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What Is Methylation & Why Is It A Deal Breaker For Health & Performance? | Poliquin Article

  /  Fitness   /  What Is Methylation & Why Is It A Deal Breaker For Health & Performance? | Poliquin Article

What Is Methylation & Why Is It A Deal Breaker For Health & Performance? | Poliquin Article

Methylation is a simple biochemical process that has complex implications for health. Occurring billions of times every second, methylation is when a methyl group is donated to cytosine, one of the four nucleic acids that make up DNA.

When optimal methylation occurs, it has a positive impact on many systems in the body, including function of the heart, brain, metabolism, and muscle. When methylation processes break down, there is a break down in DNA that impacts cardiovascular inflammation, detoxification, neurotransmitters, and energy use.

The easiest way to understand methylation is its role in detoxification. If your body cannot methylate properly, toxins build up in your bloodstream and will eventually cause disease. For example, when certain proteins accumulate in the body they can be harmful, so they need to be efficiently detoxified through the liver. Homocysteine is an amino acid that harms blood vessels and increases risk of cardiovascular disease. Via methylation, homocysteine is converted into the benign amino acid methionine when methylcobalamin (the active form of vitamin B12) donates its methyl group to homocysteine. 

Methylation has several other important actions in the body:

1. Production of the active, bioavailable form of vitamins B9 and B12

2. Modification of gene expression

3. Synthesis of neurotransmitters such as serotonin and norepinephrine

4. Synthesis and regulation of hormones such as melatonin and estrogen

5. Synthesis of DNA

6. Regulation of the stress response

7. Production and function of immune cells

How Does Methylation Happen?

There are several compounds that act as methyl groups, including vitamin B6, vitamin B9, vitamin B12, betaine, SAMe, choline, and methionine. Methylation allows for vitamin B9 (folate) and B12 (cobalamin) to be converted to the active forms in the liver. Folate, the form of B9 that is supplied in food, is converted to the active 5-methyltetrahydrofolate by the MTHFR enzyme. 5-methyltetrahydrofolate then donates its methyl group to B12 to produce methylcobalamin, supporting the detoxification pathway of homocysteine mentioned above.

In addition to regulating homocysteine, methylation inhibits the expression of certain genes. For example, the methylation process might stop a tumor-causing gene from “turning on,” preventing cancer. It also impacts mood and psychiatric health by regulating neurotransmitters, including serotonin and norepinephrine. When methylation processes breakdown due to poor nutrition or genetics, your risk of schizophrenia, depression, Alzheimer’s, insomnia, and other illnesses all increase.

What Factors Impact Methylation?

Aging, genetics, medication use, and nutrition are the primary factors regulating your body’s methylation pathways.


DNA methylation is at higher levels in young children and it appears to decrease with age. Hypomethylation means genes that were once repressed by methylated DNA start to become active, possibly resulting in a variety of diseases. Healthy nutrition and lifestyle habits can support methylation as the years go by.


Certain medications deplete the B vitamins that are necessary for methylation. Acetaminophen, aspirin, ibuprofen, oral contraceptives, antacids, glucose-lowering drugs, and anti-depressants have all been shown to impair methylation pathways. If you are taking any of these medications regularly, getting extra B vitamins in their most active form can increase levels of key methylating nutrients.


Diets low in B vitamins and the other methyl donors put you at risk of poor methylation and illness. Processed foods, especially those high in simple carbs, are nutrient poor and don’t supply the nutrition for optimal methylation. Eating a wide variety of colorful fruits and vegetables (especially leafy greens) and organic animal products (seafood, dairy, eggs, meat) will provide nutrients that support methylation.


Genetic mutations also play a role. Remember that the entire methylation system is reliant on the presence of 5-methyltetrahydrofolate, which acts as a switch turning methylation on or off. In 30 to 40 percent of the population, the gene that codes for 5-methyltetrahydrofolate is compromised by a mutation that prevents proper methylation.

Known as an MTHFR mutation, studies have linked this mutation with increased risk of heart disease, migraines, miscarriages, Alzheimer’s, depression, cancer, and autoimmune disease, such as lupus and rheumatoid arthritis. Those with this polymorphism can still utilize methylfolate, but their livers are much less efficient at producing it. Supplying methylfolate in supplemental form bypasses the genetic mutation and allows for efficient methylation throughout the body.

We have developed a methylation support product in our B Excellence supplement that supplies all of the B vitamins in their most active form along with the nutrients betaine and n-acetyl-cysteine for optimal absorption and function.