The effects of creatine supplementation [review]

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The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching

Jeff S. Volek1 Contact Information, Nicholas A. Ratamess1, Martyn R. Rubin1, Ana L. Gómez1, Duncan N. French1, Michael M. McGuigan1, Timothy P. Scheett1, Matthew J. Sharman1, Keijo Häkkinen2 and William J. Kraemer1

Accepted: 6 November 2003 Published online: 18 December 2003

Abstract To determine the effects of creatine supplementation during short-term resistance training overreaching on performance, body composition, and resting hormone concentrations, 17 men were randomly assigned to supplement with 0.3 g/kg per day of creatine monohydrate (CrM: n=9) or placebo (P: n=8) while performing resistance exercise (5 days/week for 4 weeks) followed by a 2-week taper phase. Maximal squat and bench press and explosive power in the bench press were reduced during the initial weeks of training in P but not CrM. Explosive power in the bench press, body mass, and lean body mass (LBM) in the legs were augmented to a greater extent in CrM (Ple0.05) by the end of the 6-week period. A tendency for greater 1-RM squat improvement (P=0.09) was also observed in CrM. Total testosteron (TT) and the free androgen index (TT/SHBG) decreased in CrM and P, reaching a nadir at week 3, whereas sex hormone binding globulin (SHBG) responded in an opposite direction. Cortisol significantly increased after week 1 in CrM (+29%), and returned to baseline at week 2. Insulin was significantly depressed at week 1 (–24%) and drifted back toward baseline during weeks 2–4. Growth hormone and IGF-I levels were not affected. Therefore, some measures of muscular performance and body composition are enhanced to a greater extent following the rebound phase of short-term resistance training overreaching with creatine supplementation and these changes are not related to changes in circulating hormone concentrations obtained in the resting, postabsorptive state. In addition, creatine supplementation appears to be effective for maintaining muscular performance during the initial phase of high-volume resistance training overreaching that otherwise results in small performance decrements.

Keywords Cortisol - Muscle strength - Overtraining - Power - testosteron - Weight training
Introduction

We have previously demonstrated that creatine supplementation enhances performance of maximal strength, explosive power, and muscular endurance after 7 days (Volek et al. 1997b, 1999). In a follow-up study, we reported that creatine supplementation in conjunction with a resistance training program augmented gains in muscular strength, lean body mass, and muscular hypertrophy (Volek et al. 1999). Several others studies lasting 3 weeks (Burke et al. 2000) to 13 weeks (Larson-Meyer et al. 2000) have reported similar ergogenic effects of creatine on adaptations to resistance training. The mechanism(s) by which creatine exerts this ergogenic effect on chronic adaptations to training is/are controversial and may be due to greater gains in lean body mass (Volek et al. 1999), an effect on protein metabolism (Parise et al. 2001), an increase in myosin heavy chain mRNA and protein expression (Willoughby and Rosene 2001), an alteration in the expression of myogenic transcription factors (Hespel et al. 2001), an increase in satellite cell mitotic activity (Dangott et al. 1999), an increase protein synthesis secondary to an increase in cell swelling (Bemben et al. 2001; Haussinger et al. 1993), or simply an increase in the intensity of individual workouts resulting from a better match between ATP supply and demand during exercise (Casey et al. 1996).

Resistance training results in increases in muscle fiber hypertrophy and muscle size, a result of an increase in net protein balance. The magnitude of muscle hypertrophy is heavily influenced by nutrition and the anabolic and catabolic hormonal milieu (Kraemer et al. 1995). Such hormonal signals create greater stimuli for increased receptor interactions and gene level transcription and translation of proteins (Turner et al. 1988). In turn, protein synthesis is increased, which sets the stage for greater protein accretion and muscle fiber hypertrophy with chronic resistance training. Only a few studies have examined whether the ergogenic effect of creatine on adaptations to training is mediated by a change in circulating hormones. Our laboratory reported that acute creatine supplementation for 7 days did not alter responses of testosteron, cortisol, and hormones involved in regulation of water balance (renin, aldosterone, angiotensin, arginine vasopressin) to a single bout of heavy resistance exercise (Volek et al. 1997b, 2001). Creatine supplementation (20 g/day for 5 days) failed to alter testosteron, cortisol, and growth hormone (GH) responses to a single bout of heavy resistance exercise (Op lsquoT Eijnde and Hespel 2001). Although acute creatine supplementation does not appear to alter the responses of testosteron, cortisol, and GH to a single bout of resistance exercise, hormone levels could be altered over a prolonged resistance training program, especially an overreaching-type program, which often results in perturbations of the endocrine system (Fry et al. 1993).

We have previously shown that amino acid supplementation is effective for maintaining muscular strength and power during high-volume resistance training overreaching (Ratamess et al. 2003). In that investigation, we developed a model of overreaching that resulted in performance decrements initially, followed by a substantial ldquorebound effectrdquo leading to improvements in muscular strength and power. However, the effect of creatine supplementation on resistance training overreaching is not well understood. Therefore, the primary purpose of the present study was to investigate whether creatine supplementation affected the hormonal responses to short-term resistance training overreaching and the relationship to changes in muscular performance and body composition.
Methods
Experimental design

A double-blind, randomized study was employed using two experimental groups (creatine or placebo supplementation) who underwent 4 weeks of resistance training (5 days/week) and supplementation. The training program consisted of 2 weeks of moderate-intensity/high-volume and 2 weeks of high-intensity/moderate-volume resistance training. Acute overreaching was produced by training the whole body on consecutive days, thereby minimizing recovery in between workouts (Ratamess et al. 2003). At the end of each training week, resting blood samples were obtained and muscular performance was assessed. This experimental design enabled us to investigate the time course of potential ergogenic effects of creatine supplementation (e.g., recovery enhancement) during resistance training overreaching in resistance-trained men.
Subjects

Seventeen resistance-trained men were randomly assigned to a creatine monohydrate (CrM) or a placebo (P) group. The subjects had the following characteristics [mean(SE)]: CrM group (n=9): age=20.7 (1.9) years; height=179.3 (4.7) cm; body mass=88.5 (17.0) kg; and training experience=5.4 (2.1) years; P group (n=8): age=21.3 (3.0) years; height=179.4 (6.4) cm; body mass=88.9 (11.1) kg; and training experience=5.1 (3.0) years. There were no significant differences between groups in physical characteristics. Each of the subjects was informed of the benefits and risks of the investigation and subsequently signed an approved consent form in accordance with the guidelines of the University Institutional Review Board for use of human subjects. No subject had any medical or orthopedic problem that would compromise his participation and performance in the study. None of the subjects were taking any medications, nutrition supplements (including creatine for at least 8 weeks), or anabolic drugs that would confound the results of this study.
Resistance training
Prior to initiation of the 4-week overreaching program, each participant underwent 4 weeks of base resistance training. This ensured that each subject began the study in a trained state. Base training consisted of five exercises per workout (squat, bench press, lat pull down, leg press, and seated shoulder press) for three sets of 8–10 repetitions with 1–3 min of rest in between sets performed for 2 days/week. Multiple-set, periodized resistance training was performed on 4 consecutive days using a total-body program (Table 1). Due to time limitation constraints with the subjects, the overreaching program utilized training each muscle group on consecutive days, thereby limiting recovery. The first 2 weeks consisted of a higher volume, moderate intensity of resistance exercise whereas the last 2 weeks consisted of high intensity with a moderate volume of resistance exercise. All sets were performed with repetition maximum (RM) loads such that all sets were either performed to or near muscular exhaustion. When each subject was able to complete the desired number of repetitions with the current load, weight was added to subsequent sets or during the next workout. All workouts were supervised by a certified strength and conditioning specialist who also monitored the training loads (Mazzetti et al. 2000). Following the 4-week experimental period, each participant underwent a 2-week reduced-volume/frequency resistance training phase. The program used during this phase was identical to the base resistance training program used prior to initiation of the 4-week overreaching protocol. Only week squat, bench press, peak power attained during the ballistic bench press, and jump squat were assessed following this training 2-week phase.

