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  • Written by: Kyla Reda

  • Medically reviewed by: Lara Zakaria PharmD, CNS, IFMCP

Methylation is a biochemical process in the body that affects numerous bodily functions and plays a major role in overall health. When imbalanced, it can also lead to disease. Keep reading to find out how taking a methylation test can help you create personalized treatment plans to support your patients’ long-term health.

What is methylation?

Methylation is a chemical reaction in the body in which a molecule called a methyl group attaches itself to DNA, proteins, or other molecules. National Cancer Institute (n.d.) Not all genes are active all the time, and methylation is the process that either activates or silences them. Each person’s body typically follows a methylation pattern, but if this pattern gets disrupted by genetic predisposition or lifestyle factors such as diet, exercise, smoking, and alcohol intake, the imbalance can negatively impact the way cells operate. This can cause certain diseases to develop. (Phillips 2008)

Methylation imbalance and disease risk

When methylation is imbalanced, cellular function is also disrupted. One of the most significant diseases linked to methylation imbalance is cancer. In healthy cells, methylation suppresses genes that could lead to cancer if left unregulated. However, in cancerous cells, methylation balance disruption can activate oncogenes (genetic mutations that can cause cancer) and silence genes that normally suppress tumors. (Lakshminarasimhan 2016)

DNA methylation imbalance has also been linked to osteoporosis, atherosclerosis (the buildup of plaque on artery walls that can block blood flow), immune diseases, and neurological diseases. In neurological diseases, it can alter brain structure and function. With Alzheimer’s disease specifically, gene silencing caused by methylation can lead to cognitive decline and neural degeneration. (Ehrlich 2019)

Methylation tests can give insights into a patient's biological age, making them a great tool for assessing overall health levels. (Hannum 2012)

Clinical indications for methylation testing

Methylation testing may be helpful for patients who have demonstrated specific symptoms.

Aging

Methylation patterns change with age, and when studied, they can give insight into a patient’s biological age compared to their chronological age, which allows healthcare providers to assess their overall health. (Hannum 2012) Methylation changes and abnormalities have also been associated with age-related diseases like Alzheimer’s disease and type 2 diabetes. (Salameh 2020)

Cancer

One of the main uses of methylation testing is in oncology, as many cancers have specific methylation patterns and abnormalities that can be analyzed for early detection and treatment monitoring. It's common to see hyper- or hypomethylated genes, meaning an abnormal increase or decrease in methylation levels respectively, in patients with breast, colon, and lung cancer. (Baylin 2011)

Cardiovascular diseases

Methylation imbalances can influence the development and progression of certain cardiovascular diseases, playing a role in blood pressure and cardiac function. (Krolevets 2023) They have specifically been associated with cardiomyopathy, coronary artery disease, and inflammation. (Cuadrat 2023)

Psychiatric disorders

Genetic mutations linked with methylation have been associated with major depressive disorder and anxiety. (Dempster 2014) (Emeny 2017) Studies have also shown that methylation imbalance has been found in patients with schizophrenia, although more research is needed to determine whether schizophrenia is the cause or result of these imbalances. (Nishioka 2012)

How methylation tests work

Methylation tests assess the function of the methylation process within a patient’s body, looking at specific genes to better understand their impact on the relevant pathways. Methylation tests usually involve taking a blood or saliva sample for testing.

There are various types of methylation tests that report different markers, so always be sure to communicate with your patient beforehand to discuss the best way to prepare for the test they’re taking. Certain blood tests may require discontinuing specific medications and supplements or fasting overnight prior to taking the test to ensure nothing in their system interferes with the results. Fasting can include avoiding chewing gum, smoking, and drinking anything besides water. (MedlinePlus n.d.)

Once the sample has been collected, follow proper sealing, packaging, and labeling instructions before shipping it to the lab for testing. For example, many tests recommend taking and shipping the test between Mondays and Thursdays to ensure there are no shipping delays.

When the test results return, healthcare providers can gain insights into a patient's overall health needs, prioritize treatment, and create a personalized treatment plan that includes lifestyle changes to optimize methylation.

