The impact of MTHFR genetic variants

Methylenetetrahydrofolate reductase …have you heard of it? 

Sadly, many find this out as a result of recurrent miscarriage or difficulty trying to conceive.

MTHFR refers to a genetic variation that encodes for an enzyme involved in converting to the biologically active folate or methyl-folate (this form represents 95–98% of folate in serum + passes through to placenta).  

Folate is critical for many bodily functions especially fetal development hence is important before and during pregnancy. 

The active folate (5-MTHF) also provides the body with methyl-groups, which in everyday biology is critical for growth, development, detoxication, neurotransmitter production, fat metabolism and so much more. 

For example, the methyl from the folate pathway is donated into the methionine cycle and is required to re-cycle homocysteine back into methionine (alongside other B vitamins + nutrients like betaine).  Methionine is used to make proteins and other important compounds.

Elevated homocysteine is associated with:

• inflammation

• heart disease

• pregnancy complications

• and even miscarriages

Other important functions of methylation include:

• Turns genes on and off (cancer promoting genes)

• Building DNA and RNA (important for fertility)

• Reduces ageing process (telomeres)

• Detoxifies chemicals and heavy metal

• Processes hormones (COMT needs methyl to work, clears toxic oestrogen)

• Builds immune cells

• Turns the stress response on and off (critical as you need enough to turn it off)

• Provides us with energy

• Reduces histamine (HNMT)

There are over 30 MTHFR polymorphism. But the 2 we look at are C677T and A1298C.

• Heterozygous = 1 copy of the gene from mum or dad

• Homozygous = 2 copies from mum and dad

• Compound heterozygous =  heterozygous for C677T and heterozygous for A1298C

So what is the impact on the enzyme function:

• MTHFR C677T heterozygous  - 30-40% loss of function 

• MTHFR C677T homozygous - 60-70% loss of function 

• MTHFR A1298C Heterozygous = 20% loss of function 

• MTHFR A1298C - homozygous = 40% loss of function

• Compounds heterozygous = 40-50% loss of function. 

As scary as that all sounds, there is a reason I haven’t written about the MTHFR gene variation before

1. It’s just one gene variation that affects methylation (there are a dozen others) and they all function as a complex web. So hyper focusing on just one variation doesn’t make sense.

2. Methylation is complex, and even someone without the genetic variation can struggle with methylation, likewise someone with it, can be methylating fine.

3. Genes load the gun, environment pulls the trigger (focus on the latter)

4. You can’t change your genetics but you can change your environment (again focus on the latter)

5. Knowing this gene mutation doesn’t significantly change my recommendations as I focus on improving gut dysbiosis, optimising nutrient status with food and the most biologically appropriate supplements (in this case not folic acid), addressing adrenal health, thyroid health, controlling stress, improving sleep, reducing environmental toxins - all if which will optimise methylation

6. In saying all that, I have spoken about the importance of getting adequate FOLATE not folic acid on my Instagram TV - which is really relevant for everyone and especially those with a MTHFR genetic variation. I invite you to read this article, by dietician Lily Nichols - FOLATE: WHY IT’S SUPERIOR TO FOLIC ACID FOR PREGNANCY (EVEN IF YOU DON’T HAVE MTHFR)

What can you do to support methylation:

• Check if you are actually having trouble methylating (just having the gene variation doesn’t always mean there is going to be issues)

  • Functional methylation markers (low serum folate, low serum B12, high serum MMA, and high serum homocysteine)

• If planning on becoming pregnant, work with a Practitioner who is knowledge about MTHFR

• Avoid supplementing with folic acid and limit consumption of foods fortified with folic acid

• Remove gluten, dairy and processed foods

• Support key nutrients

  • methylcobalamin (B12) and methyl-folate, but other nutrients such as cysteine, taurine, DHA, zinc, magnesium, potassium, riboflavin, niacin, pyridoxine, betaine (beets), choline (eggs), and sulfur

  • Foods high in these methylation-supporting nutrients include beets, spinach, mushrooms, eggs, organ meats, and shellfish.

• Restore good gut health

  • Stool test to assess for any infections, dysbiosis or low levels of beneficial bacteria

• Reduce environmental toxins

  • personal care items, cleaning products, etc (one big reason why I recommend and use doTERRA essential oils)

• Reduce chemicals and heavy metals

  • filter water

  • remove mercury amalgams and root canals (see a biological dentist)

• Address histamine intolerance

  • limit high histamine foods

  • check for gut dysbiosis (stool testing)

  • rebalance high oestrogens (drive histamine and histamine drives high oestrogens) (DUTCH testing)

• Manage stress * the biggest way to deplete methyl donars - this is often when you notice symptoms

• Avoid alcohol (deplete all B vitamins, of which folate is one )

• Increase intake of methylation adaptogens

  • these are phytonutrients found in nutrient-dense diet, but additional supplementation may be helpful in some

  • curcumin (in turmeric), betaine (in beets), anthocyanins (berries), quercetin (variety of fruit and veg), rosmarinic acid (rosemary), lycopene (tomatoes), and sulforaphane (broccoli sprouts + cruciferous vegetables).

• Sauna or sweat at least three times per week

• For more insights check out MTHFR.net by Dr. Ben Lynch.

I did choose to check my own MTHFR genetic variation as a part of my pre-conception plan and I am homozygous for C677T.

So I will be more diligent with checking how I am functionally methylating and I’ll be all over consuming liver (a wonderful source of folate) and supplementing with a good pre-natal that contains methylated B’s and other supportive nutrient when it comes closer to my prep work. 

In reflection - knowing this now, it has probably lead me to a lot of the environmental changes that I have made along the way through listening to what my body was telling me eg. addressing gut dysbiosis, histamine intolerance, eliminating major sources of stress, focusing on a whole foods nutrient dense diet and eliminating environmental toxins

I hope this help a shed some light for other fellow variants. I by no means feel like an expert on this topic but as I continue to dive into things I will share more along the way.

To my fellow variants, I’d love to hear from you, too.

What impact did finding out you have it, have on your fertility outcomes and or health? 

If you have more questions, feel free to reply or get in contact at chantelhutnan@gmail.com or you can check out the “work with me” section on my website HERE