Table 1 Resistance–training program *KNIP*

Subjects assigned to the CrM group ingested creatine monohydrate in capsule form (Creatine Fuel, Twin Laboratories, Hauppauge, N.Y., USA) at a dose 0.3 g/kg per day (divided into three equal doses) for the 1st week and 0.05 g/kg per day (one dose) for the remaining 3 weeks of training. This supplementation protocol increased muscle creatine levels in our prior work (Volek et al. 1999). Subjects in the P group consumed the same number of capsules identical in appearance (powdered cellulose). All supplement doses were administered by a registered dietician who calculated each serving size and distributed the supplements in clearly marked plastic bags. All subjects recorded the times of supplementation in accordance with the investigatorrsquos instructions. In order to control for possible confounding effects of alterations in dietary intake over the training period and to isolate the independent effects of the supplementation treatments, an attempt was made to standardize dietary nutrient intake at an isocaloric level for each subject. Prior to beginning the study, subjects were weighed before and after a seven-day period during which time they recorded all fooday/beverages consumed according to instructions provided by the same registered dietitian. If body weight fluctuated >1 kg during the 7-day period, then subjects were provided with nutritional counseling to either increase or decrease food intake in order to maintain body weight. The seven-day food records were subsequently photocopied and returned to subjects. Subjects reproduced this 7-day diet during each week of the training and supplementation period.
Performance testing

Muscle testing (strength, power, local muscular endurance) was performed prior to initiation of the 4-week overreaching period, and after the completion of each training week. In addition, 1-RM testing was performed after a 2-week reduced volume and frequency period. 1-RM strength was determined for the free-weight squat and bench-press exercises according to methods previously described by Kraemer and Fry (1995). A warm-up set of five to ten repetitions was performed using 40–60% of the perceived maximum 1-RM. After a 1-min rest period, a set of two to three repetitions was performed at 60–80% of the perceived maximum 1-RM. Subsequently, three to four maximal trials (one-repetition sets) were performed to determine the 1-RM. Rest periods in between trials were 2–3 min. A complete range of motion and proper technique were required for each successful 1-RM trial. For the squat exercise, each subject was instructed to descend until the upper thighs were parallel to the ground. A research assistant was located lateral to the subject and gave a verbal ldquouprdquo signal to initiate the concentric action of the exercise. For the bench press, each subject lowered the bar until it came in contact with the chest musculature. ldquoBouncingrdquo the weight off of the chest and excessive arching of the back were not permitted. Strength testing was performed at the same time each session and approximately 24 h following the last training session. All subjects refrained from activity not related to the present investigation for at least 24 h prior to testing.

Power testing was performed prior to initiation of the training program and after each 2-week phase. Upper and lower body power was measured using the ballistic bench press and jump squat exercises, respectively, with the Ballistic Measurement System (BMS; Norsearch Limited, Lismore, Australia). The BMS enables ballistic movement and has been described in detail elsewhere (Volek et al. 1997b). For the jump squat, each subject descended to a position in which the thigh musculature was parallel to the ground. In a ballistic manner, each subject ascended as rapidly as possible and proceeded to jump as high as possible while minimizing any contributions from the arms. The weight was released upon jumping and bar displacement was calculated via a rotary encoder attached to the BMS and interfaced with a computer. For the ballistic bench press, each subject lowered the weight from the fully extended elbow position until it came in contact with the chest musculature. The concentric action of the exercise was performed as rapidly as possible and the weight was released upon completion. The BMS incorporates a unidirectional electromagnetic braking system, which immediately prevented descending bar movement once engaged; thus, the bar was safely released. The jump squat and ballistic bench press were performed with a load corresponding to 30% of the squat and bench press 1-RM, respectively, attained during the pre-training testing period. Testing order was randomized such that half of the subjects began with the squat jump and half began with the ballistic bench press. Each subject was given three to five maximal trials with 2 min of rest in between trials and the largest power output attained was recorded for analysis.

Following peak power testing, each subject performed a 20-repetition jump squat protocol used to measure high-intensity local muscle endurance. Loading for this assessment consisted of 30% of each subjectrsquos pre-training 1-RM squat. Subjects were instructed to jump as high as possible for each repetition while maintaining proper exercise technique and range of motion. Mean power was assessed at five repetition intervals and the percentage decline was calculated: [(mean power reps. 1–5)–(mean power reps 16–20)/mean power rep 1–5]×100.
Body composition

Body mass was measured on a digital platform scale to the nearest 100 g. Total body water (TBW) was estimated via bioelectrical impedance analysis using a modified scale platform mounted with pressure electrodes in contact with the feet (TBF-105 Body Fat Analyzer; Tanita Corporation of America, Skokie, Ill., USA). Repeat TBW measurements obtained on 12 men on four occasions separated by 1 week between tests demonstrated a coefficient of variation of 1.8%. Percentage body fat and bone mineral density were obtained using dual-energy X-ray absorptiometry (DEXA) with a total body scanner (Prodigy; Lunar Corporation, Madison, Wis., USA) that uses a constant potential X-ray source of 76 kVp and a cerium filter that produces dual-energy peaks of 38 and 62 keV. All analyses were performed by the same technician using computer algorithms (software version 2.17.008). Quality assurance was assessed by analyzing a phantom spine provided by the company and daily calibrations were performed prior to all scans using a calibration block provided by the manufacturer. Intra-class correlation coefficients (Rge0.98) were obtained for bone mineral content, lean body mass, and fat mass from repeated scans on a group of ten men and women in our laboratory who were tested on 2 consecutive days.
Side effects

Resting pulse was measured by palpation of the radial artery and blood pressure was measured with a sphygmomanometer by the same investigator. In order to assess potential side effects and subjective changes in body function to the supplementation regimen a questionnaire used in prior creatine studies by our laboratory (Volek et al. 2000, 2001) was provided to subjects at the end of the study. The questionnaire asked subjects which group they thought were in and assessed changes in appetite, thirst, skin, muscle cramping, stomach distress, diarrhea, flatulence, headache, sex drive, sleepiness, nervousness, and aggression.
Biochemical analyses

