Food, Nutrition, and the Methylation Balancing Act

Methylation has garnered much attention in recent years, especially now that health professionals are beginning to understand the clinical significance of methylation and have the ability to test for single nucleotide polymorphisms (SNPs) that mediate DNA methylation pathways and gene expression. Methylation is an ever-changing, dynamic process that responds to nutritional and environmental influences, also known as epigenetics, which is why diet and nutrition is so important to healthy methylation balance and optimal gene expression.

Methylation Basics

Methylation is the transfer of one carbon methyl group from one molecule to another that either activates or deactivates that molecule. It is the process by which our epigenetics regulate gene expression. This single carbon metabolic process is mediated by enzymes such as methyltetrahydrofolate reductase (MTHFR), catechol-O-methyltransferase (COMT), and cystathione beta-synthase (CBS). Each person’s genetic fingerprint in the form of single nucleotide polymorphisms (SNPs) dictates how efficiently these enzymes work. Methylation is greatly dependent on the presence of certain nutrients that act as co-factors to keep the process moving smoothly. These methylation nutrients include choline, betaine, methionine, folate, vitamins B₁₂ and B₆, as well as certain minerals like magnesium, zinc and sulfur.₁

Methylation is critical to a multitude of metabolic processes including:

• Cell division, DNA and RNA synthesis
• Detoxification and hormone biotransformation
• Neurotransmitter biosynthesis
• CNS development and neural tube formation
• Histamine clearance
• Phospholipid synthesis
• Myelination of peripheral nerves

Methylation and Nutrient Status

Particular attention has been focused on folate and MTHFR and other potential gene variants that influence folate metabolism and methylation. In those with MTHFR gene variants, folate and folic acid metabolism is inhibited in such that the vitamin is not efficiently reduced to its active form, 5-methyl-tetrahydrofolate (5-MTHF). In such cases, methylated b-vitamins, including naturally derived 5-MTHF are often recommended and synthetic folic acid is specifically avoided. This is to prevent a possible build-up of unmetabolized folic acid, which is potentially genotoxic and may pose health risks, though studies have been mixed. While methyl-folate and methylated B₁₂ supplements are commonly used in high doses, long term studies for the safety and efficacy of this practice is lacking.₁

While it’s important to replenish suboptimal levels of B vitamins and other nutrients from methylation foods to support healthy methylation, there have been some concerns about the potential negative effects of overmethylation, or “hypermethylation.”_2,3 These concerns paired with the clinical observation that some people do not tolerate methyl donor supplementation well, lead some to suggest that the safest way to support balanced methylation may be through the diet. Because methylation is dependent on nutrient co-factors, one’s diet can support proper methylation by providing plenty of these essential nutrients that act as methyl donors, or fuel for methylation pathways.

Foods to Support Methylation

Diets naturally high in methylation foods can be used to support methylation either with or without supplementation. In addition to the vitamins and minerals present in food, certain phytonutrients have epigenetic activity that supports methylation balance. It is worth noting that pesticides put a strain on methylation pathways, another important reason to support organic practices.

Many phytonutrients are considered methylation adaptogens, as they have been found to influence DNA methyl transferases (DNMT). DNMT are the enzymes that carry out methylation, and are therefore the transcribers of epigenetic influences on gene expression. DMNT regulators include curcumin, ellagic acid, lycopene, quercetin, resveratrol, rosmarinic acid, and sulforaphane.₅

A methylation balancing dietary approach underscores the benefits to obtaining most of one’s nutrient needs through food, as there are other compounds within food that work synergistically with one another to support human health. Methylation is a key pathway by which a healthy diet with methylation foods can influence optimal gene expression, thereby promoting overall health and wellness.

References

1. Fitzgerald, K, Hodges R, The Methylation Diet & Lifestyle for healthy methylation and optimal gene expression. Presented at Maryland University of Integrative Health, June 2017.
2. Smith AD¹, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr. 2008 Mar;87(3):517-33.
3. Rees JR, Morris CB, Peacock JL Unmetabolized Folic Acid, Tetrahydrofolate, and Colorectal Adenoma Risk. Cancer Prev Res (Phila). 2017 Aug;10(8):451-458.
4. Fitzgerald, K, Hodges R, The Methylation Diet & Lifestyle for healthy methylation and optimal gene expression. Presented at Maryland University of Integrative Health, June 2017.
5. Yang H¹, Hwang I, Kim S, et al. Preventive effects of Lentinus edodes on homocysteinemia in mice. Exp Ther Med. 2013 Aug;6(2):465-468.
6. Fumio Watanabe,^* Yukinori Yabuta, Tomohiro Bito, and  Fei Teng Vitamin B₁₂-Containing Plant Food Sources for Vegetarians. Nutrients. 2014 May; 6(5): 1861–1873.
7. http://nutritiondata.self.com/facts/vegetables-and-vegetable-products/2488/2
8. Fitzgerald, K, Hodges R, The Methylation Diet & Lifestyle for healthy methylation and optimal gene expression. Presented at Maryland University of Integrative Health, June 2017.
9. Morris J, Moseley VR, Cabang AB. Reduction in promotor methylation utilizing EGCG (epigallocatechin-3-gallate) restores RXRα expression in human colon cancer cells. Oncotarget. 2016 Jun 7;7(23):35313-26.