Supplementation with 3,3-dimethyl-1-butanol (DMB) mitigates Western-style diet (WD)-induced frailty and impaired grip strength. In mice fed standard rodent chow (SC) or WD for 5 mo and given either normal drinking water (control; SC-C, WD-C) or water supplemented with 1% DMB (SC-DMB, WD-DMB) for the last 8–10 wk: scores from a clinically validated 31-point frailty index (A), measured just before euthanasia and forepaw grip strength normalized to body weight (BW; B), measured at baseline (after 3 mo of diet, but before beginning the control vs. DMB intervention) and following 8 wk of intervention. All data are means ± SE, with individual data points. n = 11–13 mice/group. There were no statistical outliers. Statistics are two-way diet × treatment ANOVA with Šidák’s multiple comparisons test (A) or two-way mixed (group × time) ANOVA with Tukey’s post hoc test (B). Symbols denote pairwise comparisons: *P < 0.05 vs. SC-C within time point; †P < 0.05 vs. WD-C within time point; ‡P < 0.05 vs. baseline within group. Comparisons of grip strength at 8 wk (B) using two-way diet × treatment ANOVA showed similar differences (diet effect: P = 0.03; treatment effect: P = 0.03; SC-C vs. WD-C: P = 0.03; WD-C vs. WD-DMB: P = 0.03).