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In a long-term randomized, double-blind, placebo-controlled study among sufferers of cerebrovascular accidents at high risk of depression, daily supplementation with 2 mg of folic acid, 25 mg of vitamin B6, and 500 g vitamin B 12 significantly lowered the risk of major depressive episodes during a seven-year follow-up period compared to placebo (111)

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Gradual dose reduction rather than abrupt cessation may improve weight maintenance, though evidence is limited

These studies have contributed to understanding the potential role of NNMT in metabolic disorders