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SAMe is biochemically produced through the folate-methionine cycle (see Figure 1), requiring many nutrients, including vitamin B12 and the healthy conversion of folic acid to 5-methyltetrahydrofolate (Guildford, n.d.)

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Future trials should also measure important outcomes such as the clinical signs and symptoms of vitamin B 12 deficiency, health related-quality of life, socioeconomic effects, and report adverse events adequately, preferably in a primary care setting. Clinical practice guidelines British Columbia Medical Services Commission (MSC)