Objective: To determine whether creatine monohydrate (CrM) supplementation increases strength and fat-free mass (FFM) in boys with Duchenne muscular dystrophy (DD). Methods: Thirty boys with DD (50% were taking corticosteroids) completed a double-blind, randomized, cross-over trial with 4 months of CrM (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements were completed of pulmonary function, compound manual muscle and handgrip strength, functional tasks, activity of daily living, body composition, serum creatine kinase and γ-glutamyl transferase activity and creatinine, urinary markers of myofibrillar protein breakdown (3-methylhistidine), DNA oxidative stress (8-hydroxy-2-deoxyguanosine [8-OH-2-dG]), and bone degradation (N-telopeptides). Results: During the CrM treatment phase, there was an increase in handgrip strength in the dominant hand and FFM (p < 0.05), with a trend toward a loss of global muscle strength (p = 0.056) only for the placebo phase, with no improvements in functional tasks or activities of daily living. Corticosteroid use, but not CrM treatment, was associated with a lower 8-OH-2-dG/creatinine (p < 0.05), and CrM treatment was associated with a reduction in N-telopeptides (p < 0.05). Conclusions: Four months of CrM supplementation led to increases in FFM and handgrip strength in the dominant hand and a reduction in a marker of bone breakdown and was well tolerated in children with DD.

While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.

Resistance training changes the balance of muscle protein turnover, leading to gains in muscle mass. A longitudinal design was employed to assess the effect that resistance training had on muscle protein turnover in the fed state. A secondary goal was investigation of the potential interactive effects of creatine (Cr) monohydrate supple mentation on resistance-training-induced adaptations. Young (N = 19, 23.7 ± 3.2 year), untrained (UT), healthy male subjects completed an 8-week resistance-training program (6 d/week). Supplementation with Cr had no impact on any of the variables studied; hence, all subsequent data were pooled. In the UT and trained (T) state, subjects performed an acute bout of resistance exercise with a single leg (exercised, EX), while their contralateral leg acted as a nonexercised (NE) control. Following exercise, subjects were fed while receiving a primed constant infusion of [d₅]- and [¹⁵N]-phenylalanine to determine the fractional synthetic and breakdown rates (FSR and FBR), respectively, of skeletal muscle proteins. Acute exercise increased FSR (UT-NE, 0.065 ± 0.025 %/h; UT-EX, 0.088 ± 0.032 %/h; P < 0.01) and FBR (UT-NE, 0.047 ± 0.023 %/h; UT-EX, 0.058 ± 0.026 %/h; P < 0.05). Net balance (BAL = FSR – FBR) was positive in both legs (P < 0.05) but was significantly greater (+65%) in the EX versus the NE leg (P < 0.05). Muscle protein FSR and FBR were greater at rest following T (FSR for T-NE vs. UT-NE, +46%, P < 0.01; FBR for T-NE vs. UT-NE, +81%, P < 0.05). Resistance training attenuated the acute exercise-induced rise in FSR (T-NE vs. T-EX, +20%, P = 0.65). The present results demonstrate that resistance training resulted in an elevated resting muscle protein turnover but an attenuation of the acute response of muscle protein turnover to a single bout of resistance exercise.Key words: myofibrillar protein, hypertrophy, protein synthesis, protein breakdown.

