What are the effects of folate (Vitamin B9) deficiency?

From the Guidelines

Folate deficiency should be treated with oral folic acid supplementation at a dose of 5 mg daily for a minimum of 4 months, as recommended by the most recent guidelines 1.

Treatment of Folate Deficiency

The treatment of folate deficiency is crucial to prevent serious complications such as anemia, neural tube defects in developing fetuses, and potentially increased risk of cardiovascular disease.

• The dose of 5 mg daily is recommended for adults until the deficiency is corrected, typically for 4 months, followed by maintenance therapy if needed.
• For severe deficiency or malabsorption issues, higher doses may be necessary, but the initial recommended dose is 5 mg daily.
• During pregnancy, women should take at least 400-600 mcg daily to prevent neural tube defects in the developing fetus, but this is a separate consideration from treating folate deficiency.

Causes and Symptoms of Folate Deficiency

Folate deficiency occurs when the body lacks sufficient folate (vitamin B9), which is essential for DNA synthesis, cell division, and red blood cell production.

• Common causes include inadequate dietary intake, increased requirements (pregnancy, hemolytic anemia), malabsorption disorders, certain medications (methotrexate, some anticonvulsants), and alcoholism.
• Symptoms include fatigue, weakness, irritability, headache, palpitations, and megaloblastic anemia.
• Dietary sources rich in folate should be incorporated into the diet, including leafy green vegetables, citrus fruits, beans, and fortified grains.

Diagnosis and Prevention

Blood tests measuring serum folate and red blood cell folate levels can confirm the diagnosis of folate deficiency.

• Untreated folate deficiency can lead to serious complications, and prevention is key, especially in pregnant women or those planning to become pregnant.
• The USPSTF recommends daily folic acid supplementation at a dose of 400–800 μg (0.4–0.8 mg) daily in all reproductive-age women 1.
• However, for treating folate deficiency, the dose of 5 mg daily is recommended, as stated in the most recent guidelines 1.

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 Folic acid requirements are markedly increased during pregnancy, and deficiency will result in fetal damage The main causes of folate deficiency are:

• Increased loss of folate (e.g. renal dialysis)
• Interference with metabolism (e.g. folic acid antagonists like methotrexate)
• Administration of certain anticonvulsants (e.g. diphenylhydantoin, primidone, barbiturates)
• Alcohol consumption and alcoholic cirrhosis
• Administration of pyrimethamine and nitrofurantoin 2

From the Research

Folate Deficiency

• Folate deficiency can lead to numerous common health problems, including hyperhomocysteinemia and the possibility of malignancy developments 3
• The primary cause of folate deficiency is low intake of sources rich in the vitamin, such as legumes and green leafy vegetables 4
• Other situations in which the risk of folate deficiency increases include lactation and alcoholism 4
• Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure 5

Causes and Consequences

• Folate deficiency can have severe consequences, particularly in early life, such as hereditary folate malabsorption and cerebral folate deficiency 5
• High physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells 5
• Folate deficiency is closely intertwined with vitamin B12 deficiency, and diagnosis of folate deficiency often involves laboratory testing for both vitamins 6, 7

Interactions with Other Nutrients

• Vitamin B12 malabsorption and renal function are critical considerations in studies of folate and vitamin B12 interactions in cognitive performance 7
• Concurrent high folate and insufficient vitamin B12 concentrations were not associated with poor cognitive performance, but consumption of vitamin B12 supplements concurrent with low vitamin B12 status may indicate vitamin B12 malabsorption 7
• The relationship between folate and vitamin B12 is complex, and further research is needed to understand the interactions between these two nutrients 3, 6