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Over-Methylation vs. Under-Methylation: What You Need to Know for Better Health

Methylation is a crucial biochemical process occurring in all cells of the body. It involves adding a methyl group (CH₃) to molecules such as DNA, proteins, and lipids, significantly influencing their functions and activities. Methylation regulates various physiological mechanisms, including gene expression, detoxification, mood regulation, energy production, immune system function, and cellular maintenance. Particularly important is the role of methylation in the liver, where it helps neutralize and eliminate toxins, which is essential for overall health.

Types of Methylation

Methylation can be categorized into three types: Under-Methylation, Over-Methylation, and Normal Methylation.

  • Under-Methylation: When methylation is insufficient, the body fails to produce enough methyl groups. This can lead to issues with detoxification, reduced immune protection, nervous system dysfunction, and chronic inflammation.
  • Over-Methylation: Excessive methylation may cause excessive gene suppression, disrupting normal cellular functions and potentially leading to various diseases.
  • Normal Methylation: A balanced level of methylation maintains equilibrium in these processes, ensuring optimal bodily function, including cell repair and genetic stability.

Genotype, Phenotype, and the Role of Methylation in Gene Expression

Genotype and phenotype play a key role in how inherited traits manifest.

  • Genotype refers to the genetic information inherited from parents. It determines the potential characteristics and predispositions of an organism. In short, it is your innate genetic code.
  • Phenotype is the sum of all visible and measurable traits of an organism, shaped by both genetic code and external factors. It includes physical traits, biochemical processes, and behavioural characteristics.
  • Epigenetic processes are mechanisms that regulate gene activity without changing the DNA sequence itself. Epigenetic changes can be triggered by external factors such as diet, stress, toxins, and even behavioural habits. These changes can be passed from cell to cell during division and, in some cases, inherited from parents to offspring, influencing the phenotype without changes to the genetic code.

Methylation, as an epigenetic process, influences the expression of genetic information from genotype to phenotype. It can activate or deactivate genes, altering their expression in response to external conditions and environmental factors. Although epigenetic changes do not affect the DNA sequence itself, they can be inherited. With improvements in external conditions, epigenetic changes can also occur, but this will require certain efforts, including lifestyle changes, dietary adjustments, and stress management to restore normal methylation and other mechanisms.

Role of Methylation in the Body

Methylation is a fundamental intracellular process necessary for the proper functioning of every cell in the body. Now, let’s review the key roles of methylation:

  • Energy Production: Methylation is critical for intracellular energy production. It converts methionine into S-adenosylmethionine (SAMe), which is involved in synthesizing and activating molecules essential for energy production, such as creatine and ATP.
  • Detoxification: Methylation plays a key role in detoxification, especially in the liver. This process helps convert and eliminate toxins, such as heavy metals and metabolic byproducts.
  • Mood Regulation: Methylation affects neurotransmitter levels, including serotonin and dopamine, which regulate mood. Imbalances in methylation can lead to depression, anxiety, brain fog, and other emotional disorders.
  • Immune System Function: Methylation also influences the immune system, supporting its normal function. It helps modulate inflammatory responses and regulate immune cells.
  • Stress and Relaxation: Methylation is important for regulating stress responses and relaxation. Stress activates the sympathetic nervous system, releasing adrenaline and other hormones. Insufficient methylation can hinder the body’s ability to relax and recover, leading to chronic tension and fatigue.
  • Cardiovascular Health: Disruptions in methylation can contribute to atherosclerosis and hypertension due to increased homocysteine levels and heightened inflammation, raising the risk of cardiovascular diseases.
  • DNA Repair: Methylation plays a crucial role in repairing DNA damage, protecting it from free radicals and other harmful factors. This is vital for proper cell function and mutation prevention.
  • Regulation of DNA Function: Methyl groups are essential for methylating DNA regions, directly influencing gene expression. Both a deficiency and excess of methyl groups can disrupt normal cell function, leading to DNA instability and increased risk of mutations and diseases such as cancer and other genetic disorders.

Under-methylation

Cellular methylation can be insufficient, and this can affect the overall functioning of the body.

Symptoms of Under-methylation

Cellular methylation can be insufficient, affecting the overall function of the body.