Blood samples were obtained before and after each training week via venipuncture, after 5 min in a supine position, in the early morning hours (between 0500 and 0930 hours), and after a 10-h overnight fast and abstinence from exercise for at least 12 h. Blood sampling occurred during a standardized time of day for each subject in order to minimize the effects of diurnal hormonal variations. Whole blood samples were processed and centrifuged at 1,500 g. Serum and/or plasma was harvested and stored at –80°C until analyzed. Whole blood was used to determine hemoglobin in duplicate using the cyanmethemoglobin method at 540 nm (Sigma Diagnostics, St. Louis, Mo., USA) and hematocrit was analyzed in triplicate via standard microcapillary techniques and microcentrifugation. Serum glucose concentrations were measured in duplicate using standard colorimetric procedures at 450 nm (Sigma Diagnostics). Serum creatine kinase (CK) and plasma ammonia concentrations were determined in duplicate using standard colorimetric procedures at 340 nm (Sigma Diagnostics). Serum uric acid concentrations were determined in duplicate using standard colorimetric procedures at 520 nm (Sigma Diagnostics). Serum total testosteron, human GH, sex-hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), insulin, and cortisol concentrations were determined in duplicate using standard radioimmunoassay (RIA) techniques. Serum total testosteron, cortisol, insulin, and SHBG were measured with 125I solid-phase RIA (Diagnostic Products, Los Angeles, Calif., USA). Serum IGF-1 was measured with 125I solid-phase RIA using an extraction procedure (Diagnostic Products). Serum 22 kDa GH was measured using a 125I liquid-phase RIA with double-antibody technique (Nichols Institute Diagnostics, San Juan Capistrano, Calif., USA). All samples for each hormone were determined in duplicate in the same assay to avoid interassay variance and were thawed only once for each assay procedure. Intra-assay variance was less than 5% for all hormones.
Statistical analyses

Statistical evaluation of the data was accomplished by using a two-way analysis of variance (ANOVA) with one between- (CrM and P) and one within- (time) factor after normal data distribution was determined. When a significant F value was achieved, a Fisherrsquos LSD test was used to locate the pairwise differences between means. An independent t-test was used to analyze the delta change in performance improvements between 0 and 6 weeks of the study. Relationships among baseline hormones and the changes in hormone concentrations to changes in performance and body composition measures were examined using Pearsonrsquos product-moment correlation coefficients. Using the nQuery Advisor software (Statistical Solutions, Saugus, Mass., USA) the statistical power for the n size used ranged from 0.80 to 0.92. Significance was set at Ple0.05.
Results
Performance
There were significant main time effects for 1-RM squat and bench press and a significant interaction effect for the squat when considering the change from week 0 to week 1 (Fig. 1). Maximal squat was unchanged at week 1 in CrM and progressively increased each week thereafter. However, 1-RM squat was significantly reduced after week 1 in P but returned to baseline values by week 2. 1-RM bench press significantly decreased in P but remained unchanged in CrM at week 1, was not different from baseline at week 2, and progressively increased each week thereafter. Analysis of the delta change in 1-RM squat performance from weeks 0–6 revealed only a trend for greater improvement in CrM than P (P=0.09) but not with the 1-RM bench press. There were significant main time effects for explosive peak power in the jump squat and a significant time and interaction effect for the ballistic bench press (Fig. 2). Jump-squat peak power was unchanged at weeks 2 and 4 and significantly increased after the reduced frequency/volume phase. There was a trend for the CrM group to experience a greater increase at week 6 (group×time, P=0.154). Ballistic bench press peak power significantly decreased at week 2 in P but did not change in CrM (group×time, P=0.053) and was significantly higher at weeks 4 and 6 in CrM than P. The decline in mean power during the 20 repetition jump squat protocol ranged between –12% and –14% for both groups. Power output was unchanged at weeks 2 and 4 but increased significantly after the reduced volume/frequency phase at week 6 (Table 2).
MediaObjects/s00421-003-1031-zfhb1.jpg
Fig. 1 Maximal squat (upper graph) and bench press (lower graph) strength during 4 weeks of resistance training overreaching and after a 2-week reduced volume/frequency phase. Data analyzed with a 2×6 (weeks 0–6) and 2×2 (week 0–1) ANOVA. *Ple0.05 from baseline for collapsed means; #significant (Ple0.05) group×time (week 0–1) interaction effect. Values are mean (SE).
MediaObjects/s00421-003-1031-zfhb2.jpg
Fig. 2 Peak power during the jump squat (upper graph) and ballistic bench press (lower graph) during 4 weeks of resistance training overreaching and after a 2-week reduced volume/frequency phase. There were significant main time effects and a group×time interaction effect for the ballistic bench press. *Ple0.05 from baseline for collapsed means (upper graph) and from corresponding creatine or placebo baseline (lower graph). Values are mean (SE).

Table 2 Mean power output (W) during the 20-repetition jump-squat protocol. Values are mean (SD). % Decline=[(mean power repetitions 1–5)–(mean power repetitions 16–20)/mean power repetitions 1–5]×100 *KNIP*


Body composition
There were significant main time effects for changes in total body mass, lean body mass, fat mass and percentage body fat (Table 3). The increases in body mass and lean body mass tended to be greater in the CrM group. A similar pattern of response was observed for the legs with the CrM group demonstrating a significantly greater increase in lean body mass in this region. Compared to baseline, total body water (kg) was significantly increased at weeks 1, 2, 3, and 4 in the creatine group. There were no significant changes in TBW expressed as a percent of body mass nor were there any changes in bone mineral content or bone mineral density for either group (data not shown).

Table 3 Total and regional body composition responses determined using dual-energy X-ray absorptiometry (DXA). Values are mean (SD). BM Body mass, LBM soft tissue lean body mass, FM fat mass, BMC bone mineral content *KNIP*

Hormonal responses
Hormonal responses are presented in Table 4. There were significant main time effects for total testosteron, free androgen index (FAI: total testosteron/SHBG), cortisol, and insulin, and a trend for SHBG (P<0.06). Total testosteron decreased in CrM and P, reaching a nadir at week 3 (–11% and –19%, respectively) and returning to baseline at week 4. Serum SHBG responded in an opposite direction to that of total testosteron. The FAI was significantly decreased at week 1 and reached the lowest point at week 3. Free testosteron responded in a similar fashion but the changes were not significant. The CrM group exhibited a significant increase in cortisol after week 1 (+29%), which returned to baseline by week 2; whereas cortisol was unchanged in the P group. Insulin levels were significantly depressed at week 1 and drifted back toward baseline during weeks 2–4. GH and IGF-I levels were not significantly altered over the training study. There were no significant relationships between baseline hormone levels or the changes in hormones with changes in performance or body composition.

Table 4 Blood hormonal responses in subjects who supplemented with creatine monohydrate (CrM) or placebo (P). Values are mean (SD). FAI Free androgen index, GH growth hormone, IGF-I insulin-like growth factor-I, SHBG sex hormone binding globulin, TT total testosteron *KNIP*

Blood metabolite responses
Metabolic responses are presented in Table 5. There was a significant time and interaction effect for uric acid. Uric acid increased in the P group at week 1 (+18%) and gradually returned to baseline by week 3, whereas values declined in the CrM group at week 1 (–11%) and remained below baseline through week 4. Ammonia values were reduced at week 1 and tended to remain below baseline through week 4. CK was significantly elevated at week 1 and returned toward baseline over the remainder of the study. Glucose was significantly lower at week 1 and remained below baseline through week 4. There were no significant changes in total cholesterol and triglycerides. Hemoglobin and hematocrit values were reduced at week 1 and remained below baseline through week 4. Plasma creatinine was significantly increased in the CrM group (+5–8%) and unchanged in the P group.

