From the Guidelines
The use of methyl folate instead of folic acid is not recommended for the general population due to its higher cost, instability, and potential side effects, as well as the established safety and efficacy profile of folic acid. While methylfolate may offer benefits for individuals with specific genetic mutations, such as MTHFR, its drawbacks make it a less desirable choice for most people. Some of the potential hazards associated with increased folate consumption, including masking of megaloblastic anemia caused by vitamin B12 deficiency, slightly increased risk of wheeze and respiratory tract infections, and potential increased risk of certain cancers, are also relevant to methylfolate supplementation 1. Additionally, methylfolate is less widely available in fortified foods and standard multivitamins, and its benefits are unnecessary for the general population who can adequately convert folic acid to its active form in the body. Key points to consider include:
- Higher cost: Methylfolate supplements are often 3-5 times more expensive than folic acid
- Instability: Methylfolate has a shorter shelf life and degrades more quickly when exposed to heat, light, or air
- Potential side effects: Some people may experience anxiety, irritability, insomnia, and headaches when taking methylfolate
- Less extensive research: While folic acid has been extensively studied, particularly for pregnancy outcomes and neural tube defect prevention, methylfolate has not been as thoroughly researched 1.
From the Research
Drawbacks of Using Methyl Folate Instead of Folic Acid
- The use of methyl folate (5-methyltetrahydrofolate or 5-MTHF) instead of folic acid has several implications, including the potential to mask hematological symptoms of vitamin B12 deficiency 2.
- High-dose folic acid supplementation, which could also apply to methyl folate, may cause significant reductions in serum B12, potentially exacerbating B12 deficiency 3.
- While methyl folate has advantages over synthetic folic acid, such as better absorption and reduced potential for masking B12 deficiency symptoms, its use does not entirely eliminate the risk of interacting with other nutrients or health conditions 2.
- The metabolism of folate and vitamin B12 are closely linked, and deficiency in either can lead to similar neurological manifestations, including cognitive impairment, dementia, and depression 4.
- Inappropriate administration of folic acid or its derivatives, including methyl folate, in the presence of vitamin B12 deficiency may lead to neurological and hematologic relapse 4.
Considerations for Methyl Folate Use
- Methyl folate may prevent the potential negative effects of unconverted folic acid in the peripheral circulation 2.
- The use of methyl folate instead of folic acid reduces interactions with drugs that inhibit dihydrofolate reductase and overcomes metabolic defects caused by methylenetetrahydrofolate reductase polymorphism 2.
- However, high physiological folate concentrations and folate overload, regardless of the form used (folic acid or methyl folate), may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells 5.
Importance of Balanced Nutrient Intake
- It is crucial to maintain a balanced intake of folate and vitamin B12 to prevent deficiencies and potential neurological and hematological complications 3, 4.
- The institution of folic acid fortification and the widespread use of folic acid supplements have rekindled concerns about masking and exacerbating B12 deficiency 3.
- Healthcare professionals should be vigilant in identifying B12 deficiency in at-risk individuals, including older adults and those with low B12 intake or conditions associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed high doses of folic acid or its derivatives 3.