  • Depression and Anxiety: Methylation imbalances can lead to neurotransmitter dysregulation, causing emotional disorders such as depression and anxiety.
  • Addictions: Insufficient methylation can lower dopamine and serotonin levels, increasing susceptibility to addictions as a way to boost these neurotransmitters.
  • Insomnia or Difficulty Falling Asleep: Reduced serotonin and melatonin activity can hinder the ability to fall asleep and impair sleep quality.
  • Obsessive-Compulsive Behavior: A lack of methylation can decrease serotonin levels, contributing to the development of obsessive-compulsive symptoms.
  • Fatigue and Low Energy: Since methylation is involved in energy production, its deficiency can lead to persistent fatigue and reduced vitality.
  • Problems with Concentration and Memory: Cognitive functions can suffer, leading to attention issues, brain fog, and memory deterioration.
  • Sensitivity to Chemicals and Foods: Inadequate methylation can impair detoxification processes, causing heightened sensitivity to various substances.
  • Increased Inflammatory Processes: Methylation disturbances can lead to skin issues such as acne and eczema due to increased inflammation.
  • Reduced Pain Threshold: Individuals with under-methylation may have a lower pain threshold, making them more sensitive to pain and discomfort.
  • High Histamine Levels: A lack of methylation can impair the body’s ability to break down histamine, leading to its accumulation and associated symptoms like inflammation, allergies, and headaches.

Possible Causes of Methylation Deficiency

Several factors can contribute to methylation deficiency:

  • Genetic Mutations: Mutations in genes such as MTHFR can disrupt the methylation process, reducing the effectiveness of necessary conversions.
  • Nutrient Deficiencies: B vitamins, especially methyl-folate (B9), B12, and B6, are crucial for methylation. Other important cofactors include magnesium, zinc, and certain amino acids.
  • Stomach Acidity Issues: Low acidity levels can reduce the activity of betaine, which is essential for both nutrient absorption in the stomach and methylation in liver cells.
  • Poor Diet: A diet low in essential nutrients can negatively impact methylation even in the absence of genetic predisposition.
    • Foods containing gluten or excessive folic acid can block methylation due to high folic acid intake.

Over-methylation

Symptoms of Over-methylation

Symptoms of over-methylation can significantly affect the quality of life and may manifest through various conditions:

  • High Creative Potential: Individuals with elevated levels of methylation may exhibit high creativity, particularly in music and the arts, due to enhanced activation of brain areas associated with creative thinking.
  • Depression and Emotional Instability: Excessive methylation disrupts neurotransmitter balance, potentially causing depression, mood swings, and emotional instability.
  • Attention Deficit Hyperactivity Disorder (ADHD): People with over-methylation may experience problems with concentration and impulsivity, related to disturbances in dopamine and norepinephrine regulation.
  • Sleep Issues: Over-methylation can lead to insomnia, difficulty falling asleep, and frequent nighttime awakenings.
  • Panic Attacks: Increased serotonin and adrenaline activity due to over-methylation can trigger panic attacks.
  • Behavioral Problems: Over-methylation can lead to aggressive and impulsive behavior, linked to imbalances in neurotransmitters affecting emotional states.
  • Paranoia and Psychosis: Excessive methylation can heighten anxiety and paranoia, sometimes progressing to psychotic states.
  • Predisposition to Schizophrenia: Over-methylation may disrupt gene expression, increasing the risk of psychotic disorders, including schizophrenia. However, some of these conditions may also be related to under-methylation.
  • Food Sensitivity: Over-methylation can increase sensitivity to food, causing allergic or inflammatory reactions.
  • Self-harming Behavior: Methylation disturbances may contribute to self-harming behaviours due to changes in neurotransmitter regulation.
  • Altered Pain Threshold: Methylation can affect pain perception, making individuals either more sensitive to pain or less sensitive.
  • Negative Reactions to Histamines: Excessive methylation may lower blood histamine levels, increasing sensitivity to histamine-containing foods and causing symptoms like headaches, itching, skin redness, and digestive issues.

Possible Causes of Over-methylation

Over-methylation can be caused by various factors:

  • Genetic Predispositions: Genetic factors (such as MTHFR mutation) can make some individuals more susceptible to over-methylation.
  • High Doses of B Vitamins: Prolonged and unnecessary intake of high doses of methyl B12 or methyl folate can lead to hypermethylation.
  • Excess Methylating Substances: Taking supplements containing methylating components, such as SAMe (S-adenosylmethionine) and methionine, can result in over-methylation.

