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. 2022 Feb 26;52(7):1623–1645. doi: 10.1007/s40279-022-01640-z

Table 2.

Methodological description for route of supplement administration, muscle-damaging protocol, and the type of outcome measures

Study Administration method EIMD protocol Resultsa
Atashak and Jafari [45] One packet dissolved in 250–300 ml of water (5 g CrM plus 10 g of flavoured dextrose powder per packet equal to 0.3 g/day/kg) QID at regular intervals for 7 days A bout of circuit weight training consisting of eight exercises, 3 sets, 15 repetitions, and 60% 1RM, with 60–90 s rest between each station (1) CK and LDH, (2) none, (3) none, (4) none, (5) none
Bassit et al. [46] CrM 20 g/day diluted in same amount of water divided in two equal doses for 5 days Half-ironman competition consisting of 1.9 km swimming, 90 km cycling, and 21 km running (1) None, (2) plasma IL-1b, IL-6, TNFα, IFNα, and PGE2, (3) none, (4) none, (5) none
Bassit et al. [47] CrM 20 g/day diluted in same amount of water divided in two equal doses for 5 days Ironman competition consisting of 3.8 km swimming, 180 km cycling, and 42 km running (1) CK, LDH, (2) none, (3) none, (4) none, (5) none
Basta et al. [48] CrM 20 g daily in four 5 g doses dissolved in the Isostar carbohydrate nutrient for 5 days and CrM 10 g in two 5 g doses for next 30 days Ergometric exercise test starting with load of 50% of maximum power; the load was increased every 3 min to 60, 70, 80, and 90% of maximum power. The highest load was maintained until refusal (1) CK, (2) TBARS, SOD, GPX, (3) none, (4) none, (5) none
Boychuk et al. [49] Creatine (0.3 g/kg) in four equal aliquots (i.e., 0.075 g/kg) throughout the day, mixed in juice for 8 days A bout of maximal eccentric contractions of 6 sets of 8 repetitions at a velocity of 90°/second, with 1 min rest between each set (1) None, (2) none, (3) none, (4) measured using 100 mm VAS scale, (5) measured using the dominant arm for elbow flexion
Brose et al. [50] CrM 5 g + dextrose 2 g/d mixed with juice for 14 weeks A 14-week resistance training programme consisting of 12 exercises targeting the upper and lower body in a circuit set system. Each arm exercise was performed for 10 repetitions, and the remaining exercises were performed for 12 repetitions. Training progressed from one set of each exercise at 50% of the initial 1RM strength to three sets at 80% of 1RM over the training period. The 1RM was re-evaluated every 2 weeks and the load adjusted accordingly (1) CK, (2) none, (3) none, (4) none, (5) measured using handgrip, ankle dorsiflexion, and knee extensor isometric strength
Cooke et al. [27] 1.5 g/kg of bodyweight/day, providing a loading dose of creatine 0.3 g/kg of bodyweight/day, mixed in water for 5 days before the exercise bout A bout of 4 sets of 10 reps of eccentric-only contractions at 4-s cadence during leg press; leg extension and leg curl at 120% of participants' predetermined concentric 1RM, with 3 min rest between each set (1) CK and LDH, (2) none, (3) none, (4) none, (5) measured using isokinetic/isometric knee extension
Fernandez-Landa et al. [31] 0.04 g/kg/day of CrM mixed with chocolate recovery shake for 10 weeks 10 weeks of training, consisting of six exercise sessions per week for 1.5 h/day (distributed as 60% aerobic work on a traditional boat, 30% resistance training in a gym, and 10% complementary training: injury prevention, core stability, and articular mobility) (1) CK and LDH, (2) none, (3) none, (4) none, (5) none
Hayward et al. [34] Micronised CrM 5 g/d with their supplemental protein for 4 weeks 4 weeks of training consisting of exercise sessions four times a week that also included a split-body workout (1) None, (2) CRP, IL-6, (3) none, (4) measured using 100 mm VAS scale, (5) none
Kaviani et al. [32] Creatine 0.07 g/kg/d with 250 mL grape juice, divided into two doses per day 8 weeks of resistance training consisting of three sets of 10 repetitions at 75% 1RM. Resistance increased based on a new 1RM measured every 2 weeks (1) CK and LDH, (2) none, (3) none, (4) none, (5) none
Machado et al. [51] 20 supplemental packages containing 50% creatine and 50% dextrose at 0.6 g.kg−1 of bodyweight in four daily doses over 5 consecutive days One bout of resistance training of five exercises (bench press, seated row, leg extension, leg curl, and leg press), each in three sets of ten repetitions at 75% of 1RM, with 2 min rest between each exercise (1) CK, (2) none, (3) none, (4) none, (5) none
McKinnon et al. [35] 40 g of creatine·day−1 divided into two equal servings taken once in the morning and once in the evening for 5 days One bout of 60 maximal eccentric contractions divided into 6 sets of 10 repetitions, with a 45-s rest period between repetitions on a dynamometer (1) None, (2) none, (3) none, (4) measured using a scale ranging from 1 to 10, (5) measured using isometric elbow flexion strength
Mirzaei et al. [52] 20 g/day in four equal servings of 5 g for 7 days. The powder was mixed in 200 mL of water and ingested Incremental exercise test to exhaustion began at 50 W for 5 min, and the power output was increased by 30 W every 3 min until voluntary exhaustion or the participant could no longer maintain a pedal cadence of 60 rpm (1) 8-OHdG, 8-iso PGF, (2) none, (3) none, (4) none, (5) none
Percario et al. [33] For the first 5 days, CrM was administered at a daily dose of 20 g, taken as four doses of 5 g each, dissolved in 100 ml of water. On the remaining 27 days, creatine 5 g/day, diluted in 100 ml of water was administered after training 32-day resistance training programme consisting of bench press, inclined chest fly, lat pull down, seated row, shoulder press, biceps curl, squatting, and leg extension. 3–4 sets of 3–12 repetitions and 90–180 s of rest between each set (1) CK, urea, TBARS, TAS, uric acid, (2) none, (3) none, (4) none, (5) none
Rahimi [53] CrM 20 g divided into four doses of 5 g for 7 days A bout of resistance exercises consisting of 7 sets of 3–6 repetitions of bench press, leg press, lat pull down, and seated rows with 80–90% of 1RM using a pyramid loading method (1) MDA, 8-OHdG, (2) none, (3) none, (4) none, (5) none
Rawson et al. [36] Creatine 5 g and dextrose 7 g QID for 5 days. Participants ingested one serving of Gatorade following ingestion of the supplement at four equal intervals throughout the day A bout of eccentric exercise test consisted of 2 sets of 25 maximal eccentric contractions, with each repetition lasting 5 s, followed by a 15-s rest between each repetition and a 5-min rest between each set (1) CK and LDH, (2) maximum isometric force of elbow flexors, (3) none, (4) none, (5) none
Rawson et al. [38] During the loading phase, administered creatine 0.3 g/kg of bodyweight per day in three equal doses for 5 days. Post-loading phase, creatine 0.03 g/kg of bodyweight per day for 5 days. Participants ingested the supplements with food in three equal doses per day A bout of squat exercises consisting of 5 sets of 15–20 repetitions at 50% of 1RM with 2 min recovery between each set (1) CK and LDH, (2) none, (3) measured using a VAS scale ranging from 1 to 10, (4) none, (5) none
Santana et al. [54]

