Methylmalonic acid (MMA) in cats and dogs

What it shows

Inside cells, B12 is a helper (cofactor) for an enzyme, methylmalonyl-CoA mutase, that turns methylmalonyl-CoA into succinyl-CoA, part of normal metabolism. Without enough B12 the reaction slows and MMA accumulates. Think of a conveyor line where one worker is missing: half-finished parts pile up, and the pile itself tells you the worker is absent.

Blood B12 shows how much vitamin is circulating, but the reactions that need it happen inside cells, and the two do not always match. So MMA is measured together with cobalamin, mainly when B12 is low or low-normal and the vet wants to know whether the cells are truly short. The method is gas chromatography–mass spectrometry.

Higher than reference — what it may be a sign of

• B12 deficiency at the cell level — the main meaning. In dogs, MMA rises as serum B12 falls; in cats with severe deficiency, MMA can reach up to 50 times the upper limit of normal.
• Poor B12 absorption — chronic intestinal disease (in cats also intestinal lymphoma) and exocrine pancreatic insufficiency, in which the pancreas makes little or no intrinsic factor, the protein needed to absorb B12. The cause itself is found with other tests.
• Normal B12 with high urine MMA — some dogs show this pattern; it may mean a cellular shortage despite a normal blood level, and what to make of it is still being studied. In a study of Border Collies, over a third of healthy dogs with normal B12 had high urine MMA.
• Kidney failure — MMA leaves the body through the kidneys, so a high result in an animal with kidney failure is interpreted with caution.

Lower than reference

A result within the interval means there is no sign of a B12 shortage inside the cells at the moment. Low blood B12 with normal MMA is possible: body stores may be running down before the cells feel the lack. In puppies with parvovirus or other acute intestinal disease, serum B12 was lower than in healthy dogs while MMA stayed normal — a sign that MMA responds to a true cellular shortage rather than to every dip in blood B12.

Look at together with

• Cobalamin (B12) — always alongside; together they show both the circulating and the cellular picture.
• Folate — measured with B12 in chronic intestinal disease.
• TLI — shows whether exocrine pancreatic insufficiency is behind a low B12.
• Creatinine — kidney function, because kidney failure can raise MMA on its own.

Units and conversion

In the app serum MMA is recorded in µmol/L. Some laboratories report it in nanomoles per litre: 1 µmol/L equals 1,000 nanomoles per litre, so 500 nanomoles per litre is 0.5 µmol/L. Forms may write MMA or “methylmalonic acid”. Urine MMA is a separate test: it is reported as a ratio to urine creatinine and is not compared with serum results.

Reference range

The reference range is on your lab’s form, and it differs between dogs and cats. As an example, the Texas A&M Gastrointestinal Laboratory gives 415–1,193 nanomoles per litre (0.415–1.193 µmol/L) for dogs and 139–898 (0.139–0.898 µmol/L) for cats. A value above the upper limit is read together with B12, the clinical signs and kidney function; one number on its own is not a diagnosis.

A hemolysed sample is not suitable, and the serum travels frozen. The vet may repeat MMA later to see whether it returns to the interval: in a feline study it normalised once the B12 shortage was corrected.

Cats and dogs

Sources

1. Texas A&M University Gastrointestinal Laboratory. MMA — Methylmalonic Acid (assay information).
2. Texas A&M University Gastrointestinal Laboratory. Cobalamin (Vitamin B12) Information.
3. Siani G, Mercaldo B, Alterisio MC, Di Loria A. Vitamin B12 in Cats: Nutrition, Metabolism, and Disease. Animals (MDPI), 2023;13(9):1474.
4. Serum cobalamin, urine methylmalonic acid, and plasma total homocysteine concentrations in Border Collies and dogs of other breeds. Am J Vet Res, 2012;73(8):1194–1199 (PubMed abstract).