpha ketoglutarate, malate, and citrate: Citric acid cycle intermediates
Summary
Alpha-ketoglutarate, malate, and citrate are organic acids that serve as intermediates in the citric acid (Krebs) cycle. This metabolic cycle releases stored energy through the oxidation of carbohydrates, fats, and proteins, and is fundamental to life. These intermediates can be synthesized in the body, and are not required in the diet. The role of citric acid cycle intermediates in the treatment of ASD has not been studied. Several lines of evidence support the notion that some children with ASD have abnormal mitochondrial metabolism.
Alpha-ketoglutarate, malate, and citrate in Spectrum Needs
These citric acid cycle intermediates are added in order to support mitochondrial energy metabolism. In addition to alpha-ketoglutarate, these intermediates are provided in the forms of magnesium malate, magnesium citrate, and potassium citrate. Side effects are unexpected.
The Details
What Is It? Alpha-ketoglutarate, malate, and citrate are organic acids that serve as intermediates in the citric acid cycle.
What Does It Do? The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a series of chemical reactions used to release stored energy through the oxidation of carbohydrates, fats, and proteins into carbon dioxide and chemical energy in the form of NADH and ATP. This cycle is fundamental to all aerobic (oxygen-requiring) life, including humans.
What Does Deficiency Appear as? Alpha-ketoglutarate, malate, and citrate can be synthesized in the body by the citric acid cycle, and are not required in the diet. Deficiency is unknown.
What About Its Use in Autistic Spectrum Disorders (ASD)? The role of citric acid intermediates in the treatment of ASD has not been studied. Several lines of evidence support the notion that some children with ASD have abnormal mitochondrial metabolism (this topic is reviewed in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910649/pdf/cmped-10-2016-043.pdf).
What About Its Use in Other Conditions? Alpha-ketoglutarate is sometimes used to boost athletic performance and to help heal wounds. In addition, alpha-ketoglutarate can reduce levels of ammonia (and excess nitrogen) formed in the brain, muscles and kidneys. Malate and citrate are all frequently provided as part of mineral supplements. Citrate is sometimes used to prevent kidney stones and to alkalize the blood or urine in various conditions.
What Are the Common and/or Important Side Effects? Side effects are rare at usual doses used in supplementation.
Is There Any Laboratory Testing? Urine organic acid testing can quantify these citric acid intermediates, but this is not likely to be of clinical utility other than in screening for metabolic/mitochondrial disorders.
How and Why is this Nutrient Used in Spectrum Needs
The inclusion of citric acid cycle intermediates in Spectrum Needs is based on the hypothesis that improved function of this cycle can benefit some children in which mitochondrial dysfunction is a factor in their disease, whether or not they have an ASD. Citric acid cycle intermediates added in Spectrum Needs include alpha-ketoglutarate, magnesium malate, magnesium citrate, and potassium citrate. Side effects are unexpected at the doses used in Spectrum Needs.