What causes low folate levels?

Causes of Low Folate Levels

Low folate levels are primarily caused by inadequate dietary intake, malabsorption, increased utilization, medication interactions, and certain disease states that affect folate metabolism. 1

Primary Causes of Folate Deficiency

Inadequate Dietary Intake

• Low consumption of folate-rich foods (legumes, green leafy vegetables, fruits) 2
• Poor diet quality, particularly in:
  • Elderly populations (68% have very low folate intake) 3
  • Adolescents and adults (59% and 58% respectively have intake <300 µg/day) 3
  • Only about 12% of people achieve the WHO recommended level of 400 µg/day 3

Malabsorption

• Gastrointestinal disorders:
  • Inflammatory bowel disease, particularly Crohn's disease (22.3% prevalence of folate deficiency) 4
  • Celiac disease 5
  • Gastric atrophy in the elderly 2
  • Helicobacter pylori infection 2

Medication-Induced Deficiency

• Folate antagonists that inhibit dihydrofolate reductase:
  • Methotrexate 4, 6
  • Trimethoprim 6
  • Pyrimethamine 6
  • Triamterene 6
• Medications causing malabsorption:
  • Sulfasalazine 4, 1
• Anticonvulsants:
  • Phenytoin 7, 6
  • Primidone 7
  • Barbiturates 7
• Other medications:
  • Antituberculosis drugs 6
  • Oral contraceptives 6

Increased Utilization

• Pregnancy and lactation (markedly increased requirements) 4, 7
• Hemolytic anemia (increased folate requirements for red cell production) 1
• Inflammatory conditions (excess folate utilization due to mucosal inflammation) 4

Alcohol Consumption

• Chronic alcohol use 7, 6
• Alcoholic cirrhosis (particularly severe impact) 7

Risk Factors and Contributing Factors

Demographic and Lifestyle Factors

• Living environment (urban vs. rural) 3
• Lower education level 3
• Employment status 3
• Higher BMI 3
• Male sex (in adolescents and elderly) 3

Genetic Factors

• Gene polymorphisms in transcobalamins (affect folate transport) 2
• Genetic variations affecting folate metabolism 8

Clinical Implications

Masking B12 Deficiency

• High-dose folate supplementation (>1 mg/day) can mask vitamin B12 deficiency 1, 7
• This can allow neurological symptoms to progress while correcting hematologic manifestations 7
• Always check vitamin B12 status before initiating folate treatment 1

Disease Associations

• Neural tube defects in pregnancy 4, 1
• Megaloblastic anemia 6
• Cardiovascular disease 8
• Potential increased cancer risk with excessive supplementation 1
• Neurological and psychiatric effects 6

Diagnostic Approach

• Measure serum folate for short-term status assessment 1
• Consider red blood cell folate for long-term status 1
• Measure homocysteine levels concurrently for better interpretation 1
• Check complete blood count for macrocytic anemia 1
• Always assess vitamin B12 status simultaneously 1, 7

Understanding these diverse causes of folate deficiency is essential for proper diagnosis and management, especially given the critical role of folate in DNA synthesis, amino acid metabolism, and prevention of developmental anomalies.