ABSTRACT
I. Introduction .................................................................................................. 410 II. Clinical Folate De ciency ............................................................................ 410
A. Megaloblastic Anemia ............................................................................. 410 1. Hematological Changes Associated with Megaloblastic Anemia Resulting from Folate De ciency ........................................................ 410 2. Other Nutrient De ciencies That May Affect Diagnosis Based on Hematological Indices ......................................................................... 411
B. Megaloblastic Changes in Other Tissues ................................................. 412 C. Pathophysiology of Megaloblastic Anemia ............................................. 412
1. Use of Animal Models to Study Pathophysiology ............................... 412 2. Impaired DNA Synthesis ..................................................................... 413 3. Impaired Methylation .......................................................................... 413
III. Metabolite Abnormalities in Folate and Cobalamin De ciency .................. 414 A. Hcy and Methylmalonic Acid ................................................................. 414 B. Other Folate and Cobalamin-Dependent Metabolites ............................. 415
IV. Experimental Folate De ciency ................................................................... 417 A. Severe Dietary Folate De ciency ............................................................ 417 B. Controlled Folate Feeding Studies ........................................................... 418
V. Alcohol and Folate De ciency...................................................................... 418 A. Alcohol-Related Syndromes .................................................................... 418 B. Alcohol and Megaloblastic Anemia ......................................................... 419 C. Alcohol and Hyperhomocysteinemia ....................................................... 419
VI. Malabsorption of Folates and Other Causes of De ciency .......................... 420 A. Postgastrectomy ....................................................................................... 420 B. Tropical Sprue and Gluten Enteropathy ................................................... 420 C. In ammatory Bowel Disease ................................................................... 420 D. Clinical Conditions That May Increase Cellular Folate Requirements .. 421
1. Hemolytic Anemia and Psoriasis ......................................................... 421 2. Sickle Cell Disease .............................................................................. 421 3. Renal Dialysis ...................................................................................... 421 4. Drugs Inducing Folate De ciency ....................................................... 421
VII. Diagnosis and Treatment of Folate De ciency ............................................. 422 A. Blood Folate Concentration ..................................................................... 422 B. Hcy Measurements for Diagnosis of Folate Status .................................. 423
C. Attributing Anemia to Folate De ciency................................................. 423 D. Folic Acid Therapy .................................................................................. 423
VIII. Summary ......................................................................................................424 References .....................................................................................................424
