Methylation and Why it Matters

Methylation is a natural biochemical process that is constantly occurring within the cells of your body. You may have heard recently about the importance of healthy methylation, and why some people have more challenges with this process than others. But just what does methylation do, and why is it important? 

Chemically speaking, methylation is the transfer of one “methyl group”-- a carbon atom and three hydrogen atoms (CH3) -- from one molecule to another. This may not seem like a big deal, but it is the switch that triggers many other important chemical processes in your body. Methylation influences your hormones, your metabolism, your detox processes, and the production of homocysteine in the body. It can affect your brain chemistry, your reproductive health, your immune function, your inflammation response, and even gene expression. Pretty big deal!

Your methylation process is influenced by your nutrition, as well as your genes. Certain key nutrients are needed to activate healthy methylation, particularly the B complex vitamins, as well as magnesium and zinc. With our busy lifestyles and nutrient-depleted foods, it’s easy to run a little short on these nutrients -- especially if you are vegan, since B vitamins are found mostly in animal-based foods. As we get older, it also gets more difficult to absorb certain nutrients from food -- particularly B12, a crucial vitamin for methylation.

But it gets more complicated: In order for your body to use B vitamins to activate methylation, it must first convert those B vitamins into their active form. And thanks to a fairly common genetic variation, not all of us can make this conversion very well. At least 30% of the American population has a variation in the MTHFR gene, which affects the body’s ability to convert folate (B9) into its active form and to break down homocysteine in the body. These people can end up with high levels of homocysteine, a heart health risk, and low levels of important B vitamins.1

Folate is one of the most critical vitamins for healthy methylation. The active form of folate -- 5-MTHF, or methyl folate -- is what turns on the switch that produces SAMe  (S-adenosylmethionine), a universal methyl donor that keeps methylation running smoothly. Without enough SAMe, your body has trouble producing crucial molecules like serotonin, melatonin, norepinephrine, coenzyme Q10, nitric oxide, glutathione, and L-carnitine, which play a major role in your mental health, heart health, healthy aging, and more.2

In short, if you aren’t getting enough B vitamins in your diet, or your body has trouble converting them into active form, your methylation process may be compromised. Taking activated B complex vitamins can help support a healthy methylation process. Methylated B vitamins such as methyl folate (L-5-MTHF), methylcobalamin (B12), and vitamin B6 as pyridoxal-5-phosphate (P-5-P) are already in their active form, which saves your body the extra step of having to convert them before it can use them to support methylation.

Here are just a few examples of the many ways that methylation influences your health, and what can happen when methylation is impaired:

Reproductive Health

Methylation is responsible for making and maintaining healthy DNA, so it’s crucial for both male and female fertility, maintaining a healthy pregnancy, and supporting healthy fetal growth and development. Folate plays a major role in activating the methylation, which is why it’s the number one recommended vitamin during pregnancy. It’s no coincidence that the risk of birth defects doubles for mothers with genetic variants that make it harder to activate and use folate.3 Studies also link MTHFR gene variations with male infertility4 and recurrent miscarriages.5 If you are pregnant or trying to become pregnant, look for a prenatal multivitamin that contains active methyl folate and other methylated B vitamins.

Heart Health

Poor methylation is associated with low levels of B6, B12, and folate, and high levels of homocysteine, an amino acid strongly linked with heart health risks. High homocysteine levels can lead to excess inflammation and oxidative stress, which can damage blood vessels and lead to hardening of the arteries.6 Healthy methylation is also required for the body to produce nitric oxide, which helps blood vessels to relax and expand, and coenzyme Q10, an antioxidant that helps protect blood vessels from oxidative damage. Methylation challenges can lead to poor circulation, putting stress on the heart and increasing the risk of heart health problems.

Mental Health

Methylation is required for the production and breakdown of important neurotransmitters and hormones such as serotonin, dopamine, cortisol, adrenaline, and noradrenaline, which play a major role in regulating your mood and stress response. When methylation is impaired, the body can’t maintain proper balance between stress hormones and relaxed, feel-good hormones, which can lead to mood imbalances. It makes sense that folate deficiency is linked with depression,7 since folate is needed to activate SAMe, the methyl donor for mood-balancing neurotransmitters such as serotonin. Adults with mood imbalances have seen positive improvements in their mental health after taking methylated B vitamins to support healthy methylation.8 

Liver Health

Your liver plays a major role in your detox functions, digestive health, and healthy metabolism, and it relies on healthy methylation to keep those processes running smoothly. Methylation helps ”tag” toxic substances for elimination and then helps the liver convert those toxins into a form that can be safely eliminated from the body. Methylation is also needed to produce phosphatidylcholine, a key component of liver bile, which helps detox the bowels and supports healthy fat metabolism. Poor methylation and resulting lack of choline has been linked with the development of nonalcoholic fatty liver disease.9 

Other Signs You May Need Methylation Support:

Sleep Issues: Healthy methylation is needed to produce serotonin and melatonin, the hormones that govern your sleep/wake cycle. If you’re taking supplemental melatonin to help you fall asleep, you may need to boost your methylation.

