Methylation and Methylation Disorders

Imagine your body as a vast symphony orchestra: every cell, every organ and every tissue plays its own melody. Only when everything is perfectly attuned does a harmonious composition emerge — and the invisible conductor directing this interplay in our body is called methylation. But this conductor can fall out of time, and that can lead to a methylation disorder.

In this article you will find out what methylation actually is, what part nutrients play, how methylation problems are recognised, what complaints they can trigger and how they can be put right. We will look not only at how mainstream science sees methylation but also at what alternative experts say about it, including those from integrative, functional and holistic medicine.

Methylation is a biochemical process that takes place in every cell of your body. Tiny groups of molecules (called methyl groups) are attached to various places on our DNA or our proteins, or removed from them. The process works like an on-off switch for our genes and influences which proteins our body produces and how it responds to its surroundings.

Methylation plays a decisive part in many vital bodily functions:

• Gene regulation: methyl groups can switch genes on or off. That influences whether particular inherited information comes into play at all.
• Making and breaking down neurotransmitters: among them serotonin, dopamine and noradrenaline, which matter for mood, drive and concentration.
• Hormone balance: in breaking down oestrogens, for example.
• Detoxification: numerous environmental toxins and metabolic products have to be converted into excretable forms with the help of methylation.
• Regulating inflammation: methylation that works can keep inflammatory processes in the body in check.

When these processes do not run smoothly, the whole organism can tilt out of balance. It is comparable to a conductor giving the wrong cues and throwing the orchestra into disarray.

Nutrients that matter for methylation

As in any good orchestra, the conductor needs the right instruments to produce harmonious sound.

For our body those are primarily:

• Folic acid (vitamin B9) in its activated form (5-methyltetrahydrofolate): one of the main players in the methylation cycle.
• Vitamin B12: helps pass on the methyl groups and is indispensable for healthy nerves.
• Vitamin B6: supports many enzymes involved in the methylation process.
• Betaine (trimethylglycine, TMG): serves as a direct donor of methyl groups.
• Methionine: an amino acid needed to form SAMe (S-adenosylmethionine) — the universal „methyl donor".
• Choline: can be partly converted into betaine and is therefore likewise essential for a smooth methylation cycle.

If one or more of these nutrients is missing, the cycle starts to stumble. A low folate or vitamin B12 level, for instance, can bring important processes to a halt and allow harmful intermediates (homocysteine, for example) to build up. More on vitamin B12 in the article „Vitamin B12 – The Miracle for the Nerves".

We speak of a methylation disorder when methylation is not working as it should.

Mainstream science sees the following reasons for it:

• Genetic variants such as mutations in the MTHFR gene (methylenetetrahydrofolate reductase), which is responsible for converting folic acid into its active form.
• Nutrient deficiencies (too few B vitamins, for example).
• Environmental toxins and other stress factors that place further strain on the methylation cycle or block it.

In essence it means the conductor can no longer coordinate the musicians properly, and the orchestra sounds correspondingly out of tune. That usually shows not in one symptom but can affect very different parts of the body (detoxification, hormone balance, nerve function).

How can you test whether a methylation disorder is present?

Anyone who suspects a methylation disorder can, as science stands today, use various testing methods.

Blood tests:

• Homocysteine level: a raised value can point to suboptimal methylation.
• Folic acid, vitamin B12 and methylmalonic acid values: a deficiency or imbalance gives important clues about the supply of B vitamins.

Genetic tests:

• Checking the MTHFR gene and other relevant genes, to uncover any variants.
• Epigenetic tests that analyse the current methylation pattern on the genes.

Specialised laboratory values:

• SAMe (S-adenosylmethionine) and SAH (S-adenosylhomocysteine), which give a more detailed picture of methylation status.

As a rule you start with basic blood values and widen the analysis where there is a concrete suspicion. That way disturbances can be pinned down more precisely and tackled specifically.

What problems and symptoms can methylation disorders cause?

Disturbed methylation can trigger a whole range of complaints, because so many processes in the body are affected.

Possible symptoms of a methylation disorder:

• Raised homocysteine: raises the risk of cardiovascular problems.
• Tiredness and exhaustion: poor detoxification and repair mechanisms weaken the body.
• Mood swings, depression, anxiety: neurotransmitters such as serotonin and dopamine depend on methylation.
• Neuropathy: a vitamin B12 deficiency through disturbed methylation can damage the myelin sheath of the nerves (tingling, numbness, pain).
• Neurodegenerative diseases (Alzheimer's, Parkinson's): inadequate detoxification and a high homocysteine level raise the risk of damage to the nerves.
• Muscle and joint complaints: chronic inflammation can be made worse where methylation is faulty.
• Hormonal imbalance: using oestrogen depends on methylation working (cycle problems, PMS).
• Greater susceptibility to environmental toxins: anyone who does not detoxify effectively reacts more sensitively to chemicals or heavy metals.
• Cognitive problems and memory trouble: suboptimal methylation can contribute to the brain working less efficiently, which can show as trouble concentrating, forgetfulness or „brain fog".
• Sleep problems: neurotransmitters such as serotonin and melatonin depend on methylation running smoothly. When something is amiss here, trouble falling or staying asleep can follow.
• A weak immune system and greater susceptibility to infection: methylation influences immune regulation. In some cases a disturbance means the immune system can no longer work as effectively.
• Anaemia: a lack of vitamin B12 and folic acid through disturbed methylation can lead to unusually large red blood cells forming (megaloblastic anaemia). That shows as pallor, rapid exhaustion or breathlessness, for example.
• Changes in the skin: some people report dry, irritated or unusually sensitive skin. With a B12 deficiency the skin barrier can deteriorate, for instance.
• Digestive problems: disturbances in methylation can affect the gut indirectly, through changes in the balance of neurotransmitters (which can also influence gut movement and gut flora). Some report digestive trouble such as bloating, diarrhoea or constipation.
• Headaches and migraine: raised homocysteine values or a lack of B vitamins in the context of a methylation disorder are sometimes linked to frequent headaches or migraine attacks.
• Fertility and pregnancy problems: since folic acid and a well-functioning methylation cycle are essential for early embryonic development, disturbances can raise the risk of complications in pregnancy, among other things.
• Autoimmune reactions: faulty gene regulation through disturbed methylation could possibly be involved in the development or worsening of some autoimmune conditions, since certain inflammation-promoting genes can be more active.

