What causes folate deficiency?

From the Guidelines

Folate deficiency occurs due to inadequate dietary intake, increased requirements, malabsorption, or medication interference, and addressing it requires a comprehensive approach that includes dietary modifications and supplementation. The most recent and highest quality study, 1, suggests that nutritional sources of folate, such as pulses, leafy green vegetables, egg, nuts, and whole grain products, are essential for maintaining adequate folate levels. However, food folates have a lower bioavailability than synthetic folic acid, and therefore, the dietary folate equivalent (DFE) is defined to account for this difference.

Some key points to consider in addressing folate deficiency include:

• Dietary sources: leafy greens, legumes, citrus fruits, and fortified grains are good sources of folate
• Supplementation: folic acid supplements at 1 mg daily for most adults, though higher doses of 5 mg daily may be needed in severe cases or pregnancy
• Treatment duration: typically continues for 4 months or longer until blood levels normalize
• Monitoring: regular monitoring of blood levels during treatment helps ensure adequate replacement
• High-risk groups: pregnant women, individuals with celiac disease, inflammatory bowel disease, and alcoholism are at increased risk of folate deficiency

According to 1, the DRI of DFE varies from 250 to 400 mg/d, and for pregnant and lactating women, the needs are about twice as high. Additionally, 1 suggests that folic acid deficiency may indicate non-adherence with the daily multivitamin and mineral supplement or malabsorption, and treatment with oral folic acid 5 mg daily should be given for a minimum of 4 months. However, it is essential to note that folate supplementation may mask severe vitamin B12 depletion, and therefore, vitamin B12 deficiency should be treated immediately before initiating additional folic acid, as recommended by 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 Folate deficiency may occur due to:

• Increased loss of folate, such as in renal dialysis
• Interference with metabolism, for example, due to folic acid antagonists like methotrexate
• Administration of certain medications, including:
  • Anticonvulsants like diphenylhydantoin, primidone, and barbiturates
  • Pyrimethamine and nitrofurantoin
• Alcohol consumption, particularly in cases of alcoholic cirrhosis 2

From the Research

Folate Deficiency Causes

• Inadequate folate status is associated with an increased risk for chronic diseases, and may result from inadequate intake, genetic polymorphisms, and interactions with various drugs 3
• Folate deficiency may be caused by gastrointestinal tract disease, such as celiac disease or liver disease, which can compromise folate function and lead to important consequences on the whole organism 4
• Poor diet, malabsorption, alcohol consumption, obesity, and kidney failure can also contribute to acquired folate deficiency 5
• Additionally, 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

Health Consequences of Folate Deficiency

• Folate deficiency can produce gastrointestinal alterations, and the gastrointestinal tract could be both the responsible and the victim of folate deficiency 4
• Inadequate folate status is associated with an increased risk for chronic diseases, such as atherosclerotic vascular disease, changes in DNA that may result in pro-carcinogenic effects, and increased risk for cognitive dysfunction 3
• Severe folate deficiencies can manifest in early life, and are seen in hereditary folate malabsorption and cerebral folate deficiency 5

Risk Factors for Folate Deficiency

• Older adults and individuals with low B12 intake or conditions associated with B12 malabsorption are at risk for folate deficiency, particularly if they ingest excessive folic acid or are prescribed folic acid in high doses 6
• Individuals with gastrointestinal disease, such as celiac disease or liver disease, are also at risk for folate deficiency 4
• People with poor diet, malabsorption, alcohol consumption, obesity, and kidney failure are at risk for acquired folate deficiency 5