How to Treat Overmethylation

Methylation is a vital biochemical process involving the transfer of an active methyl group among molecules. Its significance is evident in various physiological functions such as cell division, DNA and RNA synthesis, early central nervous system development, gene expression, immune cell differentiation, post-transcriptional modification, neurotransmitter synthesis and metabolism, histamine clearance, detoxification, hormone clearance, cellular energy metabolism, phospholipid synthesis, and myelination of peripheral nerves.

Furthermore, methylation of DNA is crucial in epigenetics, determining the activation or repression of genes. In general, reduced methylation leads to gene activation, while increased methylation results in gene repression. These methylation patterns can be inherited and impact the gene expression of subsequent generations, but they are also susceptible to modulation by diet and environmental factors.

Due to its multifaceted roles, deficits in methylation can contribute to various conditions. Impaired methylation may manifest as depression, anxiety, histamine intolerance, heightened cancer risk, hormonal imbalances, compromised detoxification, infertility, congenital disabilities, fatigue, and low energy levels.

Functional Methylation Testing: Beyond MTHFR

The identification of the MTHFR SNP has significantly highlighted the role of methylation. MTHFR, the key enzyme in the methyl cycle, activates folate for converting homocysteine to methionine. Specific single nucleotide polymorphisms (SNPs) or gene variants can reduce the enzyme's capacity. MTHFR variants are linked to an elevated risk of various diseases, including depression, fertility issues, insomnia, and thyroid conditions.

However, relying solely on genetic testing for MTHFR and related methylation genes to initiate supplements for addressing perceived "methylation deficiency" is a flawed approach. Genetic results alone do not provide insights into functional methylation capacity. Possessing an SNP associated with impaired methylation doesn't necessarily indicate actual impairment. Conversely, an individual with no SNPs in methylation genes might have severe methylation imbalance requiring treatment. Therefore, a more comprehensive evaluation beyond genetic testing is essential for understanding and addressing methylation issues.

While genetic information is valuable, it is crucial to complement genetic results with an assessment of functional methylation markers. Indicators of impaired methylation in a standard functional blood chemistry panel include low serum folate, low serum B12, elevated serum MMA, and increased serum homocysteine. Additional markers include low RBC folate, elevated urine MMA, and increased urine FIGLU.

The Health Diagnostics and Research Institute (HDRI) offers a comprehensive Methylation Pathways Panel, measuring various folate derivatives in the methylation cycle, oxidized and reduced glutathione, as well as levels of the methyl donor SAM-e and the methylation inhibitor SAH. Doctor's Data provides a similar panel with a quicker turnaround time, although it may not be as comprehensive as the HDRI test. These tests play a crucial role in obtaining an accurate assessment of a patient's real methylation capacity.

Treating Methylation Imbalance

Certainly, given the potential adverse effects of high-dose methyl donors, it's important to discuss strategies for restoring methylation balance instead.

• Alleviate Nutrient Deficiencies
  Impaired methylation is often attributed to nutrient deficiency, with B12 and folate being the crucial players in methylation pathways. Other essential nutrients like methionine, cysteine, taurine, DHA, zinc, magnesium, potassium, riboflavin, niacin, pyridoxine, betaine, choline, and sulfur also contribute significantly to methylation. Insufficient intake of any of these nutrients can hinder the methylation process. Foods rich in these methylation-supporting nutrients include beets, spinach, mushrooms, eggs, organ meats, and shellfish.
• Support Gut Health
  It might be surprising, but bacteria indeed have a role in the methylation cycle. Certain bacteria, such as Bifidobacteria, contribute to folate production, while others, like Lactobacilli, are folate consumers. Imbalances in the gut microbiota, known as gut dysbiosis, can lead to either hypo- or hypermethylation, depending on the predominant bacterial genera. Reestablishing a healthy gut microbiota is crucial in bringing methylation back into balance.
• Reduce Competition for Methyl Donors
  Impaired methylation can also be attributed to competition for methyl donors. When a specific methylation function is overly active, it can deplete available methyl donors, compromising other methylation processes. This competition is frequently triggered by factors such as environmental toxins, elevated histamine intake, heightened estrogen levels, acute or chronic stress, and persistent infections or immune challenges.
• Reduce Exposure to Methylation Inhibitors
  Methylation inhibitors pose another challenge to methylation-dependent functions in the body. Certain drugs, such as valproic acid, cholestyramine, oral contraceptives, proton pump inhibitors (PPIs), and antibiotics, can interfere with methylation. Nitrous oxide, commonly administered at dental offices, is recognized for oxidizing cobalamin (B12). Research indicates that metabolites generated by beneficial bacteria act as essential cofactors and allosteric regulators of epigenetic processes.
• Rebalance Methylation with Methylation Adaptogens
  An "adaptogen" refers to a plant-based compound that encourages the body's natural balance within a biochemical pathway, restoring the body to homeostasis. The term "methylation adaptogen," coined by Dr. Michael Stone in Oregon, pertains to any compound that aids in reestablishing methylation balance, promoting appropriate methylation, and hindering abnormal methylation.

