Borderline levels between 2 to 4 ng/mL warrant further confirmation by measurement of methylmalonic acid (MMA) and homocysteine levels. Generally, serum folate levels 4 ng/ml are considered as normal. Ordering serum vitamin b12 and folate levels can help differentiate between the two. In addition, a PS would show macrocytic red blood cells (RBCs)and/or megaloblasts and hypersegmented neutrophils. The mean corpuscular volume (MCV) would be increased to a level greater than 100 consistent with a diagnosis of macrocytic anemia. Laboratory tests in folic acid deficiency would reveal anemia, manifesting as a decrease in hemoglobin and hematocrit levels. Initial laboratory tests should include a complete blood count (CBC) and a peripheral smear (PS). Patients being evaluated for folic acid deficiency should also be evaluated for vitamin B12 deficiency as both cause macrocytic anemia. Folate deficiency may take 8-16 weeks to become evident.
The body has about 1,000-20,000 mcg of folate stores, and adults need about 400 mcg/d to replenish the daily losses. The deficiency of folate, as a result, leads to impairment of cell division, accumulation of toxic metabolites, and impartment of methylation reactions required for regulation of gene expression. THFA is involved in the formation of many coenzymes in metabolic systems, particularly for purine and pyrimidine synthesis, nucleoprotein synthesis, and maintenance in erythropoiesis. Cobalamin (B-12) serves as a co-factor for this demethylation to occur, and in its absence, folate is “trapped” inside cells as 5-methyl THFA.
Upon entering cells, 5-methyl THFA demethylates to THFA, the biologically active form involved in folate-dependent enzymatic reactions. Most of the serum folate is present in the inactive 5-methyltetrahydrofolate (5-methyl THFA) form. Folate is poorly stored, and deficiency can develop in weeks to months in persons with folate-deficient diets. Pregnancy, hemolytic anemia, and dialysis can also result in folate deficiency.įolate is present in abundance in green leafy vegetables, citrus fruits, and animal products. Alcoholism is a significant cause of folate deficiency. Folic acid deficiency can occur subsequent to vitamin B-12 deficiency due to an impairment of methionine synthase resulting in the trapping of folate as methyltetrahydrofolate whereby methylene THFA accumulates in serum leading to folate trap phenomenon and increased urinary excretion of folate.
Congenital deficiencies of enzymes required in folate metabolism can lead to folate deficiency. Drugs such as methotrexate, phenytoin, sulfasalazine, and trimethoprim can antagonize folate utilization, inhibit its absorption or conversation to its active form resulting in folate deficiency. Elevated pH, as occurs in achlorhydria, can also lead to poor folate absorption. Heating during cooking destroys folic acid. Folate is absorbed in the jejunum by active and passive transport mechanisms across the intestinal wall. Hence, diseases such as celiac disease, tropical sprue, short bowel syndrome, amyloidosis, gastric bypass, or mesenteric vascular insufficiency can inhibit folate absorption resulting in a deficiency. Folic acid deficiency can arise from multiple causes, including inadequate dietary intake.