Overmethylation vs undermethylation – A Starter Guide to Understanding Methylation

December 29, 2023 7 mins to read

Nutrigenomics is the study of how diet and genes are interrelated…Methylation is a process that involves various substances and facilitates many different process in the body. Methylation can be affected by mutations in certain genes like MTHFR. Most people are aware of undermethylation, but did you know you can overmethylate? This is often the case when individuals begin supplementing for an MTHFR (or other gene mutation connected with impaired methylation) without consulting a professional; they feel great at first, but soon start experiencing a range of horrible side effects from overmethylation.

Methylation: The Basics

Methylation involves transferring a methyl group (one carbon atom and three hydrogen atoms) to various substances within the body. This process is pivotal for things like: DNA repair, gene expression, and neurotransmitter synthesis (to name a few).

What is undermethylation?

Undermethylation, or hypomethylation, occurs when the body lacks sufficient methylation, a vital biochemical process. It can be caused by various factors including:

  • Genetic Predispositions: Certain genetic mutations, such as those in the MTHFR gene, can impair the body’s methylation processes.
  • Nutrient Deficiencies: Deficiencies in key nutrients like folate, vitamin B6, vitamin B12, and methionine can lead to undermethylation.
  • Dietary Choices: A diet low in methylation-supporting nutrients can contribute to undermethylation.
  • Environmental Factors: Exposure to toxins or heavy metals can disrupt methylation.
  • Lifestyle Factors: High stress levels and lack of sleep may affect methylation processes.

More on Gene Mutations That can Contribute to Undermethylation

  • MTHFR (Methylenetetrahydrofolate Reductase): The most well-known gene affecting methylation. It’s estimated that over 46% of the population has a mutation in the MTHFR Gene, which can reduce the body’s ability to process folate and affect methylation.
  • COMT (Catechol-O-Methyltransferase): Variations in the COMT gene can influence neurotransmitter metabolism, impacting methylation processes.
  • BHMT (Betaine-Homocysteine Methyltransferase): Plays a role in the methylation of homocysteine, a key part of the methylation cycle.
  • CBS (Cystathionine Beta-Synthase): Mutations can affect the transsulfuration pathway, indirectly impacting methylation.
  • MAOA (Monoamine Oxidase A): Influences the breakdown of neurotransmitters and can interact with methylation pathways.

Symptoms of Undermethylation

Physical Symptoms:

  • Fatigue
  • Poor energy production
  • Joint pain
  • Swelling
  • Stiffness
  • High libido
  • Seasonal allergies
  • Frequent colds/flu
  • Unexplained nausea
  • Good tolerance of cold
  • Poor tolerance of heat

Psychological Symptoms:

  • Obsessive-compulsive tendencies
  • Strong-willed
  • Competitive behavior
  • Ritualistic behaviors
  • Perfectionism
  • Chronic depression
  • High fluidity (tears, saliva)
  • Phobias
  • Inner tension
  • Social isolation
  • Strong-willed nature
  • Delusions or beliefs not based in reality
  • Difficulty maintaining focus
  • Headaches
  • High achievement and accomplishment tendencies
  • Addictive tendencies

Health Conditions and Diseases Associated with Undermethylation

Physical Conditions:

  • Seasonal allergies
  • Frequent colds/flu

Psychological Conditions:

  • Obsessive-compulsive disorder (OCD)
  • Depression
  • Anxiety
  • Phobias
  • High achievement and accomplishment tendencies (often seen in top athletes, CEOs, and professionals)
  • Perfectionism
  • Strong-willed behavior
  • Social isolation
  • Delusions or beliefs not based in reality

What is Overmethylation?

Overmethylation aka hypermethylation, occurs when there’s an excess of methylation in the body. It can be triggered by several factors, including:

  • Excessive Supplement Intake: Probably the most common trigger is overuse of supplements like SAMe or methylated B vitamins, which can lead to overmethylation.
  • Genetic Predispositions: Certain genetic mutations can affect how the body methylates, and in some cases taking methylated supplements may not help, and could even have negative effects. This is why it’s best to get a methylation panel before taking methylated supplements.
  • Diet and Environment: High methionine foods and exposure to certain environmental toxins can also play a significant role. Again this is why it’s recommended to work with a professional so they can inform you of the potential side effects or symptoms of overmethylation, and adjust your diet or supplementation accordingly.

The Reality of Overmethylation with Responsible Supplement Use

As an integrative nutrition student and holistic nutritionist, I have been asked about the risk of overmethylation from taking methylation supplements. Here’s the good news: When methylated supplements are used responsibly and under professional guidance…the risk of becoming overmethylated is relatively low. It’s all about balance and following recommended dosages.

Symptoms of Overmethylation

Understanding the symptoms is key to recognizing and addressing overmethylation. If you experience any of these symptoms it is best to stop supplementing and consult a genetic expert or naturopathic practitioner:

Psychological Signs:

  • Anxiety
  • Panic attacks
  • Paranoia
  • Depression

Physical Symptoms:

  • Headaches
  • Fatigue
  • Muscle pain
  • Sleep disturbances.

These symptoms occur because overmethylation can disrupt the delicate balance of neurotransmitters in the brain. It’s also important to note that when you begin taking a methylated supplement, you may not experience (or notice) these symptoms right away, as it may take a while of supplementing before your body switches from undermethylation to overmethylation.

The Importance of Professional Guidance

When individuals begin supplementing with methylated nutrients and methyl donors, it’s easy to begin overmethylating, which can lead to a range of side effects…and may discourage users from continuing with beneficial precision nutrition. That’s why it’s best to work with a professional with knowledge in nutrigenetics and MTHFR; they can tailor a plan for your specific genetics, and make adjustments to your diet and supplementation as your body begins to adjust to your methyl-donor supplements and re-balance it’s methylation systems.

Final Thoughts | Conclusion

Methylation is all about balance! While the symptoms and health conditions associated with undermethylation can be alarming, getting a proper methylation panel (testing) and working with a professional, ensures that your diet and nutrition plan are safe, effective and optimized to your unique biology. With the right knowledge and professional advice, you can effectively manage your methylation levels and support your overall well-being. There are also many books written by genetic experts, including my personal favorite Dirty Genes by Dr. Ben Lynch which has a ‘Clean Genes’ protocol you can follow.

Stay informed, listen to your body, and always prioritize professional guidance. Make sure you follow my socials and subscribe to my newsletter for more great articles and content just like this.


My MTHFR Guru TikTok

Be sure to check out my MTHFR Guru TikTok, Telegram and other socials to learn about Nutrigenetics, MTHFR and Methylation.

The Best MTHFR Supplement

Anyone that follows me on social media, knows I am extremely particular about quality and I have expensive tastes. I only promote the absolute best and highest quality supplements, formulated by experts in their prospective fields. One of my select few favorite MTHFR supplements is Physician Designed MTHFR Daily by Genomics Trained doctor (and my friend on TikTok) Dr. Dan Purser. First of all he’s trained in genomics and has run his formulat through some of the best independent lab testing available. Secondly I’ve looked into the formula and it’s one of the best I’ve seen for MTHFR support. FOr my other recommended brands check out my shop and search for MTHFR.


The information provided in this article is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of any health care agency or government entity in Canada or the United States.

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