What is being tested?
The methylmalonic acid (MMA) test measures the amount of MMA in the blood or urine. MMA is a compound produced in very small amounts during amino acid metabolism. Increased production of MMA serves as a sensitive and early indicator of vitamin B12 deficiency. Normally, vitamin B12 acts as a coenzyme, promoting the conversion of methylmalonyl CoA to succinyl CoA. If there is not enough B12 available to act as a coenzyme, then methylmalonyl CoA concentrations begin to rise, and the body converts the methylmalonyl CoA to MMA instead. Decreased availability of B12 leads to increases in blood and urine MMA levels.

Over time vitamin B12 deficiency can cause hematologic changes, such as anemia and large red blood cells. It can also cause signs and symptoms of neuropathy, such as numbness and tingling in the hands and feet and/or mental or behavioral changes (confusion, irritability, depression). Increased concentrations of MMA are often detectible before the occurrence of hematologic changes. An affected person may not have any symptoms at all or may have some degree of neuropathy.

The relationship between MMA and B12 has been known for about 40 years, but the use of MMA testing is not widespread nor is there agreement on its clinical utility. Some in the medical community think that MMA may be a better measure of bioavailable B12 than the usual vitamin B12 test. This is because a relatively large amount of the B12 found in the blood is bound to proteins and is not freely available to act in chemical processes. Some health professionals are convinced that MMA and homocysteine (which may be elevated when either B12 or folate are deficient) are valuable in detecting early and mild cases of B12 deficiency. Others argue that many of the mild deficiencies detected do not progress to more severe deficiencies and do not necessarily need to be identified or treated.

How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in your arm. A single random urine sample may be collected (the second morning sample is preferred) or a 24-hour collection of urine may be requested.

Is any test preparation needed to ensure the quality of the sample?
For the MMA blood test, the patient should be fasting. For a random urine sample, the patient should fast overnight, discard the first urine sample of the morning, and then collect the second sample.