Examples of methylation adaptogens include curcumin, betanin, anthocyanins, quercetin, rosmarinic acid, lycopene, and sulforaphane. While these phytonutrients are abundant in a nutrient-dense diet, some individuals may benefit from additional supplementation.

What is Overmethylation?

Overmethylation in the context of biochemical processes and human health denotes a state characterized by an excessive level of methylation activity within the body. Methylation, a critical biochemical process involving the transfer of methyl groups, plays a vital role in various physiological functions, as mentioned previously.

In the context of overmethylation, it typically signifies an imbalance in the methylation process with an abundance of methyl groups being added to molecules. This imbalance can have repercussions for gene expression, neurotransmitter synthesis, and other cellular functions. It's crucial to acknowledge that the term "overmethylation" is commonly utilized in the alternative and complementary medicine domain, and its specific definition and implications may vary.

Certain practitioners and theories propose that overmethylation might be linked to specific health conditions or symptoms, such as anxiety, hyperactivity, elevated histamine levels, and potential imbalances in neurotransmitters. However, it's essential to approach discussions about overmethylation cautiously, as the scientific understanding of these concepts and their clinical relevance may not be universally acknowledged.

Responses to methylation imbalances can differ among individuals, and it is recommended to adopt a personalized approach that takes into account an individual's overall health and genetic makeup. If there are concerns regarding methylation-related issues, seeking guidance from a healthcare professional for a comprehensive evaluation and appropriate advice is advisable.

Biochemistry of Overmethylation

Overmethylation represents the opposite end of the spectrum compared to undermethylation. In cases of overmethylation, there is a tendency for increased serotonin levels, reduced histamine levels, and a probable decrease in absolute basophil count. Furthermore, individuals experiencing overmethylation may observe elevated copper levels but diminished zinc and histamine levels throughout the body.

• High Histamine: When an individual lacks the capacity for adequate methylation, it is believed to result in a metabolic imbalance, leading to unusually elevated histamine levels, such as reaching 70 ng/ml.
• Low Zinc: Chronic undermethylation is often associated with individuals experiencing deficiencies in zinc.
• Low Copper: Individuals with compromised methylation abilities commonly exhibit low levels of copper.
• High Basophil Count: In blood tests, an increased basophil count, especially surpassing 50 cells/cu mm, is frequently observed and is linked to infections and allergic reactions. Elevated levels increase the likelihood of undermethylation.
• High Homocysteine: Increased undermethylation is associated with elevated homocysteine levels; the more extensive the undermethylation, the higher the anticipated levels of homocysteine.
• High Heavy Metals: Efficient methylation is believed to play a role in detoxifying the body from heavy metals and toxins. There is speculation that individuals who are undermethylated may experience an enhanced accumulation of heavy metals.

Overmethylation Symptoms

The following is a compilation of potential symptoms that one might encounter during overmethylation. It's important to note that overmethylation may not necessarily manifest every symptom listed, and the intensity of each symptom can vary significantly among individuals.

• ADHD: Overmethylators might experience attention deficits and may have a prior diagnosis of ADHD.
• Anxiety: Increased anxiety levels and susceptibility to panic attacks can be associated with overmethylation in some cases.
• Artistic Inclinations: There is a debated link between overmethylation and artistic or musical pursuits, according to some sources.
• Depression: Overmethylation can lead to depression due to elevated serotonin levels, lack of motivation, and a sense of failure.
• Dry Skin: Individuals prone to overmethylation may be more susceptible to occasional bouts of dry skin.
• Food Sensitivities: Overmethylators may notice heightened sensitivity to specific foods and chemicals.
  
