Methylation: How It Works + 6 Key Ways to Support It - Vital Plan

Methylation: How It Works + 6 Key Ways to Support It

If you haven’t yet heard the term methylation, there’s a good chance you’ll soon start hearing it a lot more. Many people are beginning to clue into the importance of this biochemical process, which is a key component of overall wellness, and yet myths and misconceptions are more common than facts. Understanding methylation, and knowing how to optimize it, can give you an edge on staying healthy as you age.

What is Methylation, Anyway?

In biochemical terms, methylation is when a “methyl group,” consisting of three hydrogen atoms, and one carbon atom are linked to another molecule. Attaching a methyl group to an organic molecule (a chemical compound that contains carbon) makes it less reactive.

Simply put, methylation is a process of making molecules more stable, which is important for a wide range of metabolic functions in the body. For starters, it balances hormone and neurotransmitter activity, and it regulates protein synthesis and cellular energy. It processes DNA and RNA, the molecules that are responsible for storing and reading our genetic information, and repairs DNA. It also optimizes the functions of T-cells, white blood cells that play a key role in immune response, and assists in glutathione production, the body’s master antioxidant.

hex 3d model methylation molecule

Methylation also helps neutralize toxic substances: When methyl groups attach to organic toxins such as heavy metals, it reduces their toxicity and allows for easier removal from the body. When you consider that the modern world is loaded with higher concentrations of artificial toxins than ever before in history, maintaining optimal methylation is increasingly vital for a vibrant, healthy life.

One of the most important roles of methylation is regulating the expression of genes. At any given time, you are using only about 1% of your genetic material; the rest of it is in “off” mode. But there are certain factors notorious for turning on “bad” genes that are associated with chronic illness, many of which are unique to the modern world. These include:

  • Eating a diet high in processed food products
  • Exposure to environmental toxicants
  • An abundance of chronic stress
  • Having a sedentary lifestyle
  • Exposure to stealth microbes

This is where methylation comes in — the way the body turns off “bad” genes is by attaching methyl groups to genetic material. Of course, if you don’t change your diet and lifestyle habits, the bad genes will turn on or stay on. If you continue stressing your genes, all the methyl groups in the world aren’t going to help you feel your best.

Poor Methylation and Chronic Health Conditions

This is a huge misconception: People with symptoms associated with chronic health conditions — typical ones being fatigue, neurological symptoms, mood disorders like anxiety, and insomnia, to name a few — are being told that poor methylation is the cause of their illness. But in fact, those symptoms often add to the daily stressors that activate bad genes and increase susceptibility to illness; poor methylation just compounds the problem.

Closeup woman with hands holding her shoulder pain.

The Western diet is the biggest culprit. The body relies on a steady stream of methyl donors — substances that can transfer a methyl group to another substance — from certain foods to support the metabolic functions that are dependent on methylation. It can use a variety of methyl donors, but the four most important components are methionine (an amino acid) and the B vitamins: methylfolate (B9), B12, and B6.

Unfortunately, modern grain- and meat-based diets are very poor sources of methylfolate and other B vitamins. Food companies often try to compensate for the loss of natural folate by adding folic acid to their products, but it’s not an adequate substitute because it’s not the most active form of the vitamin. What’s more, people who over-consume processed foods tend to develop gastrointestinal problems and lose the ability to produce a substance called intrinsic factor, which is essential for absorption of vitamin B12.

Genetics also play a role in methylation proficiency. About 50% of the population carries a mutated gene (MTHFR) for an enzyme called 5-MTHF reductase. This gene is necessary to convert homocysteine (an amino acid most abundant in meat) into methionine, an amino acid that’s essential for the methylation process. About 40% of the population carries one MTHFR mutation, and 12% of the population carries a double mutation.

Having MTHFR mutations, however, may be less of a factor in chronic health conditions than some experts suggest. The evidence linking concerns such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, and Parkinson’s disease to the presence of a mutated 5-MTHF reductase gene is mild at best. Scientific investigations have shown only a very slight increased incidence of chronic illnesses in affected individuals.

That’s because this genetic pathway is only one of a variety of methylation pathways. The human body would never rely on a single option for a function like methylation, which is so essential for life. In addition, for most of history, humans consumed large amounts of plant matter that provided all the components necessary for methylation (again, methionine, B9, B12, and B6). It’s only in recent history, as our diet has become more plant- and nutrient-deficient, that this particular genetic methylation pathway has become noteworthy.

