Methylation Pathways

Chemical Modification of DNA Based On Your Environment

What is Methylation?

The human DNA (deoxyribonucleic acid) is the ‘instruction manual’ containing information needed for the production of proteins in the body. Each portion of the DNA that contains the information needed to produce a particular protein is called a gene.

Nucleotide bases are essential components of the DNA and they include cytosine, adenine, guanine, and thymine. The DNA can undergo various changes that ultimately impact cell function such as point mutation, insertion, or deletion.

DNA methylation is a chemical modification of the DNA in which methyl groups are inserted into the DNA. This insertion occurs at the 5th carbon position of cytosine, forming 5-Methyl cytosine. The process is induced by a family of enzymes called DNA methyltransferases. This modification of the DNA can be passed from parents to offspring.

Why is methylation important?

  • It has a significant effect on gene expression and can cause the inactivation of genes in the body, a phenomenon known as ‘gene silencing.
  • It helps maintain the integrity and stability of the DNA.
  • It is required for standard cell multiplication.
  • It helps the body to achieve detoxification of harmful chemicals.
  • It protects the immune system.
  • It helps to improve the function of hormones in the body.
  • It is crucial for the normal functioning of the brain cells.

Why is methylation essential for detoxification?

The body is constantly exposed to a myriad of toxic substances present in food, water, inhaled air, body care products et cetera. The liver is saddled with the responsibility of removing these substances via a process called detoxification.

Detoxification is a crucial process required for balanced emotional and physical well-being. Inefficient detoxification has been linked with diseases such as cancer, Parkinson’s disease, fibromyalgia, and chronic fatigue syndrome.

The by-products released from the methylation reaction include S-adenosyl methionine and homocysteine. Homocysteine is further converted to cysteine, which combines with the amino acids - glutamate and glycine to form glutathione.

Glutathione is a potent antioxidant that helps to remove free radicals, toxins, and carcinogens from the body. The role it plays in the detoxification process can not be over-emphasized.

Glutathione detoxifies endogenous and exogenous compounds by enhancing their excretion first from the cells and then from the body. It also directly neutralizes free radicals that can damage cell membranes. High levels of glutathione in the body have been linked with longevity and well-being.

Since methylation provides one of the substrates needed for the production of this essential detoxicant, it is highly paramount for detoxification.

What are the causes of abnormal methylation?

  1. Diet: Studies have shown that diet plays a key role in the process of methylation in the body. Methyl-donor diets are foods rich in folate and B vitamins. They serve as sources for the methyl group inserted into the DNA. Consuming foods low in these nutrients can impair the methylation process in the body.
  2. Genetics: Recent molecular research has revealed that mutations in the gene responsible for folate metabolism – the MTHFR gene can have detrimental effects on DNA methylation.
  3. Aging: As people grow older, their genomes undergo a lot of changes and disordered methylation could occur.
  4. Inflammation: Studies have shown an association between longstanding inflammatory diseases such as ulcerative colitis or hepatitis and exaggerated methylation in the body.
  5. Smoking: Toxins in cigarette smoke can cause lower vitamin B12 concentrations in the body and this has a negative ripple effect on DNA methylation.

What are the diseases linked with abnormal methylation?

Aberrant methylation in the body could either be hypomethylation or hypermethylation. Both forms are harmful and have been associated with several diseases.

An abnormal methylation process is found in almost all forms of cancer. Many mechanisms by which it occurs have been proposed. It has been proposed that disruption of methylation can cause the inactivation of genes that protect a person from cancer, such as tumor suppressor genes, leading to cancer. Other studies have also shown that DNA hypomethylation can result in the instability of the chromosomes, leading to cancer.

Other diseases associated with defective methylation include:

  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Congenital heart disease
  • Multiple sclerosis
  • Hyperlipidemia
  • Diabetes
  • Parkinson’s disease
  • Schizophrenia
  • Liver disease

How can you improve methylation in your body?

  1. Dietary modification: Eating diets rich in folate, betaine, and vitamins B2, B6, and B12 can improve methylation in the body. These nutrients provide the much-needed methyl groups for the methylation reaction to occur. Some methyl-donor-rich foods include fish, cauliflower, broccoli, beans, and spinach.
  2. Zinc supplementation: Research has shown that zinc deficiency leads to DNA hypomethylation. Thus, zinc supplementation can help to improve methylation in the body.
  3. Smoking cessation: Smoking antagonizes the effect of many nutrients in the body, including the B vitamins. It also releases numerous toxins into the body that can trigger a chronic inflammatory state, thereby impairing methylation. Quitting smoking can help correct defective methylation.
  4. Exercise: Exercise has been shown to significantly impact DNA methylation in many body cells, such as heart cells and sperm cells. Regular exercise can improve methylation and slow down the aging process.

