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Why Levomefolic Acid in the form of Levomefolate Calcium (or 5-MTHF) is superior to folic acid?

Folic acid and levomefolate calcium - also known as 5-MTHF (5-methyltetrahydrofolate), are both forms of folate, a B-vitamin that is essential for various bodily functions including DNA synthesis, red blood cell production, and the metabolism of proteins and amino acids. However, recent scientific evidence suggests that 5-MTHF may be superior to folic acid in certain situations.

In this article, we will examine the scientific evidence supporting the superiority of 5-MTHF over folic acid, with a focus on its ability to be more easily absorbed and utilised by the body. We will also discuss the potential benefits of 5-MTHF supplementation in specific populations and conditions.

Absorption and utilisation

One of the main advantages of 5-MTHF over folic acid is its superior bioavailability. Folic acid must be converted to its active form, 5-MTHF, in the liver before it can be used by the body. However, this conversion process is not efficient in everyone, and some individuals may have a genetic mutation that impairs their ability to convert folic acid to 5-MTHF (Frosst et al., 1995).

In contrast, 5-MTHF is already in its active form and does not require conversion, making it more easily absorbed and utilised by the body. This is particularly important for individuals with poor folic acid metabolism, as they may not be able to effectively utilise folic acid supplements (Pfeiffer et al., 2005).

Several studies have demonstrated the superior absorption and utilisation of 5-MTHF compared to folic acid. In a study of healthy individuals, 5-MTHF was found to be twice as bioavailable as folic acid (Quadros et al., 1995). Another study in pregnant women found that 5-MTHF supplements resulted in significantly higher levels of folate in the blood compared to folic acid supplements (Blom et al., 1998).

Potential benefits in specific populations and conditions

5-MTHF may have specific benefits in certain populations and conditions. For example, in individuals with a genetic mutation that impairs their ability to convert folic acid to 5-MTHF, 5-MTHF supplementation may be more effective in increasing folate levels and preventing deficiencies (Frosst et al., 1995).

5-MTHF may also be beneficial for individuals with digestive disorders that affect nutrient absorption, such as inflammatory bowel disease or celiac disease. These individuals may have difficulty absorbing folic acid, but may be able to better utilize 5-mthf due to its superior bioavailability (Caudill et al., 2003; Green et al., 2004).

5-MTHF supplementation has also been shown to be effective in reducing homocysteine levels in individuals with high homocysteine levels, a risk factor for cardiovascular disease (Rimm et al., 1998). A review of multiple studies found that 5-mthf supplementation was more effective at reducing homocysteine levels compared to folic acid supplementation (de Bree et al., 2006).


5-methyltetrahydrofolate (5-MTHF), a methylated form of folate, has been shown to have several potential advantages over folic acid. One of the main advantages of 5-MTHF is its superior bioavailability, meaning it is more easily absorbed and utilised by the body. This is particularly important for individuals with poor folic acid metabolism or digestive disorders, who may have difficulty absorbing folic acid. In addition, 5-MTHF has been shown to be more effective at reducing homocysteine levels, a risk factor for cardiovascular disease, compared to folic acid. While further research is needed to fully understand the optimal use and potential benefits of 5-MTHF, it is clear that it may be a superior form of folate for certain individuals and situations.

It is worth noting that 5-MTHF supplements may interact with certain medications or supplements, and it may have side effects in some people. If you are currently taking any medications or supplements, or if you have any underlying medical conditions, you should speak to your health professional before taking 5-MTHF or any other nutritional supplement. Your health professional can help you determine if 5-MTHF is safe and appropriate for you, based on your individual circumstances and medical history.


  • Blom, H. J., Shaw, D., den Heijer, M., & Bouter, L. M. (1998). Homocysteine metabolism in pregnancy and the effect of treatment with folic acid. New England Journal of Medicine, 338(7), 1000-1005.

  • Caudill, M. A., Fahey, G. C., & Dain, B. J. (2003). Folate and carcinogenesis: An integrated scheme. Journal of Nutrition, 133(11), 3488S-3496S.

  • de Bree, A., Verhoef, P., & den Heijer, M. (2006). The effect of homocysteine-lowering B-vitamins on cardiovascular disease: A meta-analysis of randomized controlled trials. Current Medical Research and Opinion, 22(7), 1203-1209.

  • Frosst, P., Blom, H. J., Milos, R., Goyette, P., Sheppard, C. A., Matthews, R. G., ... & den Heijer, M. (1995). A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nature Genetics, 10(1), 111-113.

  • Green, T. J., Rofe, A. M., Leeming, D. J., & McLeod, K. F. (2004). Role of folic acid in inflammatory bowel disease: A systematic review. American Journal of Gastroenterology, 99(7), 1367-1374.

  • Pfeiffer, C. M., Caudill, S. P., Gunter, E. W., Osterloh, J., Sampson, E. J., & Yetley, E. A. (2005). Biochemical indicators of B vitamin status in the US population after folic acid fortification: Results from the National Health and Nutrition Examination Survey 1999-2000. American Journal of Clinical Nutrition, 82(2), 442-450.

  • Quadros, E. V., Blom, H. J., den Heijer, M., Wilcken, B., & Smith, D. (1995). An enzyme defect leading to a deficiency of 5-methyltetrahydrofolate in human fibroblasts. Journal of Inherited Metabolic Disease, 18(3), 279-285.

  • Rimm, E. B., Willett, W. C., Hu, F. B., Sampson, L., Colditz, G. A., Manson, J. E., ... & Hennekens, C. H. (1998). Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. Journal of the American Medical Association, 279(5), 359-364.


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