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2024 (PMID: 38969654) : Aged mice tolerated NNMTi treatment without reported adverse effects No apparent toxicity in combination with exercise Limitations of Animal Safety Data# The apparent safety in mouse studies should not be interpreted as evidence of human safety: Treatment durations were short (11 days in the obesity study) Mice were monitored for gross adverse effects only, not subtle metabolic or organ-specific toxicity No formal toxicology studies (single-dose, repeat-dose, reproductive, carcinogenicity) have been published Mouse metabolism differs substantially from human metabolism Subcutaneous injection route in studies differs from oral route in commercial products Theoretical Safety Concerns# Based on the biological role of NNMT, several theoretical concerns warrant consideration: Methylation Balance# NNMT consumes SAM (S-adenosylmethionine) as a methyl donor