The Methylation Revelation – A Light Bulb Moment for Female Fertility

This blog has been a long time in the making on a subject close to my heart:  female fertility. Albeit only one half of the baby making equation, I wanted to tackle this topic through experiential knowledge. I know what women are reading and researching and I am well aware that this information can be confusing, conflicting and sometimes frustrating. I wanted to not just talk about prenatal care in a general sense, but really speak to those women past and present who have had fertility challenges. While some people’s questions about “why it is not happening for them” remain largely unanswered, Naturopaths like myself turn to new research that is emerging in our understanding of parental nutritional and wellbeing.

There are definite diagnosable female reproductive conditions like endometriosis and PCOS (polycystic ovarian syndrome) that have a bad reputation as far as increasing the chances of fertility problems.1 But beyond that, and beyond the conventional treatments for these conditions, what other factors are worth considering when addressing female fertility? There are many, many likely culprits that negatively affect fertility including poor nutritional status, thyroid conditions, maternal age and stress, but one that is often overlooked is methylation cycle issues (what on earth?!?)2

The focus of this discussion is to briefly touch on the “methylation cycle”, in an effort to gently introduce the concept to those who have not heard of such things. Please keep in mind that it will barely scratch the surface of the far-reaching importance of methylation and its consequences. So *spoiler alert*: I won’t be covering all aspects of this one puzzle piece in its entirety.

What is the methylation cycle?

To the average 25 plus year old, here’s where it might start to sound a little like an episode of Breaking Bad. On the contrary, the methylation cycle is a natural series of chemical changes that occur all the time within most human cells. These reactions are constantly changing one chemical to another by helping to shift around and sharing “methyl” groups. These methylation reactions are necessary for the production and the recycling of many critical proteins (hormones, neurotransmitters etc) involved in processes right throughout the body, ultimately effecting the growth and development of all cells. Sounds pretty important and it is, particularly when it comes to conceiving and growing a baby. We need this methylation cycle to be working well in order for successful baby making to happen. In certain individuals there can be challenges to how well this cycle works: poor intake of nutrients, stress, toxic load, lack of exercise and genetic glitches (AKA gene mutations / single nucleotide polymorphisms / SNPs) to name a few.3,4

In clinical practice, this is the point where I would get out some coloured diagrams and highlighters and spend about an hour giving a basic explanation on how the cycle works and which nutrients are involved. The importance of seeing a diagram like this,5 is not to get bogged down in its complexity, but to demonstrate that there is a lot of steps in this cycle and a lot of spots where things can go haywire. Conversely, that there are many opportunities to help improve the cycle.

 

A useful place to start the explanation is with the nutrient folate. Most women who are seeking to fall pregnant soon become aware that folic acid is an ingredient included in all pregnancy multivitamins for the prevention of neural tube defects in the baby, so they can immediately see the relevance of folate. Dietary folate and /or synthetic folic acid needs to undergo a few changes before it becomes ACTIVE folate. The ACTIVE folate (5-MTHF) then helps with the chemical changes of the methylation cycle, along with some other key nutrients. If we don’t make adequate ACTIVE folate, there is a risk that the methylation cycle will not be working optimally and there may be a build-up of Homocysteine.6 Elevated Homocysteine has been associated with pregnancy complications including neural tube defects, 7,8 along with higher risk of blood clotting issues and cardiovascular risk.9 Taking in dietary amounts of the key nutrients and, in some cases, supplementing can often offset the chance of elevated Homocysteine.10 Some of these key nutrients are: folate in various forms, active B12, choline, Magnesium, Vitamin B2, Vitamin B6, Serine. There are also lifestyle modifications that improve Homocysteine levels and the methylation cycle in general, including spending time in ‘green space’ and exercising regularly.11

What is MTHFR and what does it have to do with fertility?

You might be mistaken for thinking that I am swearing at you when you read the acronym MTHFR (and secretly that’s how we commit it to memory). But all jokes aside, MTHFR is actually the shortened version of “methylenetetrahydrofolate reductase” which is an enzyme that is critical for making ACTIVE folate.

It has been found that quite a high percentage of the population (approximately 20% or more) have SNPs in the genes that code for MTHFR.12 If you have a genetic fault in the code, your MTHFR enzyme may not work as well as a person that doesn’t have this glitch and it may put you at higher risk of methylation issue and increased levels of Homocysteine.13 Remembering that high levels of Homocysteine are what we want to avoid when trying for pregnancy.

