Methylmalonic Acid

Optimal Result: 0 - 24.9 nmol/mg Creatinine.

Other names: MMA, Methylmalonate

- Methylmalonic acid has been used as a marker for need of vitamin B12 and in the diagnosis of methylmalonic acidurias.

- A linear relationship between methylmalonic acid concentrations in serum and urine.

- Insufficient B12 or folate has also been shown to result in elevated blood levels of cystathionine.

Methylmalonic Acid (MMA) is formed from propionylCoA via methylmalonyl-CoA. Major dietary sources of propionyl-CoA include valine, isoleucine, methionine, threonine, and odd chain fatty acids. MethylmalonylCoA is converted to succinyl-CoA to feed the Citric Acid Cycle via the enzyme methylmalonyl-CoA mutase. This enzyme is very vitamin B2 dependent. In B12 deficiency, methylmalonyl-CoA is hydrolyzed to methylmalonic acid.


- Wongkittichote P, Mew NA, Chapman KA. Propionyl-CoA carboxylase–a review. Mol Genet Metab. 2017;122(4):145-152.

- Fowler B, Leonard J, Baumgartner M. Causes of and diagnostic approach to methylmalonic acidurias. J Inher Metab Disease. 2008;31(3):350-360.

- Harrington DJ. Laboratory assessment of vitamin B12 status. J Clin Pathol. 2017;70(2):168-173.

- Herrmann W, Obeid R, Schorr H, Geisel J. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med. 2003;41(11):1478-1488.

- Ward MG, Kariyawasam VC, Mogan SB, et al. Prevalence and Risk Factors for Functional Vitamin B12 Deficiency in Patients with Crohn’s Disease. Inflamm Bowel Dis. 2015;21(12):2839-2847.

- Hin H, Clarke R, Sherliker P, et al. Clinical relevance of low serum vitamin B12 concentrations in older people: the Banbury B12 study. Age Ageing. 2006;35(4):416-422.

- Tangney CC, Tang Y, Evans DA, Morris MC. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. Neurology. 2009;72(4):361-367.

- Klee GG. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B12 and folate. Clin Chem. 2000;46(8):1277-1283.

- Kwok T, Cheng G, Lai WK, Poon P, Woo J, Pang CP. Use of fasting urinary methylmalonic acid to screen for metabolic vitamin B12 deficiency in older persons. Nutrition. 2004;20(9):764-768.

- Favrat B, Vaucher P, Herzig L, et al. Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial. BMC Fam Pract. 2011;12:2- 2.

- Sun AL, Ni YH, Li XB, et al. Urinary methylmalonic acid as an indicator of early vitamin B12 deficiency and its role in polyneuropathy in type 2 diabetes. J Diab Res. 2014;2014:921616.

What does it mean if your Methylmalonic Acid result is too high?

The most common cause of Methylmalonic Acid (MMA) in the urine is vitamin B12 deficiency. However, a rare deficiency of the methylmalonyl-CoA mutase enzyme is another. Any underlying condition which results in vitamin B12 deficiency should be considered, such as reduced intestinal absorption, chronic alcoholism, or strict vegan diets.

Methylmalonic acid, as a functional biomarker, is considered a more sensitive index of B12 status when compared to serum B12.

Urinary MMA correlates with serum MMA, making the simple urine test a useful screening tool for B12 deficiency in at-risk populations, such as the elderly or patients with GI dysfunction.

Vitamin B12 therapy lowers MMA. Monitoring this metabolite may help prevent the consequences of B12 deficiency, such as cognitive decline and neuropathy.

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