MMA

Your cells break down some fatty acids and amino acids along a route in which methylmalonic acid arises. The last stretch of that route, the conversion into a building block for energy production, runs through an enzyme that needs vitamin B12 as a helper. If there is too little usable B12 in the cell, that step stalls, methylmalonic acid accumulates and leaks into your blood. The number therefore rises as soon as the cells run short, and it falls again within weeks after B12 has been replenished. That makes MMA sharper than an ordinary B12 test. That test also counts the part of the B12 in your blood that is attached to a protein your cells cannot use, and can therefore look normal while the cells are genuinely short; that happens in about one in five people with a real deficiency. MMA measures the consequence instead of the store, and together with homocysteine, which also rises with a B12 deficiency but also with a deficiency of folate or B6, it points to the cause. Your report prints MMA in µmol/L, or sometimes in nmol/L: 0.35 µmol/L and 350 nmol/L are the same. Normal is roughly 0.10 to 0.35 µmol/L between 18 and 65 years, and 0.12 to 0.35 µmol/L from 65 years, where the labs overlap; one lab lets the upper limit run slightly higher above 65. A lower limit does not exist in practice: low means enough B12.

A B12 deficiency creeps up, with tiredness, tingling in hands and feet, a poorer memory and eventually nerve damage that no longer recovers. Anyone who eats plant-based, uses acid suppressants or metformin for years or gets older runs the greatest chance of it. The blood number of B12 misses part of those people; MMA shows whether the cells are genuinely short, and that is the difference between waiting on a borderline case and replenishing. The second reason is that MMA also shows whether replenishing works. After tablets or injections the number falls within weeks, and if it does not fall, the B12 has not arrived or the cause lies elsewhere. Homocysteine beside it says whether a deficiency of folate or B6 is also at play, because that lifts homocysteine and not MMA. The honest limitation is kidney function. MMA is excreted by the kidneys, and with a lower eGFR more of it stays in your blood without there being a deficiency; getting older lifts it for that reason too. Without creatinine and eGFR beside it a high MMA cannot be read. And each upper limit is chosen differently, from 0.35 to 0.46 µmol/L, so compare with the band on your own report.

A low MMA does not exist in practice: low means your cells have enough usable B12 and the metabolic route runs through. There is no lower limit and nothing to replenish; a low number never needs explaining. A high MMA means your cells can use too little B12, or your kidneys excrete the acid less. The most common explanation first: a vitamin B12 deficiency, through plant-based eating, acid suppressants, metformin or a stomach that can no longer absorb the vitamin; a reduced kidney function, which lifts the number without a deficiency; getting older, which does both at once, because the stomach absorbs less and the kidneys excrete less; plant-based eating, in which the only source of B12 is missing; and metformin, which inhibits absorption in the gut. Above 0.35 µmol/L with a normal kidney function a B12 deficiency is likely, even if the B12 number itself still sits within the band. Read MMA beside vitamin B12, because MMA says whether the cells are short where B12 counts the store, beside homocysteine, which also rises with a deficiency of folate or B6, beside creatinine and eGFR, because a lower kidney function lifts MMA without a deficiency, and beside MCV, which becomes large with a longer-standing deficiency.