What is methylation and why I should know about it

So why should you be concerned about methylation?

Are you concerned at all about the way you age?

And do you have some neurological or chronic illness or an unexplained illness?

I must admit this blog has bought out the biochemistry nerd in me..

Methylation may not be an easy concept to understand straight off for everyone so forgive yourself if you need to read this a few times to comprehend it all. I did an honours degree in biochemistry over 20 years ago and I even had a difficult time trying to explain it in a clear way. I hope i've done it some justice and I couldn't have done it without some great resources and research articles.

First of all..why methylation is important. Methylation is required for cell division, DNA and RNA synthesis, early central nervous system (CNS) development, gene expression, immune cell differentiation, post-transcriptional modification, neurotransmitter synthesis and metabolism, histamine clearance, detoxification, hormone clearance, cellular energy metabolism, phospholipid synthesis, and myelination of peripheral nerves.(1)

These all sound like big complicated words but in a nutshell, methylation is involved in the action and health of just about every cell in our body, including its genetic material DNA and RNA as well as biologically active substances such as histamine which is what is released to help your body fight and rid of your allergies and hence makes you sneeze and itch.

Methylation is a biochemical process involving the transfer of an active methyl group (CH3) between molecules which are certain compounds in the body. This allows some internal switches (i.e. bodily receptors) to turn on and off to function efficiently. SAMe—also known as S-adenosyl-L-methionine—is known as the universal methyl molecule that donates a methyl (CH3) group to enable proper methylation to occur. If methyl-folate and other nutrients are not present, this methylation process simply halts, resulting in a myriad of symptoms (2).

In fact, methylation is now considered one of the most important determinants in many chronic degenerative diseases. For example, DNA methylation is an important regulator of gene transcription. Abnormal DNA methylation has now been implicated in a range of degenerative diseases associated with ageing including cardiovascular disease (CVD), cancer and neurological diseases and so it’s not surprising that methylation deficits can impact a wide range of other conditions such as depression, anxiety, histamine intolerance, hormone imbalance, poor detox capacity, infertility, birth defects, fatigue, and low energy (3)

Methylation defects were discovered during the completion of the Human Genome Project where they found and mapped out genes in the human body and so researchers were able to look at the genes involved in methylation called MTHFR genes and realised that there was an association between mutations in these genes involved in methylation and particular conditions such as ADHD, autoimmune and alzheimers, etc. MTHFR mutations affect every person differently, sometimes contributing to hardly any noticeable symptoms at all, while other times leading to serious, long-term health problems. However as humans age, our endogenous ability to maintain adequate levels of methylation declines. The result is considered a major determinant of how quickly humans age (4).

What is MTHRF and what is an MTHFR mutation?

According to the Genetics Home Reference Library, MTHFR is a gene that provides the body with instructions for making a certain enzyme called methylenetetrahydrofolate reductase. In fact, “MTHFR” is the shortened name for this enzyme. When you eat processed foods or supplements that contain folic acid (synthetic folate), MTHFR converts it into methyl-folate (folate’s active form). Methyl-folate is critical to methylation, hence important to consume foods naturally high in folate and other vitamins that assist in this conversion also such vitamin b6, vitamin b12 and choline.

A MTHFR gene mutation can change the way some people metabolise and convert these important nutrients such as vitamin B12 and folate from their diets into "active" vitamins, mineral and proteins that the body can utilise. Genetic mutations can also alter neurotransmitter and hormone levels. In some cases, although not all, changes in how this enzyme works can affect your health including cholesterol levels, brain function, digestion, endocrine functions, immune system and more.

There are two main MTHFR mutations that researchers focus on most often. These mutations are often called “polymorphisms” and affect genes referred to as MTHFR C677T and MTHFR A1298C. Mutations can occur on different locations of these genes and be inherited from only one or both parents. Having one mutated allele is associated with increased risk of certain health problems, but having two increases the risk much more.

A specific example of methylation that has wide ranging consequences is the methylation cycle of homocysteine. Elevated homocysteine is a marker of increased risk of CVD (cardiovascular disease), poor heart health and ageing. Homocysteine is created when the body uses methionine, an amino acid, for methylation purposes. It is normally converted back to methionine or other useful metabolites such as cysteine. It is when these conversions are impaired that homocysteine can rise to dangerous levels.

Genetic and lifestyle factors, including inadequate nutrient status such as low folate and the B group vitamins including vitamin B12 and B6 in particularly, systemic disease, smoking, poor diet, use of certain drugs, alcohol and stress can all accelerate the progression of these diseases and increase the level of homocysteine as well.

Folate occurs naturally in foods, such as leafy green vegetables, avocado, citrus fruits, and beans, and there are several forms/types of folate in dietary supplements, such as folic acid and 5-methyltetrahydrofolate (5-MTHF). Note that folic acid is the synthetic version of folate.

Vitamin B12 as well as other B group vitamins are important too for proper methylation. Be aware of supplements that contain cyanocobalamin, which is a synthetic form of vitamin B12 which can be harmful when taken longterm due to cyanide toxicity especially in people with kidney disease. This is due to the cyanide chain and demands a lot of cellular energy and can deplete glutathione, a compound necessary for detoxification, to convert into the chemical form the body can actually use. It also has poor availability.

Supplements with methylcobalamin or hydroxycobalamin are safer to use longterm. Some manufacturers of vitamins are slowly beginning to phase out cyanocobalamin and some companies such as Metagenics and Mediherb, which are practitioner only prescribing, already have (5).

