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Methylation cycle hypothesis
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===Yasko's Protocol=== The Yasko protocol looks at two different pathways of the methylation cycle, which she calls the '''long route''' and the '''short cut'''. The short cut utilizes [[betaine homocysteine methyltransferase|BHMT]], while the long route is via [[methionine synthase gene|MTR]]/MTRR and [[Cobalamin|Vitamin B12]] (Yasko, 2013).<ref name="Yasko_2013" /> Yaskoโs protocol has undergone a number of adaptations over the years. The information below refers to her 2013 Simplified Road Map to Health.<ref name="Yasko_2013" /> The Yasko protocol views methylation cycle support as a six-step process: #Regulate [[glutamate]] and [[GABA]] #*Since a high glutamate: [[GABA]] ratio can be hyperexcitatory, this is the number one priority in Yasko's version of the protocol. #Support the short cut pathway to help restore the methylation pathways without producing too many detoxification symptoms #Regulate [[lithium]] levels #*Since lithium is involved in B12 transport, lithium balance is important to the methylation cycle. Low levels of lithium in the blood or high amounts excreted the urine may require lithium supplementation. #Determine which kind of B12 is most absorbable based off of [[Catechol-O-methyltransferase|COMT]] and [[vitamin D receptor|VDR]] SNP status #Support the Long Route pathway utilizing folate or [[5-methyltetrahydrofolate|5-methyl-THF]] (5-MTHF), for [[methyltetrahydrofolate|MTHFR]] mutations #Customized support #*Yasko goes on to recommend a variety of different supplements depending on the patients' SNP status for COMT, VDR, MAO A, [[Acyl-coenzyme A cholesterol acyltransferase|ACAT]], MTHF, MTR, MTRR, BHMT, [[S-adenosylhomocysteine|AHCY]], CBS, [[Sulfite oxidase|SUOX]], [[Serine hydroxymethyltransferase|SHMT]], and [[Nitric oxide synthase|NOS]] genes.<ref name="Yasko_2013" />
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