5-MTHF ES (60 Capsules)

Scientific Information/Data

5-MTHF (5-methyltetrahydrofolate)
5-MTHF is the most biologically active form of folate. It is the predominant type of folate present in food and the form into which the body must convert all other forms of folate.[1] Along with vitamin B12, folate serves as a donor of methyl groups. The body utilizes methyl groups in many nervous system and metabolic processes, including the conversion of homocysteine to methionine, the synthesis of monoamine neurotransmitters, the production of melatonin, and the synthesis of DNA. In addition, sufficient folate is necessary for brain and nervous system functions and for a healthy pregnancy outcome.*

5-MTHF—Preferred Over Folic Acid
Folic acid is the synthetic form of folate that is used to fortify foods. It is often found in dietary supplements as well. Despite some research showing that folic acid and 5-MTHF have equivalent bioavailability, 5-MTHF is often the preferred form to replenish folate. This is due, primarily, to the presence of digestive or metabolic variabilities that can affect the conversion of folic acid to 5-MTHF.[2-4] Furthermore, studies have shown that 5-MTHF increased plasma folate more effectively than folic acid irrespective of genetic differences in metabolism.[1,5] A study in women of childbearing age showed that 5-MTHF was more effective than folic acid in improving overall folate status.*[6]

Using 5-MTHF instead of folic acid has several important advantages.5-MTHF provides the biologically active form of folate, reducesthe potential for masking hematological symptoms of vitamin B12 deficiency, reduces interactions with drugs that inhibit dihydrofolatereductase, overcomes folate metabolism challenges associated with functioning of methylenetetrahydrofolate reductase (MTHFR), and prevents the potential negative effects of UMFA in the peripheral circulation.*[7]

Quatrefolic®
In XYMOGEN’s formulas, 5-MTHF is provided as Quatrefolic—the glucosamine salt of 5-MTHF. Quatrefolic is proven to have greater stability, solubility, and bioavailability over the commonly used calcium salt form of 5-MTHF. In a randomized crossover study, subjects received 400 mcg/d of Quatrefolic or 5-MTHF calcium salt. Titernormalized Cmax and AUC demonstrated a 10% higher bioavailability of Quatrefolic.[8] Quatrefolic has several in vitro and in vivo preclinical and clinical studies to characterize and assure the safety profile of the
product.*[9]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

References

1. Prinz-Langenohl R, Brämswig S, Tobolski O, et al. [6S]-5- methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C–>T polymorphism of methylenetetrahydrofolate reductase. Br J Pharmacol. 2009 Dec;158(8):2014- 21. [PMID: 19917061]

2. Yakut M, Ustün Y, Kabaçam G, et al. Serum vitamin B12 and folate status in patients with inflammatory bowel diseases. Eur J Intern Med. 2010
Aug;21(4):320-23. [PMID: 20603044]

3. Venn BJ, Green TJ, Moser R, et al. Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma
homocysteine: a randomized placebo-controlled study. Am J Clin Nutr. 2003 Mar;77(3):658-62. [PMID: 12600857]

4. 5-methyltetrahydrofolate. Monograph. Altern Med Rev. 2006 Dec;11(4):330-37 [PMID: 17176169]

5. Willems FF, Boers GH, Blom HJ, et al. Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol. 2004 Mar;141(5):825-30. [PMID: 14769778]

6. Lamers Y, Prinz-Langenohl R, Brämswig S, et al. Red blood cell folate concentrations increase more after supplementation with [6S]-5- methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006 Jul;84(1):156-61. [PMID: 16825690]

7. Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014 May;44(5):480-8. [PMID: 24494987]

8. Crossover Comparative Bioavailability Study of 5-Methyltetrahydrofolate Glucosamine Salt (GN10G) Compared to the Reference Metafolin® in Healthy Volunteers. IPAS-5MTHFA-583-09 final report. Desio, Italy: Gnosis S.p.A.; March 15, 2010: 1-33. [available from the manufacturer Gnosis S.p.A. upon request]

9. Thomas J, Heimbach, J, Soni M. Determination of the Generally Recognized as Safe (GRAS) Status of (6S)-5-Methyltetrahydrofolic acid Glucosamine Salt. Expert panel statement. Desio, Italy: Gnosis S.p.A.; July, 2010: 1-46. [availablefrom the manufacturer Gnosis S.p.A. upon request]

10. Methylcobalamin. Altern Med Rev. 1998 Dec;3(6):461-3. Erratum in: Altern Med Rev 1999 Feb;4(1):9. [PMID: 9855571]

11. Kuzminski AM, Del Giacco EJ, Allen RH, et al. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998 Aug 15;92(4):1191-98. [PMID: 9694707]

12. Kim HI, Hyung WJ, Song KJ, et al. Oral vitamin B12 replacement: an effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients. Ann Surg Oncol. 2011 Dec;18(13):3711-17. [PMID: 21556950]

13. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists’ Collaboration. BMJ. 1998 Mar;316(7135):894-98. [PMID: 9569395]

14. Koury MJ, Ponka P. New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr. 2004;24:105-31. [PMID:15189115]

15. Kiuchi T, Sei H, Seno H, et al. Effect of vitamin B12 on the sleep-wake rhythm following an 8-hour advance of the light-dark cycle in the rat. Physiol Behav. 1997 Apr;61(4):551-54. [PMID: 9108574]

16. Honma K, Kohsaka M, Fukuda N, et al. Effects of vitamin B12 on plasma melatonin rhythm in humans: increased light sensitivity phase-advances the circadian clock? Experientia. 1992 Aug 15;48(8):716-20. [PMID: 1516676]