Medications Affecting Methylation

Medications such as blood sugar regulators, contraceptives and hormonal treatments, anticonvulsants, antidepressants, and cancer treatments can influence methylation, altering its balance depending on its mechanism of action and individual genetic predisposition. These drugs can shift methylation towards either under-methylation or over-methylation, which can significantly impact health and bodily functions.

Laboratory Testing for Methylation

Genetic testing (saliva test) can identify predispositions to methylation disorders, such as mutations in the MTHFR (methylenetetrahydrofolate reductase) gene, providing information on how your genes may influence this process.

However, it is important to understand that genetic predisposition is not the only factor. Many other factors, including lifestyle, medications, diet, and environment, can significantly alter the expression of genetic predisposition and its impact on methylation. Ultimately, phenotypic manifestations and interactions among these factors often play a more significant role than genetic information alone.

Methylation profile testing (blood test) provides a functional assessment of the methylation phenotype by evaluating levels of methionine, cysteine, SAM (S-adenosylmethionine), SAH (S-adenosylhomocysteine), homocysteine, adenosine, and cystathionine in the plasma. It also provides an important “methylation index,” the ratio of SAM to SAH. This test reflects the methylation phenotype, showing how methylation functions in your body.

Factors Affecting Methylation

Regardless of the type of methylation (under-methylation or over-methylation), several factors influence its normalization:

  • Improving Sleep Quality: Lack of sleep disrupts methylation and decreases melatonin production, which is essential for normal deep sleep.
  • Reducing Stress: Prolonged stress accelerates the consumption of methyl groups, leading to their depletion and disruption of methylation, as well as causing energy deficiencies.
  • Reducing Exposure to Harmful Chemicals: Toxins can overload the body, disrupting methylation. Examples of toxins include:
    • Alcohol: Depletes methyl groups and reduces folate metabolism.
    • Tobacco Smoke: Damages DNA and suppresses methylation.
    • Nitrous Oxide (Laughing Gas): Frequent use can cause vitamin B12 deficiency and disrupt methylation.
  • Correcting Digestive System Function:
    • Optimal Stomach Acid Production: Normal stomach acidity is important for absorbing substances necessary for methylation.
    • Antacids: They may reduce acidity and hinder nutrient absorption.
    • Excessive Yeast and Bacterial Growth (SIBO): Disrupts methylation through microbiota imbalance.
  • Reducing Exposure to Chemicals:
    • Bisphenol A (BPA): May increase methylation of certain genes, potentially affecting their expression.
    • Heavy Metals: Can decrease methylation by increasing oxidative stress, which disrupts normal cell function.
    • Pesticides: Their impact on methylation varies depending on the specific substance and its concentration.
    • Medications: Some medications may be outdated or unnecessary. It’s recommended to discuss with your doctor the need to review your medication list to ensure all are still needed.
  • Maintaining Overall Health:
    • Oxidative stress: It damages cells and disrupts methylation. Antioxidants can help reduce oxidative stress, with glutathione being particularly beneficial as a universal intracellular antioxidant.
    • Inflammation: Chronic inflammation increases oxidative stress and disrupts methylation.
    • Infections: Chronic infections can disrupt methylation through inflammatory processes.

Correcting Methylation Through Diet and Supplements

Necessary precursors for the methylation cycle (vitamins and minerals) and related biochemical cycles should be obtained from food or high-quality supplements on a regular basis. Additionally, adjusting methylation speed can be achieved with several supplements, such as:

  • Methyl-Folate and Methyl-B12: May be beneficial for under-methylation.
  • Folic Acid: This can be useful for over-methylation but requires proper dosage and frequency.
  • Niacin (Vitamin B3): Helps slow down methylation in over-methylation and reduce homocysteine levels.
  • Zinc and Magnesium: Support important enzymes involved in methylation.
  • Trimethylglycine (Betaine): Supports methylation and detoxification processes in the liver.
  • Methionine and SAMe: Generally not used for various reasons.

This comprehensive approach will help maintain the balance of methylation in the body.

Conclusion

Methylation is a dynamic process that can change over time due to various factors such as stress, diet, exposure to toxins, or chronic illnesses. Even if a person initially has a normal level of methylation, deviations can occur over time, leading to either over-methylation or under-methylation.

To maintain health and optimal functioning of the body, it is crucial to understand the balance of methylation and its impact on health. Genetic testing can help identify predispositions to methylation disorders, but it is important to also consider the influence of lifestyle, diet, and environmental factors. A comprehensive approach to correcting methylation can significantly improve quality of life and overall health.


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