Symptoms and Treatment of Folic Acid Deficiency
Folic acid deficiency should be treated with oral folic acid 5 mg daily for a minimum of 4 months, but it is crucial to first exclude vitamin B12 deficiency before initiating treatment to avoid precipitating subacute combined degeneration of the spinal cord. 1
Clinical Manifestations of Folic Acid Deficiency
Folic acid deficiency presents with various symptoms affecting multiple body systems:
Hematological Symptoms
- Megaloblastic anemia (identical to that seen in vitamin B12 deficiency)
- Macrocytosis (enlarged red blood cells)
- Fatigue and weakness due to anemia
- Pallor
Neurological Symptoms
- Irritability
- Headaches
- Difficulty concentrating
- Memory impairment
- Depression
- Cognitive decline (especially in elderly)
Gastrointestinal Symptoms
- Glossitis (inflammation of the tongue)
- Smooth, red, and painful tongue
- Mouth ulcers
- Diarrhea
- Poor appetite
Other Symptoms
- Growth impairment in children
- Increased susceptibility to infections
- In pregnant women: increased risk of neural tube defects, growth retardation in the fetus 1
Causes of Folic Acid Deficiency
Folic acid deficiency may occur due to:
- Poor dietary intake (insufficient consumption of leafy greens, fruits, and fortified foods)
- Malabsorption disorders (celiac disease, inflammatory bowel disease)
- Increased demand (pregnancy, lactation, hemolytic anemia)
- Medications that interfere with folate metabolism:
- Anticonvulsants
- Sulfasalazine
- Methotrexate 1
- Non-adherence to multivitamin supplements in high-risk individuals (e.g., post-bariatric surgery patients)
Diagnosis
The diagnosis of folic acid deficiency involves:
- Serum folate levels (reflects recent intake)
- Red blood cell folate (better indicator of tissue stores)
- Complete blood count (to detect macrocytic anemia)
- Peripheral blood smear (may show hypersegmented neutrophils)
- Important: Always check vitamin B12 levels concurrently, as the symptoms of both deficiencies overlap
Treatment Approach
Critical First Step
- Always check and treat for vitamin B12 deficiency before initiating folic acid treatment to avoid precipitation of subacute combined degeneration of the spinal cord 1
Treatment Protocol
- Oral folic acid 5 mg daily for a minimum of 4 months 1
- For pregnant women or those planning to conceive: 400 μg daily from preconception through 12 weeks of gestation to prevent neural tube defects 1
- Higher doses (4-5 mg daily) are recommended for women with higher risk of neural tube defects (previous affected pregnancy, taking anticonvulsants) 1
Special Considerations
- In patients with malabsorption, further investigations and specialist referral may be needed if response to oral therapy is inadequate 1
- For post-bariatric surgery patients, folic acid deficiency may indicate non-adherence to prescribed multivitamin supplements 1
Monitoring and Follow-up
- Recheck folate levels after 3 months of treatment
- Monitor complete blood count to ensure resolution of anemia
- In patients with persistent deficiency despite treatment, investigate for:
- Ongoing malabsorption
- Medication interactions
- Poor adherence to supplementation
Prevention
- Regular consumption of folate-rich foods (leafy greens, fruits, beans, fortified cereals)
- Routine multivitamin supplementation for high-risk individuals
- Folic acid 400 μg daily for women of childbearing age, especially those planning pregnancy
Important Cautions
- High-dose folic acid supplementation in those with undiagnosed B12 deficiency can mask the hematological manifestations while allowing neurological damage to progress 2
- Excessive folic acid intake may potentially reduce natural killer cell cytotoxicity and affect response to certain medications 3
- In elderly individuals with low B12 status, high folate levels may be associated with increased risk of cognitive impairment 3
Remember that early diagnosis and appropriate treatment of folic acid deficiency are essential to prevent complications and improve quality of life.