Did you know that methylation plays a role in facilitating detoxification (especially in the liver), is important for proper functioning of the hypothalamic-pituitary-adrenal (HPA) axis, and helps determine which genes are expressed in your body? Methylation is a topic of great interest in the health care world today, as the addition of a methyl group is vital to a wide variety of biological processes.
A variety of factors including stress, nutritional deficits, certain diseases, and genetics can contribute to insufficient methylation. Poor methylation can result in a reduced ability of the body to make monoamine neurotransmitters and to remove toxins and metabolic waste. This can lead to a wide variety of symptoms including low mood, anxiousness, sleep issues, fatigue, and decreased cognition. Regaining appropriate neurotransmitter synthesis by supporting methylation pathways can lead to increased health and the improvement of symptoms.
Let’s take a closer look at methylation processes in our body.
Methylation is important for neurotransmitter formation
Methylation is critical for the synthesis of all monoamine neurotransmitters as well as histamine. For example, the enzyme that converts norepinephrine to epinephrine, phenylethanolamine N-methyltransferase, requires SAMe as a cofactor for activation. The folate and biopterin (BH4) cycles (Figure 1) help ensure adequate monoamine neurotransmitter production. Biopterin is necessary for the conversion of tryptophan to 5-hydroxytryptophan (5-HTP), phenylalanine to tyrosine, and tyrosine to L-DOPA (L-3,4-dihydroxyphenylalanine).
Figure 1. The methionine, folate, and biopterin cycles function coordinately to facilitate the production of methyl groups for key biomolecules and to drive the biosynthesis of a variety of neurotransmitters. Left: the methionine cycle is vital to the overall process of methylation. The derivative of methionine, SAMe, serves as the main methyl donor in the methylation pathways. The methionine cycle also facilitates the synthesis of homocysteine, which is an intermediate int he production of taurine and glutathione. Center: the folate cycle converts folate into 5-MTHF by utilizing MS, vitamin B12, as well as MTHFR. Right: the bipterin cycle also utilizes MTHFR as a reaction enzyme. BH4 is a cofactor involved in the production of the catecholamine neurotransmitters and serotonin.
Epigenetics affect methylation
Epigenetics is the study of heritable changes that occur without a change in the DNA sequence. Waterland and Jirtle (2003) performed a study on agouti mice; mice that carry the agouti gene are ravenous, yellow, and prone to cancer and diabetes. The study found that when the diet of the pregnant agouti mothers was supplemented with methyl donors (folic acid, vitamin B12, choline, and betaine) the deleterious agouti gene was dimmed in the offspring. This made the offspring slender and mousy brown without their parents’ susceptibility to cancer and diabetes.
Oxidative stress affects methylation
A study by Panayiotidis and colleagues (2009) found that low and moderate levels of oxidative stress significantly decreased levels of SAMe in lung epithelial cells. However, when oxidative stress was severe, concentrations of SAMe were increased, despite severe methionine depletion. The researchers concluded that the high levels of SAMe released were probably an adaptive response to increased oxidative stress.
While each of these points highlights an aspect of methylation in health, the overall theme is that methylation is vital to a wide variety of biological processes. Without proper methylation, there can be impacts on neurotransmitter synthesis, metabolic activity, and gene expression. Insufficient methylation can also lead to a wide variety of symptoms such as low mood, anxiousness, sleep issues, fatigue, and decreased cognition. Supporting healthy neurotransmitter synthesis with methyl donors can lead to increased overall health as well as the improvement of symptoms.
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Part of this blog post was based off the white paper “Methylation: Fundamental to a Healthy Nervous System”