1 Introduction
2 Rhabdomyolysis
2.1 Background
2.2 Resistance vs. Endurance Exercise
2.3 Effects of Hydration
2.4 Sex Differences
2.5 Children and Adolescents
2.6 Other Precipitating Factors
3 Metabolic Myopathies and Rhabdomyolysis
3.1 Overview of Metabolic Myopathies
3.2 Fatty Acid Oxidation Defects
3.3 Disorders of Carbohydrate Metabolism/Glycogen Storage Disease
3.4 Mitochondrial Myopathies
3.5 Statin Myopathies
4 Creatine Supplementation and Exertional Rhabdomyolysis
4.1 Creatine Metabolism and Supplementation
4.2 Creatine Supplementation, Muscle Damage, and Rhabdomyolysis
4.3 Creatine Supplementation and Resting Markers of Muscle Damage
Supplementation protocol and study design | Exercise stress | Biological outcomes | Functional outcomes | Perceived outcomes | Overall effect of creatine on muscle-damage | References |
---|---|---|---|---|---|---|
20 g/day for 5 days; DB, PC | Unstressed | No increase in resting CK | NA | NA | No effect | [134] |
20 g/day for 1 day, 20 g/day for 5 days, followed by 3 g/day for 8 wks with training; DB, PC | Unstressed and supervised resistance exercise 3 × week | No increase in resting CK | NA | No reports of cramping or muscle injury | No effect | [133] |
Mean loading dose 13.7 g/day, mean maintenance dose 9.7 g/day, duration 0.8–4 years; RET | Maintained training; subjects were elite athletes | ND in LDH | NA | No reports of muscle tears, greater number of reported muscle cramps in control group | No effect | [135] |
20 g/day for 5 days; DB, PC | 50 maximal eccentric contractions of elbow flexors | ND in post-exercise CK, LDH between groups | ND in post-exercise strength, ROM between groups | ND in DOMS between groups | No effect | [46] |
15.75 g/day for 5 days followed by 5 g/day for 21 mo; OL | Maintained training; subjects were division IA college football players | ND in CK and LDH between groups | NA | NA | No effect | [136] |
20 g/day for 5 days; DB, PC | 30-km running race | Reduced post-exercise CK, LDH, PGE2, TNF-α in creatine group | NA | NA | Beneficial effect | [114] |
0.3 g/kg/day for 5 days followed by 0.03 g/kg/day for 5 days; DB, PC | 5 sets of 15–20 squats with 50% 1-RM | ND in post-exercise CK, LDH between groups | ND in post-exercise strength, ROM between groups | ND in post-exercise DOMS between groups | No effect | [140] |
20 g/day for 5 days; DB, PC | Half-distance Ironman triathlon | Reduced post-exercise TNF-α, IFN-α, IL1-β and PGE2 in creatine group, ND in IL-6 between groups | NA | NA | No effect | [110] |
0.3 g/kg/day for 5 days followed by 0.1 g/kg/day for 14 days; DB, PC | 4 sets of 10 eccentric only leg press, leg extension, and leg curl with 120% concentric 1-RM | Reduced post-exercise CK and LDH (trend p = 0.09) in creatine group | Increased recovery of isometric and isokinetic knee extensor strength | NA | Beneficial effect | [112] |
0.6 g/kg/day for 5 days; DB, PC | 3 sets of 10 of bench press, seated row, leg extension, leg curl, and leg press with 75% of 1-RM | ND in post-exercise CK between groups | NA | NA | No effect | [139] |
20 g/day for 7 days followed by 6 g/day for 29 days; DB, PC | 7 sets of 10 eccentric leg extension at 150% concentric 1-RM (opposite leg tested at day 30) | ND in post-exercise CK or LDH | ND in post-exercise ROM, dynamic strength, or isometric force at 8 days; increased isometric force at 30 days | ND in post-exercise DOMS | Beneficial effect | [138] |
20 g/day for 5 days; DB, PC | Ironman triathlon | Reduced post-exercise CK, LDH, ALD, GOT, GPT, ND in CRP between groups | NA | NA | Beneficial effect | [111] |
40 g/day for 5 days followed by 10 g/day for 5 days; DB, PC | 6 sets of 10 eccentric contractions at 75°, 90°, and 120° per sec | NA | ND in post-exercise muscle force production | ND in post-exercise DOMS | No effect | [137] |
20 g/day for 5 days; DB, PC | Repeated bouts of 4 (14 days apart) sets of biceps curls with 75% of 1-RM to concentric failure | Reduced post-exercise CK in creatine group after second bout | No decrease in post-exercise ROM in creatine group after second bout | Reduced post-exercise DOMS in creatine group after second bout | Beneficial effect | [115] |
0.3 g/kg/day for 7 days; DB, PC | Six 35-m maximal sprints with 10-sec rest between bouts | Reduced post-exercise TNF-α, CRP, LDH in creatine group. No effect on oxidative stress markers | NA | NA | Beneficial effect | [113] |
