Snapshot A 50-year-old alcoholic man presents to the hospital in a florid alcohol withdrawal. He confabulates and trembles uncontrollably. He is started on supportive therapy for now. An alcohowal withdrawal score is done regularly to assess for the need for medical therapy. In the meantime, bloodwork comes back with megaloblastic anemia and increased homocysteine and normal methylmalonic acid. He is immediately started on folic acid supplementation. Introduction Folic acid (or vitamin B9) is found in leafy green vegetables Associated conditions chronic hemolytic anemias malnutrition alcoholism elderly psychiatric comorbidity pregnancy increased folate requirement malabsorption celiac disease tropical sprue pregnancy risk of neural tube defects in infant certain drugs (anti-folates) phenytoin methotrexate trimethoprim Epidemiology Most common vitamin deficiency in the US Most common cause of megaloblastic anemia Can manifest after 4 months (depleted storage from liver) ETIOLOGY Pathogenesis folic acid is absorbed in duodenum and jejunum used in tetrahydrofolate (THF) as coenzyme important for DNA and RNA synthesis small reserve pool in liver causes megaloblastic anemia due to impaired DNA synthesis Presentation Symptoms no neurological symptoms (unlike in B12 deficiency) anemia fatigue weakness shortness of breath Physical exam glossitis pallor Evaluation Peripheral blood smear hypersegmented lobes seen in neutrophils macrocytosis basophilic stippling Serum ↓ folic acid ↑ homocysteine NORMAL methylmalonic acid (MMA) unlike in vitamin B12 deficiency, which has ↑MMA ↓ reticulocyte count may see pancytopenia due to destruction of abnormal cells increased MCV folate is more readily depleted than B12 Also test for B12 deficiency and TSH (to rule out hypothyroidism) Differential Vitamin B12 deficiency Pernicious anemia Other causes of macrocytic anemia alcoholism hypothyroidism liver dysfunction drugs Treatment Folic acid supplementation Eat a more balanced diet fruits and vegetables Prevention folic or folinic acid supplementation, especially if chronically on drugs such as methotrexate Complications Neural tube defects in infant if deficient during pregnancy In the setting of a B12 deficiency, the anemia can correct with aggressive folate supplementation but the patient will still be at risk for neurological complications of B12 deficiency including peripheral neuropathy and posterior column defects due to deficiencies in myelin production Prognosis Good with supplementation