• Frustration: Frequent frustration or becoming easily frustrated in seemingly benign situations is a common sign among overmethylators.
• High Pain Threshold: Unlike poor methylators, overmethylation is associated with higher pain tolerance.
• Low Libido: Reduced sexual drive is another symptom of overmethylation, with individuals exhibiting less interest in sex than average.
• Low Motivation: Overmethylators often struggle with achieving success in the workplace or competitive settings due to motivational deficits associated with overmethylation.
• Nervousness: Nervousness is tied to the generalized anxiety experienced by some individuals as a result of overmethylation.
• Obsessive Thoughts: Overmethylation may be linked to clear obsessions, although these are typically not accompanied by compulsions.
• Weight Gain: Overmethylated individuals may be more prone to weight gain, partially due to motivational deficits and depression.
• Paranoia: Strongly affected individuals may experience paranoid thoughts and possibly auditory hallucinations as a result of overmethylation.
• Restless Legs: Restless legs can be a possible symptom of overmethylation.
• Self-Imposed Isolation: Individuals who isolate themselves from others may do so partly due to depression and anxiety resulting from overmethylation.
• Self-Harm: Overmethylation is believed to be present among individuals who engage in acts of self-harm and mutilation.
• Sleep Disorders: Overmethylation may be more common among individuals experiencing sleep problems.

Overmethylation Treatment

When addressing overmethylation, many experts suggest following a specific supplement regimen for a period of 3 to 6 months. Some believe that mitigating the effects of overmethylation is relatively more manageable than addressing undermethylation. While significant improvements may not be immediately apparent, gradual betterment over several months is possible.

It is advised to collaborate with a professional to create a tailored supplement regimen for effectively managing overmethylation. These supplements are designed to correct nutritional imbalances and are expected to enhance symptoms associated with the condition.

Supplements for Overmethylation

Collaborating with a professional can assist in developing a supplement plan that effectively counteracts overmethylation. The objective is to diminish excessive methylation through specific nutritional interventions gradually. The following are examples of supplements that individuals may incorporate if they are experiencing overmethylation.

• DMAE
• Folic Acid (Folate)
• Niacinamide
• Omega-3 fatty acids
• Vitamin B6
• Vitamin C
• Vitamin E
• Zinc

Medication Outcomes

If you're on medication and possess an MTHFR mutation leading to overmethylation, here are probable reactions to specific drugs:

• Antihistamines: Due to already low histamine levels, individuals experiencing overmethylation may respond poorly to antihistamine medications. Overmethylated individuals typically exhibit reduced allergic responses because of their low endogenous histamine.
• Benzodiazepines: Overmethylated individuals often display favorable responses to benzodiazepines.
• Lithium: The mood stabilizer lithium is believed to bring noticeable improvement to those dealing with overmethylation.
• Oestrogen Therapy: Overmethylators are likely to experience adverse reactions to estrogen therapy.
• SAM-e: Individuals dealing with overmethylation should avoid SAM-e supplementation, as it may lead to adverse reactions by further increasing methylation.
• SSRIs: People who are overmethylated already have elevated serotonin levels and typically do not require SSRIs. Increasing serotonin levels further may pose problems and result in unwanted side effects or adverse reactions.

Conclusion

In summary, effectively managing overmethylation requires a holistic strategy that takes into account genetic considerations, functional markers, and environmental factors. While genetic testing is valuable, a more precise evaluation involves integrating it with functional methylation markers. The treatment of overmethylation includes addressing nutrient deficiencies, promoting gut health, mitigating competition for methyl donors, avoiding methylation inhibitors, and integrating methylation adaptogens. A tailored supplement plan, under the guidance of a healthcare professional, plays a crucial role. Awareness of potential medication reactions and a nuanced understanding of methylation's intricate dynamics contribute to successful management. Achieving methylation balance necessitates a comprehensive and individualized approach, addressing both genetic and environmental aspects.