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Why is the Methylation Cycle Important? http://www.dramyyasko.com/our-unique-approach/methylation-cycle/ The Methylation Cycle is a biochemical pathway that manages or contributes to a wide range of crucial bodily functions, including: Detoxification Immune function Maintaining DNA Energy production Mood balancing Controlling inflammation All these processes help the body respond to environmental stressors, to detoxify, and to adapt and rebuild. That’s why lowered methylation function may contribute to many, major chronic conditions, including: Cardiovascular Disease Cancer Diabetes Adult neurological conditions Autism and other spectrum disorders Chronic Fatigue Syndrome Alzheimer’s disease Miscarriages, fertility, and problems in pregnancy Allergies, immune system, and digestive problems Mood and psychiatric disorders Aging Methylation is involved in almost every bodily biochemical reaction, and occurs billions of times every second in our cells. That’s why figuring out where the cycle can better perform its tasks contributes to health improvement and reduce symptoms. What is DNA Methylation? http://www.news-medical.net/health/What-is-DNA-Methylation.aspx DNA methylation is vital to healthy growth and development and is linked to various processes such as genomic imprinting, carcinogenesis and the suppression of repetitive elements. DNA methylation also enables the expression of retroviral genes to be suppressed, along with other potentially dangerous sequences of DNA that have entered and may damage the host. Another important purpose of DNA methylation is the formation of the chromatin structure, which enables a single cell to grow into a complex multicellular organism made up of different tissues and organs. 1 In addition, DNA methylation plays an important part in the development of cancer and is a key regulator of gene transcription. Studies have shown that genes with a promoter region that contains a high concentration of 5methylcytosine are transcriptionally silent. Aberrant methylation of DNA has been associated with an increased rate of malignancy. DNA hypermethylation is linked to the activation of genes and DNA hypomethylation has been associated with the development of cancer through various mechanisms. Nutrition and Depression: Nutrition, Methylation, and Depression, Part 2 https://www.psychologytoday.com/blog/health-matters/201011/nutrition-anddepression-nutrition-methylation-and-depression-part-2 Nutritional support for the methylation cycle is another area in which nutrition plays a critical role. The methylation cycle is essential for mental and physical health. It is critical to the metabolism of catecholamines in the synapse via an enzyme (COMT) as well as the synthesis of ‘depression-relevant' compounds such as melatonin, myelin basic protein, carnitine, CoQ10, etc. Methylation is required to inactivate histamine. Basic nutrients necessary for normal function of this cycle include B12, glycine, serine, activated B6, selenium, cysteine, methionine and folic acid . Several studies have shown the utility of folic acid as an adjunct to medication use for depression. In one study (10) the average HAM-D (a standard measure of depression) score decreased from 27 to 7 in those receiving P (fluoxetine) plus F (folic acid), and from 27 to 12 in those on P plus Pl (placebo (p<0.001). Recovery (full) was attained in 73% of the women receiving P +F, but only 47% of those on P + Pl (p<0.06). A variety of genetic polymorphisms (single nucleotide polymorphisms or SNP's) exist, which can alter function the methylation cycle. One important SNP is the MTHFR SNP, which when present in both copies of a persons genes, indicates the need for a special form of folic acid: L-methyl folate (which crosses the blood brain barrier). This gene acts by reducing the function of the methylation cycle-specifically reducing the conversion of 5,10 methyl-tetrahydrofolate to 5-methyltetrahydrofolate. This reduces the synthesis of methionine (needed for the COMT enzyme, which requires sadenosylmethionine to function), results in increased homocysteine (a marker of methylation status), and altered (decreased or increased) DNA methylation, leaving certain genes turned on or off, when they should not be. In fact, in a review of 1280 psychiatric cases and 10,429 controls, the odds of having depression was 36% greater if a person had two copies of the MTHFR SNP (8). This means low levels of available folic acid, in this case for genetic reasons, but in other cases due to medications or diet, increases one's risk for depression by 36%. 2 In some fascinating research in the area of epigenetics (epigenetics describes the part of the genome that is modified by experience as well as methylation, acetylation, ubiquitination, phosphorylation) suggests that genes that are turned on or off by one's environment, one's diet, by stress, or by one's experience are transmitted to subsequent generations. One author suggests that the biological underpinnings of bipolar affective disorder are not primarily genetic, but are epigenetic (10). Another author (11) presents data that suggests that the fact that identical twins are not fully concordant for depression may have to do with reduced methylation of the COMT gene may be associated with bipolar disorder and schizophrenia, as only 26-29% of these patients, when compared with controls showed normal methylation of the COMT gene in the pre-frontal cortex. The environmental exposures at key developmental phases may result in long standing neuro-biological changes leading to pathology. Direct evidence is limited at this point. One of the critical ingredients for the methylation cycle is B12. B12 plays a vital role in the metabolism of fatty acids essential for the maintenance of myelin in the brain. Absorption of B12 requires the secretion from the cells lining the stomach of a glycoprotein, known as intrinsic factor. The B12intrinsic factor complex is then absorbed in the ileum (part of the small intestine) in the presence of calcium. Many physicians think that to assess B12 one must measure B12 levels. However, it is well-established that B12 levels are not a sensitive marker for adequacy of B12 function (17). Some people suggest that measuring methylmalonic acid (MMA) is more sensitive. But at least one study (18) shows that B12 function has a minimal effect on levels of MMA. Assessment of B12 status in practice involves measurement of a number of parameters, including the physical exam (depression, impaired balance, panic, neuropathy) the size of red blood cells (MCV), Hematocrit, homocysteine, and functional immunoassays. 3