Methlyation Imbalance and it’s effect on Mental Health

Written September 2018 by Phoebe Wynne-Lewis, BHSc, Dip Nat Med, Dip Herb Med – FxMed Technical Support

“Nearly 3 million Australians live with depression and/or anxiety which affect their well being, personal relationships, career and productivity”.

This was one of the opening statements from the recent Methylation Summit in Sydney, hosted by Carolyn Ledowsky from MTHFR Support and proudly sponsored by FxMed.

I was fortunate enough to attend the summit which was based on the theme Anxiety and Depression and included high calibre presenters such as Carolyn Ledowsky, Dr Ben Lynch, Dr Carrie Jones and Dr Andrew Rostenberg.

Presentations covered the connection between genes, SNPS, methylation, biochemical pathways and lifestyle factors as key drivers of mental ill health.

It was reiterated that in order to really assist your patients back to full physical and mental health, it is vital to understand their biochemistry, which as we know affects methylation.  DNA methylation is profoundly connected to mental health and is one of several epigenetic mechanisms that cells use to control gene expression (protein production). For example, if serotonin is not properly methylated, it will become inactive, which in turn can lead to depression.

The methylation cycle in general is such an important factor in keeping our genes and health in good shape.  More than two hundred of our body’s functions rely on methylation.  As Dr Ben Lynch aptly describes; “Think of those two hundred functions as gardens located throughout our body. Just as gardens need water, so do those processes need methyl groups. The methylation cycle is like an irrigation system that draws water from a clean lake and distributes it to all the gardens. If something blocks or disrupts the irrigation system, some or all of those 200 gardens won’t get the water they need”.

In other words, if something blocks or disrupts our methylation cycle, some or all of our body processes won’t get the methyl groups they need or won’t be able to use them properly.

Methylation – a general guide

What is Methylation?

Methylation is a vital metabolic process that happens in every cell and every organ of the human body, taking place a million times a second. Life would simply not exist without it.

Think of billions of little on/off switches inside our body that control everything from our stress response and how the body makes energy from food, to our brain chemistry and detoxification.

That’s methylation!

Methylation is the transfer of a methyl group (1 Carbon atom & 3 Hydrogen atoms) onto amino acids, proteins, enzymes and DNA.  The addition of a methyl group onto these molecules facilitates biochemical reactions vital to critical functions in our body such as: thinking, repairing DNA, turning on and off genes, fighting infections and detoxification (especially in the liver).

It is also important for the proper functioning of the Hypothalamic-Pituitary-Adrenal (HPA) axis and critical for the synthesis of all neurotransmitters and histamine. For example, the enzyme that converts norepinephrine to epinephrine is dependent on methylation for activation.

Recommendations for Treatment of Mycotoxins

HPA Axis Support

  • Those with chronic mould exposure may have inefficient immune systems and impaired HPA Axis function contributing to chronic fatigue and other symptoms.

Energy Production/Mitochondrial Function

  • Mycotoxins have the ability to bind to DNA and RNA, alter protein synthesis and act as potent mitochondrial toxins, affecting mitochondrial function and ATP production.

Gastro Intestinal Support

  • GI support is required to help repair the damaged intestinal lining and leaky cell membranes that may result from mycotoxin exposure. Nutrients such as glutamine will improve GI health by providing fuel to the intestines to rebuild and repair and improve cellular detoxification. Probiotics aid repopulating your GI tract with beneficial bacteria and help keep other organisms (like mould and yeast) in check.

Anti Inflammatory Support

  • Chronic inflammation is the underlying commonality in diseases caused by mould and other fungi. The toxins produced by these microorganisms cause our innate immune system to respond to the foreign antigens, resulting in inflammation.

Anti Viral/Bacterial Support

  • Microbes exist in communities. Bacterial infections/viruses may surround themselves with other microbes including mould.

Cognitive Support

  • Neurological symptoms are commonly seen with mould toxicity as fungal toxins can affect our brain. There are specific nutrients to reduce the free radical inflammation in the cells that surround and support the brain cells.