Whether these symptoms appear, and which ones, varies greatly from person to person. Some people with methylation disorders show only mild complaints, others have a whole range of symptoms. Where complaints are chronic or hard to explain, it is therefore worth thinking not only of the usual causes but possibly of methylation as well.

What can be done about methylation disorders?

Here there is good news, because there is a great deal you can do yourself to bring the body back into rhythm.

Making up nutrient deficiencies

• Food: dark green leafy vegetables (spinach, broccoli), pulses and wholegrain products for folate; animal products (meat, eggs, fish, milk) or supplements for B12; beetroot and wheat bran for betaine.
• Supplementation: where a deficiency has been shown in the laboratory (or where there are genetic variants), active folic acid (5-MTHF) can help. Vitamin B12 should be supplemented in bioavailable forms such as methylcobalamin.

Strengthening gut health

• Probiotics and prebiotic foods (fermented vegetables, yoghurt, kombucha) encourage a balanced gut flora.
• A diet rich in fibre (wholegrain products, pulses, vegetables) improves digestion and has a positive effect on the uptake of B vitamins.
• A healthy gut barrier and avoiding dysbiosis (imbalance in the gut flora) can support methylation indirectly, because nutrients are then used better.

Supporting the antioxidant system

• Glutathione counts as one of the most important antioxidants the body makes itself. An optimised glutathione system can improve detoxification, which in turn takes pressure off methylation. Some people therefore take N-acetylcysteine (NAC) or liposomal glutathione. More on glutathione and its many benefits in the article „Glutathione – Our Invisible Shield".
• Polyphenols and other antioxidants from berries, turmeric, green tea and so on further strengthen the body's own defence and detoxification processes.

Specific supplements

• SAMe (S-adenosylmethionine) can help some people with pronounced methylation problems, provided there is a deficiency (do seek expert advice).
• Choline and betaine (TMG) can be taken as supplements alongside a normal diet where the methylation cycle is clearly stalling.

A healthy way of living

• Reduce stress: constant stress encourages inflammation and uses up B vitamins and other nutrients faster.
• Relaxation techniques such as meditation, breathing exercises, yoga or progressive muscle relaxation can have a positive effect on the autonomic nervous system and take pressure off the body.
• Improve sleep quality: during sleep the body recovers and carries out important repair processes.
• Movement: moderate, regular activity supports metabolism and detoxification, encourages circulation and with it the supply of nutrients to your cells.
• Sunlight supports the formation of vitamin D, which improves many metabolic processes and keeps the immune system stable.

Supporting detoxification

• Drink enough: water or unsweetened teas help flush out pollutants.
• Food that is kind to the liver: artichokes, dandelion or milk thistle can take pressure off the liver.
• Minimise everyday toxins: organic food, household cleaners low in chemicals, natural cosmetics and airing the rooms regularly.
• Possibly check for heavy metal exposure.

Checking for chronic infection or inflammation

• Where complaints persist and remain unclear, it is worth ruling out or treating hidden infections (Lyme disease, for example) or chronic sites of inflammation. These can place strain on metabolism and on the methylation cycle in particular.
• Dental foci or smouldering inflammation (in the mouth or the gut, for instance) play a part in some people too.

Hormonal balance

• If you have strong hormonal complaints, it can make sense to have the thyroid (T3/T4), the adrenal hormones (cortisol) or your sex hormone status checked. An imbalance can affect methylation indirectly as well.

Tending the mind-body connection

Chronic emotional burdens and unresolved conflicts often work their way through to the physical level. Psychological support or coaching can help where stress or emotional matters are part of what throws the methylation cycle off course.

Professional support

In complex cases and with pronounced complaints, advice from doctors or naturopaths who know about methylation disorders is worth seeking.

Research in the field of methylation is moving fast. Scientists keep discovering further links between disturbed methylation and illnesses such as cancer, Alzheimer's and other degenerative processes. That may open new paths for individualised treatments, where one looks closely at how a person's genes are switched epigenetically. Knowledge of our genetic and epigenetic switches could play a large part in prevention in future as well.