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Understanding Methylation: Risks, Genes, and Medications

Methylation is a process in the body that controls the replication of DNA, the aging process of each individual cell, and ultimately can play a role in the development, or lack thereof, of chronic disease.

Understanding Methylation: Risks, Genes, and Medications

While it may sound like a big word, methylation is a process your body undertakes trillions of times in a single second.

Methylation is absolutely essential for every single cell in your body to function. It's used to control the replication of DNA, the growth of a brand new embryo, as well as the aging process of each individual cell. It also affects your bloodstream, with improper methylation leading to high homocysteine levels, too-large red blood cells, and possibly anemia.

When you do not have the ability to methylate properly within cells, over time it can lead to conditions such as heart disease, dementia, depression, migraines with aura and menstrual migraines, as well as many different types of cancer [Shaik].

And worst of all, a deficiency in the nutrients that provide methyl groups (such as folate) in a woman who is pregnant can have devastating effects, such as early miscarriage and the development of birth defects, such as spina bifida [Cordero].

Nutrients that provide methyl groups – which are made up of just a single carbon molecule with hydrogen molecules surrounding it –include vitamin B12, folate, vitamin B6, choline, and the amino acids methionine and betaine. These nutrients all provide the methyl groups that your body uses to regulate DNA processes. These methyl groups are the stop and go signals that are used to turn genes on and off [Waterland].

If your dietary intake of these nutrients is low, especially for an extended period of time, then your risk of chronic diseases can skyrocket.

Foods that contain methylation nutrients are the same foods that contain B-vitamins, such as leafy green vegetables, fruits, whole grains, beans, peas, lentils, sunflower seeds, nuts and animal foods like egg yolk, chicken, turkey, fish, beef, pork, lamb, and liver.

How All of this Relates to Disease Risk

Methylation is a topic that is probably most well-researched as it relates to cancer, because when researchers change which regions of DNA are "methylated" then they can stop the growth and reproduction of cancer cells. By changing which parts of DNA are methylated, researchers can 'turn off' cancer genes and 'turn on' cellular repairing genes [Chango].

Individuals who do not consume enough leafy greens, fruit, and whole grains may not be getting enough methylating nutrients – like Vitamin b12, folate, vitamin B6, choline, and the amino acids methionine and betaine - which puts those individuals at an increased risk for developing certain chronic diseases like heart disease, cancer, and dementia.

Egg yolks, meat, liver, and fish are primary sources of Vitamin B12, and so long-term vegetarian and vegan diets might lead to depletion of this vital nutrient for methylation. People who choose to consume a vegetarian or vegan diet for an extended period of time need to ensure they supplement with Vitamin B12 in order to maintain a healthy methylation status.

Betaine is a methyl donor that can protect against the non-alcoholic fatty liver disease (NAFLD) that results from a eating a high fat diet [Zhang]. Betaine and choline are two methylators which can help ensure your liver does not develop the damaging inflammation that can lead to permanent scarring of the liver from long-term non-alcoholic fatty liver disease.

Habits and Medications that Affect Methylation

Smoking can decrease your ability to achieve optimal methylation because carbon monoxide from cigarettes can inactivate vitamin B6. Certain medications like acid blockers, oral contraceptives, HCTZ for high blood pressure, and Dilantin for seizures can all influence your levels of B vitamins. Methotrexate, which is given to treat some types of cancer, is a folate-blocker, which can significantly alter your body's methylation ability.

Genetics Can Affect Methylation, too

Genetics can play a huge role in your ability to properly methylate, as approximately 40% of people have a genetic variation in folate metabolism, while other individuals are genetically predisposed to higher homocysteine levels. Both of these genetic variations can result in improper methylation in the body [Castro].

It's relatively easy for your doctor to test your methylation status, by assessing a few blood parameters, including:

1. Homocysteine level – to assess your ability to convert homocysteine to the less-harmful amino acids cysteine and methionine.

2. Methylmalonic acid level – this assesses your Vitamin B12 status

3. Complete blood count – to ascertain if you have too-large red blood cells, or anemia.

It's also important to remember that taking extra doses or getting too much methylation in your diet is not a good idea. Excessive folate intake, for example, may increase your risk for developing colon cancer. Eating a balanced diet that contains 4-5 servings of vegetables and fruits, as well as plenty of lean proteins and healthy fat will help ensure you have a healthy methylation status in your body on a daily basis.


Shaik MM, Gan SH. Vitamin Supplementation as Possible Prophylactic Treatment against Migraine with Aura and Menstrual Migraine. Biomed Res Int. 2015;2015:469529. Epub 2015 Feb 28.

Cordero AM, Crider KS, Rogers LM, Cannon MJ, Berry RJ. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: world health organization guidelines. MMWR Morb Mortal Wkly Rep. 2015 Apr 24;64(15):421-3.

Chango, A, Pogribny, IP. Considering Maternal Dietary Modulators for Epigenetic Regulation and Programming of the Fetal Epigenome. Review. Nutrients 2015, 7(4), 2748-2770; doi:10.3390/nu7042748.

Waterland, R.A. Assessing the effects of high methionine intake on DNA methylation. J. Nutr. 2006, 136, 1706S–1710S. R Castro, I Rivera, P Ravasco, M E Camilo, C Jakobs, H J Blom, I T de Almeida. 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T and 1298A→C mutations are associated with DNA hypomethylation. J Med Genet 2004;41:454-458 doi:10.1136/jmg.2003.017244.

Zhang W1, Wang LW, Wang LK, Li X, Zhang H, Luo LP, Song JC, Gong ZJ. Betaine protects against high-fat-diet-induced liver injury by inhibition of high-mobility group box 1 and Toll-like receptor 4 expression in rats. Dig Dis Sci. 2013 Nov;58(11):3198-206. doi: 10.1007/s10620-013-2775-x. Epub 2013 Jul 17.

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Written By Sarah Asay, RDN. Published on October 27, 2015. Updated on August 06, 2019.


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