From the Guidelines
Folic acid deficiency primarily manifests as megaloblastic anemia, fatigue, weakness, shortness of breath, and neurological symptoms, which can be effectively diagnosed and treated with folic acid supplementation, typically 5 mg daily for a minimum of 4 months, as recommended by the most recent guidelines 1. The clinical manifestations of folic acid deficiency can be categorized into several key areas, including:
- 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
- Poor appetite
- Other symptoms:
- Hair changes (graying)
- Growth problems in children It is essential to diagnose folic acid deficiency through blood tests measuring serum folate and red blood cell folate levels, with optimal levels being 10 nmol/L for serum folate and 340 nmol/L for red blood cell folate 2. Folic acid plays a crucial role in DNA synthesis and cell division, and its deficiency can lead to impaired production of new red blood cells, resulting in megaloblastic anemia, while also affecting neurotransmitter synthesis and methylation processes in the brain, leading to neurological symptoms. In the context of treatment, it is crucial to exclude vitamin B12 deficiency before initiating folic acid supplementation, as folic acid can mask severe vitamin B12 depletion 1. The recommended treatment for folic acid deficiency involves oral folic acid supplementation, typically 5 mg daily for a minimum of 4 months, as stated in the guidelines 1, which is essential for addressing the underlying cause of the deficiency and preventing long-term complications.
From the FDA Drug Label
Folate deficiency may result from increased loss of folate, as in renal dialysis and/or interference with metabolism (e. g. folic acid antagonists such as methotrexate); the administration of anticonvulsants, such as diphenylhydantoin, primidone, and barbiturates; alcohol consumption and, especially, alcoholic cirrhosis; and the administration of pyrimethamine and nitrofurantoin 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.
The clinical manifestations of folate (folic acid) deficiency include megaloblastic and macrocytic anemias.
- Megaloblastic anemia is characterized by the presence of megaloblasts in the bone marrow.
- Macrocytic anemia is characterized by large red blood cells. Folic acid deficiency can result from various factors, including increased loss of folate, interference with metabolism, and certain medications [3] [4].
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 5
- Mental symptoms that can be non-specific and correspond to symptoms of a psychosis with physical causes 5
- Increased risk of neural tube defects (NTDs) in fetuses, particularly if the mother has a folate deficiency during pregnancy 6, 7
- Hyperhomocysteinemia, a condition associated with increased cardiovascular disease and NTDs 6, 8
- Macrocytic anemia, although this may be masked by folic acid supplementation in individuals with pernicious anemia 5, 7
- Cognitive impairment, dementia, and psychiatric disorders such as depression, which have been linked to hyperhomocysteinemia 8
- Skin diseases like psoriasis, where folic acid supplementation may be beneficial, especially in patients with concomitant hyperhomocysteinemia and low plasma folate 8
Diagnosis and Treatment
Diagnosis of folate deficiency is typically made by determining the folic acid concentration in the serum 5. 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 5, 6. It is essential to note that high-dose folic acid supplementation can mask vitamin B12 deficiency and potentially exacerbate its neuropathological progression 7, 9. Therefore, careful consideration and monitoring are necessary when prescribing folic acid supplements, especially in individuals at risk of B12 deficiency.