Adipic acid

Low levels of adipate can occur if there is insufficient dietary fat or digestive fat malabsorption. While adipate can be synthesized, it is primarily produced by the gastrointestinal microbiome from dietary fats and absorbed from the gastrointestinal system. Adipate and suberate levels may also be low if there are inherited low activity enzyme variants present in the synthesis pathway. An insufficiency of zinc or vitamin B3 may inhibit omega oxidation pathways and decrease adipate levels. Adipate can be used to synthesize succinate and support the Citric Acid Cycle.

- Consider supporting adipate synthesis with vitamins B2, B3, CoQ10 (ubiquinone), L-carnitine, magnesium, and zinc.

- Adipate may be combined with malonate and converted into succinate to drive the CAC forward. If adipate is low, but succinate is adequate and alpha-ketoglutarate is elevated, conversion to succinate may cause lower adipate levels. Consider increasing healthy fats and supporting fat digestion with digestive enzymes.

- Celiac disease or inflammatory bowel syndrome (IBD) may impair digestion and absorption of fats, proteins, minerals, and vitamins. Fat malabsorption can present with gastrointestinal bloating and cramping with pale or greasy stools.

- Consider an evaluation of gastrointestinal function to determine the need for digestive supports and improved fat assimilation.

High levels of adipate can occur if there is a high dietary fat load, during fasting, or if there are inherited low-activity enzyme variants in the beta-oxidation pathway. Metabolic syndrome or type II diabetes may increase adipate and suberate levels. An L-carnitine deficiency can inhibit normal beta-oxidation and promote omega-oxidation, increasing adipate and suberate levels. Adipate is converted into succinate and other products in the liver. Dicarboxylic acids (cis- aconitate, isocitrate, succinate, malate, suberate, and adipate) may be excreted in high amounts due to increased mobilization of fatty acids, beta-oxidation defects, increased gut permeability or fasting. In some autistic individuals, there is an inverse relationship between adipate levels and social deficit/communication scores and a direct association with adipate levels and total ASD symptom scores. Adipate levels may increase if liver disorders are present. Exposure to phthalates or butane can also increase adipate levels.

- Consider supporting the beta-oxidation pathway with vitamins B2, B3, iron (if deficient), L-carnitine, sulforaphane and a lower-fat diet. Individuals with beta-oxidation defects may have trouble producing enough ketone bodies to successfully accommodate fasting or a “keto” or high-fat diet.

    - Beta-oxidation defects may also increase suberate, ethylmalonate, and methylsuccinate

- Omega oxidation products can be converted into products that support the CAC. Levels of dicarboxylic acids (cis-aconitate, isocitrate, succinate, malate, suberate, and adipate) can increase when this occurs.

- Adipate is primarily produced by the gastrointestinal microbiome from dietary fats. A high dietary fat load may increase levels of adipate, suberate, and beta-hydroxybutyrate.

- Type II diabetes or metabolic syndrome can increase not only adipate but suberate, alpha- hydroxybutyrate, lactate, and pyruvate.

- Liver disorders:

    - Some liver disorders, or later stage liver disease, may result in lactic acidosis and increase the levels of lactate, pyruvate, the Fatty     Oxidation and Ketone analytes, and other organic acids. General symptoms of acidosis in infants include poor feeding, vomiting, loss of     appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). In adults, acidosis or acidemia is characterized by headaches,     confusion, feeling tired, tremors, sleepiness, and seizures.

    - Other liver disorders or early-stage liver disease may instead increase the levels of adipate and suberate, while blocking the synthesis     of ketones such as beta-hydroxybutyrate. Levels of alpha-keto-isovalerate, hydroxymethylglutarate, pyroglutamate, benzoate, and 3-     indoleacetate may be elevated, while vanilmandelate, 5-hydroxyindolacetate, and orotate may be lower than expected.

- Butane exposures may occur due to deliberate inhalation (“huffing”) or from industrial, aerosol propellant or petroleum exposures. Butane “huffing” may result in neurological and cardiovascular symptoms.

- Phthalate exposures can inhibit beta-oxidation and increase levels of adipate, suberate, ethylmalonate, and methylsuccinate.