From the Guidelines
Elevated methylmalonic acid levels are a sensitive marker for vitamin B12 deficiency, and treatment typically involves vitamin B12 supplementation, usually 1000 mcg daily orally or via injection depending on absorption status, as recommended by the most recent guidelines 1. Methylmalonic acid (MMA) is a metabolic compound that accumulates in the blood when vitamin B12 is deficient or when certain metabolic disorders are present. It serves as a more sensitive marker for vitamin B12 deficiency than serum B12 levels alone, as MMA levels rise earlier in the deficiency process. Normal MMA blood levels typically range from 70-270 nmol/L, with elevated levels strongly suggesting functional B12 deficiency even when serum B12 appears normal.
Key Points to Consider
- MMA testing is particularly valuable for diagnosing subtle B12 deficiencies in patients with neurological symptoms, elderly individuals, vegans, or those with malabsorption conditions.
- When elevated MMA is detected, treatment typically involves vitamin B12 supplementation, usually 1000 mcg daily orally or via injection depending on absorption status, as supported by recent studies 1.
- For those with genetic methylmalonic acidemia disorders, specialized dietary restrictions and medical management are required.
- MMA elevation occurs because vitamin B12 is essential for converting methylmalonyl-CoA to succinyl-CoA; without adequate B12, methylmalonyl-CoA accumulates and converts to methylmalonic acid, which can be measured in blood or urine.
Recent Guidelines and Recommendations
- The ESPEN guideline recommends that CD patients with ileal involvement and/or resection and/or clinical deficiency features should be screened yearly for B12 deficiency, and patients with clinical deficiency should receive 1000 mg of vitamin B12 by intramuscular injection every other day for a week and then every month for life 1.
- A more recent study suggests that B vitamins, including B12, can reduce the risk of stroke by 43% 1, highlighting the importance of adequate B12 levels for overall health.
Clinical Implications
- It is essential to prioritize vitamin B12 supplementation in patients with elevated MMA levels to prevent long-term complications, such as neuropathy, dementia, and increased risk of stroke.
- Clinicians should consider MMA testing in patients with suspected B12 deficiency, particularly those with malabsorption conditions or neurological symptoms.
- The choice of oral or injectable vitamin B12 supplementation should be based on individual patient needs and absorption status, with parenteral supplementation remaining the reference standard 1.
From the Research
Methylmalonic Acid
- Methylmalonic acid (MMA) is a functional marker of vitamin B12 deficiency 2, 3, 4, 5, 6
- MMA concentrations are influenced by vitamin B12 status, renal function, and endogenous production of propionic acid 3
- Elevated MMA levels are associated with an increased risk of mortality, independent of vitamin B12 and renal function 3
Diagnosis and Measurement
- Measurement of serum MMA can be used to confirm vitamin B12 deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12 2
- MMA levels are more strongly associated with poor functional status and physical performance than serum B12 4
- A large proportion of individuals with a decreased serum B12 concentration still have normal MMA concentrations 4
Relationship with Vitamin B12 and Other Metabolites
- There is a significant weak negative correlation between vitamin B12 and MMA, as well as between B12 and homocysteine (HC) 5
- MMA has the best discriminatory power in predicting B12 deficiency, compared to vitamin B12 and HC 5
- Serum MMA and HC can be useful in identifying subclinical or tissue deficiency of vitamin B12 6
Clinical Implications
- Vitamin B12 deficiency can be difficult to diagnose, and MMA and HC levels can be useful in identifying patients with functional deficiency 5
- Clinicians should be aware of the risk of vitamin B12 deficiency in older people and consider using serum metabolites for screening 6
- Elevated MMA levels are associated with poor functional performance and increased risk of mortality, highlighting the importance of monitoring and addressing vitamin B12 deficiency 3, 4