What is the purpose of drawing a Methylmalonic Acid (MMA) level?

From the Guidelines

Methylmalonic Acid (MMA) levels are primarily drawn to help diagnose vitamin B12 deficiency, particularly when B12 blood levels are borderline or inconsistent with clinical symptoms. MMA is a metabolic byproduct that accumulates when B12 is insufficient, making it a more sensitive marker for functional B12 deficiency than serum B12 measurements alone, as indicated by the European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases 1. This test is especially valuable for detecting early or subtle B12 deficiencies before anemia or neurological symptoms become apparent.

Key Points to Consider

• MMA levels can also help distinguish true B12 deficiency from other conditions that might affect serum B12 readings.
• Additionally, MMA testing is useful for monitoring the effectiveness of B12 replacement therapy, as levels should decrease with successful treatment, with a threshold of >270 mM indicating clinical B12 deficiency, as per the ESPEN guideline: clinical nutrition in inflammatory bowel disease 1.
• The test may be ordered alongside homocysteine levels, which also elevate in B12 deficiency, to provide a more complete diagnostic picture.
• Elevated MMA levels can occasionally indicate certain genetic disorders of metabolism or kidney dysfunction, so clinical context is important when interpreting results.

Clinical Application

In clinical practice, MMA levels are crucial for identifying patients at risk of B12 deficiency, especially those with ileal involvement or resection, and for guiding the initiation and monitoring of vitamin B12 therapy, with recommendations including parenteral supplementation as the reference treatment 1.

From the Research

Purpose of Drawing a Methylmalonic Acid (MMA) Level

The purpose of drawing a Methylmalonic Acid (MMA) level is to detect functional vitamin B12 deficiencies, as MMA accumulates early when intracellular deficits arise 2.

• MMA is a reliable method for diagnosing vitamin B12 deficiency, with good nosographic sensitivity 3.
• Elevated MMA levels can also come from other sources, such as genetic mutations, gut microbiota, and aggressive cancers 4.
• MMA testing is useful in detecting vitamin B12 deficiency, especially in patients with elevated creatinine levels 5.
• The test can help identify patients with vitamin B12 deficiency who may require treatment, and can also be used to monitor the effectiveness of treatment 5.

Clinical Applications

MMA levels are used in various clinical applications, including:

• Diagnosing vitamin B12 deficiency 2, 3, 5.
• Monitoring the effectiveness of vitamin B12 treatment 5.
• Identifying patients with methylmalonic acidemia, a severe autosomal recessive inborn error of metabolism 6.
• Studying the metabolic and signaling functions of MMA in aging and disease 4.