Research is now showing that dietary nutrients involved in this one-carbon metabolism pathway involving methyl group (eg, folate, vitamin B6, vitamin B2 and vitamin B12) are particularly important to DNA methylation because they are coenzymes needed for one-carbon metabolism and ultimately affect the physiologic availability of methyl groups, therefore deficiency in these vitamins can impair methylation.

So what can I do to make sure my methylation is working properly?

If you do suspect impaired methylation in the form of tiredness, impaired mental health, ADHD, fertility issues such as recurrent miscarriages or had low vitamin B12/low folate levels on previous blood test results, your GP, usually an integrative or holistic GP, can work it out from there and possibly test you for MTHFR gene defect. While genetic information can certainly be useful, it’s important to look at genetic results alongside functional methylation markers. Markers of impaired methylation on a typical functional blood chemistry panel can include low serum folate, low or high serum B12 depending on whether the person is supplementing with synthetic vitamins, high serum MMA, and high serum homocysteine (1).

Research suggests that people with MTHFR mutations might have a harder time converting folic acid into its useable form and actually experience worsened symptoms from taking synthetic supplements containing folic acid. Folate is the natural form of folic acid found in foods, otherwise if you need to supplement, 5-methyltetrahydrofolate is already converted form of folate if you have a MTHFR gene mutation. Having more folate in your diet means you’re better able to create the active form of 5-MTHF. (4) Some of the best high-folate foods include beans and lentils, leafy green vegetables like raw spinach, asparagus, broccoli, avocado and bright-colored fruits, such as oranges and mangoes and green tea.

So make sure you're getting enough natural folate and vitamin B6 and vitamin B12 which all help with proper methylation. Naturally diet is the best way, however for some people it may be a bit more difficult than what you might think. People eating not enough greens don't get enough folate and vegans have to pretty much rely on supplementation or having lots of mushrooms which have to be grown on animal manure in order for the mushrooms to have vitamin B12 as vitamin B12 is only found in foods from animal sources such as eggs and meat. Those with a MTHFR mutation are more likely to be low in related vitamins, including vitamin B6 and vitamin B12. These are easier to obtain from supplements if you do have a mutation. Otherwise to get more B vitamins, focus on eating enough quality protein foods, organ meats, nuts, beans, nutritional yeast and raw/fermented dairy products (4).

If you do have an HTMFR gene mutation and blood tests for folate and vitamin B12 are low or vitamin B12 abnormally high taking a vitamin B supplement and homocysteine is high, you will need a supplement containing the already converted form of folate called 5-methytetrahydrofolate, levomefolate or L-methylfolate which should all be 500-1000ug daily total dose. This is because your body cannot convert folic acid in supplements or folate in food into the active methyl folate. Make sure vitamin B12 is in the form of hydroxycobalamin or methylcobalamin which was explained earlier in this blog (1).

Treat digestive issues including leaky gut

Digestive issues are common in people with the MTHFR A1298C. Treating leaky gut or IBS means that your body is better to absorb your nutrients whether from food or supplements as having digestive issues such as leaky gut can compromise nutrient intake from your gut into your bloodstream if the mucosal membrane that lines your gut is inflamed. This then can contribute to systemic inflammation and immune dysfunction as your gut is the centre of your adaptive and innate immune system.

These in turn can contribute to digestion issues or and perpetuate the cycle. Factors such as nutrient intake, inflammation, allergies, neurotransmitter levels and hormone levels all affect digestive health.

To improve digestive/gut health, the following dietary adjustments can be very beneficial:

Reduce intake of inflammatory foods, such as gluten, added sugar, preservatives, synthetic chemicals, processed meats, conventional dairy, refined vegetable oils, trans fats and processed/enriched grains (which often include synthetic folic acid).

Increase intake of probiotic foods, which are fermented and supply “good bacteria” that aids in digestion.

Consume other gut-friendly foods, including bone broth, organic vegetables and fruit, flaxseeds and chia seeds, and fresh vegetable juices.

Focus on consuming healthy fats only, like coconut oil or milk, olive oil, grass-fed meat, wild-caught fish, nuts, seeds, and avocado (4).

Reduce stress/anxiety levels

This is important because some MTHFR mutations are linked to mental/emotional disorders such as anxiety, depression, bipolar disorder, schizophrenia and chronic fatigue. Therefore being pro active in other ways can also make a great impact on your overall health and also improve sleep which is integral to healing and repair. Also as stress can make MTHFR mutation symptoms even worse. Therefore try the following:

Supplementing with omega-3 fatty acids: Help to reduce inflammation and are beneficial for cognitive health.

Regularly practicing natural stress relievers: These include meditation, journaling, spending time outside, giving back or volunteering, praying, etc.

Regularly exercising: Helps to improve hormonal balance and sleep quality.

Using soothing essential oils, including lavender, chamomile, geranium, clary sage and rose.

Eliminating use of recreational drugs and reducing alcohol intake, which can both make symptoms worse by interfering with methylation (4).

So as you can see, methylation is a bit of a complex process to explain however fundamental to one's health and wellbeing as it impacts just about every cellular process underlying ALOT of conditions/illness, therefore if you are having difficulties diagnosing your signs and symptoms and have had everything else excluded, you may want to consider getting a blood test done to check whether you have a mutation in the MTHFR gene as from personal experience, it has provided me with some answers. And on that note, I say a big thank you to my wonderful GP for going that step further with blood tests to help me better my wellbeing!