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Vitamin B12 and Folate
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At a Glance

Why Get Tested?

To help detect early and/or mild vitamin B12 deficiency; sometimes to help diagnose newborns with methylmalonic acidemia, a rare inherited metabolic disorder

When To Get Tested?

When you have a low vitamin B12 level and/or have symptoms of B12 deficiency such as numbness, tingling in the hands or feet, trouble walking, swelling of body tissues, or yellowing of the skin or eyes; as part of newborn screening

Sample Required?

A blood sample is obtained by inserting a needle into a vein in your arm. For newborns, blood may be collected from a heelstick. A single random urine sample may be collected (the second morning sample is preferred) or a 24-hour collection of urine may be requested.

Test Preparation Needed?

Fasting is typically required for the blood test. For a random urine sample, you should fast overnight, discard the first urine sample of the morning, and then collect the second sample.

You may be able to find your test results on your laboratory’s website or patient portal. However, you are currently at Testing.com. You may have been directed here by your lab’s website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab’s website or portal, or contact your healthcare practitioner in order to obtain your test results.

Testing.com is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called “normal” values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are “within normal limits.”

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

Methylmalonic acid (MMA) is a substance produced in very small amounts and is necessary for human metabolism and energy production. This test measures the level of MMA in blood or sometimes urine.

Vitamin B12 is responsible for two critical enzymatic reactions that promote cell metabolism. B12 promotes the conversion of methylmalonyl CoA (a form of MMA) to succinyl Coenzyme A, and with folic acid, aids in converting homocysteine to methionne.

Blood and/or urine levels of MMA rise when your B12 level begins to decrease. The measurement of elevated amounts of methylmalonic acid in the blood or urine serves as a sensitive and early indicator of vitamin B12 deficiency.

A B12 deficiency can occur when your nutrition intake is poor or you have gastrointestinal malabsorption issues. Over time, vitamin B12 deficiency can cause blood cell changes, leading to anemia and the production of large red blood cells (macrocytes). It can also cause signs and symptoms of neuropathy, such as numbness and tingling in the hands and feet and/or, in advanced cases, mental or behavioral changes such as cognitive impairment, confusion, irritability, and depression. An increased concentration of MMA is often detectable even before B12 levels abnormally decrease, presence of blood cell changes, and/or before full-blown symptoms are apparent, though some people may have some degree of neuropathy.

The relationship between MMA and B12 has been known for over 40 years, but the use of MMA testing is not widespread nor is there agreement on its usefulness. Because a relatively large amount of the B12 found in the blood is bound to proteins and is not biologically active, some in the medical community think that MMA may be a better measure of bioavailable B12 than the usual vitamin B12 test. Others believe that MMA and homocysteine (which may also be elevated when either B12 or folate is deficient) are valuable in detecting early and mild cases of B12 deficiency. Still 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.

Common Questions

How is the test used?

The methylmalonic acid (MMA) test may be used to help diagnose an early or mild vitamin B12 deficiency. It may be ordered by itself but generally with a homocysteine test as a follow-up to a vitamin B12 test result that is in the lower end of the normal range.

There are currently no official guidelines for screening for average-risk adults. Testing may be warranted for asymptomatic adults with one or more risk factors, such as when you are elderly with inconsistent nutrition practices, in alcoholics, strict vegans/vegetarians, or when you have taken certain drugs, like Metformin, proton pump inhibitors, or H2 receptor antagonists for a long time. Also, cancer patients who have gastrointestinal malabsorption problems, have a poor dietary intake, or have had certain surgeries may be tested for B12 deficiency. In general, confirmation tests for MMA and/or homocysteine may be necessary to establish a diagnosis of B12 deficiency. MMA is a very sensitive test in indicating a B12 deficiency. It is more specific than homocysteine and is the confirmatory test of choice for a B12 deficiency.

When is it ordered?

MMA is usually ordered, sometimes along with a homocysteine test, when your vitamin B12 test result is in the lower portion of the normal range, especially when you have symptoms associated with B12 deficiency, or if one or more risk factors are present.

