MTHFR & Methylation

"MTHFR is a key gene in methylation"


The MTHFR gene provides the code for the MTHFR enzyme to metabolize folate. It takes folate from food and converts it into its active form, 5-methyltetrahydrofolate (5-MTHF). The body uses this methyl form of folate in a process called methylation.


In a biochemical process called methylation, it transfers a methyl group, consisting of 1 carbon and 3 hydrogen atoms, onto a substrate, including DNA, RNA, neurotransmitters, hormones, immune cells, and nerve cells. Once these compounds are methylated, they are able to commence their required functioning.


 “A Webinar explaining what MTHFR means for patients”



Some of the main functions of methylation are:

  • Breakdown of histamine via the Histamine-N-Methyltransferase (HNMT) enzyme
  • Detoxification of environmental toxins including heavy metals such as mercury, arsenic, cadmium, and lead
  • Detoxification of oestrogen via the Catechol-O-Methyltransferase (COMT) enzyme
  • Synthesis of neurotransmitters including dopamine, noradrenalin, and adrenalin which are important for a mood and a healthy stress response
  • Synthesis of melatonin for sleep
  • Synthesis of bile acids for the metabolism of fats
  • Synthesis of healthy cell membranes which is essential for protecting cells from harmful substances, cell signaling and differentiation
  • Gene expression regulation: Methylation plays a critical role in regulating gene expression, which can impact various cellular processes, including cell differentiation and growth.
  • Methylation involves in the metabolism of homocysteine, a byproduct of amino acid metabolism, which can affect energy production and overall cellular health.
  • Methylation plays a role in repairing damaged DNA and maintaining genome stability.


1. Fatigue

Poor methylation can lead to decreased energy production, resulting in fatigue and low energy levels.

2. Brain fog

Methylation participates in synthesizing neurotransmitters, such as dopamine and serotonin, which are essential for cognitive function. Poor methylation can result in decreased neurotransmitter synthesis and cognitive impairment, including brain fog and memory problems.

3. Mood disorders

Methylation actively regulates mood and behavior, and inadequate methylation has been associated with an increased risk of depression, anxiety, and other mood disorders.

4. Cardiovascular disease

Inadequate methylation can cause an increase in levels of homocysteine, an amino acid that researchers have linked to an increased risk of cardiovascular disease.

5. Hormonal imbalances

Methylation actively participates in the metabolism and elimination of hormones, and inadequate methylation can lead to hormonal imbalances, including estrogen dominance, which researchers have associated with various health problems.

6. Digestive issues

Poor methylation has been linked to digestive issues, including inflammatory bowel disease and leaky gut syndrome.

7. Autoimmune disorders

Methylation actively regulates the immune system, and inadequate methylation has been linked to an increased risk of allergies and sensitivities.

8. Allergies

Methylation is involved in regulating the immune system, and poor methylation has been linked to an increased risk of allergies and sensitivities. 

9. Insomnia

The regulation of the sleep-wake cycle involves methylation, and researchers have associated poor methylation with insomnia and other sleep disorders.

10. Skin problems

Methylation actively participates in the synthesis and metabolism of collagen, a key component of skin health. Researchers have linked inadequate methylation to skin problems, including premature aging, dryness, and acne.


1. Identify the cause of your methylation issues

Having worked with hundreds of patients with MTHFR and methylation issues, Joanne has identified the major causes of methylation issues which are:

A. Poor gut health

This causes malabsorption of the essential nutrients required for methylation including protein, folate, vitamin B12, Vitamin B6, zinc and choline.

B. Stress

Stress depletes the body of methyl groups so that you don’t have enough for other processes such as detoxification and histamine break down. 

C. Heavy alcohol consumption

Alcohol depletes B vitamins, which are essential for the proper functioning of the methylation pathways.

D. Consumption of Folic acid

Folic acid is a synthetic form of folate that blocks the uptake of natural folate from food.

E. Environmental toxin exposure

These place a heavy burden on the methylation pathways in the liver as well as deplete glutathione (the body’s major antioxidant).

F. Bacterial, viral, fungal, parasitic infections

Infections cause inflammation, which will deplete the body of glutathione. In turn, methylation lowers homocysteine, resulting in inadequate amounts of homocysteine needed for the process.

G. Mould illness and oxalate toxicity

 Both can cause low homocysteine.

H. Inadequate Vitamin B12 intake

The proper functioning of the methylation pathways requires essential vitamin B12, which is only present in adequate amounts in animal protein.

I. Low Vitamin B6 and Zinc

People with pyrroluria and/or an overload of oxalate in the body exhibit a deficiency in B6 and zinc. Oxalates can build up due to gut issues (yeast overgrowth, low levels of good bacteria, poor fat absorption), calcium deficiency, Vitamin B6 deficiency, and consuming foods high in oxalates.

2. Refer to the right tests

Doing the right tests is important to identify the cause of poor methylation.  It’s not always necessary to test for the MTHFR gene mutation as it’s only one gene in the methylation pathway.  Understanding what is impacting the MTHFR gene from the internal and external environment (ie, epigenetics) is more important.

We use the following blood tests to help assess each individual patient:
  • Full blood count
  • Biochemistry
  • Lipid studies
  • Iron studies
  • TSH
  • RBC folate
  • Active B12
  • Fasting homocysteine
  • Plasma zinc
  • Serum copper
  • Vitamin D 
We also use the following functional medicine tests:

Please note that not every patient requires to undergo these tests.  Often signs and symptoms clearly indicate the cause of poor methylation. At your initial consultation, we will advise you if you require any testing.

3. Prescribe the right supplements

The market offers so many supplements that it’s easy for individuals to get overwhelmed and confused. Having treated hundreds of patients with MTHFR & methylation issues, Joanne has identified the supplements that really work to provide positive results for her patients.  Simply taking methylfolate, methylcobalamin, B vitamins or SAMe is not the answer.  Often these supplements can make your symptoms worse.


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