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SAMe breaks down into homocysteine where it then relies on the rest of the methylation cycle to turn it back into SAMe. For some people that is a problem. High homocysteine causes things like heart attack and stroke and can be an indication of methyl cycle problems (esp in those not taking SAMe). That is why many suggest to take folic acid and b12 with it, but that is not going to work for everyone, not everyone can convert those vitamins into their active forms, that is what the 23andme test is all about.