Table 5 Blood metabolite responses in subjects supplemented with creatine monohydrate (CrM) or placebo (P). Values are mean (SD). CK Creatine kinase, TC total cholesterol, TG triglycerides, Hb hemoglobin, Hct hematocrit *KNIP*

There were no significant changes in resting heart rate or blood pressure responses. Reported side effects were minimal and occurred at a similar frequency for both groups. The most common complaint was increased thirst (two placebo and three creatine subjects) and sleepiness (three creatine subjects). In the CrM group, seven subjects reported not knowing their supplement group and two thought they were in the P group. In the P group, two subjects reported not knowing their supplement group, five thought they were in the CrM group, and one thought he was in the P group.

Discussion

A major aim of this study was to assess whether the resting circulating hormonal milieu was altered by creatine supplementation and whether this was related to changes in performance and body composition during resistance training overreaching. The findings from this study indicate that alterations in resting hormones do not explain the performance and body composition responses to creatine supplementation and short-term resistance training overreaching in a group of men with similar training backgrounds. Although the overreaching protocol resulted in significant changes in the circulating endocrine milieu, creatine supplementation does not appear to be mediating its effect though hormonal mechanisms. These results were obtained in a homogenous group of resistance-trained men. We intentionally chose men with a resistance training background in order to reduce the large variations that can occur in strength gains at the onset of a structured program in untrained individuals (e.g., neural adaptations which could potentially mask any supplementation benefits). To further equate the training status of all subjects, we trained each subject for 4 weeks using a structured base program before matching and randomizing subjects into supplementation groups. This type of standardization is also necessary in order to minimize the effect of differences in hormone concentrations that may exist between subjects as a result of training.

Previous work indicates that 5–7 days of creatine supplementation does not alter hormonal responses to a single bout of heavy resistance exercise (Op lsquoT Eijnde and Hespel 2001; Volek et al. 1997a, 2001). However, exercise-induced (acute) and resting (chronic) hormone concentrations may be controlled by different regulatory mechanisms and reflect the systemrsquos ability to cope with an applied exercise stress versus a regulatory mechanism to which the involved tissues are constantly exposed (Fry et al. 1991). Since changes in resting hormones would be more likely to contribute to the changes in performance and body composition resulting from a training program, this study focused on the effects of creatine supplementation on resting hormones. The overreaching protocol resulted in significant decreases in total testosteron, FAI, and insulin whereas SHBG and cortisol were significantly increased.

The reduction in total testosteron was expected since it has been shown that resting total testosteron decreases during high volume or high intensity resistance training overreaching (Fry et al. 1993; Raastad et al. 2001). Although not significant, SHBG concentrations tended to increase more in the P group, which may have been due to the need to increase the carrying capacity of testosteron stimulated by a reduced availability of free testosteron. It has been previously shown that free testosteron also decreases when the volume anday/or intensity are significantly increased (Häkkinen et al. 1987; Häkkinen and Pakarinen 1991).

The significant increase in cortisol concentrations at week 1 in the CrM but not the P group was unexpected since we failed to observe changes in resting or exercise-induced levels of cortisol after 7 days of creatine supplementation in our prior work (Volek et al. 1997b, 2001). However, Op lsquoTeijnde and Hespel (2001) recently reported that cortisol levels were significantly higher 90 and 120 min after an acute bout of heavy resistance exercise following 5 days of creatine supplementation. Resting concentrations of cortisol have been shown to be highly variable over the course of various resistance training programs (Fry and Kraemer 1997). Generally, significant increases in volume or intensity result in higher resting concentrations of cortisol (Häkkinen et al. 1987; Häkkinen and Pakarinen 1991). The increased cortisol response at week 1 could have been due to a direct effect of creatine or more likely due to the greater force-producing capabilities (and exertion during training) exhibited by the CrM group.

Resting concentrations of serum 22-kD GH were not significantly altered by the resistance training program, which is consistent with our prior work in younger and older populations (Kraemer et al. 1999). A recent study demonstrated that creatine supplementation augmented the GH response to a bout of heavy resistance exercise (Schedel et al. 2000); however, creatine had no effect on GH responses to resistance exercise in another study (Op lsquoT Eijnde and Hespel 2001). GH has been shown to stimulate the release of IGF-I from the liver with peak values of IGF-I occurring approximately 16–28 h following GH stimulation (Copeland et al. 1980). Circulating IGF-I levels also tend to be more sensitive to changes in nutritional intake than exercise stress, and can be elevated by protein and carbohydrate supplementation in young men engaged in daily bouts of heavy resistance exercise (Kraemer et al. 1999). The results of the present study indicate that short-term resistance training overreaching, with or without creatine supplementation, does not alter resting concentrations of GH or IGF-1.

Resting serum glucose and serum insulin concentrations were reduced throughout the experimental period in both groups at several time points. These findings are unique as to our knowledge reductions in resting serum glucose have not typically been observed during resistance training. However, basal concentrations of insulin are not regulated by normal basal serum glucose concentrations (e.g., 80–100 mg/dl) and have been shown to be lower during strength training (Miller et al. 1984) and in bodybuilders with large muscle mass (Szczypaczewska et al. 1989). Although insulin secretion is pulsatile and a basal value may not be indicative of a positive training adaptation, our data support previous investigations and may show greater insulin sensitivity during resistance training overreaching.

In several of our performance measures, creatine supplementation generally resulted in improved performance responses to the overreaching protocol [i.e., maintenance of muscular performance during the high-volume phase, a statistically greater improvement in the ballistic bench press peak power output, and a tendency (P=0.09) for a greater improvement in week squat]. Several other studies have reported that creatine supplementation augments gains in muscular after resistance training programs lasting 3 weeks (Burke et al. 2000), 4 weeks (Arciero et al. 2001; Earnest et al. 1995; Kelly and Jenkins 1998; Kreider et al. 1998), 5 weeks (Stone et al. 1999), 6 weeks (Burke et al. 2001), 8 weeks (Noonan et al. 1998), 9 weeks (Bemben et al. 2001), 10 weeks (Vandenberghe et al. 1997), 12 weeks (Volek et al. 1999), and 13 weeks (Larson-Meyer et al. 2000). Unique to this study, the same muscle groups were trained 5 days in a row, thus reducing the amount of recovery time between workouts to less than 24 h. The mechanism for the performance improvements in the creatine group could be due to a number of factors, but a hormonal-mediated effect is not likely.

Creatine supplementation during resistance training has been shown to accentuate muscle fiber hypertrophy (Hespel et al. 2001; Volek et al. 1999), muscle cross-sectional area (Hespel et al. 2001), myosin heavy chain mRNA and protein expression (Willoughby et al. 2001), and whole body leucine oxidation and plasma leucine rate of appearance (Parise et al. 2001). In the present study, the CrM group gained more lean body mass and this was statistically significant in the legs. The magnitude of change in total body lean body mass (+3.4 kg) was slightly greater than previously reported gains ranging from 1.6 to 2.5 kg after 4 weeks of resistance training and creatine in previous studies (Arciero et al. 2001; Earnest et al. 1995; Kelly and Jenkins 1998; Kreider et al. 1998). This may be attributed to the overreaching program used in the present study. The short-term program used in the present study was periodized (i.e., variation in the volume and intensity) and supervised by a certified strength and conditioning specialist, thus ensuring optimal effort during training (Mazzetti et al. 2000). In addition, the subjects had ~5 years of resistance training experience. It has been shown that hypertrophy may be the major mechanism for strength improvement in trained individuals whereas neural mechanisms predominate in novice lifters (Häkkinen 1989). Thus, training status may have been an influential factor affecting the magnitude of lean body mass gain in the present study and in other studies using previously untrained individuals.