Signs and symptoms of B12 deficiency may include:

  • Diarrhea
  • Dizziness
  • Fatigue, muscle weakness
  • Loss of appetite
  • Pale skin
  • Rapid heart rate, irregular heartbeats
  • Shortness of breath
  • Sore tongue and mouth
  • Tingling, numbness, and/or burning in the feet, hands, arms, and legs (with B12 deficiency)
  • Confusion or forgetfulness
  • Paranoia

What does the test result mean?

If your MMA and homocysteine levels are increased and your vitamin B12 level is mildly decreased, then an early or mild B12 deficiency may be present. This may indicate a decrease in your available B12 at the tissue level.

If only your homocysteine level is elevated and not MMA, then you may have a folate deficiency. This distinction is important because giving folate to someone who is B12-deficient will treat the anemia but does not treat the neurologic damage, which may be irreversible.

If both your MMA and homocysteine levels are normal, then it is unlikely that you have a B12 deficiency.

A decreased level of MMA is not common and is not considered clinically significant.

My newborn had an MMA test done. Why?

Occasionally, specialized MMA testing may be ordered to help diagnose methylmalonic acidemia. Moderately to severely elevated levels of MMA may be seen in infants with the rare inherited metabolic disorder methylmalonic acidemia, caused by genetic mutations of chromosome 6.

An acutely ill infant with methylmalonic acidemia who shows sepsis, poor feeding, lethargy, and vomiting may progress to coma and death if not promptly treated. Laboratory testing for ketones, lactic acid, ammonia, hypoglycemia, decreased blood cell counts, and elevated C3 acylcarnitines and organic acids in the urine may be done. MMA testing may also be ordered.

Methylmalonic acidemia occurs in about 1 in 25,000 to 100,000 newborns. Screening for this disorder is part of mandatory programs in all 50 states in the U.S. Babies with this disease are unable to convert methylmalonyl CoA to succinyl CoA. They appear normal at birth, but as they consume protein, they begin to show symptoms such as excessive tiredness, vomiting, dehydration, weak muscle tone, seizures, mental retardation, strokes, and severe metabolic acidosis.

If I have an elevated MMA, why might my doctor hesitate to diagnose me with vitamin B12 deficiency?

If your B12 test result is in the lower end of the normal range and you do not present with significant clinical symptoms, your healthcare provider may feel that you have adequate B12 and will rely on these findings rather than an elevated MMA. This may be especially true if your homocysteine level is normal. Your health care provider may want to monitor your condition over time and may be reluctant to start you on what could be lifelong treatment with B12 injections and/or oral supplementation unless it is truly necessary.

Can either blood or urine be used for the MMA test?

In most cases, it is okay to use blood or urine for this test. Sometimes, a health care provider may want to test both blood and urine in order to compare the MMA results. Since homocysteine is a blood test, it may be more efficient and convenient to draw blood for both the MMA and homocysteine tests when they are ordered together.

Is there anything else I should know?

An elevated MMA test may indicate a B12 deficiency, but the amount of MMA measured does not necessarily reflect the severity of the deficiency, its likelihood of progressing, or the presence or severity of any symptoms.

If you have kidney disease, you may have a high level of MMA in your blood. If your kidneys are not functioning properly, they cannot properly eliminate MMA in the urine, causing MMA to accumulate in the blood.

Some studies have found a high variation in MMA levels when they are measured over time.

Related Content

View Sources

Sources Used in Current Review

LoCicero, R. et. al. (2018 January 19, Updated). Vitamin B12 deficiency anemia. MedlinePlus Medical Encyclopedia. Available online at https://medlineplus.gov/ency/article/000574.htm. Accessed July 2020.

Nagalla, S. and Schick, P. (2019 February 18, Updated). Pernicious Anemia. Medscape Hematology. Available online at https://emedicine.medscape.com/article/204930-overview. Accessed July 2020.

Frank, E. and Straseski, J. (2019 October, Updated). Megaloblastic Anemia. ARUP Consult. Available online at https://arupconsult.com/content/megaloblastic-anemia. Accessed July 2020.

