Methylmalonic

Optimal Result: 0 - 2 mmol/mol creatinine.

Other names: Methylmalonic Acid or MMA

Methylmalonic acid (MMA) is a substance produced in very small amounts and is necessary for human metabolism and energy production. In one step of metabolism, vitamin B12 promotes the conversion of methylmalonyl CoA (a form of MMA) to succinyl Coenzyme A. If there is not enough B12 available, then the MMA concentration begins to rise, resulting in an increase of MMA in the blood and urine. The measurement of elevated amounts of methylmalonic acid in the blood or urine serves as a sensitive and early indicator of vitamin B12 deficiency.

This marker is considered superior to measuring serum B12 levels directly. A 2012 publication by Miller showed that 20% of those tested had a genetic defect in the protein that transports B12 to cells. These patients may have a functional B12 deficiency, even if serum levels of B12 are normal.

What does it mean if your Methylmalonic result is too high?

Elevated levels of methylmalonate 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 (branch-chain amino acids, methionine, threonine), or if there are higher levels of its downstream products (methylsuccinate). Digestive disorders may prevent the absorption of vitamin B-12 and raise levels. Methylmalonate can also be converted into CAC intermediary succinyl-CoA via enzymes dependent upon vitamin B2 and B12. High levels of methylmalonate can inhibit mitochondrial functions and may induce oxidative damage in nerves. High levels of urinary methylmalonate correlate with serum vitamin B12 levels in diabetics and may be an early indicator of diabetic polyneuropathy. If both urinary methylmalonate and serum or urine homocysteine (not measured) are elevated, enzyme blocks (nutritional, acquired, or inherited) are likely in B12 metabolism and the methylation pathway.

→ Support the conversion of methylmalonate into succinyl-CoA with vitamin B2 and adenosylcobalamin (B12). Dietary cobalt (cobalamin) is available is higher amounts in animal products.

  • Vitamins B2, B3, iron (if deficient), L-carnitine and sulforaphane may be useful if there is evidence of a beta-oxidation defect (increased adipate, suberate, succinate, and beta-hydroxybutyrate).

→ Antioxidants can help decrease oxidative stress associated with nerve damage and diabetic polyneuropathy.

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