What is methylation?
Methylation is the name of a particular chemical reaction. It means that four atoms (one carbon atom and three hydrogen atoms) transfer themselves from one molecule to another. The receiving molecule has then been methylated.
When these reactions occur, they take multiple steps and enzymes in a series of reactions. These build up to creating S-adenosylmethionine (usually shortened to SAM-e), which is the “master methylator”.
What role does methylation play in the human body?
SAM-e methylates a wide range of molecules in our bodies by transferring methyl group molecules to them. These include our DNA each time a new cell is created. They also include neurotransmitters and enzymes.
This section explains how methylation is one of the most important chemical reactions in the body.
Stable healthy DNA
Methylation helps regulate gene expression, which means it keeps all our body cells behaving as they should. It suppresses the expression of harmful stretches of DNA that have found their way into human DNA over time, such as endogenous retroviruses and mutations.
What’s more, methylation makes embryonic stem cells differentiate irreversibly into different types of body tissue. It keeps DNA stable and unchanged, and it controls other molecules in the body, including proteins, lipids, hormones and neurotransmitters. Parts of the DNA in living cells are methylated. In humans, 60% to 90% of the DNA needs to be methylated.
Detoxing
Methylation of toxic heavy metals, such as mercury and lead, makes them water soluble. This means we can excrete them out of our bodies in urine.
Brain and mental health
Methylation is very important in neural development of foetuses and young children, and it appears to be essential to long-term memory formation.
Cancer
Abnormal DNA methylation (hypermethylation and hypomethylation) is associated with cancer. In particular, a lower level of white blood cell DNA methylation is associated with many types of cancer. In most types of cancer there is hypermethylation of tumour suppressor genes and hypomethylation of oncogenes or cancer-causing genes.
Heart health
The cells lining blood vessels must be methylated to repair them, and undermethylation results in cardiovascular disease and hardened arteries. Many medical research papers have found a high correlation between this medical condition and high homocysteine.
Two types of white blood cells (monocytes and lymphocytes) must be methylated. Under-methylation in these cells leads to excessive blood clotting, causing thromboses and strokes.
Impaired immune system
Under-methylation of certain white blood cells leads to impairment in the functionality of aspects of the immune system which are dependent on these cells. This may play a role in autoimmune conditions, chronic inflammatory conditions and other diseases. We need more research to understand this properly.
Why do some people methylate poorly?
Several factors can contribute to people having a limited methylation capacity, which is sometimes called being “under-methylators”.
Factors you CANNOT change
Genetic Variations
Genetic features (called polymorphisms) influence how fast the body produces enzymes needed to carry out methylation processes. For example, the MTHFR gene encodes an enzyme crucial for converting folic acid into its active form, methyl folate. Variations in this gene can result in reduced enzyme activity, leading to decreased methylation capacity.
Whilst you cannot change your genetics, you could compensate by taking a folic acid supplement that is already methylated. This is called methyl folate.
Environmental Toxins
Exposure to environmental toxins, such as heavy metals, pesticides, and pollutants, can place extra demands on the body’s methylation resources. This is because they need to be methylated to make them water-soluble, so we can pee them out safely. Not only this, they can disrupt enzyme function by inhibiting our ability to produce the enzymes involved in methylation.
In theory it’s possible to steer clear of toxins, but in reality moving home is impracticable for most people, and avoiding fish that may contain mercury can be a challenge. Further, you could be affected by exposure to heavy metals in the past which remain in your body.
Medications and Drugs
Certain medications and drugs can interfere with methylation processes by inhibiting enzyme activity or depleting essential nutrients involved in methylation. For example, methotrexate, a medication used to treat cancer and autoimmune diseases, can inhibit dihydrofolate reductase, an enzyme involved in folate metabolism, leading to reduced methylation capacity. We have some choice over this, but many medications are essential so our control over this is limited.
Risk factors you CAN change
Nutritional Deficiencies
Not eating enough of the essential nutrients involved in methylation, such as folate, vitamin B12, vitamin B6, and betaine (trimethylglycine), can impair our methylation processes. The body may struggle to produce methyl groups or build methylated compounds, affecting our overall methylation capacity.
Chronic Stress
Chronic stress can dysregulate the hypothalamic-pituitary-adrenal (HPA) axis and increase cortisol levels, which may deplete methyl donor molecules, such as S-adenosylmethionine (SAMe), needed for methylation reactions. Prolonged stress can lead to a state of methylation insufficiency, affecting various physiological processes and potentially contributing to health problems.
Age and Lifestyle Factors
Age-related decline in enzyme activity and changes in lifestyle factors, such as diet, exercise, and alcohol consumption, can impact methylation capacity. Older people may experience decreased methylation efficiency due to age-related changes in enzyme function and nutrient absorption. Unhealthy lifestyle habits, such as poor diet, sedentary behaviour, and excessive alcohol intake, can also impair methylation processes.
What are the signs that methylation isn’t working well?
With methylation playing so many roles in the body, it’s hardly surprising the signs of under-methylation are many and varied.
Heart health problems
You may very gradually develop signs of cardiovascular disease such as abnormal blood pressure, enlarged heart, orthostatic intolerance, chest pain or postural orthostatic tachycardia syndrome. However, many people have no indication of problems at all until they suffer a heart attack.
Thromboses or strokes become more of a risk because you may be more likely to have blood which clots too rapidly.
Impaired memory and mental health
You are likely to suffer memory impairment and may have a range of other neurological problems. These can include issues with mental wellbeing.
The methylation process is vital for the correct development of baby and toddler brains.
