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Table 3 Performance outcomes and training adaptations in long-term (> 10 day) MIPS studies

From: Multi-ingredient pre-workout supplements, safety implications, and performance outcomes: a brief review

Study Subjects Design Supplement Ingredients (Sorted by order listed on Supplement Facts label) Timing Training Protocol Performance Testing Protocol Results (d or RE) Ref #
Stout et al. 2008 38 sedentary males and females Double-blind, placebo controlled, resistance and endurance training study Prop. Blend: (1810 mg) Taurine Guarana extract Green tea leaf extract Caffeine Glucuronolactone Ginger 15 min prior to exercise or ad libitum on off days 10 weeks of resistance and endurance training based on ACSM guidelines Body composition, VO2peak, TTE3 ↓ FM (NA) ↑ VO2peak (NA) ↑ TTE (NA) [62]
Hoffman et al. 2010 19 recreationally-active males and females Randomized, Double-blind, placebo-controlled supplementation study. Acetyl-L-carnitine (500 mg) L-tyrosine (500 mg) Α-glycerophosphocholine (150 mg) Choline bitartrate (125 mg) Caffeine (60 mg) Phosphatidylserine (50 mg) 10 min prior to testing. Timing not specified on off days. NA Choice Reaction Time Test before and after the following: WAnT, Maximum Pushup Repetitions Completed in one Minute, Maximum Situp Repetitions Completed in one Minute1 ↔ Reaction Time ↔ Peak Power ↔ Mean Power ↔ Pushups Completed ↔ Sit-ups Completed [36]
Shelmadine et al. 2009 18 non-resistance trained males Double-blind, placebo controlled, resistance training study a Prop. Blend 1: (5350 mg) L-Leucine L-nor-Valine L-Valine L-Isoleucine Prop. Blend 2: (10,952 mg) Methyl Hydroxy Chalcone Polymer Creatine Arginine Glutamine Ariginine Citrulline Malate Prop. Blend 3: (229 mg) L-Tyrosine Caffeine 30 min prior to exercise or immediately upon waking on off days3 28-days of resistance training (4 sessions/week; upper/lower body split) DEXA, muscle biopsies, BP & LP 1RM3 ↑ FFM (d = 0.24) ↑ Relative BP 1RM (d = 0.23) ↔ Relative LP 1RM [53]
Schmitz et al. 2010 20 resistance trained males Double-blind resistance training study using comparator control c Prop. Blend 1: Whey protein (7 g) L-Leucine (4 g) L-Isoleucine L-Valine Prop. Blend 2: Creatine (4 g) Prop. Blend 3: Taurine L-alanyl-L-glutamine Magnesium glycyl glutamine *Comparator matched for carbohydrate, whey, and creatine Begin 10–15 min prior to exercise and complete before end of session. No supplement on off days. 9 weeks of periodized resistance training (4 sessions/week; upper/lower body split) DEXA, BP 1RM, 3 sets of RTF at pretesting body weight3 ↑ BP 1RM (RE = 106.5) ↑ RTF (RE = 131.8) ↓ FM (RE = 87.1) ↑ FFM (RE = 102.1) [51]
Smith et al. 2010 24 recreationally trained males Single-blind, placebo controlled, HIIT training study Prop. Blend: (2100 mg) Cordyceps sinensis Arginine Creatine Citrulline Taurine Leucine Valine Isoleucine Caffeine Whey protein 30 min prior to exercise/testing. Nothing on off days. 3 weeks of HIIT interval training (3 sessions/week) BodPod, VO2max followed by four sprints to exhaustion1 ↑ Training volume (NA) ↔ FFM ↔ VO2max, critical velocity [63]
Spillane et al. 2011 19 non-resistance trained males Double-blind, placebo controlled, resistance training study a Prop. Blend 1: (5350 mg) L-Leucine L-nor-Valine L-Valine L-Isoleucine Prop. Blend 2: (10,952 mg) Methyl Hydroxy Chalcone Polymer Creatine Arginine Glutamine Ariginine Citrulline Malate Prop. Blend 3: (229 mg) L-Tyrosine Caffeine *Subjects also consumed a post-workout supplement 30 min prior (pre) and within 30 min of end of exercise (post). Immediately upon waking on off days (post). 28 days of resistance training (4 sessions/week) DEXA, BP & LP 1RM, muscle biopsies3 ↓ FM (d = − 0.08) ↑ FFM (d = 0.17) ↑ Myofibrillar protein mass (d = 0.32) ↑ Upper (d = 0.57), lower-body (d = 0.62) relative strength [54]
