Useful for:

When you have an abnormal complete blood count (CBC) with a blood smear showing large red blood cells (macrocytosis) or abnormal (hypersegmented) neutrophils; when you have symptoms of anemia (weakness, tiredness, pale skin) and/or of neuropathy (tingling or itching sensations, eye twitching, memory loss, altered mental status); when you are being treated for vitamin B12 or folate deficiency

Overview

B12:

Vitamin B12 (cobalamin) is necessary for hematopoiesis and normal neuronal function. In humans, it is obtained only from animal proteins and requires intrinsic factor (IF) for absorption. The body uses its vitamin B12 stores very economically, reabsorbing vitamin B12 from the ileum and returning it to the liver; very little is excreted.

Vitamin B12 deficiency may be due to lack of IF secretion by gastric mucosa (eg, gastrectomy, gastric atrophy) or intestinal malabsorption (eg, ileal resection, small intestinal diseases).

Vitamin B12 deficiency frequently causes macrocytic anemia, glossitis, peripheral neuropathy, weakness, hyperreflexia, ataxia, loss of proprioception, poor coordination, and affective behavioral changes. These manifestations may occur in any combination; many patients have the neurologic defects without macrocytic anemia.

Pernicious anemia is a macrocytic anemia caused by vitamin B12 deficiency that is due to a lack of IF secretion by gastric mucosa.

Serum methylmalonic acid and homocysteine levels are also elevated in vitamin B12 deficiency states.

Folate:

The term folate refers to all derivatives of folic acid. For practical purposes, serum folate is almost entirely in the form of N-(5)-methyl tetrahydrofolate.

Approximately 20% of the folate absorbed daily is derived from dietary sources; the remainder is synthesized by intestinal microorganisms. Serum folate levels typically fall within a few days after dietary folate intake is reduced and may be low in the presence of normal tissue stores. RBC folate levels are less subject to short-term dietary changes.

Significant folate deficiency is characteristically associated with macrocytosis and megaloblastic anemia. Lower than normal serum folate also has been reported in patients with neuropsychiatric disorders, in pregnant women whose fetuses have neural tube defects, and in women who have recently had spontaneous abortions.(5) Folate deficiency is most commonly due to insufficient dietary intake and is most frequently encountered in pregnant women or in alcoholics.

Other causes of low serum folate concentration include:

  • Excessive utilization (eg, liver disease, hemolytic disorders, and malignancies)
  • Rare inborn errors of metabolism (eg, dihydrofolate reductase deficiency, forminotransferase deficiency, 5,10-methylenetetra-hydrofolate reductase deficiency, and tetrahydrofolate methyltransferase deficiency)

Natural Occurrence

While there are folic acid supplements, the vitamin is also naturally found in several foods, including:

  • liver
  • citrus fruits
  • whole grains
  • beans
  • lentils
  • peas
  • milk
  • dark green, leafy vegetables, such as spinach and kale
  • bok choy
  • broccoli
  • avocados
  • Brussels sprouts
  • fortified cereals

If you aren’t consuming enough folic acid, you may develop a folic acid deficiency. While mild folic acid deficiency usually doesn’t trigger symptoms, severe folic acid deficiency can cause diarrhea, fatigue, and a sore tongue. The deficiency may also lead to a more serious condition known as anemia, which is caused by a lack of healthy red blood cells.

Since folic acid levels can be measured in the bloodstream, a folic acid test can determine whether someone has folic acid deficiency.

Symptoms?

You may need this test if you are taking medicines that could interfere with how your body absorbs B-12 or folate. You may also have this test if you have a disease or condition that could lead to B-12 deficiency. Symptoms of B-12 deficiency include:

The symptoms of a folic acid or vitamin B-12 deficiency include:

  • diarrhea or constipation
  • a swollen, red tongue
  • bleeding gums
  • a lack of appetite
  • fatigue
  • headaches
  • numbness
  • difficulty walking
  • memory loss

The symptoms of anemia include:

  • unusually pale skin
  • fatigue
  • dizziness
  • lightheadedness
  • weakness
  • rapid heart rate
  • shortness of breath
  • headaches
  • confusion

Symptoms of having too little folate are diarrhea, weight loss, and other vague symptoms that could be caused by many other conditions.

