Methylmalonic Acid (MMA)

•Observational— Most sensitive functional B12 marker

What it is

Methylmalonyl-CoA is converted to succinyl-CoA by a B12-dependent enzyme. When B12 is insufficient, methylmalonyl-CoA accumulates and is hydrolysed to methylmalonic acid, which rises in blood and urine.

Why it’s better than serum B12

Serum total B12 is dominated by inactive bound forms, so it doesn’t reliably reflect tissue B12 status. MMA rises before serum B12 falls in early deficiency.

In adults >60, atrophic gastritis is common, and the prevalence of functional B12 deficiency is approximately 10–15%. Many of these adults have "normal" serum B12.

Causes of elevated MMA

• B12 deficiency (the question of interest).
• Renal impairment (cleared by kidney; rises with eGFR decline).
• Genetic mutations in methylmalonyl-CoA mutase (rare).
• Volume depletion mildly raises it.

Practical algorithm

If symptoms suggest B12 deficiency (neuropathy, cognitive change, fatigue) or risk factors are present (age, metformin, PPI, vegan):

1. Serum B12 + MMA + homocysteine.
2. If MMA elevated → functional B12 deficiency, treat regardless of serum B12.
3. Watch eGFR for confounding.

Related entries

Vitamin B12, Homocysteine, eGFR.