Nelson, S. and Gerstein, B. (2017 December 26, Updated). Methylmalonic Acidemia Brief Overview of Methylmalonic Acidemia. Medscape Neurology. Available online at https://emedicine.medscape.com/article/1161799-overview. Accessed July 2020.

LoCicero, R. (2018 January 19, Updated). Pernicious anemia. MedlinePlus Medical Encyclopedia. Available online at https://medlineplus.gov/ency/article/000569.htm. Accessed July 2020.

Pernicious Anemia. National Heart, Lung, and Blood Institute. Available online at https://www.nhlbi.nih.gov/health-topics/pernicious-anemia. Accessed July 2020.

(© 1995–2019). Methylmalonic Acid, Quantitative, Plasma. Mayo Clinic Laboratories. Available online at https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/31927. Accessed July 2020.

Sources Used in Previous Reviews

Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp 406.

Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 740-741.

Greco, F. (2007 October 15). Methylmalonic acid test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003565.htm. Accessed on 2/17/08.

Hurd, R. (2007 April 26, Updated). Methylmalonic acidemia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/001162.htm. Accessed on 2/17/08.

(2008 January, Reviewed). Methylmalonic acidemia. Genetics Home Reference [On-line information]. Available online through http://ghr.nlm.nih.gov. Accessed on 2/17/08.

Grund, S. (2007 August 27). Pernicious anemia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000569.htm. Accessed on 2/17/08.

Venditti, C. (2007 January 18, Revised). Methylmalonic acidemia. GeneReviews [On-line information]. Available online through http://www.genetests.org. Accessed on 2/24/08.

Thomas, Clayton L., Editor (1997). Tabers Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosbys Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Klee, G. (2000). Cobalamin and Folate Evaluation: Measurement of Methylmalonic Acid and Homocysteine vs Vitamin B12 and Folate. Clinical Chemistry. 46:1277-1283 [Abstract]. Available online at http://www.clinchem.org/cgi/content/abstract/46/8/1277.

Oh, R. and Brown, D. (2003 March 1). Vitamin B12 Deficiency. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20030301/979.html.

Elin, R. and Winter, W. (2001 January 18). Methylmalonic Acid, A Test Whose Time Has Come? Archives of Pathology and Laboratory Medicine Vol. 125, No. 6, pp. 824827. [On-line journal]. Available online through http://arpa.allenpress.com.

Hvas, A., et. al. (2001 June 25). Increased Plasma Methylmalonic Acid Level Does Not Predict Clinical Manifestations of Vitamin B12 Deficiency. Arch Intern Med vol 161.

Smith, D. (2000 October 1). Anemia in the Elderly. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20001001/1565.html.

Mandava, P. and Kent, T. (Updated 2011 March 29). Methylmalonic Acidemia. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1161799-overview. Accessed November 2011.

Dugdale, D. (Updated 2010 February 1). Pernicious anemia. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000569.htm. Accessed November 2011.

(© 1995-2011). Unit Code 80289: Methylmalonic Acid (MMA), Quantitative, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/80289. Accessed November 2011.

Frank, E. et. al. (Updated 2010 September). Megaloblastic Anemia. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/MegaloblasticAnemia.html?client_ID=LTD#tabs=0. Accessed November 2011.

Bodamer, O. and Lee, B. (Updated 2011 September 14). Genetics of Methylmalonic Acidemia. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/947154-overview. Accessed November 2011.

Dugdale, D. (Updated 2009 November 15). Methylmalonic acid test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003565.htm. Accessed November 2011.

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Ueland PM, Schneede J. Measurement of methylmalonic acid, homocysteine and methionine in cobalamin and folate deficiencies and homocysteinuria. Pubmed online. Available online at http://www.ncbi.nlm.nih.gov/pubmed/18337849. Accessed November 2011.

2015 reviewer: Kristin Luckenbill, PhD, JD, DABCC, Clinical Chemist, Sanford Bismarck Laboratory.

Genome.gov. NIH National Human Genome Research Institute. Clinical and Basic Investigations of Methylmalonic Acidemia (MMA) and Related Disorders. Available online at http://www.genome.gov/19016900. Accessed September 2015.

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