Tarnopolsky, M. A., M. Bosman, J. R. MacDonald, D. Vandeputte, J. Martin, and B. D. Roy. Postexercise protein-carbohydrate and carbohydrate supplements increase muscle glycogen in men and women. J. Appl. Physiol. 83(6): 1877–1883, 1997.—We have previously demonstrated that women did not increase intramuscular glycogen in response to an increased percent of dietary carbohydrate (CHO) (from 60 to 75% of energy intake) (M. A. Tarnopolsky, S. A. Atkinson, S. M. Phillips, and J. D. MacDougall. J. Appl. Physiol. 78: 1360–1368, 1995). CHO and CHO-protein (Pro) supplementation postexercise can potentiate glycogen resynthesis compared with placebo (K. M. Zawadzki, B. B. Yaspelkis, and J. L. Ivy. J. Appl. Physiol. 72: 1854–1859, 1992). We studied the effect of isoenergetic CHO and CHO-Pro-Fat supplements on muscle glycogen resynthesis in the first 4 h after endurance exercise (90 min at 65% peak O₂ consumption) in trained endurance athletes (men, n= 8; women, tested in midfollicular phase, n = 8). Each subject completed three sequential trials separated by 3 wk; a supplement was provided immediately and 1-h postexercise: 1) CHO (0.75 g/kg) + Pro (0.1 g/kg) + Fat (0.02 g/kg), 2) CHO (1 g/kg), and 3) placebo (Pl; artificial sweetener). Subjects were given prepackaged, isoenergetic, isonitrogenous diets, individualized to their habitual diet, for the day before and during the exercise trial. During exercise, women oxidized more lipid than did men ( P< 0.05). Both of the supplement trials resulted in greater postexercise glucose and insulin compared with Pl ( P < 0.01), with no gender differences. Similarly, both of these trials resulted in increased glycogen resynthesis (37.2 vs. 24.6 mmol ⋅ kg dry muscle⁻¹ ⋅ h⁻¹, CHO vs. CHO-Pro-Fat, respectively) compared with Pl (7.5 mmol ⋅ kg dry muscle⁻¹ ⋅ h⁻¹; P < 0.001) with no gender differences. We conclude that postexercise CHO and CHO-Pro-Fat nutritional supplements can increase glycogen resynthesis to a greater extent than Pl for both men and women.

Aging is associated with lower muscle mass and an increase in body fat. We examined whether creatine monohydrate (CrM) and conjugated linoleic acid (CLA) could enhance strength gains and improve body composition (i.e., increase fat-free mass (FFM); decrease body fat) following resistance exercise training in older adults (>65 y). Men (N = 19) and women (N = 20) completed six months of resistance exercise training with CrM (5g/d)+CLA (6g/d) or placebo with randomized, double blind, allocation. Outcomes included: strength and muscular endurance, functional tasks, body composition (DEXA scan), blood tests (lipids, liver function, CK, glucose, systemic inflammation markers (IL-6, C-reactive protein)), urinary markers of compliance (creatine/creatinine), oxidative stress (8-OH-2dG, 8-isoP) and bone resorption (Ν-telopeptides). Exercise training improved all measurements of functional capacity (P<0.05) and strength (P<0.001), with greater improvement for the CrM+CLA group in most measurements of muscular endurance, isokinetic knee extension strength, FFM, and lower fat mass (P<0.05). Plasma creatinine (P<0.05), but not creatinine clearance, increased for CrM+CLA, with no changes in serum CK activity or liver function tests. Together, this data confirms that supervised resistance exercise training is safe and effective for increasing strength in older adults and that a combination of CrM and CLA can enhance some of the beneficial effects of training over a six-month period. Trial Registration. ClinicalTrials.gov NCT00473902

Roy, B. D., M. A. Tarnopolsky, J. D. MacDougall, J. Fowles, and K. E. Yarasheski. Effect of glucose supplement timing on protein metabolism after resistance training. J. Appl. Physiol. 82(6): 1882–1888, 1997.—We determined the effect of the timing of glucose supplementation on fractional muscle protein synthetic rate (FSR), urinary urea excretion, and whole body and myofibrillar protein degradation after resistance exercise. Eight healthy men performed unilateral knee extensor exercise (8 sets/∼10 repetitions/∼85% of 1 single maximal repetition). They received a carbohydrate (CHO) supplement (1 g/kg) or placebo (Pl) immediately ( t = 0 h) and 1 h ( t = +1 h) postexercise. FSR was determined for exercised (Ex) and control (Con) limbs by incrementall-[1-¹³C]leucine enrichment into the vastus lateralis over ∼10 h postexercise. Insulin was greater ( P < 0.01) at 0.5, 0.75, 1.25, 1.5, 1.75, and 2 h, and glucose was greater ( P < 0.05) at 0.5 and 0.75 h for CHO compared with Pl condition. FSR was 36.1% greater in the CHO/Ex leg than in the CHO/Con leg ( P = not significant) and 6.3% greater in the Pl/Ex leg than in the Pl/Con leg ( P = not significant). 3-Methylhistidine excretion was lower in the CHO (110.43 ± 3.62 μmol/g creatinine) than Pl condition (120.14 ± 5.82, P < 0.05) as was urinary urea nitrogen (8.60 ± 0.66 vs. 12.28 ± 1.84 g/g creatinine, P < 0.05). This suggests that CHO supplementation (1 g/kg) immediately and 1 h after resistance exercise can decrease myofibrillar protein breakdown and urinary urea excretion, resulting in a more positive body protein balance.