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Vitamins, minerals and amino acids · Urine

Methylmalonic acid (urine)

A breakdown substance that builds up when the cells have too little active vitamin B12; used when a B12 deficiency is in doubt.

At a glance

  • Measured in urine
  • In 1 test panel
  • No special preparation

Methylmalonic acid (urine)

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

Explanation

Methylmalonic acid (urine): what is measured?

Methylmalonic acid (MMA) is formed during the breakdown of certain amino acids and fatty acids; further breakdown requires active vitamin B12. If the cells have too little B12, methylmalonic acid builds up and more of it ends up in the blood and urine. This test measures methylmalonic acid in the urine, usually relative to creatinine to correct for how concentrated the urine is.

What can it detect?

  • 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 (urine) too high

A raised methylmalonic acid fits a deficiency of active vitamin B12, even when the B12 in the blood is still in the gray area. The causes are the same as for a B12 deficiency: poor absorption due to inflammation of the stomach lining or a bowel 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 can raise methylmalonic acid without a B12 deficiency; that is why kidney function is part of the assessment. Strongly raised values in babies and young children may point to a rare inherited metabolic disease.

Methylmalonic acid (urine) too low

A low or normal value is the usual result and makes a deficiency of active vitamin B12 unlikely. According to the Dutch GP guideline (NHG) on anemia, a methylmalonic acid that is not raised virtually rules out a B12 deficiency; that evidence mainly concerns measurements in blood. A low value causes no symptoms and has no other meaning. If you already take B12 as tablets or injections, the treatment often gives a normal value.

After an abnormal result

With a raised value, the GP assesses the result together with the 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 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: according to the Dutch GP guideline (NHG) on anemia, the test is preferred over homocysteine when the total B12 is low-normal or slightly low (the gray area, about 150 to 250 pmol/L) and the suspicion of a deficiency remains. The guideline and the Dutch Society for Clinical Chemistry (NVKC) mainly assume methylmalonic acid in blood; for urine, the collection method and the cutoff values differ between laboratories. A raised value is always assessed together with the B12, the blood count and kidney function.

What can affect the result?

  • Reduced kidney function can raise the value without a B12 deficiency.
  • B12 supplements or injections lower the value, so that an earlier deficiency is no longer visible.
  • The collection method (a single sample or 24-hour urine) and the correction for creatinine affect the result; reference values differ between laboratories.
  • Rare inborn metabolic diseases raise the value strongly, regardless of B12 intake.

Who it is for

Who is the test useful for?

Useful for

Useful with a low-normal or slightly low vitamin B12 (or active B12 in the gray area) 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 without symptoms who eat a varied diet, the test is not useful.

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 (urine): test panels

Methylmalonic acid (urine) 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) (Urine)

    Urine

    Methylmalonic Acid (MMA)

    Methylmalonic acid in urine; for suspected B12 deficiency.

    € 78,00

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)
  • H&W 2014: NHG-Standaard Anemie, eerste herziening (openbare volledige tekst)
  • 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
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