From the Guidelines
Elevated folate levels can be caused by excessive dietary intake, certain medications, medical conditions such as vitamin B12 deficiency, liver disease, and myeloproliferative disorders, as well as pregnancy and genetic variations affecting folate metabolism. The potential causes of elevated folate levels are multifaceted and can be attributed to various factors.
- Excessive dietary intake of folate-rich foods or high-dose folic acid supplements can lead to elevated levels, as noted in the context of increased folate consumption 1.
- Certain medications, such as methotrexate, trimethoprim, and some anticonvulsants, can also increase folate levels.
- Medical conditions like vitamin B12 deficiency, which can mask megaloblastic anemia, liver disease due to impaired storage, and myeloproliferative disorders are associated with elevated folate levels.
- Pregnancy can cause higher folate levels due to increased requirements and supplementation, and genetic variations affecting folate metabolism, such as mutations in the MTHFR gene, may contribute to abnormal levels. It is crucial to identify the underlying cause of elevated folate levels, particularly if it may be masking a vitamin B12 deficiency, which can lead to neurological damage if left untreated, as suggested by the potential hazards of folate supplementation or fortification 1. Evaluation of vitamin B12 status is recommended to rule out this potentially serious condition when elevated folate is found incidentally.
From the Research
Causes of Elevated Folate Levels
- High-dose folic acid supplements (>5 mg/d) can cause elevated folate levels, which may mask vitamin B12 deficiency and exacerbate its neuropathological progression 2
- Excessive folic acid intake can lead to elevated folate status, potentially causing adverse health effects, including exacerbation of vitamin B12 deficiency 3, 4
- Folic acid fortification in foods and widespread use of folic acid supplements can contribute to elevated folate levels, particularly in individuals with low B12 intake or conditions associated with B12 malabsorption 2, 3
- Inadequate folate status can be influenced by inadequate intake, genetic polymorphisms, and interactions with various drugs, but excessive intake can also have adverse effects 3, 5
- Certain populations, such as older adults, supplement users, and individuals with low B12 intake, may be at greater risk of exposure to elevated serum folate concentrations 6
Risk Factors for Elevated Folate Levels
- Age: increasing age is associated with higher odds of elevated serum folate levels 6
- Supplement use: supplement users are more likely to have elevated folate concentrations 6
- Race or ethnicity: white subjects are more likely to have elevated folate concentrations 6
- Smoking: smoking reduces the odds of elevated folate exposures in women and men 6