Vitamin B9 is important for red blood cell formation and basic cell functions. The nutrient is crucial during early pregnancy to reduce the risk of birth defects of the brain and spine. Low levels of vitamin B9 have been associated anemia, cognitive impairment, cardiovascular disease, and certain types of cancer.
Folate is the naturally occurring form of vitamin B9 that is found mainly in dark-green leafy vegetables, beans, peas, and nuts. Fruits rich in folate include oranges, lemons, and melons. Folic acid is a synthetic form used in over-the-counter supplements and enriched foods such as rice, pasta, bread, and some breakfast cereals.
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Both folate (dietary) and folic acid (synthetic) must be converted into the active form of vitamin B9, called or L-methylfolate (also known as 5-methyltetrahydrofolate or 5-MTHF). In this active form it can be transported into cells, tissues and even across the blood-brain barrier. There are multiple steps in the activation process and the final step requires vitamin B2 and an enzyme called MTHFR (methylene-tetrahydrofolate reductase). Some people have a genetic variant in the MTHFR enzyme that results in decreased enzyme activity. Supplementing with L-methylfolate bypasses the entire folic acid metabolism cycle and may be beneficial to those with folate deficiency due to an MTHFR variation.
L-methylfolate (active form of vitamin B9) is available as an over-the-counter supplement and medical food. Medical foods are not simply recommendations by a physician as part of an overall diet to manage symptoms or reduce the risk of a disease or condition. According to the FDA, medical foods are required to be used under medical supervision as specific dietary management for conditions or diseases with distinctive nutritional requirements.
Folic acid is significantly more bioavailable than naturally occurring folate in food at equivalent intake levels. The bioavailability of L-methylfolate in supplements is greater than or equal to that of folic acid. Since supplementing L-methylfolate bypasses the body’s natural checkpoints so it is important to be cautious with the dose and duration of use. High levels of folate have been linked with several issues including increased cancer risk. Talk to your doctor about checking your folate level if there is concern for deficiency. L-methylfolate and folic acid supplementation can interact with numerous medications, so be sure to speak with your provider before taking.
- Patanwala I, King MJ, Barrett DA, Rose J, Jackson R, Hudson M, Philo M, Dainty JR, Wright AJ, Finglas PM, Jones DE. Folic acid handling by the human gut: implications for food fortification and supplementation. Am J Clin Nutr. 2014 Aug;100(2):593-9. doi: 10.3945/ajcn.113.080507. Epub 2014 Jun 18. PMID: 24944062; PMCID: PMC4095662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095662/
- Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48. doi: 10.2165/11532990-000000000-00000. PMID: 20608755. https://pubmed.ncbi.nlm.nih.gov/20608755/