It strikes me that my city counterparts and their clients seem to be very well educated on the value of checking for gene SNPs that might affect the methylation cycle and it seems that EVERYONE is talking about MTHFR gene mutations, dare I say sometimes overstating or misrepresenting its relevance. However, as a rural practitioner, I notice that people in general remain unaware of these potential issues and DON’T talk about it or investigate it ENOUGH.

In my opinion, detection of methylation issues and MTHFR gene mutations doesn’t hold all the answers for fertility problems, but we should be at least be screening for them to identify if this is likely to have an impact on any woman that is struggling. One of the tests that you can do is a simple and relatively inexpensive one to check for MTHFR gene mutations – either a blood test or a buccal swab. Also, to check blood levels of Homocysteine would be useful, again a relatively inexpensive, fasting blood test. These tests need a referral from your doctor, specialist or Naturopath.

During my Naturopathic career, I have learnt from experience that it is better to jump into considering these methylation issues as important factors as soon as possible, rather than waiting for the right moment to bring them up. In my opinion, the more you can learn about your own body and move towards giving it the best chance and hence your potential baby the best chance, the better. I have met some amazing women in my time, some that are so committed to working on their diet and lifestyle and seem by any standards to be perfectly healthy and well. Yet they are struggling with conception or retaining pregnancies, so exploring these issues and addressing them has been integral to their pregnancy success.

It is definitely a worthwhile investment in energy, time and expense to question your Healthcare Practitioner about methylation issues and how it might be affecting your fertility. The intricacies and potential solutions can be explored in great detail and can be tailored to suit your individual context, so it is always advisable to consult your Healthcare Practitioner for accurate, evidence based information about fertility.

Written by Emily Grieger – Naturopath.

1.Centers for Disease Control and Prevention. Reproductive Health. Available at: www.cdc.gov/reproductivehealth/infertility/index.htm. Accessed October 25, 2018.

 

2.Metagenics Clinical Seminar. Perinatal Planning for Future Generations. Metagenics Australia. Sept-Nov 2019: 11.

  1. Gomes SLopes CPinto E. Folate and folic acid in the periconceptional period: recommendations from official health organizations in thirty-six countries worldwide and WHO. Public Health Nutr.2016 Jan;19(1):176-89.
  2. 4. Li KWahlqvist MLLi D. Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review. 2016 Nov 23;8(11).

 

  1. Boyd A. Figure 2. What is Methylation? FxMedicine 2019. Published online Feb 2017.

6.Nazki FHSameer ASGanaie BA. Folate: metabolism, genes, polymorphisms and the associated diseases.Gene. 2014 Jan 1;533(1):11-20.

  1. Mascarenhas M, Habeebullah S, Sridhar MG. Revisiting the role of first trimester homocysteine as an index of maternal and fetal outcome. J Pregnancy. 2014;2014:123024.

 

  1. Micle O, Muresan M, Antal L, Bodog F, Bodog A. The influence of homocysteine and oxidative stress on pregnancy outcome. J Med Life. 2012 Feb 22;5(1):68-73.

 

  1. Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease.N Engl J Med. 1997 Jul 24; 337(4):230-6.
  2. Li KWahlqvist MLLi D. Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review. Nutrients.2016 Nov 23;8(11).
  3. Okura TRankinen TGagnon JLussier-Cacan SDavignon JLeon ASRao DCSkinner JSWilmore JHBouchard C. Effect of regular exercise on homocysteine concentrations: the HERITAGE Family Study. Eur J Appl Physiol.2006 Nov;98(4):394-401. Epub 2006 Sep 19.
  4. Dajani RFathallah RArafat AAbdulQader MEHakooz NAl-Motassem YEl-Khateeb M. Prevalence of MTHFR C677T single nucleotide polymorphism in genetically isolated populations in Jordan.Biochem Genet.2013 Oct;51(9-10):780-8.
  5. Avinash KumarHenry A. PalfreyRashmi PathakPhilip J. KadowitzThomas W. Gettys, and Subramanyam N. Murthy. The metabolism and significance of homocysteine in nutrition and health. Nutr Metab (Lond).2017;14:78. Published online 2017 Dec 22.

 

 

 

 


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