Take home points

  • Methylation is a vital body process that is needed for maintaining cellular functions.
  • Glutathione, a powerful antioxidant required for detoxification, is synthesized using products of methylation.
  • Diets poor in vitamins and folate can impede proper methylation by the body.
  • Adequate nutritional intake and exercise can improve methylation in the body.
Methylation mthfr genetic mutation
MTHFR Is A Common Gene Mutation That Impacts Methylation

Methylation is an important biochemical process that occurs in every cell and organ of your body.

Methylation is the process of taking one carbon molecule and three hydrogen molecules, known as a methyl group, and applying it to every bodily function such as thinking, repairing DNA, turning on and off genes, fighting infections, how the body responds to environmental stressors, detoxification, mental well-being, and so much more.

More than two-thirds of those diagnosed with a behavioral problem or mental health disorder have a methylation imbalance or defect. A person’s methyl status is established during the first few months of in-utero development and tends to persist throughout life. Hence, the importance of a healthy Mom and Dad prior to conception.

Genetic testing can provide valuable information about how to support your biochemical pathways to facilitate optimal health. An inexpensive test through 23andme assesses your genetic profile, deficiencies or excesses in methylation, and other related pathways. Test results from 23andme must then be uploaded to one of the various websites available to translate your raw genetic data and SNPs.

Homocysteine and MCV are simple blood tests that can assess methylation functionality. Homocysteine is an amino acid byproduct of methionine metabolism. Increased homocysteine is like ground up glass—it’s a damaging molecule that interferes with methylation. A high homocysteine >8 and an increased MCV >90 are indicators of methylation dysfunction or a vitamin B12 or folate deficiency. Homocysteine tends to be inversely associated with circulating levels of folate and B12.

Epigenetics is what happens to the gene based on how it’s influenced. We have tremendous power over our genes and how they’re expressed or not expressed such as . . .

• physical choices (diet, exercise, clean water, hydration, sleep, daily sunlight, taking nutrients to support and balance body chemistry)
• biochemical impacts (anything you cannot see but affects you internally such as toxic metals, pesticides, hidden infections, EMFs, dirty electricity, air pollution, gratitude, your thoughts, perception, and attitude)
• relationships, spiritual, emotional, environmental, and lifestyle choices

First things first! Before factoring in methylation issues, MTHFR defects, and genetic test results, it’s essential to look at an individual’s diet, lifestyle, toxic burden, gut health, proper breathing techniques, sunlight exposure, balanced circadian rhythms, and environment first. Exhaust these fundamentals first before digging deeper into genetics and methylation.

If a person lives or works in a moldy environment, has a heavy metal body burden, hidden dental infections or cavitations, underlying viral, yeast, parasite, or bacterial infections, blood sugar imbalances, drinks a 12-pack of beer every day, or works with or are exposed to toxic chemicals, it will be challenging to address their methylation issues adequately.

It’s essential to start with the basics first– balance blood sugar, get rid of infections, mycotoxins, and toxic heavy metals, heal the gut, optimize the microbiome, correct nutrient deficiencies, create healthy outlets to deal with inevitable stressors, sleep well, balance our natural circadian rhythm, get a daily dose of sunlight, develop healthy relationships with others, God and ourselves, and eat nutrient-dense organic foods. Only then can the body begin to heal naturally.

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References

Jin Z, Liu Y. DNA methylation in human diseases. Genes Dis. 2018 Jan 31;5(1):1-8. doi: 10.1016/j.gendis.2018.01.002.

Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013 Jan;38(1):23-38. doi: 10.1038/npp.2012.112.

Nishiyama A, Nakanishi M. Navigating the DNA methylation landscape of cancer. Trends Genet. 2021 Nov;37(11):1012-1027. doi: 10.1016/j.tig.2021.05.002.

Sellami M, Bragazzi N, Prince MS, Denham J, Elrayess M. Regular, Intense Exercise Training as a Healthy Aging Lifestyle Strategy: Preventing DNA Damage, Telomere Shortening and Adverse DNA Methylation Changes Over a Lifetime. Front Genet. 2021 Aug 6;12:652497. doi: 10.3389/fgene.2021.652497.

Suzuki H., Toyota M., Sato H., Sonoda T., Sakauchi F., Mori M. Roles and Causes of Abnormal DNA Methylation in Gastrointestinal Cancers. Asian Pacific Journal of Cancer Prevention, 2006;7: 177-185.

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