Serum concentrations of uric acid were significantly elevated in the P group, whereas values were reduced in the CrM group. Elevated concentrations of uric acid may reflect an intracellular energy deficit (via greater stimulation of the purine nucleotide cycle) and may be a possible indicator of training stress (Rowbottom et al. 1997). This suggestion was based on endurance training where uric acid was inversely correlated to endurance performance (Rowbottom et al. 1997). We recently reported that a moderate-intensity/high-volume squat protocol resulted in significant increases in resting uric acid concentrations for 4 days into recovery and that carnitine supplementation attenuated this response, presumably via increasing blood flow (Volek et al. 2002). Interestingly, creatine supplementation has been shown to increase limb blood flow measured by venous occlusive plethysmography (Arciero et al. 2001). The importance of creatine-induced effects on blood flow and biomarkers for exercise stress in mediating adaptations to resistance training warrants further investigation.

There were no changes in total cholesterol and triglycerides, which is consistent with our prior work (Volek et al. 2000). In contrast, creatine supplementation reduced triglycerides in subjects with moderate hypercholesteremia who maintained their habitual training (Earnest et al. 1996) and improved HDL-cholesterol and VLDL-cholesterol in healthy young athletic men who performed a combination of resistance and sprint/agility training (Kreider et al. 1998). As expected, there was a significant increase in serum creatinine (within normal ranges), which is consistent with prior work in healthy men (Volek et al. 2000, 2001). As muscle creatine breakdown has been shown to occur at a constant rate, this small increase in creatinine is likely a result of the larger muscle creatine stores after creatine supplementation. There were small but significant decreases in hemoglobin and hematocrit, which may have been due to increases in plasma volume. Alternatively, plasma proteins and erythrocytes may be broken down to support protein anabolism during stressful training. Hemolysis and subsequent reductions in blood hemoglobin has been shown to occur in endurance athletes but also during strength training as evidenced by reductions in blood hemoglobin and haptoglobin (Schobersberger et al. 1990).

In summary, the lack of correlation among the changes in resting circulating hormones and performance/body composition suggests that resting hormonal concentrations do not explain the performance and body composition responses to creatine supplementation during short-term resistance training overreaching in resistance-trained men. Our data do not, however, address acute post-exercise endocrine responses to a workout (i.e., those anabolic responses suggested to be the primary mediators of tissue growth and repair following resistance exercise), 24-h hormonal fluctuations, nor do they address hormone kinetics including potential affects at the level of synthesis/secretion, target tissue receptor interaction, or degradation of hormones. The increases in lean body mass with creatine supplementation are consistent with other resistance training studies.

Acknowledgements The authors would like to thank Michael Robertson, Scott and Heather Mazzetti, Craig Bankowski, Lisa Larkin, Cori Stahl, John Melish, Katie Baker, Rob Phares, Stacy Peterson, and Patty Burns for their assistance in the personal training of the subjects in this study. We kindly thank Twin Laboratories (Hauppauge, N.Y.) for providing the supplements for this study.

[Sp4rky]

Nutrition Volume 20, Issues 7-8 , July-August 2004, Pages 609-614

Review article

Scientific basis and practical aspects of creatine supplementation for
athletes

Jeff S. Volek

Available online 19 June 2004.


Abstract

A large number of studies have been published on creatine supplementation
over the last decade. Many studies show that creatine supplementation in
conjunction with resistance training augments gains in muscle strength and
size. The underlying physiological mechanism(s) to explain this ergogenic
effect remain unclear. Increases in muscle fiber hypertrophy and myosin
heavy chain expression have been observed with creatine supplementation.
Creatine supplementation increases acute weightlifting performance and
training volume, which may allow for greater overload and adaptations to
training. Creatine supplementation may also induce a cellular swelling in
muscle cells, which in turn may affect carbohydrate and protein
metabolism. Several studies point to the conclusion that elevated
intramuscular creatine can enhance glycogen levels but an effect on
protein synthesis/degradation has not been consistently detected. As
expected there is a distribution of responses to creatine supplementation
that can be largely explained by the degree of creatine uptake into
muscle. Thus, there is wide interest in methods to maximize muscle
creatine levels. A carbohydrate or carbohydrate/protein-induced insulin
response appears to benefit creatine uptake. In summary, the predominance
of research indicates that creatine supplementation represents a safe,
effective, and legal method to enhance muscle size and strength responses
to resistance training.

Introduction

Creatine supplementation has become one of the most popular ergogenic aids
among athletes and one of the most profitable for the supplement industry.
A relatively large scientific body of literature has been generated over
the past decade documenting the physiologic and performance effects of
creatine supplementation in diverse populations. The large number of
studies on creatine and widespread interest among scientists have prompted
many review papers covering broad topics[1, 2, 3 and 4] and those with a
specific focus in relation to acute performance, [5 and 6] training
adaptations, [7, 8 and 9] factors affecting muscle creatine uptake, [10]
pharmacokinetics, [11 and 12] therapeutic potential in neuromuscular and
other metabolic diseases, [13] use in adolescents [14] and the elderly,
[15] reasons for inconsistent results, [16] and potential adverse effects.
[17 and 18]

Although there are some inconsistencies, most studies on the effects of
creatine supplementation on exercise performance have demonstrated an
ergogenic effect.[9] These discrepancies may be due to the large
variability associated with muscle creatine uptake after creatine
supplementation, but this is difficult to assess because many studies do
not assess muscle creatine. Small samples and inadequate statistical power
to detect the small benefits afforded by creatine supplementation are
other possible explanations for the discordant findings between studies
that demonstrate an ergogenic effect of creatine and those that do not.
[16] Perhaps the most consistent and important finding for athletes is
that creatine supplementation in conjunction with resistance training
leads to greater gains in lean body mass, maximal strength, and
weight-lifting performance. [8] In this review we briefly discuss the
studies showing a beneficial effect of creatine on resistance-training
adaptations, with an emphasis on cellular effects and mechanisms of
action. Because significantly increasing muscle creatine levels appear to
be necessary to achieve the full benefits of creatine supplementation, we
also overview the most important factors contributing to muscle creatine
uptake. We conclude with more practical aspects related to the effects of
creatine supplementation on sports performance and issues related to
dosing and maximizing creatine delivery to muscle.

