Overall study schematic (A) and acute MyoPS response protocol (B). (A) Participants were randomly assigned to consume a multi-ingredient supplement (SUPP, n = 8) or control (CON, n = 7) beverage twice per day for 21 weeks. Between weeks 8 and 19, inclusive, participants completed a 12 weeks combined RET (twice per week) + HIIT (once per week) exercise training program. Lean tissue mass (DXA) and strength (1RM) were assessed at baseline (week 0), as well as pre- (week 7; Phase 1: SUPP/CON) and post-training (week 20; Phase 2: SUPP/CON + EX). The integrated MyoPS response to acute resistance exercise was assessed during participants' initial RET session (UT, untrained; week 8) and 10 days following their last RET session (TR, trained; week 21). (B) Following a baseline saliva sample, participants consumed 150 mL 70% deuterated water (D2O; Day 0). On Days 2–4, we obtained a fasting muscle sample from the vastus lateralis. Immediately after their muscle biopsy on Day 2, participants completed a session of resistance exercise at 65% 1RM. Saliva samples were collected regularly throughout each acute response period to assess deuterium (2H) enrichment of total body water. Eight weeks prior to the untrained acute response (–8 weeks), we obtained an unenriched, fasted muscle sample for the measurement of resting FSR. SUPP, supplement; CON, control; RET, resistance exercise training; HIIT, high-intensity interval training; DXA, dual-energy x-ray absorptiometry; 1RM, one repetition maximum; MyoPS, myofibrillar protein synthesis; 2H, deuterium; D2O, deuterated water; UT, untrained; TR, trained; FSR, fractional synthesis rate.