It’s important that women who are pregnant, thinking of becoming pregnant, or breastfeeding have enough folate.

This test measures both vitamin B-12 and folate, but either of these nutrients can be measured separately in different lab tests. Your healthcare provider may order this combined test if you have a condition for which it’s important to know both levels.

How to Prepare for the Test

You should not eat or drink for 6-8 hours before the test. Your provider may tell you to stop taking any drugs that may interfere with test results, including folic acid supplements.

Drugs that can decrease folic acid measurements include:

  • Alcohol
  • Aminosalicylic acid
  • Birth control pills
  • Estrogens
  • Tetracyclines
  • Ampicillin
  • Chloramphenicol
  • Erythromycin
  • Methotrexate
  • Penicillin
  • Aminopterin
  • Phenobarbital
  • Phenytoin
  • Trimethoprim
  • Azulfidine
  • Drugs to treat malaria

Many other conditions are known to cause an increase or decrease in the serum vitamin B12 concentration including:

Increased Serum B12 Decreased Serum B12
Ingestion of vitamin C Pregnancy
Ingestion of estrogens Aspirin
Ingestion of vitamin A Anticonvulsants
Hepatocellular injury Colchicine
Myeloproliferative disorder Ethanol ingestion
Uremia Contraceptive hormones
– Smoking
– Hemodialysis
– Multiple myeloma

The evaluation of macrocytic anemia requires measurement of both vitamin B12 and folate levels; ideally they should be measured simultaneously.

What do my test results mean?

Reference Values

Vitamin B12

180-914 ng/L

Folate

Testing the folate level, which is also known as folic acid and vitamin B9, is primarily used in the diagnosis of megaloblastic anemia.

The reference range of the plasma folate level varies by age, as follows  :

  • Adults: 2-20 ng/mL, or 4.5-45.3 nmol/L
  • Children: 5-21 ng/mL, or 11.3-47.6 nmol/L
  • Infants: 14-51 ng/mL, or 31.7-115.5 nmol/L

The reference range of the red blood cell (RBC) folate level also varies by age, as follows  :

  • Adults: 140-628 ng/mL, or 317-1422 nmol/L
  • Children: Over 160 ng/mL, or over 362 nmol/L

> or =4.0 mcg/L

<4.0 mcg/L suggests folate deficiency

Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you.

Results are given in nanograms per milliliter (ng/mL). A normal range for vitamin B-12 is 200 to 900 ng/mL.

If your B-12 results are low, it may mean you have:

  • Pernicious anemia

  • Stomach issues, such as lack of stomach acid, that make it difficult to absorb the vitamin

  • Folate deficiency

Your diet can also lead to B-12 deficiency. Some vegetarians or vegans who don’t eat eggs or other dairy products may develop this deficiency.

Your B-12 results may also be higher or lower if you have had recent nuclear medicine studies using radiation. They can mean that you have:

  • Severe liver disease

  • Chronic granulocytic leukemia

If the test is done on your blood plasma, a normal range for folate is 2 to 10 ng/mL. If the test is done on red blood cells, a normal range is 140 to 960 ng/mL.

If your folate results are low, it may mean you have:

  • A diet that doesn’t provide enough folate

  • Difficulty absorbing the nutrient

  • Alcohol abuse

  • B-12 deficiency

  • Hemolytic anemia

Risks

There is very little risk involved with having your blood taken.

Other slight risks from having blood drawn may include:

  • Excessive bleeding
  • Fainting or feeling lightheaded
  • Hematoma (blood accumulating under the skin)
  • Infection (a slight risk any time the skin is broken)

Serum folate measurement is preferred over RBC folate measurement due to considerable analytic variability (coefficient of variation; CV) of assays. Both results give the same interpretation (internal Mayo study), therefore RBC folate quantitation is not recommended. Additional serum testing with homocysteine and methylmalonic acid (MMA) determinations may help distinguish between vitamin B12 and folate deficiency states. In folate deficiency, homocysteine levels are elevated and MMA levels are normal. In vitamin B12 deficiency, the analytic variability (CV) of both serum and RBC folate assays is considerable. Homocysteine and MMA levels are alternate determinates of folate deficiency.

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