Your Biomarker Questions
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      1. ODX Knowledgebase
      2. Your Biomarker Questions

      What causes elevated folate?

      Folic acid is the synthetic form of the essential vitamin folate, which is found in the 5-methyltetrahydrofolate form in foods and some supplements.

      • Synthetic folic acid is the form used for enrichment and fortification of processed grain products in the US

      Yes, elevated serum folate may reflect excess supplementation or decreased conversion to usable bioactive form.

      Think of folate and B12 as partners and assess them both at the same time.

      • It would be a good idea to evaluate both folate and B12 at the same time.
      • Your patient with elevated folate may have acceptable homocysteine levels but still be B12 deficient (as homocysteine can be processed through non-B12 pathways).
      • So, ideally, you would check serum holotranscobalamin and serum or urinary methylmalonic acid to rule out B12 deficiency.
      • The combination of low B12 and elevated folate (greater than 20 ng/mL or 45.3 nmol/L) is more likely to contribute to anemia and cognitive dysfunction than low B12 and normal folate. 1

      Heavy Metals

      We are not sure of a connection between elevated folate and chelating lead and heavy metals but it appears folate supports the detoxification of heavy metals: One study of contaminated soil found that addition of folic acid enhanced chelation/removal of heavy metals. 2

      MTHFR

      The MTHFR SNP is the most frequent genetic defect and is associated with moderate to intermediate elevations in homocysteine.

      Elevated homocysteine has been associated with elevated lead levels, especially in those with low serum levels of folate and B12. 3

      Masking B12Deficiency
      Cobalamin deficiency often presents as folate deficiency and therefore is commonly misdiagnosed.50 Elevated intakes of folate interfere with a clinical diagnosis of cobalamin deficiency by ameliorating vitamin B12defi-ciency–induced megaloblastic anemia, but does not im-pact the irreversible progression of the neurological dysfunction and cognitive decline that results from cobalamin deficiency. 4

      REFERENCES

      1. Miller JW, Garrod MG, Allen LH, Haan MN, Green R. Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate. Am J Clin Nutr. 2009;90(6):1586-1592. 

      2. PENG Ya-xi, ZHANG Shi-rong, et al. Effects of folic acid and methionine on chelating agents in the removal of heavy metals. College of Environmental Sciences, Sichuan Agricultural University.

      3. Ledda C, Cannizzaro E, Lovreglio P, et al. Exposure to Toxic Heavy Metals Can Influence Homocysteine Metabolism?. Antioxidants (Basel). 2019;9(1):30. Published 2019 Dec 28. 
      4. Stover, Patrick J. “Physiology of folate and vitamin B12 in health and disease.” Nutrition reviews vol. 62,6 Pt 2 (2004): S3-12; discussion S13.