Yoshino et al. have reported that nicotinamide mononucleotide (NMN) increases muscle insulin sensitivity in prediabetic women. However, the 13 women who received NMN had hepatic lipid content of 6.3 ± 1.2%, whereas the 12 in the placebo group had 14.8 ± 2.0% (P = 0.003). Given that a target of NMN is liver fat clearance, this was not an effectively randomized trial....It is foundational for clinical conclusions that randomization compares an intervention to placebo in people of equal metabolic health....Those that received placebo had 2.35 times the level of liver fat as those assigned to NMN (P = 0.003). This between-group, treatment-unrelated difference was greater in effect size and in statistical significance than any physiological effect of NMN in the study....The unfortunate assortment of much more fatty liver to the placebo group suggests that one cannot reasonably expect that the results reported would be reproduced in an effectively randomized trial.