How to Know When It’s Time to Test

People often ask which symptoms indicate they should get tested for poor methylation, but there are no pure telltale signs. My answer is, if you don’t feel well, or you’ve been diagnosed with a chronic illness such as fibromyalgia or ME/CFS, and you eat a lot of processed foods and very few vegetables, it’s pretty safe to assume you have poor methylation.

The biggest reason to have the test is to determine whether you have a double mutation, in which case, supplementation with natural folates may be valuable. Determining whether you have a MTHFR mutation can be done through a blood test or a range of test kits; the cost can vary widely depending on the testing method you choose.

Additionally, checking for elevations of homocysteine in your blood can tell you the degree of the problem: The higher your homocysteine levels, the lower the formation of methylfolate for making methionine, if methylation mutations are present. More than anything else, elevations of homocysteine indicate over-reliance on grains and meat as a food source.

6 Ways to Support Healthy Methylation

Maintaining proper levels of methylation is important for health, but it must be part of a more comprehensive strategy that promotes a nutrient-rich diet, toxin-free environment, stress management, and movement. Follow the simple steps below to help ensure optimal methylation, and whether or not you carry a MTHFR mutation could become a non-issue:

icon of carrot and broccoli

1. Eat Your Veggies.

To up your vegetable intake, focus especially on dark green leafy greens such as spinach and kale, as well as asparagus, broccoli, cauliflower, peas, and beans (preferably sprouted). A healthy, plant-based diet containing these foods is the number one way to ensure you take in plenty of naturally-derived methylfolate, one of the primary methyl donors.

icon of capsule with B on it

2. Get Plenty of B Vitamins.

Although folate is a B vitamin, vitamins B6 and B12 are important methyl donors, too. B6 helps to support immune health, boost heart and brain function, and encourage healthy blood sugar levels, while B12 aids in proper nerve conduction, the generation of red blood cells, and more. You’ll find both of these crucial vitamins in salmon, eggs, nuts and seeds, plus bananas, avocados, and soy.

icon of molecule structure

3. Look for Active Forms of B-Vitamin Methyl Donors.

If you take daily vitamin and mineral supplements to support your health, check ingredient lists to be sure they contain the bioactive forms of the B vitamin methyl donors, which means they’re in a form your body can actually use. Here’s what they’ll look like on the label:


Active forms: 5-Methyltetrahydrofolate or l-Methylfolate. Note that folic acid found in most multivitamin products isn’t a bioavailable form. It’s not absorbed and utilized in the body properly, especially if you have a MTHFR mutation. This is particularly true if you are pregnant, in which case supplement with methylfolate, instead of folic acid, and consume plenty of leafy greens.


Active forms: Pyridoxal 5-Phosphate


Active forms: Methylcobalamin or Hydroxocobalamin

science icon of Glutathione

4. Supplement With Glutathione, if Needed.

Glutathione is an essential antioxidant and another methyl donor, and it’s important for a myriad of processes in the body, including detoxification. Supplementing isn’t as necessary for young, healthy people, but the stress factors I mentioned earlier and aging put additional pressure on the body, so extra glutathione can be beneficial at times. Also, taking SAMe is another way to support the methylation process, but if you’re young, healthy, or if you’re getting adequate bioavailable B vitamins, it might not be necessary.

icon of supplement bottle with leaves on it

5. Consider Restorative Herbs.

Restorative herbs will help counteract a wide spectrum of stress factors in the body, and therefore, help take pressure off of the detoxification and healing systems. Not sure where to start? Opt for herbs that support your immune system, fortify your tolerance to stress, and balance the microbiome and other functions. Top herbal contenders include:

6. Stay Active, Manage Stress, and Cut Back on Alcohol.

It’s common sense that living a healthy lifestyle helps keep everything in your body running smoothly. But research has started connecting the dots between lifestyle factors such as sedentary behavior, stress, and toxins such as alcohol with changes in DNA methylation that could cause you problems later on down the line. So don’t wait until you’ve developed unwanted symptoms before you take action to feel your best.

Proper methylation impacts so many health systems of the body, and the simple steps outlined above can help support and enhance the process — MTHFR gene mutation or not. Enjoy your favorite produce, take steps to stay active, keep stress in check, and supplement with the right nutrients and herbs, and you’ll be paving a path toward a long, healthy, vibrant life.

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