3-Hydroxy-3-methylglutaric

Optimal Result: 0.14 - 38.95 mmol/mol.

3-Hydroxy-3-methylglutaric is the precursor of coenzyme Q10 and cholesterol. Slightly increased values may be caused by gastrointestinal yeast overgrowth. A moderate increase in urine HMG may also indicate decreased synthesis of coenzyme Q10. Certain cholesterol-lowering drugs may inhibit the synthesis pathway and result in high HMG values. Very elevated values may be caused by the genetic disorder, HMG aciduria.

What does it mean if your 3-Hydroxy-3-methylglutaric result is too low?

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.

What does it mean if your 3-Hydroxy-3-methylglutaric result is too high?

- Precursor of CoQ10.

- Slightly elevated levels suggest yeast overgrowth.

- Elevated levels may also indicate decreased CoQ10 synthesis. Very elevated levels may be due to HMG aciduria. 

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High 3-hydroxy-3-methylglutaric acid is seen in the genetic disease 3-hydroxy 3-methylglutaric aciduria.

Typical values observed in the genetic disease are 200-11,000 mmol/mol creatinine.

The cause of less significant increases in this urinary metabolite is unknown.

3-Hydroxy-3-methylglutaric aciduria may cause:

- vomiting,

- lethargy,

- hypotonia,

- and apnea,

...sometimes evolving to coma.

Laboratory tests reveal metabolic acidosis with severe hypoketotic hypoglycemia on fasting or during acute illness, hyperammonemia, and abnormal liver function.

Preliminary diagnosis is based on a pattern of organic acids in urine which includes:

- 3-hydroxy-3-methylglutaric,

- 3-hydroxyisovaleric,

- 3-methylglutaconic,

- 3-methylglutaric,

and 3-methylcrotonic acids.

Because yeast also produces this compound and yeast metabolites are frequently elevated along with this compound; slight increases may be yeast-related. Reduced activity of 3-hydroxy 3-methylglutaryl Co A reductase, a critical enzyme at the beginning of the cholesterol synthesis pathway, may also elevate this compound. Check cholesterol values when this compound is elevated up to 300 mmol/mol creatinine.

Slight elevations may result from coenzyme Q10 deficiency. Supplementation with coenzyme Q10 at 50 - 120 mg/day may be beneficial.

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