From the Guidelines
Interpreting methylmalonic acid (MMA) and homocysteine levels is crucial for diagnosing vitamin B12 deficiency and related metabolic disorders, with elevated levels of both MMA (>0.4 μmol/L) and homocysteine (>15 μmol/L) strongly suggesting vitamin B12 deficiency, even when serum B12 levels appear normal, as indicated by studies such as 1. When evaluating these markers, it's essential to consider that isolated homocysteine elevation may indicate folate deficiency, while isolated MMA elevation is more specific to B12 deficiency. Key points to consider when interpreting MMA and homocysteine levels include:
- Elevated MMA and homocysteine levels are associated with an increased risk of atherosclerotic vascular disease, including stroke, as noted in 1.
- The measurement of total plasma homocysteine requires precise sample collection, immediate separation and freezing of plasma, and referral to a specialized laboratory, as outlined in 1.
- Treatment for elevated MMA and homocysteine levels typically involves vitamin B12 supplementation, usually starting with intramuscular injections (1000 μg daily for one week, then weekly for four weeks, followed by monthly maintenance) or high-dose oral supplements (1000-2000 μg daily).
- Renal insufficiency can falsely elevate both markers, so kidney function should be assessed simultaneously, and other factors that can affect these levels include certain medications (metformin, proton pump inhibitors), strict vegetarian diets, pernicious anemia, and genetic disorders of B12 metabolism, as discussed in 1.
- Follow-up testing after 2-3 months of treatment helps confirm the diagnosis and treatment efficacy, as levels should normalize with appropriate supplementation. It is also important to note that elevated homocysteine levels are associated with a 2- to 3-fold increased risk for atherosclerotic vascular disease, including stroke, as indicated by 1, and that B-complex vitamins, including pyridoxine, cobalamin, and folic acid, can lower homocysteine levels, but may not necessarily reduce the risk of cardiovascular events, as noted in 1.