These tests measure the concentration of folate and vitamin B12 in the serum (liquid portion of the blood). The amount of folate inside the red blood cell (RBC) may also be measured - it will normally be at a higher concentration inside the cell than in the serum.

B12 and folate are both part of the B complex of vitamins. Folate is found in leafy green vegetables, citrus fruits, dry beans and peas, liver, and yeast. B12 is found in animal products such as red meat, fish, poultry, milk, and eggs. In recent years fortified cereals, breads, and other grain products have also become important dietary sources of both B12 and folate (identified as "folic acid" on nutritional labels).

Both B12 and folate are necessary for normal red cell formation, tissue and cellular repair, and DNA synthesis. B12 is also important for nerve health, while folate is necessary for cell division such as is seen in a fetus during pregnancy. A deficiency in either B12 or folate can lead to macrocytic anaemia, where red cells are reduced but macrocytic (abnormally large). Specifically a bone marrow test may show megaloblastic anaemia, where immature red cells called megaloblasts may be seen.

B12 deficiency can also result in varying degrees of neuropathy, nerve damage that can cause tingling and numbness in the patient's hands and feet. In severe B12 deficiency, a more serious nerve damage may occur known as subacute combined degeneration of the cord or SACD, where severe weakness and incoordination may occur. Subtle deterioration in eyesight and mental ability may occur. Folate deficiency in early pregnancy can cause neural tube defects such as spina bifida in a growing fetus.

There are a variety of causes of B12 and/or folate deficiencies. They include:

Insufficient intake
The human body stores several years’ worth of B12 in the liver. B12 is widely available in non-vegetarian foods, so a dietary deficiency of this vitamin is rare. It may be seen sometimes with general malnutrition, and in vegan vegetarians - those who do not consume any animal products including milk and eggs. It may also be seen in children and breastfed infants of vegan vegetarians. Since they do not have the stores that adults do, deficiencies in children and infants show up fairly quickly.

Folate deficiency used to be common but with the advent of fortified cereals, breads, and grain products it is less so. Since folate is stored in tissue in smaller quantities than B12, folate must be consumed more regularly than B12.

Malabsorption
Both B12 and Folate deficiencies may be seen with conditions that interfere with their absorption in the small intestine. These may include:

• Coeliac disease 
• Bacterial overgrowth in the stomach and intestines
• Reduced stomach acid production (stomach acid is necessary to separate B12 from the protein in food)
• Pernicious anaemia , the most common cause of B12 deficiency. Normally a molecule called intrinsic factor is made by parietal cells that line the stomach. B12 binds to intrinsic factor in the stomach, and the resulting complex is absorbed in the intestines. With pernicious anaemia, antibodies attack parietal cells, reducing intrinsic factor production, or attack intrinsic factor, blocking its action, in either case preventing the efficient absorption of B12.
• Surgery that removes part of the stomach (and the parietal cells) or the intestines may greatly decrease absorption

Increased loss

This may be seen with:

• Liver and kidney disease
• Alcoholism, with alcohol abuse less B12 and folate are absorbed and more are excreted from the kidneys
• Anti-seizure medications such as phenytoin can decrease folate as can drugs such as metformin and methotrexate

Increased need