What is Methylation?

You've probably heard about methylation – it's a huge deal in the natural therapies world and the medical fraternity. It's not just a buzzword – methylation is a chemical process that is essential for hundreds of physiological functions.

We'll keep the chemistry quick and simple.

A methyl group contains one carbon and three hydrogen atoms. Methylation is when a methyl group is attached to a molecule or substance (such as a protein or DNA). When a methyl group is detached, the reaction is called de-methylation. Methylation and demethylation act like an on/off switch for molecules – they signal the molecules to activate, deactivate, allow other chemical reactions to occur, or to perform a function.

Methylation occurs constantly throughout the body. Some key areas where methylation is required include:

• DNA and gene promotion
• Ageing processes
• Liver detoxification pathways
• Hormone metabolism
• Neurotransmitter synthesis & elimination
• Energy producing pathways
• Immune functionThe Methylation Cycle

The Methylation Cycle

The methylation cycle is like a factory producing methyl groups. The cycle is a metabolic process that involves nutrients like vitamin B12, folate, vitamin B6 and riboflavin (vitamin B2) to help metabolise products within the body such as homocysteine, methionine, and S-adenosylmethionine (SAMe).

Folate and B12 are key factors in the methylation cycle and are essential for the production of methyl groups, while the other B vitamins are required for enzyme activity in the cycle.

The enzymes within the methylation cycle have some funky scientific-sounding names and are often shortened to acronyms that don't make it much easier to understand. The most commonly talked about enzyme is MTHFR or “methylenetetrahydrofolate reductase” – say that three times fast.

As part of the methylation cycle, the MTHFR enzyme converts folic acid to methylfolate (5-MTHF) by attaching a methyl group. 

NOTE: Supplements and fortified foods use man-made “folic acid” form of folate. This requires MTHFR to convert to methylfolate. Methylfolate is the form of folate found in nature. If you have an MTHFR mutation, you may  still boost your methylation cycle by getting your folate from natural sources or a specialised methylfolate supplement.

Homocysteine

A major outcome of the methylation cycle is the metabolism of homocysteine into methionine, cysteine or glutathione. Homocysteine is a pro-inflammatory amino acid that has important functions within the body, but high levels have been linked to:

• ​​​Cardiovascular disease
• Stroke
• Recurrent miscarriages
• Poor fertility
• Psychiatric conditions
• Dementia and Alzheimer disease
• Anaemia
• Renal dysfunction 

A high homocysteine reading on a blood test may indicate that the methylation cycle may be struggling to keep up with demand for its metabolism.

Could you have a problem with methylation?

As we touched on earlier, methyl groups are needed for hundreds of physiological processes and chemical reactions in the body. Some notable pathways that require methylation include:

Genetic Processes

Methylation is required for gene expression and it's needed for healthy embryonic development and chromosome stability. In adults, methylation is necessary for healthy cell differentiation. 

Cellular Energy Production

Methyl groups are used to create ATP. Without adequate methyl groups, this process becomes down-regulated and may cause symptoms like fatigue, poor memory, slow wound healing and frequent infections.

Liver Detoxification Pathways

A major phase II liver detoxification process is the methylation pathway. As you might guess, this requires methyl groups! In this pathway, the liver attaches a methyl group to an otherwise toxic substance to make it safe and possible to excrete out of the body.

With inadequate methylation, this process becomes backed-up and symptoms of a sluggish phase II can occur – fatigue, headaches, moodiness and weight gain or appetite changes.

Antioxidant Synthesis

One “end point” for the methylation pathway is the synthesis of the main antioxidant, glutathione.

Immune Cell Synthesis

Methylation is involved in controlling T cell production, fighting infections and viruses, and regulating immune system activation. Researchers are linking autoimmune diseases to compromised methylation pathways.

Symptoms of low methylation include:

• Ongoing fatigue
• Frequent headaches
• Sensitivity to medications
• Poor memory
• Migraines
• Sluggishness
• Weight problems
• Depressive mood
• Appetite changes
• Addictive personality
• Autoimmune conditions 

NOTE: It's possible to over-methylate, too! Too many methyl groups may cause a surge in serotonin and dopamine, contributing to issues like depression, frustration, anxiety, hyperactivity, dry skin, and sleep disorders.

What Causes Methylation Problems?

• MTHFR mutation – A mutation of the gene that codes the MTHFR enzyme can cause sluggish processing of folic acid through the methyl cycle. Speak to a healthcare professional who can order functional testing to see if you have this mutation. 
• Stress – Methyl groups are needed in greater amounts during times of physical, emotional and mental stress.
• Inadequate nutrition – The B group vitamins are essential for the methylation pathway, and a rich supply of vitamins and minerals is needed to support the enzyme reactions that use methyl groups.
• Infections – Some conditions such as systemic lupus erythematosus may impair DNA methylation.

Natural Therapies to Boost Methylation

Methylation Diet

To reduce the load on your methylation pathway, consider changing to a plant-based diet or close to it. Lots of fresh fruits, vegetables, grains and legumes may boost your B vitamin intake and antioxidant levels to support healthy methylation and reduce the risk of damage from residual homocysteine in your system.

Methyl-Folate (5-MTHF)

Supplementing with folate has been shown to support methylation, particularly for the elderly. The 5-MTHF form of folate is found in green leafy vegetables, and now is available in many supplements specially created for people with MTHFR mutation. Speak to a healthcare professional to confirm that this is the right form of folate for you. If you do not have a MTHFR gene mutation, you may be able to supplement with simple folic acid.

Vitamin B12

As a key part of the methylation pathway, vitamin B12 works with folate to create methyl groups, support DNA methylation, and regulate homocysteine levels. Having a vitamin B12 deficiency or a low-level insufficiency may cause serious damage to nerves and mood, and getting your levels checked is easy – a simple blood test will confirm your levels. Vitamin B12 can be found as a supplement in many forms including bioavailable sublingual tablets and sprays. Supplementing has been shown to support methylation processes .

B Group Vitamins

While vitamin B12 and folate are the stars of the methylation pathway, they aren't the only B vitamin needed for healthy methylation. All of the Bs work along with one another throughout the body, and supplementing with one in isolation may throw the rest out of balance. Don't forget that vitamin B6, vitamin B2, and vitamin B3 are all needed to metabolise homocysteine. Supplementing with activated B vitamins may help support methylation pathways, ATP synthesis and relieve symptoms of fatigue.

Zinc

Methylation enzymes require zinc as a cofactor. It is the “key” to the lock. Great sources of zinc include oysters, seeds, and eggs and it is available as a supplement. NOTE: Long-term use of zinc may disrupt other nutrients like copper and iron so it’s important to work with a healthcare professional.

Antioxidants

Vitamin C and bioflavonoids are potent antioxidants that may protect the body against damage caused by high levels of homocysteine. Antioxidants are found in fruits and vegetables, especially brightly colored ones. Supplementing with vitamin C, bioflavonoids, vitamin E and carotenoids may help.

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