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5-LMTHF vs. Folic Acid in Your Prenatal

This week, let’s talk about folic acid vs. 5-LMTHF in women and men with and without the MTHFR polymorphism, and in the show notes you can find research resources to share with your care team and OB/GYN or midwife.

This is an area with very little research and at the start I would like to say that 5,000 mcg of folic acid as an intervention for repeat pregnancy loss is very successful and has helped thousands of couples get to baby-in-arms. That is an amazing thing and so as a first step, especially for people without a known MTHFR polymorphism, this can be a really great intervention.  Where I want to talk about doing something different, is when couples are still having fertility issues after trying with 5,000 mcg folic acid and failing or when one or both parties have two or more copies of an MTHFR mutation. 

Also, possibly in couples where one or both parties are dealing with 2 bad copies of an MTHFR gene.  This was the case for my husband and myself and 5,000 mcg folic acid never felt right for us.

The most important piece of research to take to your midwife or fertility practitioner is a study published in the Journal of Assisted Reproduction and Genetics in 2018.

This study followed 33 couples in which one or both of the partners had an MTHR polymorphism who had fertility problems lasting at least 4 years.  You’ll notice that these folks are really well established in their fertility journey and have been trying for a very long time.  This could include recurrent fetal loss, premature ovarian failure, or abnormal sperm parameters – so bear in mind this could be the mother or the father who has MTHFR issues. Two-thirds of these couples had previously failed assisted reproductive technology attempts.

Most of the women in this study had been previously treated, unsuccessfully, with 5000 mcg (or 5 mg) folic acid. This is really important becuase we don’t necessarily want to skip over this step.

The couples in this study were given 600 mcg 5-LMTH, which is the active form of folate, for four months before attempting conception or starting another round of assisted fertility treatment. This four-month period was chosen to allow for a complete cycle of spermatogenesis, which is approximately 74 days.

What Happened When Couples Switched from Folic Acid to 5-LMTHF?

The results of this one simple intervention were, in my opinion, absolutely astounding. Of the 33 couples:

  • 2 were still in treatment at the date of reporting.

  • 13 couples conceived spontaneously (this is after four years of unsuccessful reproductive attempts)

  • 14 achieved successful pregnancies using ART (assisted reproductive technology). ART typically refers to IVF or in-vitro fertilization. 

  • 3 couples did not achieve successful pregnancies.

  • 1 couple failed to report back.

This means that 27/33 couples got pregnant after four years of infertility struggles by changing this one simple thing. The only thing they did differently was switch from folic acid to 5-LMTHF.

I am going to read the conclusion of this research article verbatim because I can’t say it any better.

“The conventional use of large doses of folic acid (5 mg/day) has become obsolete. 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. A physiological dose of 5-MTHF (800 μg) bypasses the MTHFR block and is suggested to be an effective treatment for these couples. Moreover, it avoids potential adverse effects of the UMFA syndrome, which is suspected of causing immune dysfunction and other adverse pathological effects such as cancer (especially colorectal and prostate).”

Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJR. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genet. 2018;35(8):1431-1435. doi:10.1007/s10815-018-1225-2

What is the Optimal Dosage of 5-LMTHF in a Prenatal?

best dose of 5-LMTHF in prenatal vitamins, methylated prenatal

The most startling result of this research, I feel, is the tremendous number of couples who conceived spontaneously after a simple few-month low-dose intervention with 5-LMTHF.

In terms of amounts – it is hard to say if this low 800 mcg dose is really the optimal dose during pregnancy for 5-LMTHF because that research hasn’t been done yet.  Most prentals on the market that contain 5-LMTHF have a 1000 mcg dose, which is a good compromise between the 600 mcg folate recommended daily in pregnancy, and the whopping 5000 mcg dose often given in situations of repeat pregnancy loss of difficulty conceiving. 

Some OB-GYN and midwifery teams are still unfamiliar with the use of 5-LMTHF in pregnancy, and talking seriously with them and presenting them with this research as a basis for your conversation will help them to see your point of view and encourage them to walk down this path with you as an alternative – especially if you have already tried 5,000 mcg folic acid.

What About UMFA?

UMFA stands for unmetabolized folic acid, and it’s a risk when using a high-dose folic acid intervention, but not with methylfolate. Some research has linked high levels of UMFA in pregnant mothers to increased risk of autism in their unborn children. UMFA has been detected in all age groups in the US, in part due to food fortification programs and so it is important to understand your risks and be aware of how much fortified food you take in.  If you have an MTHFR mutation, it is best to avoid foods fortified with folic acid and all other sources of folic acid completely.

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MTHFR is a common genetic mutation that can contribute to anxiety, depression, fatigue, chronic pain, infertility, and more serious conditions like breast implant illness, heart attack, stroke, chronic fatigue syndrome, and some types of cancer. If you know or suspect you have an MTHFR variant, schedule a free 15-minute meet-and-greet appointment with MTHFR expert Dr. Amy today.

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Amy Neuzil
Amy Neuzil

Dr. Amy Neuzil, N.D. is a leading expert in MTHFR and epigenetics, and she is passionate about helping people achieve optimal health and wellness for their genetic picture. She has helped thousands of people overcome health challenges using a simple, step-by-step approach that starts with where they are today. Dr. Neuzil's unique approach to wellness has helped countless people improve their energy levels, lose weight, and feel better mentally and emotionally. If you're looking for a way to feel your best, Dr. Amy Neuzil can help. Contact her today to learn more about how she can help you achieve optimal health and wellness.

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