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While this methylation reaction was historically considered a relatively minor metabolic pathway for nicotinamide clearance, research over the past decade has revealed that NNMT plays a surprisingly important and previously underappreciated role in cellular energy metabolism, NAD+ homeostasis, adipocyte biology, and whole-body metabolic regulation

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If reticulocytes have not increased after treatment or if reticulocyte counts do not continue at least twice normal as long as the hematocrit is less than 35%, diagnosis or treatment should be reevaluated