Causes of niacin deficiency include malabsorptive conditions, malignancy (including carcinoid tumors), parenteral nutrition, psychiatric disease,74,75 and restrictive diets (eTable).76 Carcinoid tumors divert tryptophan to serotonin resulting in niacin deficiency.77
The diagnosis of niacin deficiency is based on clinical findings and response to supplementation.75 Low niacin urinary metabolites (N-methylnicotinamide and 2-pyridone) may aid in diagnosis.6 Treatment generally includes oral nicotinamide 100 mg every 6 hours; the dose can then be tapered to 50 mg every 8 to 12 hours until symptoms resolve. Severe deficiency may require parenteral nicotinamide 1 g 3 to 4 times daily.75
Vitamin B6
Vitamin B6 (pyridoxine, pyridoxamine, pyridoxal) is found in whole grains and plant and animal products. Vitamin B6 functions as a coenzyme in many metabolic pathways and is involved in the conversion of tryptophan to niacin.44 Absorption requires hydrolysis by intestinal phosphates and transport to the liver for rephosphorylation prior to release in active form.6
Cutaneous findings associated with vitamin B6 deficiency include periorificial and perineal seborrheic dermatitis,78 angular stomatitis, and cheilitis, with associated burning, redness, and tongue edema.6 Vitamin B6 deficiency is a rarely reported cause of burning mouth syndrome.79 Because vitamin B6 is involved in the conversion of tryptophan to niacin, deficiency also may present with pellagralike findings.70 Other clinical symptoms are outlined in the eTable.80,81
Conditions that increase risk for vitamin B6 deficiency are highlighted in the eTable and include malabsorptive disorders; psychiatric illness82; and chronic disease, especially end-stage renal disease.83 Vitamin B6 deficiency associated with chronic alcohol use is due to both inadequate vitamin B6 intake as well as reduced hepatic storage.78 Medications such as isoniazid, hydralazine, and oral contraceptives may decrease vitamin B6 levels (eTable).82
Vitamin B6 can be measured in the plasma as pyridoxal 5′-phosphate. Plasma concentrations of less than 20 nmol/L are suggestive of deficiency.82 Indirect tests include tryptophan and methionine loading.6 The treatment of vitamin B6 deficiency is determined by symptom severity. Recommendations for oral supplementation range from 25 to 600 mg daily.82 Symptoms typically improve on 100 mg daily.6
Vitamins B9 and B12
Deficiencies of vitamins B9 (folic acid, folate) and B12 (cobalamin) have similar clinical presentations. Folate is essential in the metabolism of amino acids, purines, and pyrimidines.6 Cobalamin, found in animal products, is a cofactor for methionine synthase and methylmalonyl-CoA mutase.84 Megaloblastic anemia is the main finding in folate or cobalamin deficiency. Neurologic findings only accompany cobalamin deficiency. Risk factors for folate deficiency include malabsorptive conditions,6 chronic alcohol use,85 and antifolate medication use (eTable).6
Cobalamin absorption requires gastric acid and intrinsic factor binding in the duodenum. Deficiency may occur from strict diets, psychiatric illness, old age,86 decreased gastric acid secretion,87 abnormal intrinsic factor function, or intestinal infections.6