Ormsbee et al. 2012 24 resistance trained males Double-blind, placebo controlled, resistance training study b Prop. Blend 1: (9660 mg) Casein Protein Whey Protein BCAAs L-arginine Prop. Blend 2: (4890 mg) Creatine Citrulline Malate Arginine Prop. Blend 3: (3170 mg) β-alanine Creatine Prop. Blend 4: (376 mg) Caffeine *Subjects also consumed a post-workout supplement 15 min prior to exercise (pre) and immediately after end of exercise (post). Ad libitum on off days (post). 6 weeks of split resistance training (3 sessions/week) DEXA, BP & LP 1RM, Isokinetic strength testing, WAnT2 ↑ FFM (d = 0.18) ↔ Peak power ↔ BP 1RM ↔ LP 1RM [55]
Willems et al. 2012 16 resistance trained males Double-blind, placebo controlled, training study Whey protein (30 g) Creatine (5.1 g) Glutamine (5.1 g) HMB (1.5 g) One dose in the morning and another within 15 min of exercise end. Similar time on off days. 2, 6-week blocks of progressive resistance training (4 sessions/week) BP, LP, & lateral pull 1-RM and RTF at 80% 1RM, peak isokinetic torque measured via a dynamometer, MVC3 ↑ BP RTF* (d = 1.2) ↑ Lateral pull RTF* (d = 1.3) ↔ 1RM* ↔ MVC, peak concentric strength* [58]
Lowery et al. 2013 20 resistance trained males Double-blind, placebo controlled, resistance training study Prop. Blend 1: (2800 mg) Creatine β-alanine Prop. Blend 2: (1600 mg) L-Taurine BCAAs Alanyl-glutamine Prop. Blend 3: (620 mg) Glucuronolactone Caffeine Prop. Blend 4: (500 mg) Natural nitrates Quercetin (67 mg) 30 min prior and 3 servings throughout the day on off days. 8 weeks of split focused resistance training (3sessions/week) DEXA, BP & LP 1RM, ultrasonography3 ↑ FFM (RE = 104.1) ↑ Quadriceps muscle thickness (RE = 108.0) ↑ BP 1RM (NA) ↔ LP 1RM [52]
Ormsbee et al. 2013 24 resistance trained males Double-blind, Placebo-controlled, resistance training study b Prop. Blend 1: (9660 mg) Casein Protein Whey Protein BCAAs L-arginine Prop. Blend 2: (4890 mg) Creatine Citrulline Malate Arginine Prop. Blend 3: (3170 mg) β-alanine Creatine Prop. Blend 4: (376 mg) Caffeine *Subjects also consumed a post-workout supplement 15 min prior (pre) and immediately after exercise (post). Ad libitum on off days (post). 6 weeks of periodized resistance training (3 sessions/week) DEXA, POMS3 ↑ FFM (d = 0.22) ↔ FM ↔ POMS [65]
Kedia et al. 2014 43 resistance trained males and females Double-blind resistance training study using comparator control Prop. Blend 1: (4580 mg) Creatine Betaine Citrulline Dendrobium extract Caffeine *Comparator product matched for energy and caffeine content 30 min prior to exercise and with breakfast on off days. 6 weeks of periodized resistance training (4 sessions/week; upper/lower body split) DEXA, BP 1RM, VAS of energy & concentration3 ↑ Energy & concentration (NA) ↔ FFM ↔ FM ↔ BP 1RM [3]
Kendall et al. 2014 17 recreationally trained males Double-blind, placebo controlled 4-week supplementation study BCAAs (6 g) Creatine (5 g) β-alanine (4 g) Citrulline (1.5 g) Caffeine (300 mg) 20 min prior to exercise and ad libitum on off days. NA Skinfolds (Brozek equation), VO2max, BP & LP 1-RM, RTF at 75% 1RM3 ↑ VT (% of VO2max) (d = 1.21) ↑ LP 1RM (d = 0.45) ↓ Relative VO2max (d = − 0.52) [57]
Spillane et al. 2014 24 resistance trained males Double-blind, resistance training study using comparator control c Prop. Blend 1: Whey protein (7 g) L-Leucine (4 g) L-Isoleucine L-Valine Prop. Blend 2: Creatine (4 g) Prop. Blend 3: Taurine L-alanyl-L-glutamine Magnesium glycyl glutamine *Comparator matched for maltodextrose, whey protein, and creatine monohydrate ½ dose consumed 15 min prior to exercise, other ½ dose consumed at start of exercise. Nothing on off days. 6 weeks of periodized resistance training (4 sessions/week; upper/lower split) DEXA, BP, LP, & knee extension 1RM, BP & LP RTF at 75% 1-RM, muscle biopsies3 ↔ Body Composition ↔ 1RM ↔ RTF [61]