Allergies: Healthy methylation is needed to break down histamine, the substance that causes many common allergy symptoms, such as sneezing and itchiness. When excess histamine builds up in the body, it can lead to histamine intolerance, creating allergy-like symptoms.

Hormone Imbalance: The liver relies on healthy methylation for its detox processes, which includes clearing estrogen from the body. Poor methylation can lead to an excess of estrogen in the body, disrupting hormonal balance.

Headaches: Migraine headaches are associated with high homocysteine levels, a symptom of poor methylation.10,11 Those with a MTHFR gene variant are also more likely to have migraines.12 Some studies have shown that taking B vitamins involved in methylation can help reduce headache symptoms.13,14

Methylation Support

Our complete B Complex supplement gives you all 8 of the B vitamins, including thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12), as well as important co-nutrients from the B-complex family, such as choline, inositol, and PABA. We made sure to include crucial methylation vitamins like folate, B12, and B6 in their active, methylated forms, so that they are ready for your body to use, whether or not you have a MTHFR genetic variant. Our plant-based supplement also includes an organic fruit and vegetable blend for whole food nutritional support.

References:

1. Marcin, Ashley. “What You Need to Know about the MTHFR Gene.” Healthline, Sep 2019.

2. Miller, Alan, ND. “What is Methylation and Why Should You Care About It.” Thorne, Sep 2018.

3. Dean L. Methylenetetrahydrofolate Reductase Deficiency. Medical Genetics Summaries. NCBI; Last updated October 27, 2016; https://www.ncbi.nlm.nih.gov/books/NBK66131/. Accessed 5/3/2017.

4.  Liu, K., Zhao, R., Shen, M. et al. Role of genetic mutations in folate-related enzyme genes on Male Infertility. Sci Rep 5, 15548 (2015). https://doi.org/10.1038/srep15548

5. Coulam, C.B., Jeyendran, R.S., Fishel, L.A. and Roussev, R. (2006), Multiple Thrombophilic Gene Mutations Rather than Specific Gene Mutations are Risk Factors for Recurrent Miscarriage. American Journal of Reproductive Immunology, 55: 360-368. doi:10.1111/j.1600-0897.2006.00376.x

6. “Heart Disease and Homocysteine.” WebMD, 2020.

7. Reynolds EH, Carney MW, Toone BK. Methylation and mood. Lancet. 1984 Jul 28;2(8396):196-8. doi: 10.1016/s0140-6736(84)90482-3. PMID: 6146753.

8.  Lewis, John E et al. “The effect of methylated vitamin B complex on depressive and anxiety symptoms and quality of life in adults with depression.” ISRN psychiatry vol. 2013 621453. 21 Jan. 2013, doi:10.1155/2013/621453

9. Mehedint, Mihai G, and Steven H Zeisel. “Choline's role in maintaining liver function: new evidence for epigenetic mechanisms.” Current opinion in clinical nutrition and metabolic care vol. 16,3 (2013): 339-45. doi:10.1097/MCO.0b013e3283600d46

10. Bokhari FA, Shakoori TA, Hassan SA, Qureshi HJ, Qureshi GA. Plasma homocysteine in patients of migraine without aura. J Ayub Med Coll Abbottabad. 2010 Apr-Jun;22(2):52-5. PMID: 21702266.

11. Oterino A, Toriello M, Valle N, Castillo J, Alonso-Arranz A, Bravo Y, Ruiz-Alegria C, Quintela E, Pascual J. The relationship between homocysteine and genes of folate-related enzymes in migraine patients. Headache. 2010 Jan;50(1):99-168. doi: 10.1111/j.1526-4610.2009.01484.x. Epub 2009 Jul 8. PMID: 19619240.

12. Rainero I, Vacca A, Roveta F, Govone F, Gai A, Rubino E. Targeting MTHFR for the treatment of migraines. Expert Opin Ther Targets. 2019 Jan;23(1):29-37. doi: 10.1080/14728222.2019.1549544. Epub 2018 Nov 28. PMID: 30451038.

13. Lea R, Colson N, Quinlan S, Macmillan J, Griffiths L. The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. Pharmacogenet Genomics. 2009 Jun;19(6):422-8. doi: 10.1097/FPC.0b013e32832af5a3. PMID: 19384265.

14. Shaik, Munvar Miya, and Siew Hua Gan. “Vitamin supplementation as possible prophylactic treatment against migraine with aura and menstrual migraine.” BioMed research international vol. 2015 (2015): 469529. doi:10.1155/2015/469529