4.4 Creatine Supplementation, High-Force Eccentric Exercise, and Markers of Exercise-Induced Muscle Damage
4.5 Creatine Supplementation, Endurance Exercise, Sprints, and Markers of Exercise-Induced Muscle Damage
4.6 Creatine Supplementation, Resistance Exercise, and Markers of Exercise-Induced Muscle Damage
4.7 Creatine Supplementation, Muscle Injury, and Muscle Dysfunction
Supplementation protocol | Population | Muscle cramps | Muscle tightness | Muscle strains | Total injuries | Contact and non-contact injuries | Missed practices and players lost for season | References |
---|---|---|---|---|---|---|---|---|
0.3 g/kg/day for 5 days followed by 0.03 g/kg/day for 115 days; OL | 72 division IA college football players | Fewer in creatine group | Fewer in creatine group | Fewer in creatine group | Fewer in creatine group | ND between creatine and non-creatine users | ND between creatine and non-creatine users | [141] |
15.75 g/day for 5 days followed by 5 g/day for rest of season; OL | 39 division I college baseball players | ND between creatine and non-creatine users | ND between creatine and non-creatine users | ND between creatine and non-creatine users | Fewer in creatine group | ND between creatine and non-creatine users | ND between creatine and non-creatine users | [142] |
15.75 g/day for 5 days followed by 5 g/day for three seasons; OL | 130 division IA college football players | Fewer in creatine group | ND between creatine and non-creatine users | ND between creatine and non-creatine users | ND between creatine and non-creatine users | ND between creatine and non-creatine users | ND between creatine and non-creatine users | [143]a
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4.8 Creatine Supplementation and Case Studies of Rhabdomyolysis
Age and sex | Training status | Creatine supplementation | Clinical manifestations of rhabdomyolysis | Treatment | Potential mitigating factors | Resolution | References |
---|---|---|---|---|---|---|---|
24 M | “Avid bodybuilder” | 25 g/day for 1 year | Peak CK > 800,000 IU, severe pain anterior thigh swelling, proteinuria, hematuria, quadriceps compartment syndrome, increased compartment pressure | Emergency tri-compartment fasciotomies, aggressive hydration, physical therapy | 8 days no exercise after muscle injury followed by 3 h lower-body resistance training | Quadriceps strength 60% of pre-rhabdomyolysis level at 6 mo post | [144] |
33 M | Unknown | Unknown dose/duration use reported by wife | Peak CK 765,910 IU, pain, swelling, myoglobinuria, metabolic acidosis, acute renal insufficiency, increased thigh compartment pressure, thigh compartment syndrome | Hydration; alkalinization, hemodialysis, fasciotomies, resuscitation for cardiac arrest | Post-exercise (collapsed at finish line of 2-mile run, army physical fitness test), obesity, recent rapid weight loss (17 lbs in 2 wk), “natural” diuretics, dehydration, ephedrine, African American | Fatal (multi-system failure) | [23] |
27 M | Unknown | 5–20 g/day; unknown duration | Peak CK 83,634 IU, myoglobin 30,000 mg/dl | Hydration, alkalinization of urine, hyperbaric oxygen therapy | 2 days of “extreme” exercise, ephedrine | Full function | [145] |
27 M | Unknown | Peak CK 114,900, myoglobin 20,000 mg/dl, dark urine, oliguria, myalgia, thigh tenderness, increased compartment pressure | Hydration, alkalinization of urine, loop diuretics, continuous venovenous hemofiltration (for respiratory failure), thigh fasciotomy, hyperbaric oxygen therapy | 2 days of “extreme” exercise, ephedrine | Full function | ||
28 M | Unknown | Peak CK > 200,000 IU, myoglobin 23,000 mg/dl, severe pain, dark urine, increased thigh compartment pressures | Hydration, alkalinization of urine, mannitol, loop diuretics, intermittent hemodialysis, thigh fasciotomies | 2 days of “extreme” exercise with dehydration, ephedrine | Full function | ||
21 M | College football player; avid weightlifter | 10 g/day for 6 wk | Peak CK 194,000 IU, Peak LDH 15,840 IU, myoglobinuria, severe pain, acute renal failure | IV fluids, IV mannitol, sodium bicarbonate, and furosemide, metoprolol, hydralazine | Hit a tree (crush injury) prior to arthroscopic knee surgery, surgical tourniquet for 100 min, immobilization/positional post-surgical rhabdomyolysis although uncommon, does occur especially in large individuals (pt was 100 kg), hypertension (156/80 mmHg), 15 mg IV ketorolac (NSAID) | Full function | [146] |