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Everything You Should Know about Calcium L-Methylfolate


Calcium L-Methylfolate is widely known to fight low levels of folate in the body. Today, we can find it in the form of numerous health products, as it’s known to aid in and restore one’s health. Read on to learn more.

What is Folate?

Folate is a B vitamin that is required for the synthesis of DNA, RNA, and amino acids involved in cell division. It is also known as vitamin B9 and folacin. Folate is required because humans do not produce it.

What is Folic Acid?

Folic acid is folate synthesized in a laboratory. Spina bifida and anencephaly can be caused by a lack of folate during pregnancy. In the United States, the FDA requires manufacturers of bread, pasta, rice, cereals, and other grain products to include folic acid. Congenital disabilities of the neural tube have decreased since then.

What is Levomefolic Acid (L-Methylfolate)?

Levomefolic acid (L-5-MTHF, L-methylfolate, L-5-methyltetrahydrofolate, and (6S)-5-MTHF) is the most active form of folate used in DNA synthesis, the cysteine cycle, and homocysteine regulation. This form circulates and crosses cell membranes as well as the blood-brain barrier. By methylating homocysteine, L-Methylfolate produces methionine and tetrahydrofolate (THF).

THF is required for thymidine-DNA, purines (RNA and DNA), and methionine synthesis. Folic acid (vitamin B9) is a synthetic form of folate that must be reduced by DHFR to be biologically active.

L-Methylfolate is a dietary supplement for folate deficiency. It is also given to patients with major depression and schizophrenia who have hyperhomocysteinemia due to a lack of folate. L-Methylfolate has no antipsychotic or antidepressant properties.

Understanding the Composition of Calcium L-Methylfolate

Calcium L-Methylfolate (L-5-MTHF-Ca; CAS#151533-22-1) is a folate source and a supplement alternative to folic acid. L-5-MTHF-Ca was tested for genotoxicity, subchronic toxicity, and prenatal developmental toxicity. The results of in vitro and in vivo studies support the use of L-5-MTHF-Ca as a safe food additive.

Food fortification programs with folic acid and daily supplementation with folic acid or the calcium salt of L-5-MTHF are recommended to improve folate status and prevent folate deficiency effects. When L-5-MTHF-Ca is consumed, it dissociates into Ca2+ and L-5-MTHF ions, which pass through intestinal mucosal cells.

L-5-MTHF-Ca outperforms folic acid. L-5-MTHF, the most common form of folate in food, serum, and breast milk, requires only glutamation during absorption and can enter the circulation directly, whereas folic acid does not occur naturally in significant quantities in foods and must be converted to L-5-MTHF via multiple enzymatic steps. 

The Consumption and Usage of Calcium L-Methylfolate

The European Food Safety Authority (EFSA) evaluated calcium L-Methylfolate as a folate source in foods for specific nutritional applications, dietary supplements, and foods for the general population in 2004.

According to previous research, calcium L-Methylfolate is not genotoxic. The study on healthy infants found no differences in growth and tolerance parameters between infants who consumed an infant formula supplemented with calcium L-Methylfolate or folic acid, nor did it raise any concerns about the infant formula containing the proposed nutrient source’s safety or tolerability. 


Indeed, calcium L-Methylfolate has found its way to offer a variety of uses in today’s world of modern healthcare. In part to medical innovations, supplementing with L-5-MTHF-Ca is being studied for the treatment of Alzheimer’s disease, depression, and other psychiatric and neurological disorders. Individuals with high homocysteine or low folate levels may also benefit from L-5-MTHF-Ca.

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