March 14, 2023

Overmethylation: Is this the cause of your anxiety?

Check out our blog post on overmethylation

Methylation is a vital process for cell clean out and DNA repair. Adequate methylation reduces the risk of conditions like cancer and makes us feel energized and alert. Methylation is an important process to rid the body of free radicals and toxins thus its important in cancer prevention. In my previous article I spoke about under – methylation being a cause for fatigue. On the flip side, what are symptoms of overmethylation?

While those who undermethylate tend to have lower levels of neurotransmitters, those who overmethylate have robust levels of dopamine, norepinephrine, and epinephrine resulting in conditions like anxiety.

The methylation process:

DNA methylation involves addition of a methyl group to the carbon 5 position of the cytosine ring – a carbon atom attached to three hydrogens (CH3) (Moore, et al). This process occurs billions of times per second! Basically the amino acid methionine with the help of SAMe donates a methyl group to form homocysteine. With the help of vitamin B12 and folate (in the form of methyltetrahydrofolate) homocysteine is turned back into methionine or is converted to glutathione with the help of cystathionine, cysteine and vitamin B6. Magnesium is also an important player as well as the enzymes that are bolded in black in the above schematic. Any SNP’s (single nucleotide polymorphisms) in these enzyme pathways (MTHFR, CBS, BHMT, MTR) could impair ones methylation capacity and require some individuals to supplement key nutrients to help over-ride these SNPs. In hypermethylators they have an abundance of SAMe and they easily make vitamins b12, b6 and folate, cofactors for the methylation process. Hypermethylators may be prone to developing higher levels of cytokines like interleukin-6 increasing anxiety and the prevalence of mental health disturbances (Murphy, T.M).


An important end product of an effective methylation cycle is our mega antioxidant glutathione. Glutathione aids in the detoxification of heavy metals like mercury and lead, mycotoxins, POPs (persistent organic pollutants), protection from alcohol, and protection from oxidative stress (Pizzorno, J). The methylation cycle is dependent of the production of SAMe to produce the methyl donors so other organ systems can function and detoxification can happen throughout the body. To little SAMe from inadequate intake of methione, b-vitamins, magnesium, choline and methylation cannot happen and the impacts can be seen throughout the body in wide array of symptoms as the body cannot function the way it needs and detoxification is impaired.

Overmethylation symptoms:

  • Anxiety

  • Poor concentration

  • Panic disorders

  • Low motivation

  • Easily frustrated

  • Insomnia

  • Paranoia

  • Hyperactivity

  • Food/chemical sensitivities

  • High pain threshold

  • Tinnitus

  • Depression (may also be a symptom of undermethylation)

  • High energy

  • Highly creative (especially in musical ability)

  • Histamine intolerance

  • ADHD (Meijer, M et al)

(Spear, N.)

Overmethylation and undermethylation are implicated in wide variety of conditions and the symptoms that can sometimes overlap. The clinical diagnosis needs to be based on laboratory findings and symptomatology. Schedule a Wellness Consult today to optimize your health for long term success!


Meijer M., Klein M., Hannon E., van der Meer D,, Hartman C., Oosterlaan J., Heslenfeld D., Hoekstra P. (2020). Genome-Wide DNA Methylation Patterns in Persistent Attention-Deficit/Hyperactivity Disorder and in Association With Impulsive and Callous Traits. Frontiers in Genetics, 11.

Murphy TM, O’Donovan A, Mullins N, O’Farrelly C, McCann A, Malone K. Anxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genes. Psychiatr Genet. 2015 Apr;25(2):71-8. doi: 10.1097/YPG.0000000000000055. PMID: 25350786.

Spear, N. (2018). .A look at Methylation. Research and Education, 06;25.

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