Effects of creatine supplementation on chronic reponses to training

There is evidence to indicate that athletes are ingesting creatine for
several months and often in conjunction with progressive
resistance-training programs.[19 and 20] As an example, Juhn et al. [19]
reported that collegiate baseball and football players ingest creatine for
3 and 5 mo, respectively, in the off-season to increase lean body mass and
strength. Athletes hope that increased muscle creatine and phosphocreatine
stores before exercise and accelerated phosphocreatine resynthesis after
exercise [21] will allow them to perform more repetitions of a given
exercise before fatigue. Although it is unknown if the potential benefits
of creatine in the weight room will translate into improved performance on
the playing field, the effects of creatine supplementation during
resistance training on tests of strength and lean body mass have been
documented. [8, 22 and 23]

Rawson and Volek[8] reported positive effects of creatine supplementation
during weight-lifting tasks in 17 of 22 studies reviewed. Specifically,
the average increase in muscle strength (1, 3, and 10 repetition maximum
[RM]) in individuals ingesting creatine was 8% greater than in individuals
ingesting placebo (20% versus 12%), and these gains were greater in
untrained subjects (untrained: 31%; trained: 14%). Also, creatine
supplementation plus resistance training resulted in a 14% difference in
weight-lifting performance (maximal number of repetitions at a given
percentage of maximal strength) in individuals ingesting creatine during
resistance training compared with individuals ingesting a placebo (26%
versus 12%). Further, recent meta-analyses by Branch [22] and Nissen and
Sharp [23] found that lean body mass and muscular strength improve with
creatine supplementation. Most recently, Volek et al. [24] examined
creatine supplementation during a high-volume resistance-training
overreaching program. Maximal squat and bench press and explosive power in
the bench press decreased during the initial weeks of training in subjects
ingesting placebo but not in subjects supplemented with creatine.
Explosive power in the bench press and a trend for greater improvement in
the maximal squat by the end of the training period also were observed in
subjects ingesting creatine. Thus, creatine supplementation appears to be
effective for maintaining muscular performance during the initial phase of
high-volume resistance-training overreaching (when performance decrements
are noted) and after the rebound phase of short-term resistance-training
overreaching. Overall, it appears that long-term use of creatine
supplements in those who are capable of significantly increasing their
muscle creatine levels with supplementation offers an advantage in terms
of lean tissue accretion and increased muscular strength.

Mechanisms of action

The physiologic mechanisms underlying increased muscle strength and
improved weight-lifting performance after creatine supplementation in
conjunction with resistance training are not known with certainty, but
several theories exist and have been investigated.
Direct effects of creatine on muscle growth and strength

Previous studies have indicated that resistance-exercise performance,
including tests of maximal one repetition and number of repetitions with a
given load, is increased after a short-term (5 to 7 d) creatine-loading
regimen.[24, 25 and 26] In one study, subjects were able to perform eight
more repetitions of bench press during a workout consisting of five sets
of bench press by using a load equal to the subject's 10-repetition
maximum before supplementation. [24] Thus, a portion of the greater
increases in strength observed with creatine supplementation in long-term
training studies is likely due to this acute effect of creatine loading.
In other words, part of the ergogenic effect of creatine supplementation
in training studies is independent of the resistance-training stimulus and
is due to the acute effects of creatine loading and subsequent increases
in muscle creatine levels.

One study has provided some indication of the relative contribution of
acute creatine loading to this independent effect of creatine. Arciero et
al.[27] compared strength gains after 4 wk of creatine supplementation in
a group who performed resistance training or no training. Maximal bench
press and leg press were increased 8% and 16%, respectively, in the group
using creatine without training and 18% and 42%, respectively, in the
group using creatine and resistance training. This study suggests that
approximately 40% of the increase in strength over a 4-wk training and
creatine supplementation period is due to the acute effects of creatine on
force production, with the remaining ergogenic effect due to some other
mechanism.

Effects of creatine on training volume

This increase in the ability to perform more repetitions with the same
weight (i.e., an increase in the volume of work) after creatine
supplementation could translate into greater gains in lean body mass and
strength if continued over several weeks of training. In other words,
there is probably an interaction between the increase in force-production
capabilities in a subject with elevated muscle creatine and the repeated
exposures to higher volume workouts. Studies that have monitored workloads
and repetitions during a training program have shown that creatine
supplementation increases the volume of work done as compared with
subjects consuming a placebo.[25 and 28] Syrotuik et al. [29] reported
that, when subjects taking creatine were required to perform the same work
as a placebo group, regardless of ability to perform a higher workload,
increases in muscle strength, weight-lifting performance, and lean body
mass were similar after an 8 wk resistance-training program. The findings
from this study are somewhat difficult to reconcile because they indicate
that all the benefits of creatine supplementation on performance gains to
resistance training are dependent on increased training volume. In another
study, a standardized electromyostimulation protocol was applied to
subjects' quadriceps femoris twice per week for 8 wk while they continued
unsupervised and unmonitored resistance training of the lower and upper
body. Creatine supplementation resulted in a similar increase in
quadriceps femoris cross-sectional area assessed with magnetic resonance
imaging of the stimulated leg, but the hypertrophic response was
significantly greater in the unstimulated than in placebo subjects. [30]
These data actually concurred with findings from Syrotuik et al. [29] in
that, when a standardized contractile stimulus is applied during a
resistance-training program, creatine supplementation does not appear to
have a stimulatory effect on muscle hypertrophy. The increase in the
cross-sectional area of the leg not exposed to electromyostimulation in
creatine subjects could be due to an increase in training volume, but
unfortunately this was not quantified. It appears that creatine
supplementation augments muscle size during voluntary resistance training
but not during voluntary resistance training plus electromyostimulation.
Additional work is warranted to address the role of increased training
volume in mediating the ergogenic effects of creatine during resistance
training.

Effects of creatine on muscle fiber hypertrophy

Regardless of the argument posed above, an increase a creatine-induced
enhancement of strength and particularly lean body mass responses to
resistance training necessitates that creatine interact in some manner
with known or postulated mechanisms of muscle fiber hypertrophy. Volek et
al.[25] first reported that creatine supplementation during 12 wk of heavy
resistance training results in significantly greater increases in type I,
IIA, and IIAB muscle fiber cross-sectional areas compared with placebo.
Recently, Burke et al. [28] reported that vegetarians and non-vegetarians
ingesting creatine had greater increases in type II but not in type I
fiber area after 8 wk of resistance training. Creatine supplementation
also has been shown to enhance hypertrophy of type I, IIA, and IIB muscle
fibers in response to 2 wk of leg immobilization followed by 10 wk of
knee-extension rehabilitation. [31] Tarnopolsky et al. [32] also reported
increased muscle fiber hypertrophy after 8 wk of resistance training in a
group who ingested creatine plus glucose, but the increase was similar to
that in a group provided with postexercise protein plus glucose.
Unfortunately, there was no control or placebo group in this study for
comparison, but the magnitude of increase in muscle fiber area (20%) was
comparable to that of other studies. There may be the potential for
additive effects of postexercise protein and carbohydrate and creatine
supplementation on muscle hypertrophy, but this has not been examined to
date.

