Methylation is a process that’s constantly occurring in your body. It’s essential to life - your body can’t function without it.

Methylation involves adding a methyl group -- one carbon atom and three hydrogen atoms -- to a chemical compound, giving it the power it needs to be utilized by the body.

The methyl group is provided by a donor known as S-adenosylmethionine (SAMe). The donor will only do its job effectively if the body is producing methylfolate, which acts as a switch for the system that makes SAMe available.

Due to our busy lifestyles and poor eating habits, it’s quite common to experience complications with the methylation process. When your body isn’t properly adding these methyl groups to the nutrients you consume, there’s a good chance those nutrients can’t be used effectively by your body.

This article will explain overmethylation, its symptoms, and how it compares to undermethylation. We will describe how methylation issues develop and how they can be managed through diet and supplementation.

As explained above, methylation is a crucial biochemical process in which one carbon atom and three hydrogen atoms are added to a molecule to create a methyl group. Methyl groups are required for numerous cellular functions[1] such as DNA methylation, phosphatidylcholine synthesis, protein synthesis, and many more. The methyl group can be delivered via dietary methyl donors[1], such as methionine, folate, betaine, and choline.

Methyl groups turn on many crucial processes, including the body’s stress response, detoxification, the synthesis of neurotransmitters, and glutathione production[2].

However, variations in the MTHFR gene can reduce the function of the MTHFR enzyme. This can have a range of downstream effects on the body.

According to some health practitioners, impaired function of the MTHFR enzyme[3] can result in undermethylation due to a deficiency of methyl groups in the body. This can then lead to a range of health issues.

Overmethylation is much less common. It is believed to occur when the body has more methyl groups than it needs or can use. This can upset the proper function of the body’s normal biochemical processes. Also known as hypermethylation, overmethylation can result from a range of factors and may be linked to MTHFR single nucleotide polymorphisms (SNPs). It can lead to poor concentration, anxiety, panic attacks, sleep disorders, and sensitivities to environmental toxins, among other symptoms.

It’s important to note that there is currently very little scientific research regarding undermethylation and overmethylation, and that sources should be checked carefully.

There is currently a lot of speculation about the causes of overmethylation, but some studies have linked “hypermethylation” or methylation alterations to various genetic and environmental factors.

Some research has indicated that toxicity from Bisphenol A may cause DNA hypermethylation.[4] BPA is an industrial chemical used to make certain plastics and resins. It has also been suggested that high levels of estrogen exposure over a woman’s lifetime can lead to changes in DNA methylation.[5]

There is also some evidence that excess intake of folate and other B vitamins may cause disruption in DNA methylation. One study found that male offspring of mice fed a high-folate diet had a decreased sperm count, altered methylation in key genes, increased postnatal mortality in offspring, and reduced litter size.

Disturbances in folate levels - due to either low or high folate status - can lead to hypo- or hypermethylation, resulting in epigenetic instability and dysregulation of gene expression.

One study found that people who were homozygous for MTHFR 677TT had an elevated copper-to-zinc ratio and a higher risk of over-methylation. High levels of free copper are also noted in those shown to be over-methylating, which may lead to irregularities in thyroid function, adrenal hormone production, and lower histamine levels.

Researchers suggested that the reduced function of the MTHFR enzyme results in elevated homocysteine, so the body tries to metabolize the homocysteine via an alternative channel using a flavin cofactor (flavin adenine dinucleotide).

Hyperactivation of this pathway may result in excessive SAMe production and low histamine.

Other research has also linked low histamine (histapenia) to overmethylation, as histamine and methyl groups are inversely related. Low histamine levels might indicate overmethylation, while high levels might indicate undermethylation.

Symptoms of overmethylation* are said to include: 

• Anxiety
• Adrenal fatigue
• Depression
• Inability to concentrate
• Hyperactivity
• Panic attacks
• Poor motivation
• Easily frustrated
• Sleep disorders, insomnia
• Paranoia
• Sensitivities to foods/chemicals
• High pain threshold
• High energy levels
• Low histamine