What causes folic acid deficiency?

Causes of Folic Acid Deficiency

Folic acid deficiency primarily occurs due to poor dietary intake, malabsorption, drug interactions, and increased metabolic demands, with inadequate consumption of folate-rich foods being the most common cause. 1

Primary Causes

1. Dietary Factors

• Inadequate intake: Low consumption of folate-rich foods such as:
  • Leafy green vegetables
  • Pulses (edible seeds from legumes)
  • Eggs, nuts, and whole grain products 1
• Poor diet quality: Diets low in fruits and vegetables
• Low-carbohydrate diets: May reduce intake of fortified grain products 1

2. Malabsorption Disorders

• Gastrointestinal conditions:
  • Inflammatory bowel disease, particularly Crohn's disease with ileal involvement 1
  • Celiac disease
  • Small intestinal bacterial overgrowth
• Surgical causes:
  • Bariatric surgery procedures 1
  • Ileal resection (particularly affecting vitamin B12, which can lead to secondary folate deficiency) 1

3. Medication-Related Causes

• Direct inhibition of folate metabolism:
  • Methotrexate: Inhibits dihydrofolate reductase 2
  • Trimethoprim
  • Pyrimethamine
  • Triamterene
• Impaired absorption:
  • Sulfasalazine: Causes folate malabsorption 1
  • Anticonvulsants
  • Antituberculosis drugs
• Other mechanisms:
  • Oral contraceptives
  • Alcohol: May reduce absorption or alter metabolism 2

4. Increased Metabolic Demands

• Pregnancy and lactation: Folate requirements approximately double 1
• Chronic hemolytic anemias: Increased cell turnover
• Malignancies: Rapid cell division increases folate requirements
• Inflammatory conditions: Excess folate utilization due to mucosal inflammation 1

5. Vitamin B12 Deficiency

• Vitamin B12 plays a crucial role in folate metabolism by converting inactive methyltetrahydrofolic acid to active tetrahydrofolic acid 1
• B12 deficiency can lead to functional folate deficiency even when folate intake is adequate

Clinical Significance

Folate deficiency can lead to several serious health consequences:

• Megaloblastic anemia: Characterized by oval macrocytes, leukopenia, and thrombocytopenia 3
• Neural tube defects: Increased risk during pregnancy, particularly in the first 28 days after conception 1
• Pregnancy complications: Associated with preterm delivery, low birth weight, and fetal growth retardation 4
• Elevated homocysteine levels: Linked to increased risk of cardiovascular disease 5

High-Risk Populations

• Pregnant women: Especially important in the periconceptional period 1
• Bariatric surgery patients: At risk due to malabsorption and reduced intake 1
• Patients with inflammatory bowel disease: Particularly those on sulfasalazine or methotrexate 1
• Individuals with alcohol use disorder: Due to poor diet and impaired metabolism
• Patients on certain medications: Anticonvulsants, methotrexate, sulfasalazine 2

Prevention Strategies

• Daily intake of 400 μg of folic acid for women of reproductive age 1
• Consumption of folate-rich foods
• Folic acid supplementation for high-risk individuals
• Food fortification programs (mandatory in many countries since 1998) 1

Understanding these causes is essential for proper diagnosis and management of folate deficiency, particularly in high-risk populations where preventive supplementation may be warranted.