Laboratory assessment of folate (vitamin B₉) status

Abstract

Folate (vitamin B) plays a crucial role in fundamental cellular processes, including nucleic acid biosynthesis, methyl group biogenesis and amino acid metabolism. The detection and correction of folate deficiency prevents megaloblastic anaemia and reduces the risk of neural tube defects. Coexisting deficiencies of folate and vitamin B are associated with cognitive decline, depression and neuropathy. Folate deficiency and excess has also been implicated in some cancers. Excessive exposure to folic acid, a synthetic compound used in supplements and fortified foods, has also been linked to adverse health effects. Of at least three distinct laboratory markers of folate status, it is the total abundance of folate in serum/plasma that is used by the majority of laboratories. The analysis of folate in red cells is also commonly performed. Since the folate content of red cells is fixed during erythropoiesis, this marker is indicative of folate status over the preceding ~4 months. Poor stability, variation in polyglutamate chain length and unreliable extraction from red cells are factors that make the analysis of folate challenging. The clinical use of measuring specific folate species has also been explored. 5-Methyltetrahydrofolate, the main form of folate found in blood, is essential for the vitamin B-dependent methionine synthase mediated remethylation of homocysteine to methionine. As such, homocysteine measurement reflects cellular folate and vitamin B use. When interpreting homocysteine results, age, sex and pregnancy, specific reference ranges should be applied. The evaluation of folate status using combined markers of abundance and cellular use has been adopted by some laboratories. In the presence of discordance between laboratory results and strong clinical features of deficiency, treatment should not be delayed. High folate status should be followed up with the assessment of vitamin B status, a review of previous results and reassessment of folic acid supplementation regime.

British Obesity and Metabolic Surgery Society Guidelines on perioperative and postoperative biochemical monitoring and micronutrient replacement for patients undergoing bariatric surgery—2020 update

“…It should be noted that megaloblastic and macrocytic anaemia, associated with vitamin B12 deficiency, can be masked by folic acid supplementation, high folate levels or iron deficiency 95 . It is essential to assess all haematinics before recommending additional folic acid supplements 97,102 …”

Cerebral folate deficiency: Analytical tests and differential diagnosis

“…Folate status is usually initially assessed by total folate in serum or plasma using a folate‐binding protein assay (see Reference for review of folate assays). The advantages of this assay are that it is easily automated, inexpensive and quick to perform, but it should be noted that it measures total folate, including folic acid, and therefore does not always accurately assess the levels of active forms of folate such as 5‐MTHF.…”

Severe megaloblastic anemia: Vitamin deficiency and other causes

“…The recommended daily allowance depends on age, sex, and pregnancy status, but is generally 400 μg in adults and 600 μg during pregnancy. 6 Folate defi ciency has 3 main causes 4,5 : • Reduced intake from diets lacking folate (rare in countries with vitamin fortifi cation) and alcoholism (see Case 1) • Decreased absorption from disorders affecting nutrient absorption in the small bowel, eg, celiac disease, infl ammatory bowel disease, and tropical sprue • Increased demand from pregnancy, hemolytic anemia, puberty, and eczematous conditions. Vitamin B 12 is produced by microorganisms and is found almost exclusively in foods of animal origin.…”

“…Fasting serum folate generally refl ects tissue levels of folate; however, postprandial increases in folate occur and can cause falsely normal results in nonfasting samples. 6 After a meal, increased serum folate occurs within 2 hours, then quickly returns to baseline. Falsely elevated folate levels can also be seen with sample hemolysis and vitamin B 12 defi ciency.…”