Interpreting methylation test results

Accurately interpreting methylation test results and knowing what to look for is vital in understanding a patient’s health status and knowing which interventions may help them. Keep reading for information on a few of the most relevant methylation-related genes.

Betaine-homocysteine methyltransferase (BHMT)

BHMT plays a role in the methylation pathway by catalyzing the conversion of homocysteine to methionine using betaine as a methyl donor, a process called demethylation. Variations can impact this pathway, influencing liver health and cellular energy. (Feng 2011) (Teng 2012)

Cystathionine beta-synthase (CBS)

CBS helps convert homocysteine into cystathionine, a precursor to glutathione, which is a crucial antioxidant. Mutations can lead to elevated homocysteine levels, increasing the risk of cardiovascular issues in part related to compromised glutathione production. (Morris 2016)

Catechol-O-methyltransferase (COMT)

COMT is responsible for the breakdown of catecholamines, such as dopamine and epinephrine. (Qayyum 2015) Variants like Val158Met can alter enzyme activity, affecting neurotransmitter metabolism and influencing mood, anxiety, and the stress response. (Antypa 2013)

Methylenetetrahydrofolate reductase (MTHFR)

MTHFR is a crucial gene, as it influences the body’s ability to process folate, converting it into a form that's usable in the methylation cycle. Mutations in MTHFR, such as C677T and A1298C, can affect homocysteine recycling and folate metabolism, which are linked to cardiovascular diseases and other health issues. Elevated homocysteine levels have been associated with an increased risk of numerous issues, including blood clots, pregnancy complications, and cardiovascular disease. (Moll 2015)

Methionine synthase/methionine synthase reductase (MTR/MTRR)

MTR and MTRR are involved in the remethylation of homocysteine to methionine, which is crucial for DNA synthesis and repair. Hypomethylation of these genes can lead to overexpression, disrupting the balance of homocysteine and methionine. On the other hand, hypermethylation of these genes can silence them, leading to elevated homocysteine levels and associated cardiovascular and neurological risks. The specific mutations MTR A2756G and MTRR A66G have been linked to an increased risk of folate deficiency and increased risk of oxidative stress and cardiometabolic disease. (Li 2015)

Beyond these main genes, hypermethylation of the BRCA1 gene has been associated with breast cancer and may indicate the aggressiveness of malignant breast tumors. (Oubaddou 2023) The tumor suppressor gene RASSF1A can be inactivated by methylation imbalances and has been strongly associated with tumor size in breast cancer tissue. (Gupta 2021) Abnormal methylation of the CDKN2A gene has been linked to an increased risk of developing melanoma. (Zocchi 2021) Analyzing genes like these alongside methylation test results could be potentially helpful in early cancer detection and in creating a personalized treatment plan for patients.

When interpreting methylation test results, it’s important to also consider each patient’s medical and family history. For more complex results, it may be helpful to consult a specialist to ensure accurate interpretation and optimal treatment strategies.

Dietary supplements may be a great way to ensure you're getting all the necessary nutrients to support healthy methylation.

Benefits of methylation testing for overall health

In conclusion, methylation is an important process in the body that can negatively affect overall health levels when altered or imbalanced. Taking a methylation test can help providers assess methylation function in patients for early disease detection and overall health status. Test results can help you personalize treatment plans for each patient, depending on their genetic needs.

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About the contributors

Kyla Reda

Health and Medical Writer

Kyla graduated from Carleton University with a Bachelor’s degree in English Literature and History, and she volunteers as a blog writer and editor for the Ottawa Design Club in her spare time. She is passionate about wellness and sustainability.

Lara Zakaria , PharmD, MS, CDN, CNS, IFMCP

Fullscript Medical Advisor

Dr. Lara Zakaria is a Pharmacist, Nutritionist, and professor specializing in Functional Medicine and Personalized Nutrition. In addition to running a clinical practice focused on providing patients with sustainable solutions that address chronic disease, she also spends her time teaching and mentoring clinicians interested in implementing nutrition and food as medicine principles into practice.

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