From the Guidelines
Methylmalonic acid (MMA) should be checked to diagnose vitamin B12 deficiency, particularly when B12 blood levels are borderline or when there's clinical suspicion despite normal B12 levels, as it is more sensitive and specific than serum B12 measurement alone. According to the most recent guideline evidence from 1, MMA testing is recommended for people who have symptoms or signs of vitamin B12 deficiency and an indeterminate total or active B12 test result. The underlying reason for checking MMA is that when vitamin B12 is deficient, the body cannot convert methylmalonyl-CoA to succinyl-CoA efficiently, causing MMA to accumulate in the blood and urine, as explained in 1.
Some key points to consider when interpreting MMA results include:
- Elevated MMA levels (typically above 0.4 μmol/L) suggest functional B12 deficiency even when serum B12 appears normal 1.
- MMA can also be elevated in kidney disease, so renal function should be considered when interpreting results.
- This test is especially valuable for early detection of B12 deficiency before anemia develops, in patients with neurological symptoms, in vegetarians/vegans, in elderly patients, and in those with malabsorption conditions like pernicious anemia or after gastric surgery.
- It's also useful for monitoring response to B12 supplementation therapy, with follow-up testing to ensure normalization, typically after vitamin B12 supplementation (usually 1000 mcg daily or weekly) is initiated 1.
Overall, checking MMA levels is a crucial step in diagnosing and managing vitamin B12 deficiency, and should be considered in clinical practice, especially when guided by the most recent evidence from 1.
From the Research
Reasons to Check Methylmalonic Acid
- Methylmalonic acid (MMA) is a biomarker used to diagnose vitamin B12 deficiency, as it is more strongly associated with poor functional status and physical performance than serum B12 2
- Elevated MMA concentrations are associated with cognitive decline and stroke in older people, making it an important marker to check in patients with suspected metabolic B12 deficiency 3
- MMA is considered a better indicator of vitamin B12 deficiency than serum B12 alone, as it reflects the functional status of vitamin B12 in the body 4
- Checking MMA levels can help identify individuals with functional vitamin B12 deficiency, which may not be detected by serum B12 levels alone 5
- Impaired methionine synthase activity, which can be caused by vitamin B12 deficiency, can lead to a range of clinical consequences, including megaloblastic anemia, nervous system involvement, and cognitive impairment 6
Clinical Significance of Methylmalonic Acid
- MMA levels can be used to assess the severity of vitamin B12 deficiency and monitor the response to treatment 2
- Elevated MMA levels have been associated with an increased risk of stroke and cognitive decline, making it an important marker to check in patients with cardiovascular or neurological disorders 3
- MMA levels can be influenced by renal function, and stratification of results by renal function is necessary to accurately interpret MMA concentrations 2
Laboratory Testing for Methylmalonic Acid
- MMA can be measured in serum or urine, and reference intervals have been established for both 4
- The establishment of optimal reference intervals for MMA excretion in urine is crucial in individuals with suspected functional vitamin B12 deficiency 4
- Laboratory testing for MMA should be performed in conjunction with other tests, such as serum B12 and holotranscobalamin, to provide a comprehensive assessment of vitamin B12 status 5