Antioxidant/Nrf2 Restorative

  • Mycotoxins create oxidative stress. A major mechanism in the cellular defense against oxidative stress is activation of the Nrf2-antioxidant signalling pathway, involved in detoxification.
Dietary recommendations (short-term to support elimination and recovery)
  • Follow a strict ‘Mould Detox Diet’ and avoid foods that fuel fungal growth—i.e. junk foods, processed foods, takeaways, left overs, foods containing sugar, vinegar, soy sauce, grains and yeast, edible fungi such as mushrooms, peanuts, beans, cheese, fruit (high in sugar), processed meat, starchy vegetables (corn and root vegetables) coffee, tea, alcohol, fruit juices and soft drinks. Be careful with fermented foods (i.e. tofu, kimchi, sauerkraut, kombucha, tempeh, miso, coconut kefir).
  • Do eat: high fibre / low starch vegetables, un-processed meat, fish, eggs.
  • Increase antioxidant and anti inflammatory rich foods.
  • Increase water intake (filtered/mineralized) – to help flush out organs and prevent dehydration.
  • Support the liver, kidneys, gall bladder, lymph system to detox with raw vegetable juices (fruit juices may be too high in sugar), herb teas.
  • Avoid smoking, drinking or drug use.

Methylation turns genes on and off

When a molecule receives a methyl group, this ‘starts’ a reaction (such as turning a gene on or activating an enzyme). For example molecules receiving methyl groups ‘turn on’ detox reactions that detox the body of chemicals, including phenols. So if you are phenol sensitive, and increase your methylation, then theoretically your body can process more phenols and you can eat high phenol containing fruits without enzymes!

Another example is molecules receiving methyl groups ‘turn on’ serotonin, and thus melatonin, production. Therefore, if you are an under-methylator, you can increase your methylation and have higher levels of serotonin and melatonin. This may mean reducing SSRIs, or having improved sleep.

When the methyl group is ‘lost’ or removed, or if we are short of methyl groups, the reaction stops. When we are short of methyl groups our body cannot respond to the nutrients, vitamins, minerals or herbs we ingest, affecting many biological reactions in the body.

What is MTHFR?

  • An enzyme that adds a methyl group to folic acid to make it usable by the body.
  • The MTHFR gene produces this enzyme that is necessary for properly converting folic acid to its active form 5MTHF. This enzyme is also important for converting homocysteine into methionine.
  • Activated folate (5MTHF) goes on to give its methyl group to other nutrients & substances – methylation.
  • 5MTHF is required for the creation of every cell in our body, and is also used to create neurotransmitters (serotonin, epinephrine, norepinephrine & dopamine); create immune cells; process hormones (i.e. estrogen); as well as to produce energy and detoxify chemicals.

MTHFR Gene Mutation

  • Those with a defective MTHFR gene have an impaired ability to produce the MTHFR enzyme (estimates range from 20%-70% or more). This can make it more difficult to break down and eliminate substances like heavy metals.
  • Individuals with the MTHFR gene mutation have difficulties processing B9 in the form of folic acid (commonly present in supplements and added to processed foods). This type of B9 may even cause a build-up in the body leading to toxicity which can raise levels of homocysteine.
  • Elevated homocysteine levels are associated with a higher risk of heart disease, inflammation, birth defects, difficult pregnancies, and potentially an impaired ability to detoxify. This also affects the conversion to glutathione, which the body needs to remove waste and which is a potent antioxidant.
  • Many factors can contribute to the expression of the MTHFR mutation including our environment, foods, chemical exposure and stress.

How do we get this mutation?

The reason for the types of mutations is variations in the specific genes passed on from each parent. In other words, if both parents pass on a healthy gene, a person won’t have a mutation at all. If one parent passes on a healthy gene but the other passes on a mutated gene, several variations can occur. If both parents pass on a mutated form, there are many more scenarios that can occur.

The two most problematic mutations in the MTHFR gene that can occur are the following SNP’s: C677T and A1298C. While a ‘normal’ MTHFR gene would be C 677C (c= cytosine), a mutation has made the gene C 677T (t= thymine). The letter represents the nucleotide base and the number refers to the location of the mutation on the gene.

The most common forms of MTHFR mutation involve various combinations of these genes being passed on from each parent:

  • Homozygous: the same gene passed on from both parents – can occur if both pass on the 677 mutation or the 1298 mutation.
  • Heterozygous: one parent passed on the 677 mutation or the 1298 mutation but the other parent passed on a normal gene.
  • Compound Heterozygous: one parent passed on the 677 mutation and the other passed on the 1298 mutation.

What is a SNP?

When the methylation cycle does its job it supports a wide range of bodily functions. However, when SNPs are present in key places in the cycle, they can cause an over or underproduction of certain chemicals, undermining the task of methylation.

SNPs (Single Nucleotide Polymorphisms) are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA. Commonly tested SNPs include; MTHFR C677T & MTHFR A1298C.