Hydroxymethylglutarate

High levels of hydroxymethylglutarate may occur when there are nutritional enzyme inhibitions of the breakdown pathways, inherited low-activity enzymes are present, if there are high levels of precursors (amino acids, pyruvate, butyrate), or if there are higher levels of its downstream products. Hydroxymethylglutarate is a metabolic intermediary in the synthesis of CoQ10 and can be used in both fatty acid breakdown and in the metabolism of ketone bodies. The majority of hydroxymethylglutarate metabolism occurs in the liver and pancreas; higher levels may indicate liver or pancreas disorders. Alcohol consumption may inhibit the hydroxymethylglutarate breakdown enzymes.

- Consider CoQ10 to restore levels (if indicated). L-carnitine may help shuttle hydroxymethylglutarate between the mitochondria and the cytoplasm for breakdown.

- Liver disorders may cause or exacerbate beta-oxidation defects and increase adipate and suberate; alpha-ketoisocaproate, other keto-acids, benzoate and pyroglutamate may also be elevated. Consider sulforaphane to support beta-oxidation.

- Pancreatic beta-cells normally take up methylsuccinate; higher methylsuccinate levels may indicate a pancreatic disorder. Type II diabetes or glucose-insulin dysregulation may decrease alpha-ketoglutarate and fumarate and increase succinate, adipate, suberate, ethylmalonate, methylsuccinate, alpha-keto-beta-methylvalerate, alpha-hydroxybutyrate, and hippurate. Consider the evaluation of metabolic syndrome or type II diabetes if indicated.

Low levels of hydroxymethylglutarate may occur if there are low levels of precursors (amino acids, pyruvate, butyrate), if there are nutritional enzyme inhibitions, or if a low-activity enzyme variant is inherited. The enzymes that synthesize hydroxymethylglutarate are located in the liver and pancreas and these enzymes have no known nutritional cofactors. Hydroxymethylglutarate may be synthesized from amino acid metabolism, from pyruvate metabolism or from butyrate metabolism. Hydroxymethylglutarate can be used in both fatty acid breakdown and is an essential step in ketogenesis. Low levels of hydroxymethylglutarate may inhibit CoQ10 synthesis.

- Consider CO-Q10 supplementation if indicated.

- Consider supporting the movement of hydroxymethylglutarate between the mitochondrial matrix and the cell cytoplasm with L-carnitine.

- If levels of adipate and suberate are also high, there may be inherited or acquired problems with liver beta-oxidation; consider sulforaphane to support beta-oxidation.

Hydroxymethylglutarate (HMG) is the precursor to Coenzyme Q10 (CoQ10) production, and when it is elevated it may indicate that the body is trying to increase its production of CoQ10.