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Vitamins, minerals and amino acids · Blood

Methylmalonic acid

A breakdown substance that builds up when the cells have too little active vitamin B12; the most sensitive measure of a deficiency.

At a glance

  • Measured in blood
  • In 2 test panels
  • No special preparation

Methylmalonic acid

  • Explanation
  • Result
  • Reliability
  • Who it is for
  • Test panels
  • Sources

Explanation

Methylmalonic acid: what is measured?

Methylmalonic acid (MMA) is formed during the breakdown of certain amino acids and fatty acids. The next step in that breakdown requires active vitamin B12. If the cells have too little of it, the conversion stalls and methylmalonic acid builds up in the blood. This test therefore does not measure how much B12 is circulating, but whether the cells can use enough of it.

What can it detect?

  • A vitamin B12 deficiency at the cell level, even when the B12 in the blood is still low-normal
  • Rarely: an inborn metabolic disease with buildup of methylmalonic acid, which is almost always already discovered in childhood

Result

What does the result mean?

Methylmalonic acid too high

A raised methylmalonic acid fits a deficiency of active vitamin B12, even when the total B12 is still in the gray area. The causes are the same as for a B12 deficiency: inflammation of the stomach lining, stomach or bowel surgery, Crohn's disease, long-term use of stomach acid inhibitors or metformin, a vegan diet without a supplement, and nitrous oxide (laughing gas) use. Reduced kidney function raises methylmalonic acid without a B12 deficiency; kidney function is therefore part of the assessment. Symptoms that go with a B12 deficiency are tiredness, tingling or a numb feeling in the hands and feet, balance problems and memory problems.

Methylmalonic acid too low

A low or normal value is the usual result. According to the Dutch GP guideline (NHG) on anemia, a methylmalonic acid that is not raised makes a vitamin B12 deficiency very unlikely; this makes the test especially strong at ruling out a deficiency when in doubt. A low value causes no symptoms and has no further meaning. If you already take B12 as tablets or injections, the treatment usually gives a normal value, even if there was a deficiency before.

After an abnormal result

With a raised value, the GP assesses the result together with the vitamin B12, the blood count and kidney function, looks for the cause of the deficiency and usually starts supplementation with tablets or injections. With a raised value without a clear cause, with severe nerve symptoms or with reduced kidney function, the GP consults an internist (specialist in internal medicine).

Reliability

How reliable is the test?

Methylmalonic acid is a follow-up test and not a first test. According to the Dutch GP guideline (NHG) on anemia, the test is preferred over homocysteine when the total vitamin B12 is low-normal or slightly low and the suspicion of a deficiency remains. Measured in blood, methylmalonic acid is the most sensitive measure of a functional B12 deficiency: it rises even before the blood count changes. A raised value is not a diagnosis on its own and is always assessed together with the B12, the blood count and kidney function.

What can affect the result?

  • Reduced kidney function raises the value without a B12 deficiency; this is the main cause of a false-positive result.
  • B12 supplements or injections lower the value, so that an earlier deficiency is no longer visible.
  • Strong bacterial overgrowth in the small intestine can raise the value without a B12 deficiency.
  • Reference values and cutoff values differ between laboratories; the unit can also differ.

Who it is for

Who is the test useful for?

Useful for

Useful with a low-normal or slightly low vitamin B12 and symptoms that fit a deficiency, such as tiredness, tingling or a numb feeling in the hands and feet, balance or memory problems. Also useful when a deficiency is in doubt with risk factors, such as a vegan diet without a supplement, stomach or bowel surgery, long-term use of stomach acid inhibitors or metformin, and nitrous oxide use. As a first test without a B12 measurement, or in people who already take B12 as tablets or injections, the result adds little.

How common is it?

In general practice, anemia due to a deficiency of vitamin B12 or folic acid newly occurs in about 2 in 1000 people per year. A B12 deficiency without anemia is more common, especially at an older age, with a vegan diet without a supplement and with long-term use of stomach acid inhibitors or metformin; exactly how common depends on the test and cutoff used.

Dutch GP guideline (NHG) on anemia

Drawbacks and risks

  • A raised value due to reduced kidney function can wrongly be read as a B12 deficiency.
  • After recent B12 supplementation, a normal result can wrongly rule out an earlier deficiency.

Get tested

Methylmalonic acid: test panels

Methylmalonic acid is part of these test panels. You order online and have your blood drawn at a collection point or collect the sample at home.

  • Methylmalonic acid (MMA) (finger-prick)

    Fingerstick

    Methylmalonic acid (MMA) (finger-prick)

    MMA in blood; an additional marker when investigating vitamin B12 deficiency.

    € 79,00

  • Methylmalonic acid (MMA)

    Blood draw

    Methylmalonic acid (MMA)

    MMA in blood; an additional marker when investigating vitamin B12 deficiency.

    € 79,00

Evidence

Sources

This explanation is based on Dutch guidelines and independent information. It is general information, not a diagnosis. Discuss an abnormal result with your GP.

More about risks and results
  • NHG-Standaard Anemie (M76)
  • NVKC, allesovertesten.nl: Methylmalonzuur
  • NVKC, allesovertesten.nl: Vitamine B12
  • Thuisarts.nl: Ik heb misschien te weinig vitamine B12

More explanations

Other tests: Vitamins, minerals and amino acids

  • AC/FC ratio
  • Acylcarnitine
  • Alanine
  • Antibodies against intrinsic factor
  • Arginine
  • Calcium
  • Calcium (albumin-corrected)
  • Carnitine, free
  • Carnitine, total
  • Coenzyme Q10
  • Copper
  • Folic acid
All tests
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