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For 5-amino-1MQ specifically: Preclinical studies have not prominently described heart rate elevation as a dominant signal The mechanism (NNMT inhibition, NAD+ preservation) does not have the same direct cardiac implications as nuclear receptor agonism Human cardiovascular data at clinically relevant exposures are limited For physicians, the current evidence base does not support a major cardiovascular safety flag, but the limited human dataset means confident statements are premature

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(PubMed) Smith AD, Refsum H

9-11 One of the RICE study objectives was to develop an IC/BPS case definition for use in epidemiological studies that had known sensitivity and specificity for use in epidemiological studies