Physiologic effects of creatine on muscle growth

Potential physiologic mechanisms underlying increases in muscle size have
been examined in other studies. Willoughby and Rosene[33] showed that
creatine supplementation results in significantly greater increases in
type I and II myosin heavy-chain (MHC) mRNA abundance and protein content
after 12 wk of resistance training, suggesting that an increase in MHC
synthesis may account in part for the greater increases in muscle size
with creatine supplementation. These results were consistent with work
done three decades ago showing that increased creatine availability
stimulates synthesis rates of animal cardiac and skeletal MHC. [34 and 35]
The apparent creatine-induced increase in MHC gene expression has been
postulated to be mediated by myogenic regulatory factors (MRFs). Hespel et
al. [31] showed that the increase in muscle hypertrophy after disuse
atrophy with creatine supplementation is directly related to the protein
expression of MRF4. Protein content of myogenin also was decreased by
creatine supplementation in this study. In agreement, Willoughby and
Rosene [36] reported that 12 wk of resistance training in conjunction with
creatine supplementation resulted in increased mRNA expression and protein
content of MRF4, but in contrast to Hespel et al., [31] myogenin
expression increased instead of decreased. The increases in MRF4 and
myogenin protein content were strongly correlated to muscle creatine
kinase mRNA expression. Collectively, these studies indicate that creatine
supplementation and resistance training influence expression of certain
MRFs that possibly upregulate expression of skeletal muscle MHC and
creatine kinase, which in turn could explain greater increases in muscle
size and strength. It remains unclear whether creatine has a direct effect
on expression of MRF and MHC or, as discussed above, whether the effect is
indirectly mediated through a greater training volume.

Effects of creatine on glycogen storage

Creatine has been shown to increase total body water including
intracellular water.[37] Experimentally, changes in the cellular water
content have been shown to influence glycogen levels. [38] Thus, there is
reason to hypothesize that elevated intramuscular creatine may influence
glycogen levels. Six studies have measured skeletal muscle glycogen levels
in humans after creatine supplementation ( Table I), with five showing a
stimulatory effect[39, 40, 41, 42 and 43] and one showing no effect. [44]

TABLE I. Studies that have assessed the effects of creatine
supplementation on muscle glycogen levels

Robinson et al.[39] first showed that creatine supplementation in
conjunction with a high-carbohydrate diet for 5 d after exhaustive
exercise results in 23% greater increases in muscle glycogen as compared
with a high-carbohydrate diet without creatine. Nelson et al. [40] showed
that a 3-d muscle glycogen-loading protocol that resulted in 41% increases
in muscle glycogen was augmented by an additional 12% when followed by a
5-d creatine-loading period. Op ′t Eijnde et al. [41] showed that
creatine supplementation had no effect on muscle glycogen during 2 wk of
leg immobilization but augmented levels 46% greater than placebo during 3
wk of strength-training rehabilitation. In a follow-up study that involved
a 2-wk leg immobilization and 6-wk rehabilitation-training phase, this
group showed that creatine supplementation augmented post-training muscle
glycogen 35% greater than placebo. [42] Van Loon et al. [43] recently
showed a 5-d creatine-loading regimen augmented muscle glycogen by 14%
compared with no change in the placebo group, but there was no difference
in glycogen levels after a 6-wk maintenance period consisting of 2.5 g/d
of creatine. This maintenance dose was not effective at maintaining
elevated muscle creatine. This study further showed a significant relation
between changes in muscle creatine (mean increase of 32%) and muscle
glycogen during the loading phase, suggesting that significantly
increasing muscle creatine is a prerequisite to augmenting glycogen
storage. This may explain the lack of a significant effect of creatine
loading on muscle glycogen reported previously by this same group [44]
because total muscle creatine was increased by only 12%. The performance
implications of the apparent stimulatory effect of creatine on glycogen
are unclear. This could explain in part the ergogenic effect of creatine
on training-induced improvements in weight-lifting performance because
enhanced glycogen levels have been shown to affect high-intensity exercise
performance in some studies, [45 and 46] including resistance exercise.
[47 and 48]

Effects of creatine on cellular swelling and protein synthesis

In addition to augmenting glycogen storage, cellular water content may
influence protein metabolism.[49] Because the majority of work showing an
effect of cellular hydration on protein metabolism (i.e., cell swelling
increases protein synthesis and cell shrinkage increases protein
breakdown) has been done in cultured hepatocytes, the validity of this
cellular hydration theory to explain the anabolic effect of creatine has
been difficult to substantiate. However, recent work in humans made
hypo-osmotic (which subsequently increases cell volume) resulted in
significantly lower rates of whole-body protein breakdown compared with
iso- and hyperosmotic conditions. [50 and 51] Whether the increases in
intracellular water with creatine are of sufficient magnitude to influence
measures of protein synthesis or breakdown remains unclear.

Another approach to addressing the mechanism of action responsible for
greater increases in muscle size with creatine is to measure protein
synthesis and breakdown. Creatine supplementation may increase rates of
muscle protein synthesis and/or decrease protein breakdown. Parise et
al.[52] first examined the effects of 5 d of creatine loading on resting,
fasting protein kinetics by using a primed continuous intravenous infusion
of labeled leucine, which allows for calculation of mixed muscle protein
fractional synthetic rate and whole-body protein breakdown from leucine
oxidation and leucine rate of appearance. Creatine had no effect on muscle
protein synthesis but significantly decreased measures of whole-body
protein breakdown in men but not in women. It cannot be determined whether
this anticatabolic effect of creatine is specific to skeletal muscle or
some other tissue that turns over rapidly, and it still does not rule out
a possible effect of creatine on the synthetic rate of specific
contractile (i.e., myosin) or non-contractile protein not detected by the
mixed-muscle approach.

Two recent studies have indicated no effect of creatine on skeletal muscle
protein synthesis and breakdown.[53 and 54] Louis et al. [53] reported
that 5 d of creatine supplementation had no significant effect on measures
of myofibrillar protein synthesis and muscle protein breakdown obtained in
the postabsorptive or postprandial state. Reasoning that any effect of
creatine on protein kinetics might be observed only in association with
physical exercise, this same group performed a similar study to test
whether creatine in conjunction with acute resistance exercise (knee
extension and flexion) had an anabolic effect. [54] Similar to their prior
study which showed no effect of creatine on protein metabolism at rest,
they found no effect of 5 d of creatine supplementation on measures of
myofibrillar and sarcoplasmic fractional synthetic rates and protein
breakdown obtained at rest and in response to resistance exercise with
postexercise feeding. [54] Collectively these studies indicate that
short-term creatine loading does not have a significant effect on measures
of skeletal muscle protein balance. These studies involved a small number
of subjects under specific conditions using methods and calculations that
involve a variety of assumptions. Thus, creatine may affect aspects of
protein metabolism under different experimental conditions (i.e., more
intense resistance exercise, longer supplementation periods, older or
atrophied subjects, etc.).

Factors affecting skeletal muscle creatine uptake

After creatine supplementation, some individuals experience a marked
increase in muscle creatine concentrations (>30%), whereas others
experience little or no change.[55] Several factors can explain this large
intersubject variability, but initial muscle creatine content may be the
most important determinant of muscle creatine uptake after
supplementation. [55] For instance, subjects with lower muscle creatine
concentrations have the largest increase in muscle creatine after
supplementation, whereas subjects with higher muscle creatine
concentrations have little or no increase in muscle creatine after
supplementation ( Figure 1).

Fig. 1. Higher baseline muscle PCr concentrations are inversely
related to the increase in muscle PCr after creatine supplementation
(adapted from Rawson et al.[63 and 67]). PCr, phosphocreatine.

