Suberic

Low levels of suberate can occur if there is insufficient dietary fat or digestive fat malabsorption. Suberate is primarily synthesized or derived from dietary oleic acid and absorbed from the gastrointestinal system. Suberate and adipate 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 suberate levels.

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

• 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.

  • Rule out Celiac disease as a cause of malabsorption.

  • Consider food allergy and sensitivity testing with IgG, IgA, IgG4, and IgE panels to rule out Ig-mediated inflammation as a cause of malabsorption or other gut symptoms.

• Consider an evaluation of gastrointestinal function to determine the need for digestive

  supports and improved fat assimilation.

High levels of suberate 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. Higher levels of circulating oleic acid have been found in diabetics and can increase suberate levels. An L-carnitine deficiency can inhibit normal beta-oxidation and promote omega-oxidation, increasing adipate and suberate levels. Adipate and suberate levels may increase if liver disorders are present. 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.

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.

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.

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

• Oleic acid is found in edible oils, meat (such as beef, chicken, and pork), cheese, nuts, sunflower seeds, eggs, pasta, milk, olives, and avocados. Excessive consumption may increase suberate levels.

Type II diabetes or metabolic syndrome can increase not only suberate but adipate, 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 and hydroxymethylglutarate, pyroglutamate, benzoate may be elevated while vanilmandelate, 5-hydroxyindolacetate, and orotate may be lower than expected.

Secondary lactic acidosis (e.g., apnea, septicemia, seizures, respiratory or cardiac insufficiency) may also elevate dicarboxylic acids (cis-aconitate, isocitrate, succinate, malate, suberate, and adipate).

• 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.

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