MMA is the metabolic debris that piles up when cells run out of B12. It is the most sensitive functional test for B12 deficiency, positive even when the B12 number itself looks passable.
Standard range versus optimal range
| Framework | MMA value | Source |
|---|---|---|
| Normal | about 70-270 nmol/L | Stabler, NEJM 2013 |
| B12 deficiency territory | above 270-400 nmol/L | Stabler, NEJM 2013 |
| Kidney disease caution | rises independently of B12 | StatPearls, Vitamin B12 Deficiency |
When it runs high
High MMA with a low or borderline B12 confirms true cellular deficiency. One major impostor exists, kidney failure raises MMA on its own, so kidney function must be checked alongside.
- Vitamin B12 deficiency, the classic cause
- Chronic kidney disease reducing clearance
- Small bowel bacterial overgrowth, sometimes
- Inherited metabolic disorders, rare and severe
When it runs low
Low MMA is the healthy state and needs no interpretation. It effectively rules out significant B12 deficiency at the tissue level.
- Normal B12 status, the usual case
The witness that cannot be bribed
B12 fuels one key enzyme that converts methylmalonyl-CoA, and when the vitamin runs out the substrate upstream, methylmalonic acid, overflows into the blood. This makes MMA a functional test, it reports what cells experience rather than what circulates. A normal B12 with a high MMA is a real deficiency, while a borderline B12 with a normal MMA usually needs no treatment.
The kidney confounder
MMA leaves the body through the kidneys, so anyone with reduced kidney function accumulates it regardless of B12 status. Interpreting a high MMA without knowing the creatinine or eGFR is a classic mistake that leads to years of unnecessary injections. In kidney disease, holotranscobalamin or the clinical picture carries more weight.
The pair that settles arguments
MMA and homocysteine together split the diagnostic table cleanly. Both high points to B12, homocysteine high with MMA normal points to folate, and both normal effectively closes the case. This logic, cheap and blood-based, has largely replaced older and more invasive workups for the common question of whether a borderline B12 truly matters.
Related calculators
Related biomarkers Vitamin B12 · Homocysteine · HoloTC · Creatinine