It has been known for many years that insulin enhances the transport of
creatine from the circulation into the skeletal muscle of rats.[56 and 57]
Supplement manufacturers exploited these early studies and marketed
supplements that combined creatine and simple sugars based on the
assumption that the simple sugars would produce a blood insulin spike that
would subsequently increase muscle creatine uptake. Several subsequent
studies addressed the influence of insulin on muscle creatine uptake in
humans by measuring muscle and urine creatine during creatine
supplementation with infused insulin, [58] carbohydrate ingestion, [59, 60
and 61] or combined protein and carbohydrate ingestion. [62]

Steenge et al.[58] demonstrated that insulin increases muscle creatine
accumulation in humans when present at physiologically high or
supraphysiologic concentrations. However, the use of insulin by athletes
to increase muscle creatine uptake is impractical and dangerous. In two
separate studies, Green et al. demonstrated reduced urine creatine losses
[60] and increased muscle creatine accumulation [59] in subjects ingesting
creatine concurrently with high-dose carbohydrate (≈ 90 g, four
times/d). However, these doses of carbohydrate are impractical because of
the caloric density (≈ 1400 kcal/d) and poor palatability. More
recent studies have examined the effects of carbohydrate and protein
combinations [62] and lower doses of carbohydrate [61] on muscle creatine
uptake. For instance, Steenge et al. [62] reported that the ingestion of
creatine with 50 g of protein and 50 g of carbohydrate results in similar
muscle creatine increases as ingesting creatine with approximately 100 g
of carbohydrate. Preen et al. [61] established that creatine
supplementation combined with 1 g of glucose per kilogram of body mass
twice per day increases muscle total creatine 9% more than creatine
supplementation alone.

Practical aspects of creatine supplementation

Maximizing creatine delivery

Blood creatine levels are sometimes used by manufacturers to indicate that
one creatine product has greater bioavailability than another. However,
the ergogenic effect of creatine supplementation is derived from increased
muscle phosphocreatine after supplementation, so plasma creatine values
without accompanying muscle creatine measurements may be misleading. For
instance, Rawson et al.[63] reported similar plasma creatine
pharmacokinetics between old and young subjects ingesting creatine, but a
greater increase (35% versus 7%) in muscle phosphocreatine uptake and
higher postsupplementation muscle phosphocreatine levels (27.6 versus 25.7
mM/kg) in young subjects. In addition, Rawson et al. [64] reported similar
plasma creatine pharmacokinetics after a 5-g oral creatine bolus on two
occasions separated by 30 d, although muscle phosphocreatine was 23%
higher at the beginning of bout 2. Thus, in the case of creatine, it is
important for consumers to know that blood levels of creatine may not
reflect muscle levels and thus are not indicative of muscle creatine
uptake.

Exercise performance in the laboratory versus sports performance in the field

Several hundred studies have examined the potential ergogenic effects of
creatine supplementation, and many support the hypothesis that creatine
supplementation can improve performance of short-term high-intensity
exercise. Recently, Kreider[9] reported that approximately 70% of
short-term studies on creatine supplementation report some ergogenic
benefit. Although creatine supplementation appears to improve performance
of short-term high-intensity exercise in controlled laboratory tests, [9
and 22] there is debate as to whether creatine supplementation can
influence sports-specific performance. [22] For instance, the recent
meta-analysis of 100 studies by Branch [22] found a significant
improvement in performance of repetitive bouts of laboratory-based
exercise tests but not of sports-specific performance tests such as
running or swimming after short-term creatine supplementation. The results
of studies that examined the effects of creatine supplementation on
sports-specific performance are not consistent. As an example, Redondo et
al. [65] reported no improvement in running velocity during a 60-m sprint,
whereas Skare et al. [66] reported increased velocity in a 100-m sprint
(11.68 s versus 11.59 s) and decreased total intermittent sprint time
performance (six 60-m sprints; 45.63 s versus 45.12 s) after creatine
ingestion. Thus, the effects of creatine supplementation on sports
performance in the field are controversial.

One factor that may account for the discrepancies in studies of creatine
supplementation on sports-specific performance is that the weight gain
associated with creatine ingestion could be detrimental to performance of
sports in which body mass is a factor (i.e., running) or for athletes
competing in sports in which weight classes are employed. In addition,
Rawson et al.[64] recently reported that after 5 d of creatine loading (20
g/d) muscle phosphocreatine remained elevated 30 d later. The increased
muscle phosphocreatine that persisted throughout the 30-d washout period
corresponded with maintenance of increased body mass (+2.0 kg). Thus,
athletes should be aware that the increase in muscle phosphocreatine that
remains for several weeks after cessation of the creatine supplement may
be accompanied by increased body mass.

Summary

A large number of studies has been published on creatine supplementation.
A substantial number of these studies has observed an ergogenic effect on
performance when muscle creatine levels are significantly elevated. It has
become apparent that accumulation of creatine in skeletal muscle or other
tissues affects a variety of cellular processes that could account for its
ergogenic and therapeutic potential. Recent work has started to provide a
better picture of the physiologic mechanisms by which creatine
supplementation affects skeletal muscle carbohydrate and protein
metabolism. Uncertainty remains as to the specific characteristics of
non-responders and optimal dosing strategies.

[alexis]

jeetje wat een lang verhaal.
wel boeiend

[George]

conclusie?

[Big T]

Dat het werkt

[Sp4rky]

Origineel gepost door TylW

Dat het werkt

uit diverse artikelen (ook andere dan hierboven) maak ik op dat relatief "ongetrainde" personen er meer voordeel van hebben dan de zwaar getrainde (aangezien je dan zelf al hoge reserves in de spier hebt opgebouwd).

is dit dan mogelijk een middel om sneller terug op niveau te komen, bijvoorbeeld nadat je door een blessure een aantal maanden nauwelijks of minder intensief hebt kunnen trainen?

[Big T]

Origineel gepost door Sp4rky

uit diverse artikelen (ook andere dan hierboven) maak ik op dat relatief "ongetrainde" personen er meer voordeel van hebben dan de zwaar getrainde (aangezien je dan zelf al hoge reserves in de spier hebt opgebouwd).

is dit dan mogelijk een middel om sneller terug op niveau te komen, bijvoorbeeld nadat je door een blessure een aantal maanden nauwelijks of minder intensief hebt kunnen trainen?

Ik denk dat het belangrijkste na een blessure is, dat je rustig aan begint om gewicht terug op te bouwen. De vraag is of creatine dan wel zo nuttig is. Sommigen gebruiken creatine om door een plateau te gaan, wat eigenlijk geen slecht idee is.

[Pat Bateman]

dit is wel zeer interessant:

The reduction in total testosteron was expected since it has been shown that resting total testosteron decreases during high volume or high intensity resistance training overreaching (Fry et al. 1993; Raastad et al. 2001). Although not significant, SHBG concentrations tended to increase more in the P group, which may have been due to the need to increase the carrying capacity of testosteron stimulated by a reduced availability of free testosteron. It has been previously shown that free testosteron also decreases when the volume anday/or intensity are significantly increased (Häkkinen et al. 1987; Häkkinen and Pakarinen 1991).

Betekend dit dat zwaar trainende krachtsporters minder aggressief zijn in het dagelijks leven, en een lager libido hebben?

[belikewater]

hoe kan Volek nou beweren dat Creatine veilig is, als er nog helemaal geen data uit longtitudinale studies verkrijgbaar is?