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Here is what a typical 6-week drug holiday timeline looks like based on pharmacokinetic data and clinical reports

When SAMe is low, the remethylation of homocysteine to methionine is prioritized in the cell (instead of the transsulfuration pathway).[ref] Drains on methyl groups: About 40% of methyl groups are used for creatine synthesis, so when creatine levels are higher, it can reduce the need for methyl groups