A lack of methyl folate (folic acid in its methylated form) in pregnant women means the foetus develops without adequate methylation. This has long been known to cause the baby to have brain and spinal abnormalities such as spina bifida.
Research suggests children with autism may have brain abnormalities which may derive from inadequate methylation of nerve cells during critical stages of brain development in early childhood. This is a hypothesis that needs more research.
Chronic immune problems and inflammation
Your immune system is likely to be weak and less effective, and you may be unable to sustain a strong immune defence against infections. This is the result of under-methylated white blood cells.
You may be susceptible to a wide range of chronic inflammatory illnesses, including some autoimmune conditions. This derives from inadequate methylation of monocytes and lymphocytes. So far, a definite link has been established between under-methylation of these cells and the development of autoimmune diabetes and systemic lupus erythematosus.
Cancer risk
Your risk of cancer, or any type, will increase. This occurs because our DNA needs to be methylated to prevent mutations. Once our body cells have undergone a series of 17 mutations, we can develop cancer.
Detox problems
You may accumulate abnormal levels of toxic heavy metals from food such as large fish (tuna, swordfish etc) and the environment.
What methylated vitamins and nutrients does the body need?
Methylation is a complex process. To methylate all the molecules in our bodies that need to be methylated, we use numerous enzymes in a complex series of reactions. The process needs quite a shopping list of nutrients!
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Methyl Folate (5-MTHF) or “active” folate (Vitamin B9) |
A bioavailable form used by the body to synthesise SAM-e (the master methylator) and perform other biochemical functions. |
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Methylcobalamin, hydroxocobalamin, adenosylcobalamin & cyanocobalamin (Vitamin B12) |
Converts homocysteine to methionine, crucial for SAM-e production. |
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Pyridoxine (Vitamin B6) |
Helps produce methionine and glutathione, a vital antioxidant. |
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Riboflavin (Vitamin B2) |
Converts folate to its active form for methylation. |
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Magnesium |
Helps convert methionine to SAM-e. |
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Betaine |
Supports methylation without sufficient folate or B12. |
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Choline |
Assists in SAM-e production and supports methylation. |
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Zinc |
Activates enzymes in the methylation process. |
Which methylated vitamins can you buy?
Methylated vitamin supplements, such as methyl folate (5-MTHF), methylcobalamin, and methylated B-complex vitamins, are available in forms that the body can use directly.
Methylfolate, the methylated folic acid
Methyl folate is the active form of folate, bypassing the need for conversion by the enzyme MTHFR, which can be deficient in some people due to genetic mutations. It helps in DNA synthesis, repair, and methylation processes.
This is particularly beneficial for anyone with less efficient forms of the MTHFR gene, with folate deficiency, and for pregnant women needing better prenatal nutritional support. It is also used on prescription for people with depression that doesn’t get better with antidepressant medication, and to help people with schizophrenia.
Pharmaceutical company Merck first developed this in tablet form as a patented medicine called Metafolin. It was created to help treat people with heart conditions and tendency to strokes and thromboses. There is another version called Deplin which is prescribed for people with depression and schizophrenia.
Methylcobalamin, methylated vitamin B12
Methylcobalamin, a methylated form of Vitamin B12, is also more bioavailable, meaning it’s easier to absorb. This activated form is especially useful for people with absorption issues or genetic variations affecting B12 metabolism. It supports nerve function, red blood cell production, and DNA synthesis, making it vital for those with pernicious anaemia, the elderly, and others with specific genetic mutations.
Why are methylated vitamins better?
The two main benefits of taking methylated vitamins is that we absorb them more efficiently, and they work faster because they’re already in the form our body needs. The alternative is taking non-methylated vitamins, which our bodies then have to modify chemically before they can get to work. In terms of subjective benefits, many people say that they gain more energy, better concentration and mood.
How to choose good quality methylated vitamins
When examining the label of methylated vitamins to assess their quality, consider the following key indicators:
Methylated vitamins are called “active” or “body ready” forms
Some brands of methylated vitamins call them “body ready” or “active forms”. You may see the word “methyl” only in the ingredients table. Look for the names of specific forms of vitamins that indicate methylation, such as methylcobalamin (methylated vitamin B12) or methylfolate (methylated form of folate). These prefixes “methyl” or “methylated” suggest that the vitamins have undergone methylation and are in a bioavailable form that the body can easily absorb and use.
Check the dosage!
Methylated vitamins are more expensive to produce than the inactive forms. To compete on price, some brands just give you really low doses. You’re unlikely to feel the benefit, so make sure you are getting adequate doses of each ingredient.
Buy methylated vitamins in a dark bottle
Methylated vitamins may degrade faster than inactive ones, so keep an eye on the expiry date to make sure that methylated vitamins are still within their shelf life. They need to be stored in a dark-coloured bottle that protects them from the damaging effects of light and oxygen. Don’t buy methylated vitamins in a pouch, as oxygen can get through the thin packaging.
Methylated vitamins must have a clear ingredient list
Some methylated vitamins are sold with a really unclear list of ingredients – for a reason! Review the ingredient list to make sure your methylated vitamins clearly state the exact chemical compound they contain.
Make sure all the vitamins are active, not just one!
Some vitamin B complex supplements include one methylated vitamin along with others that are not in their active forms. This will not get the results you are looking for! So double-check for methylcobalamin (B12) and methyl folate as well as the active versions of the other B vitamins. Whilst the term for these is not “methylated”, you will feel similar rapid benefits from active vitamin B6 (Pyridoxal-5-Phosphate), active vitamin B3 (Nicotinamide), active vitamin B2 (Riboflavin-5-Phosphate) and so on.
