Why do people need to take Calcium L-Methylfolate?

Nudlehealth Biotechnology

Nudlehealth Biotechnology

The leading Ingredients and Intermediates manufacturer from China

Why do people need to take Calcium L-Methylfolate?

Share on facebook
Share on twitter
Share on linkedin
Calciun L-Methylfolate Nudlehealth Biotechnology
What is Folate?

Folate, also known as vitamin B9 and folacin, is one of the B vitamins which is required for the body to make DNA and RNA and metabolism amino acids necessary for cell division. As humans cannot make folate, it is required in the diet, making it an essential nutrient.

Calcium L-Mehthylfolate Nudlehealth Biotechnology
And what is Folic acid?

Folic acid is the synthetic form of folate. Folate deficiency during pregnancy can lead to neural tube irregularities, such as spina bifida and anencephaly. Because of its importance for health, the Food and Drug Administration (FDA) require manufacturers to add folic acid to enriched bread, pasta, rice, cereals, and other grain products in the United States. Since they introduced this, the number of babies born with neural tube irregularities has decreased.


Do U know Levomefolic Acid / L-Methylfolate?

Levomefolic acid  (also known as L-5-MTHF, L-methylfolate and L-5-methyltetrahydrofolate and (6S)-5-methyltetrahydrofolate, and (6S)-5-MTHF) is the primary biologically active form of folate used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine. It is also the form found in circulation and transported across membranes into tissues and across the blood–brain barrier. In the cell, L-Methylfolate is used in the methylation of homocysteine to form methionine and tetrahydrofolate (THF). THF is the immediate acceptor of one carbon unit for the synthesis of thymidine-DNA, purines (RNA and DNA) and methionine. The un-methylated form, folic acid (vitamin B9), is a synthetic form of folate, and must undergo enzymatic reduction by dihydrofolate reductase (DHFR) to become biologically active.







L-Methylfolate is a medical food for use in people who have conditions related to folate deficiency. It is also used in people with major depressive disorder who have folate deficiency, or in people with schizophrenia who have hyperhomocysteinemia related to folate deficiency. L-Methylfolate is not an antidepressant or anti-psychotic medication. However, L-Methylfolate may enhance the effects of antidepressant medications.

Calcium L-Mehthylfolate Nudlehealth Biotechnology
Calcium L-Methylfolate, L-MTHF, 151533-22-1
How About Calcium L-Methylfolate?

Calcium L-Methylfolate (L-5-MTHF-Ca; CAS#151533-22-1) is a source of folate and an alternative to folic acid for use in human food and food supplements. The safety of L-5-MTHF-Ca was evaluated by testing for genotoxicity, subchronic and prenatal developmental toxicity. In in vitro assays L-5-MTHF-Ca was not mutagenic and did not induce other chromosomal events. Additionally, L-5-MTHF-Ca was not genotoxic in the in vivo micronucleus test nor did it induce DNA damage in rat liver cells. L-5-MTHF-Ca is neither teratogenic nor embryotoxic. Based on the results of the in vitro and in vivo studies, the safe use of L-5-MTHF-Ca as an ingredient in foods is supported.


Many foods naturally rich in folates are consumed in amounts that are insufficient to meet the recommended dietary folate intake levels, therefore folic acid food fortification programs have been implemented and daily dietary supplementation with folic acid or the calcium salt of L-5-MTHF are recommended to improve folate status and prevent adverse effects related to folate deficiency [[9][10][11]]. Ingested L-5-MTHF-Ca dissociates readily and completely in the aqueous environment into Ca2+and L-5-MTHF ions which pass through the intestinal mucosal cells [6]. Dietary supplementation with L-5-MTHF-Ca has several advantages over folic acid. As the predominant naturally present form of folate in food, serum and breast milk, ingested L-5-MTHF requires only glutamation during absorption and then it can directly enter the circulation, whereas folic acid does not occur naturally in foods in significant amounts and before being used must first be converted to L-5-MTHF in several enzymatic steps [6]. The physiological capacity of the enzymes involved are exceeded when folic acid is ingested at concentrations >400 μg/d resulting in exposure to unmetabolized folic acid through plasma and breast milk which may have negative effects [7,12,13]. The activity of the enzymes involved in conversion of folic acid to L-5-MTHF are influenced by several common polymorphisms in humans which reduce the capacity of the enzymes thereby reducing the bioavailability of folic acid to affected individuals [14,15].



Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the extension of use of calcium L-Methylfolate to be used as a source of folate added for nutritional purposes to infant and follow‐on formula, baby food and processed cereal‐based food pursuant to Regulation (EU) 609/2013. In 2004, EFSA assessed the use of calcium l‐Methylfolate as a source of folate in foods for particular nutritional uses, food supplements and foods intended for the general population. Based on the studies assessed in the previous evaluation, it was concluded that calcium L‐Methylfolate is non‐genotoxic The Panel considered that no additional toxicological studies are required on the nutrient source. The intervention study in healthy infants provided by the applicant did not indicate differences in growth and tolerance parameters in infants who consumed either an infant formula supplemented with calcium l‐Methylfolate or with folic acid, and did not raise concerns regarding safety or tolerability of the infant formula with the proposed nutrient source. The study also provided further supporting evidence for the bioavailability of calcium l‐Methylfolate. The Panel considers that calcium l‐Methylfolate is a source from which folate is bioavailable and concludes that calcium l‐Methylfolate is safe under the proposed uses and use levels for infants and young children.

Increasingly L-5-MTHF-Ca supplementation is being investigated for potential treatment of patients suffering from various human diseases or conditions such as Alzheimer’s disease [16], depression [17] and other psychiatric and neurologic conditions [18]. Supplementation with L-5-MTHF-Ca may have cognitive benefits particularly for subjects with elevated levels of serum homocysteine or low folate levels.

  1. Scott J. Methyltetrahydrofolate: the superior alternative to folic acid. In: Krämer K., Hoppe P.-P., Packer L., editors. Nutraceuticals in Health and Disease Prevention.Dekker; New York: 2001. pp. 75–90. [Google Scholar]
  2. Page R., Robichaud A., Arbuckle T.E., Fraser W.D., MacFarlane A.J. Total folate and unmetabolized folic acid in the breast milk of a cross-section of Canadian women. Am. J. Clin. Nutr. 2017;105:1101–1109. [PubMed] [Google Scholar]
  3. Sherwood K.L., Houghton L.A., Tarasuk V., O’Connor D.L. One-third of pregnant and lactating women may not be meeting their folate requirements from diet alone based on mandated levels of folic acid fortification. J. Nutr. 2006;136:2820–2826. [PubMed] [Google Scholar]
  4. Lewis C.J., Crane N.T., Wilson D.B., Yetley E.A. Estimated folate intakes: data updated to reflect food fortification, increased bioavailability, and dietary supplement use. Am. J. Clin. Nutr. 1999;70:198–207.[PubMed] [Google Scholar]
  5. Konings E.J., Roomans H.H., Dorant E., Goldbohm R.A., Saris W.H., van den Brandt P.A. Folate intake of the Dutch population according to newly established liquid chromatography data for foods. Am. J. Clin. Nutr. 2001;73:765–776. [PubMed] [Google Scholar]
  6. Troen A.M., Mitchell B., Sorensen B., Wener M.H., Johnston A., Wood B., Selhub J., McTiernan A., Yasui Y., Oral E., Potter J.D., Ulrich C.M. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J. Nutr. 2006;136:189–194. [PubMed] [Google Scholar]
  7. Kelly P., McPartlin J., Goggins M., Weir D.G., Scott J.M. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am. J. Clin. Nutr. 1997;65:1790–1795.[PubMed] [Google Scholar]
  8. Wilcken B., Bamforth F., Li Z., Zhu H., Ritvanen A., Renlund M., Stoll C., Alembik Y., Dott B., Czeizel A.E., Gelman-Kohan Z., Scarano G., Bianca S., Ettore G., Tenconi R., Bellato S., Scala I., Mutchinick O.M., López M.A., de Walle H., Hofstra R., Joutchenko L., Kavteladze L., Bermejo E., Martínez-Frías M.L., Gallagher M., Erickson J.D., Vollset S.E., Mastroiacovo P., Andria G., Botto L.D., Redlund M. Geographical and ethnic variation of the 677CT allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide. J. Med. Genet. 2003;40:619–625. [PMC free article] [PubMed] [Google Scholar]
  9. Botto L.D., Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am. J. Epidemiol. 2000;151:862–877. [PubMed] [Google Scholar]
  10. McCaddon A., Hudson P.R. L-methylfolate, methylcobalamin, and N-acetylcysteine in the treatment of Alzheimer’s disease-related cognitive decline. CNS Spectr. 2010;15:2–5. discussion 6. [PubMed] [Google Scholar]
  11. Zajecka J.M., Fava M., Shelton R.C., Barrentine L.W., Young P., Papakostas G.I. Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study. J. Clin. Psychiatry. 2016;77:654–660. [PubMed] [Google Scholar]
  12. Rainka M., Aladeen T., Westphal E., Meaney J., Gengo F., Capote H. L-Methylfolate calcium in adolescents and children: a retrospective analysis (P5.337) Neurology. 2018;90: P5.337. [Google Scholar]