Kreipke et al. 2015 27 resistance trained males Double-blind, placebo controlled, resistance training study BCAA (2500 mg) β-alanine (1020 mg) Long jack root (250 mg) 20 min prior and 2 h after exercise. With breakfast and lunch on off days. 4 weeks of progressive resistance training (4 sessions/week) DEXA, squat, BP, deadlight 1RM, POMS3 ↑ BP 1RM (d = 0.05) ↑ Total weight lifted (d = 0.15) ↑ Relative deadlift strength (FFM: d = 0.11; Total Mass: d = 0.08) [59]
Ormsbee et al. 2015 20 trained male runners Double-blind, placebo controlled, 4-week supplementation study b Prop. Blend 1: (9660 mg) Casein Protein Whey Protein BCAAs L-arginine Prop. Blend 2: (4890 mg) Creatine Citrulline Malate Arginine Prop. Blend 3: (3170 mg) β -alanine Creatine Prop. Blend 4: (376 mg) Caffeine 30 min prior to exercise or immediately upon waking on off days. NA Skinfolds, perceived soreness VAS, ROM, vertical jump, isokinetic and isometric strength using isokinetic dynamometer, VO2max, before and after a single bout of downhill running1 ↔ Isometric and isokinetic strength ↔ Flexibility ↔ Power ↔ Perceived soreness [56]
Köhne et al. 2016 8 trained female runners Double-blind, placebo controlled, 28-day supplementation study b Prop. Blend 1: (9660 mg) Casein Protein Whey Protein BCAAs L-arginine Prop. Blend 2: (4890 mg) Creatine Citrulline Malate Arginine Prop. Blend 3: (3170 mg) β-alanine Creatine Prop. Blend 4: (376 mg) Caffeine *Subjects also consumed a post-workout supplement 30 min prior to exercise or immediately upon waking on off days. NA VO2max (before and after supplementation), muscle pain perception, muscle damage markers, squat jump power, hamstring flexibility, and limb circumferences (before and after a single bout of downhill running after 28 days of supplementation)1 ↔ Hamstring flexibility ↔ Squat jump power ↔ Limb circumference [64]
Jung et al. 2017 80 resistance trained males Double-blind, placebo controlled, resistance training study Supplement 1: β-alanine (3000 mg) Creatine (2000 mg) L-arginine (2000 mg) N-Acetyl-L-tyrosine (300 mg) Caffeine (284 mg) Mucana pruitiens extract (15 mg) Supplement 2: Supplement 1 + Citrus aurantium extract (20 mg) 15–30 min prior to exercise or with breakfast on off days. 8 weeks of resistance training (4 sessions/week; upper/lower body split) Cognitive function, readiness to perform, BP & LP 1RM, Wingate anaerobic cycling test3 ↔ 1RM leg & bench press ↔ Power ↔ Readiness to perform ↑ Stroop Test Performance (d = 0.12–0.16) [60]
Zabriskie et al. 2017 19 recreationally active females Double blind, placebo controlled, resistance training study Prop. Blend 1: (5700 mg) β-alanine L-tyrosine L-glycine L-carnitine Beet root Hawthorn berry powder Caffeine 30 min prior to exercise or after breakfast on off days. 7 weeks of periodized resistance training BodPod, RMR2 ↔ FM ↔ FFM ↔ RMR [66]
  1. ↑ = MIPS was significantly greater (p < 0.05) than control; ↓ = MIPS was significantly less (p < 0.05) than control; ↔ = No significant difference (p > 0.05) was observed between MIPS and control; 1RM 1 repetition maximum, %BF body fat percentage, BP Bench press, d Effect Size, DEXA dual x-ray energy absorptiometry, FFM fat-free mass, FM fat mass, RE Relative Effects, RTF repetitions to fatigue, LP Leg press, mg milligram, mcg microgram, POMS Profile of Mood States, ROM range of motion, TTE time to exhaustion, VO2max maximal oxygen consumption, VT Ventilatory Threshold, WAnT Wingate anaerobic cycle test
  2. aStudies used an identical MIPS containing whey protein, caffeine, BCAAs, creatine, β-alanine, and L-arginine
  3. bStudies used a later formulation of the same brand name MIPS as a containing whey protein, caffeine, BCAAs, creatine, β-alanine, and L-arginine
  4. cStudies used an identical MIPS containing carbohydrate, whey, creatine, BCAAs and L-taurine
  5. 1Testing performed with acute MIPS supplementation
  6. 2Testing performed without acute MIPS supplementation
  7. 3Presence of MIPS during testing not explicitly reported
  8. *analysis performed using Cohen’s d effect sizes