Folate, also known as Vitamin B9, is a water-soluble nutrient required for numerous processes within the body, including the synthesis of DNA and RNA, as well as the metabolism of amino acids. This function makes it vital for cell division and the maturation of blood cells, especially during periods of rapid growth like pregnancy and infancy. While a deficiency can lead to serious health issues such as megaloblastic anemia, an overabundance of this vitamin, known as hyperfolatemia, can also introduce potential health complications. The body generally regulates naturally occurring folate well, but high intake, typically from synthetic sources, can push circulating levels beyond the normal range.
Defining Elevated Folate Levels
Folate is the umbrella term for Vitamin B9, which exists in two main forms: the natural folate found in foods like leafy greens and legumes, and the synthetic form called folic acid. Natural folate is highly unstable and easily broken down during cooking, whereas folic acid, used in supplements and fortified foods, is far more stable. Elevated serum folate levels, or hyperfolatemia, are generally defined as a concentration greater than 20 nanograms per milliliter (ng/mL) in a blood test. Some laboratory reference ranges may cite levels above 17 ng/mL as high, but values exceeding 24 ng/mL are definitively considered elevated. A more stable, long-term measure of folate status is the red blood cell (RBC) folate test, which reflects tissue stores over the lifespan of the red blood cell.
Sources of Excess Intake
The primary driver of hyperfolatemia in the general population is the widespread consumption of the synthetic form, folic acid. Many countries, including the United States, mandate or encourage the fortification of grain products like flour, bread, and cereals with folic acid to prevent neural tube defects in newborns. A second major source is the use of dietary supplements, including multivitamins, B-complex formulas, and prenatal vitamins, which often contain folic acid at or above the recommended daily allowance. When synthetic folic acid is consumed, it must be converted into its active form by the enzyme dihydrofolate reductase, a process that is slow and limited in the human body. If the amount of folic acid consumed exceeds the body’s conversion capacity, it results in the circulation of unmetabolized folic acid in the bloodstream. Consuming high-dose supplements, sometimes containing 800 to 1,000 micrograms or more, can quickly overwhelm the metabolic pathway.
Folate Metabolism and Vitamin B12 Interaction
The most significant concern regarding high folate levels centers on its complex relationship with Vitamin B12, a dynamic often referred to as the “masking” effect. Both folate and B12 are interdependent in the one-carbon metabolism cycle, which is essential for DNA synthesis. A deficiency in either vitamin can lead to megaloblastic anemia. High levels of folate, particularly from folic acid, can temporarily correct the hematological symptoms of megaloblastic anemia, even if the underlying cause is an uncorrected B12 deficiency. By resolving the anemia, the most common and earliest clinical sign of a B12 deficiency is removed, effectively masking the problem.
This delay in diagnosis is dangerous because B12 deficiency can independently cause severe and potentially irreversible neurological damage that folate cannot correct. Studies involving older adults with low B12 status have shown that high folate levels are associated with a greater risk of both anemia and cognitive impairment compared to those with low B12 and normal folate. The body’s ability to process folate is further complicated by common genetic variations, such as the MTHFR gene polymorphism. The MTHFR enzyme is responsible for converting a form of folate into 5-methyltetrahydrofolate (5-MTHF), the primary active form found in the blood. Individuals with certain variants of the MTHFR gene have reduced enzyme activity, which can impair their ability to efficiently convert synthetic folic acid into its usable form.
Assessment and Management
When elevated folate levels are detected, the initial step in assessment is always to check the patient’s Vitamin B12 status. Healthcare providers will typically order a serum B12 test alongside the folate test to ensure that hyperfolatemia is not masking an underlying deficiency. Additionally, levels of homocysteine may be measured, as this amino acid builds up when the B12-dependent metabolic pathway is impaired.
Management of hyperfolatemia focuses primarily on reducing the excess intake, as there is no specific medical treatment for elevated levels themselves. The most straightforward action is the reduction or elimination of folic acid supplements, which are often the largest source of the synthetic vitamin. For individuals with significantly high levels, a healthcare provider may also recommend temporarily moderating the consumption of heavily fortified foods.
For patients found to have high folate combined with low B12, the priority shifts immediately to treating the B12 deficiency, often with supplements or injections, to prevent neurological deterioration. Regular monitoring of both folate and B12 levels is then necessary to ensure that the levels normalize and that any symptoms of B12 deficiency are addressed. Because folate is a water-soluble vitamin, excess amounts are generally excreted through the urine, meaning that reducing intake is usually sufficient to lower concentrations over time.