From the Guidelines
Folic acid deficiency manifests clinically as megaloblastic anemia, fatigue, weakness, shortness of breath, and neurological symptoms, which can be diagnosed through blood tests measuring serum folate and red blood cell folate levels, and treated with folic acid supplementation, typically 5 mg daily for a minimum of 4 months, as recommended by the most recent guidelines 1.
Clinical Manifestations
The clinical manifestations of folic acid deficiency can be categorized into:
- Hematologic symptoms:
- Megaloblastic anemia (large, immature red blood cells)
- Fatigue and weakness
- Shortness of breath
- Pale skin
- Palpitations
- Neurological symptoms:
- Irritability
- Depression
- Cognitive impairment
- Peripheral neuropathy (in severe cases)
- Gastrointestinal symptoms:
- Glossitis (inflammation of the tongue)
- Diarrhea
- Loss of appetite
- Other symptoms:
- Hair changes (graying)
- Growth problems in children
Diagnosis and Treatment
Folic acid deficiency can be diagnosed through blood tests measuring serum folate and red blood cell folate levels, with serum folate levels should be 10 nmol/L and red blood cell folate 340 nmol/L 1. Treatment involves folic acid supplementation, typically 5 mg daily for a minimum of 4 months, as recommended by the most recent guidelines 1. Folic acid is crucial for DNA synthesis and cell division, and its deficiency impairs the production of new cells, particularly affecting rapidly dividing cells like those in the bone marrow and gastrointestinal tract, which explains the anemia and gastrointestinal symptoms, while the neurological symptoms are due to the role of folate in neurotransmitter synthesis and metabolism. It is essential to note that folic acid deficiency may indicate non-adherence with the daily multivitamin and mineral supplement or malabsorption, and some medications, such as anticonvulsants, sulfasalazine, and methotrexate, may affect folic acid levels 1.
From the FDA Drug Label
Folic acid is a precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia The clinical manifestations of folate (folic acid) deficiency include:
- Megaloblastic anemia
- Macrocytic anemia
- Megaloblast formation due to defective DNA synthesis 2
From the Research
Clinical Manifestations of Folate Deficiency
The clinical manifestations of folate deficiency can be diverse and affect various systems in the body. Some of the key manifestations include:
- Neurological disturbances such as polyneuropathy, funicular disease of the spine, and restless legs 3
- Mental symptoms that can be non-specific and correspond to the symptoms of a psychosis with physical causes 3
- Increased risk of neural tube defects (NTDs) in fetuses, particularly if the mother has a folate deficiency during pregnancy 4, 5
- Hyperhomocysteinemia, a condition associated with increased cardiovascular disease and NTDs 4, 6
- Macrocytic anemia, although this may be masked by folic acid supplementation in individuals with pernicious anemia 3, 5
- Cognitive impairment, dementia, and psychiatric disorders such as depression, which have been linked to hyperhomocysteinemia 6
- Skin diseases like psoriasis, where folic acid supplementation may be beneficial, especially in patients with concomitant hyperhomocysteinemia and low plasma folate 6
Diagnosis and Treatment
Diagnosis of folate deficiency is typically made by determining the folic acid concentration in the serum 3. Treatment involves daily administration of folic acid, with recommended doses ranging from 1.25-15 mg per day, depending on the severity of the deficiency and the individual's needs 3, 4. It is essential to note that high-dose folic acid supplementation can mask vitamin B12 deficiency and potentially exacerbate its neuropathological progression 5, 7. Therefore, careful consideration and monitoring are necessary when prescribing folic acid supplements, especially in individuals at risk of B12 deficiency.