CrM: CrM 20 g/day in four equal doses of 5 g q4h for 7 days along with 10 g of CHO. After 7 days, 5 g/day for the remaining 21 days

CrHCl: Administered 6 g/day of CrHCl in four equal doses of 1.5 g q4h for 7 days along with 10 g of CHO. After 7 days, 1.5 g/day for the remaining 21 days

10 m running performance test (1) None, (2) none, (3) measured using a VAS scale ranging from 1 to 10, (4) none, (5) none
Santi et al. [55]

Loading phase (7 days): creatine 0.3 g/kg/day associated with 1.2 g/kg/day of carbohydrate

Maintenance phase (4 days): creatine 0.1 g/kg/day plus CHO supplementation, comprising maltodextrin 0.4 g/day/kg. Supplements were diluted with 300 mL of water

Vertical jump performance test (1) CK and LDH, (2) none, (3) measured using 100 mm VAS scale, (4) none, (5) none
Santos et al. [56] CrM 20 g diluted with the same amount of water, divided in four doses of 5 g for 5 days 30 km marathon (1) CK, LDH, PGE2, TNFα, creatinine, (2) none, (3) none, (4) none, (5) none
Taylor et al. [37] Atorvastatin 80 mg plus CrM 10 g mixed in 4–6 oz of water or juice for 4 weeks 45 min of downhill walking on a treadmill at − 15% grade and a speed set to elicit 65% of maximal heart rate (1) CK, (2) none, (3) measured using VAS scale, (4) none, (5) none
Veggi et al. [28] Creatine 5 g (powder form) and dextrosol 5 g QID for 6 days A bout of four sets of barbell biceps curls to concentric failure using 75% of their predetermined 1RM, with 3 min rest between sets (1) CK, (2) none, (3) measured using a 0–100 mm VAS scale, (4) none, (5) none
Wang et al. [29] CrM 5 g plus dextrose 5 g dissolved in 300 mL of water QID for 6 days 4-week complex training programme consisting of six sets of 5RM half squats and plyometric jumps three times per week (1) CK, (2) none, (3) none, (4) none, (5) none

8-iso PGF F2-isoprostane, 8-OHdG 8-hydroxy-2-deoxyguanosine, CHO carbohydrate, CK creatine kinase, CrHCl creatine hydrochloride, CrM creatine monohydrate, CRP C-reactive protein, GPx glutathione peroxidase, IFN interferon, IL interleukin, LDH lactate dehydrogenase, MDA malondialdehyde, PGE2 prostaglandin E2, q4h every 4 h, QID four times daily, RM repetition maximum, rpm repetitions per minute, SOD superoxide dismutase, TAS total antioxidant status, TBARS thiobarbituric reactive substances, TNF tumour necrosis factor, VAS visual analogue scale, W watts

a(1) Muscle damage marker, (2) inflammatory markers, (3) oxidative stress markers, (4) delayed onset of muscle soreness, and (5) MVIC