Overmethylation: Signs and Solutions

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Is There Such a Thing as “Overmethylating?”

The short answer is “yes, overmethylation (or ‘hypermethylation’) happens”. Of course, the explanation is multifaceted.

The process of methylation plays a crucial role in various bodily functions, including mental wellness. In our small corner of the supplement world, we often discuss “undermethylation” as a reason for supplementing with l-methylfolate. But this process can, in some cases, go into overdrive. 

Overmethylation, though less commonly discussed, can have significant implications for overall well-being. In this article, we delve into what it means to overmethylate. We explore the signs indicating this condition, and steps you can take if you find yourself in this biochemical imbalance.

What is Overmethylation?

Methylation is a fundamental biochemical process that occurs in every cell of our body. It involves the transfer of a methyl group (one carbon atom and three hydrogen atoms) to a substrate molecule. This can affect the activity of enzymes, hormones, neurotransmitters, and DNA. This process is crucial for various bodily functions, including growth, detoxification, neurotransmitter synthesis, and immune system modulation.

Overmethylation occurs when there is an excessive level of methyl groups in the body, leading to imbalances in biochemical pathways. This can happen due to genetic predispositions, environmental factors, or dietary imbalances (discussed below). While methylation is essential for optimal health, too much of it can lead to health issues.

What Overmethylation is NOT

Despite the logic that “methylfolate supplements mitigate undermethylation, therefore too much causes overmethylation”, overmethylation is not usually caused by an overdose of methylfolate. In fact, methylfolate supplements are often recommended to overmethylators too.

Some people do experience negative consequences (jitters, nausea, etc.) after taking too much methylfolate. As a water-soluble B vitamin, if you take more methylfolate than your body needs, excess will be excreted through urine. 

Signs of Overmethylation

Identifying whether you’re overmethylated can be challenging, as the symptoms can vary widely among individuals. However, there are some common signs and symptoms associated with this condition:

  • Excessive worry and nervousness: Overmethylation can lead to elevated levels of neurotransmitters like serotonin and dopamine. This may contribute to feelings of agitation, restlessness, and an inability to relax [1].
  • Sleep trouble: Difficulty falling asleep or staying asleep can be a consequence of imbalanced neurotransmitter levels resulting from overmethylation.
  • Digestive issues: Overmethylation may impact gut health, leading to symptoms such as bloating, gas, constipation, or diarrhea.
  • Allergies and/or sensitivities: Overmethylated individuals may be more prone to allergies, sensitivities, or intolerances to certain foods, environmental factors, or chemicals.
  • Hyperactivity: Excess methyl groups can increase the activity of certain neurotransmitters, potentially leading to hyperactive behavior in some individuals.
  • Mood swings and irritability: Fluctuations in neurotransmitter levels can affect mood regulation, leading to mood swings, from irritability to chronic sadness.

Why Does Overmethylation Occur?

Understanding the underlying causes of overmethylation is essential for addressing this biochemical imbalance effectively. Several factors can contribute to the overproduction or impaired breakdown of methyl groups in the body:

  • Genetic predisposition: Certain genetic variations, such as mutations in genes related to methylation pathways (e.g., MTHFR gene), can predispose individuals to overmethylation. These genetic variations may affect the function of enzymes involved in methylation, leading to imbalances in methyl group metabolism.
  • Dietary imbalances: Poor dietary choices, including excessive intake of methyl-donating nutrients like choline, methionine, and folate, can contribute to overmethylation. Similarly, deficiencies in nutrients that are essential for methylation pathways, such as B vitamins (particularly B12, folate, and B6), magnesium, and zinc, can disrupt methylation balance.
  • Chronic stress: Prolonged stress can dysregulate the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, leading to imbalances in neurotransmitter levels and disrupting methylation pathways.
  • Environmental toxins: Exposure to environmental toxins, pollutants, heavy metals, and chemicals can impair methylation pathways by interfering with enzyme function or depleting essential cofactors required for methylation.
  • Microbiome imbalances: Alterations in the gut microbiome composition and function can impact methylation pathways. Dysbiosis (imbalance of gut bacteria), intestinal permeability (leaky gut), and impaired gut function can lead to inflammation, immune dysregulation, and nutrient malabsorption, all of which can affect methylation status.
  • Hormonal imbalances: Hormonal fluctuations, such as those seen in estrogen dominance or thyroid disorders, can influence methylation pathways. Imbalances in sex hormones, thyroid hormones, cortisol, and insulin can affect neurotransmitter synthesis, detoxification processes, and overall methylation balance.
  • Medications and drug use: Certain medications can impact methylation pathways and neurotransmitter metabolism. Additionally, recreational drug use, alcohol consumption, and smoking can disrupt methylation balance and contribute to oxidative stress and inflammation.

What to Do If You Are Overmethylating

If you suspect that you may be overmethylated based on the signs and symptoms you’re experiencing, it’s essential to take steps to rebalance your biochemistry. Here are some strategies that may help:

  • Testing and monitoring: If you suspect overmethylation, your first step should be working with a healthcare provider who can conduct appropriate testing to assess your biochemical status accurately. Tests such as methylation pathway analysis, neurotransmitter testing, and genetic testing can provide valuable insights into your individual biochemistry.
  • Nutritional interventions: Adopting a diet that supports methylation balance is crucial. This includes consuming foods rich in B vitamins (especially B12, folate, and B6), magnesium, zinc, and omega-3 fatty acids. These include lean meats, fatty fish, and dark green leafy vegetables. However, it’s essential to work with a healthcare professional or nutritionist to ensure that your dietary choices align with your specific needs.
  • Supplementation: Certain supplements can support methylation balance, such as methylated forms of B vitamins (e.g., methylfolate and methylcobalamin), magnesium, zinc, and SAMe (S-adenosylmethionine). Our parent company, Metabolic Maintenance offers these additional supplements at the same superior level of quality you expect from MethylPro. Again, it’s crucial to seek guidance from a qualified healthcare practitioner before starting any supplementation regimen.
  • Lifestyle modifications: Managing stress through techniques like meditation, yoga, deep breathing exercises, and regular physical activity can help support methylation balance. Additionally, avoiding exposure to toxins, chemicals, and pollutants can reduce the burden on your detoxification pathways.
  • Individualized approach: Keep in mind that each person’s biochemistry is unique, and what works for one individual may not necessarily work for another. Therefore, it’s essential to take an individualized approach to address overmethylation, guided by professional advice and personalized testing.

Final Thoughts

While methylation is a vital biochemical process for optimal health, overmethylation can lead to imbalances that manifest in various signs and symptoms. By understanding the signs of overmethylation and taking proactive steps to rebalance your biochemistry through nutritional, lifestyle, and supplementation interventions, you can support your overall well-being and vitality. 

Remember, consulting with a qualified healthcare practitioner is crucial to developing a tailored approach that addresses your specific needs and circumstances.


  1. https://www.mdpi.com/1422-0067/23/2/752