Published in the Journal of Assisted Reproduction and Genetics, the study suggests that the conventional use of large doses of folic acid (of 5 mg/day) has little benefit for couples with recurrent miscarriages.
According to the team behind the study, there is a strong link between an impaired folate cycle, due to the presence of polymorphism of the enzyme methylentetrahydrofolate reductase (MTHFR), and the capacity to achieve conception and carry a pregnancy to term.
As such they claim that the use of folic acid in people with fertility problems ‘has become obsolete’ – adding that supplementation with 'active folate’ (a 5-MTHF glucosamine salt by Gnosis, in the case of this study) may be a solution.
“Regular doses of folic acid (100–200 μg) can be tolerated in the general population but should be abandoned in the presence of MTHFR mutations, as the biochemical/genetic background of the patient precludes a correct supply of 5-MTHF, the active compound,” wrote the researchers, led by Yves Menezo from Laboratoire Clement, France, and London Fertility Associates, UK.
“A physiological dose of 5-MTHF (800 μg) bypasses the MTHFR block and is suggested to be an effective treatment for these couples,” the team wrote.
Why ‘active folate’?
While the benefits of taking folic acid are widely recognised, it has also been suggested that the many people may not gain benefit from folate or folic acid due to genetics.
Indeed, folate in its more widely recognised form of folic acid (vitamin B9) must undergo enzymatic reduction by methylenetetrahydrofolate reductase (MTHFR) to become biologically active. It has, however, been reported that a section of the population have a genetic variation that impairs their ability to properly utilise folic acid due thanks to differences in their MTFFR enzyme structure.
Levomefolic acid, otherwise known as 5-MTHF, is the primary biologically active form of folate used at the cellular level.
The new study suggests that people experiencing fertility problems and recurrent miscarries have a strong likelihood to have the genetic variant that makes folic acid supplementation essentially useless – and that use of active folate in the form of 5-MTHF is beneficial.
Study findings
The team followed 30 couples with fertility problems lasting for at least 4 years. Problems included recurrent foetal loss, premature ovarian insufficiency, or abnormal sperm parameters – with two thirds of them having failed assisted reproductive technology (ART) attempts.
“For all couples, at least one of the partners was a carrier of one of the two main MTHFR isoforms,” noted the authors – adding that most of the women had been previously treated unsuccessfully with high doses of folic acid (5 mg/day).
Couples carrying one of the isoforms were treated for 4 months with 5-MTHF (Quatrefolic, Gnosis), at a dose of 600 micrograms per day, before attempting conception or starting another attempt at ART.
“Thirteen of the couples conceived spontaneously, the rest needing ART treatment in order to achieve pregnancy,” wrote the authors. “Only three couples have, so far, not succeeded.”
Commenting on the research, Gnosis said supplementation with its Quatrefolic, instead of folic acid appears to be an effective for people carrying mutations because the 5-MTHF glucosamine salt bypasses the MTHFR block.
Source: Journal of Assisted Reproduction and Genetics
Published online, ahead of print, doi: 10.1007/s10815-018-1225-2
“MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series”
Authors: Edouard J. Servy, et al