Effects of creatine supplementation on performance and training adaptations

Creatine has become a popular nutritional supplement among athletes. Recent research has also suggested that there may be a number of potential therapeutic uses of creatine. This paper reviews the available research that has examined the potential ergogenic value of creatine supplementation on exercise performance and training adaptations. Review of the literature indicates that over 500 research studies have evaluated the effects of creatine supplementation on muscle physiology and/or exercise capacity in healthy, trained, and various diseased populations. Short-term creatine supplementation (e.g. 20 g/day for 5–7 days) has typically been reported to increase total creatine content by 10–30% and phosphocreatine stores by 10–40%. Of the approximately 300 studies that have evaluated the potential ergogenic value of creatine supplementation, about 70% of these studies report statistically significant results while remaining studies generally report non-significant gains in performance. No study reports a statistically significant ergolytic effect. For example, short-term creatine supplementation has been reported to improve maximal power/strength (5–15%), work performed during sets of maximal effort muscle contractions (5–15%), single-effort sprint performance (1–5%), and work performed during repetitive sprint performance (5–15%). Moreover, creatine supplementation during training has been reported to promote significantly greater gains in strength, fat free mass, and performance primarily of high intensity exercise tasks. Although not all studies report significant results, the preponderance of scientific evidence indicates that creatine supplementation appears to be a generally effective nutritional ergogenic aid for a variety of exercise tasks in a number of athletic and clinical populations.     

Creatine supplementation during college football training does not increase the incidence of cramping or injury

The purpose of this study was to examine the effects of creatine supplementation on the incidence of injury observed during 3-years of NCAA Division IA college football training and competition. In an open label manner, athletes participating in the 1998–2000 football seasons elected to take creatine or non-creatine containing supplements following workouts/practices. Subjects who decided to take creatine were administered 15.75 g of creatine for 5 days followed by ingesting an average of 5 g/day thereafter administered in 5–10 g doses. Creatine intake was monitored and recorded by research assistants throughout the study and ranged between 34–56% of players during the course of the study. Subjects practiced or played in environmental conditions ranging from 8–40°C (mean 24.7 ± 9°C) and 19–98% relative humidity (49.3 ± 17%). Injuries treated by the athletic training staff were recorded and categorized as cramping, heat/dehydration, muscle tightness, muscle strains/pulls, non-contact joint injuries, contact injuries, and illness. The number of missed practices due to injury/illness was also recorded. Data are presented as the total number of treated injuries for creatine users/total injuries observed and percentage occurrence rate of injuries for creatine users for all seasons. The incidence of cramping (37/96, 39%), heat/dehydration (8/28, 36%), muscle tightness (18/42, 43%), muscle pulls/strains (25/51, 49%), non-contact joint injuries (44/132, 33%), contact injuries (39/104, 44%), illness (12/27, 44%), number of missed practices due to injury (19/41, 46%), players lost for the season (3/8, 38%), and total injuries/missed practices (205/529, 39%) were generally lower or proportional to the creatine use rate among players. Creatine supplementation does not appear to increase the incidence of injury or cramping in Division IA college football players.     

URINARY CREATINE AT REST AND AFTER REPEATED SPRINTS IN ATHLETES: A PILOT STUDY

Creatine plays a key role in muscle function and its evaluation is important in athletes. In this study, urinary creatine concentration was measured in order to highlight its possible significance in monitoring sprinters. The study included 51 sprinters and 25 age- and sex-matched untrained subjects as a control group. Body composition was measured and dietary intake estimated. Urine samples were collected before and after standardized physical exercise. Creatine was assessed by gas chromatography mass spectrometry. Basal urinary creatine (UC) was significantly lower in sprinters than controls (34±30 vs. 74±3 µmol/mmol creatinine, p < 0.05). UC was inversely correlated with body mass (r = −0.34, p < 0.01) and lean mass (r = −0.30, p < 0.05), and positively correlated with fat mass (r = 0.32, p < 0.05). After acute exercise, urinary creatine significantly decreased in both athletes and controls. UC is low in sprinters at rest and further decreases after exercise, most likely due to a high uptake and use of creatine by muscles, as muscle mass and physical activity are supposed to be greater in athletes than untrained subjects. Further studies are needed to test the value of urinary creatine as a non-invasive marker of physical condition and as a parameter for managing Cr supplementation in athletes.     

Effect of a defined lacto-ovo-vegetarian diet and oral creatine monohydrate supplementation on plasma creatine concentration

This study examined the effects that preceding creatine supplementation with a lacto-ovo-vegetarian diet would have on plasma creatine concentration. Twenty-six healthy moderately fit omnivorous men were assigned to either a 26-day lacto-ovo-vegetarian (LOV; n = 12) or omnivorous (Omni; n = 14) diet. On day 22, subjects were also assigned in a double-blind manner either creatine monohydrate (CM; 0.3 g.kg(-1).day(-1) + 20 g Polycose) or an equivalent dose of placebo (PL) for 5 days. Blood samples were taken on days 1, 22 and 27. Consuming a LOV diet for 21 days was effective in reducing plasma creatine concentration (p < 0.01) in the LOV group. Regardless of diet, the CM group showed an increase in plasma creatine concentrations from day 22 to 27, whereas the PL group's levels remained the same (p < 0.05). Although the LOV diet caused a deprivation effect in plasma creatine concentration relative to the Omni diet, concurrent supplementation with creatine resulted in no difference in plasma creatine concentrations between the LOV and Omni diet groups. Dietary advice should be provided to LOV athletes that supplementation with creatine may help to increase their muscle stores of creatine, and thus their ATP resynthesis capabilities, to levels similar to those of omnivores.     

The effect of creatine supplementation upon inflammatory and muscle soreness markers after a 30km race

We have evaluated the effect of a creatine supplementation protocol upon inflammatory and muscle soreness markers: creatine kinase (CK), lactate dehydrogenase (LDH), prostaglandin E2) (PGE2) and tumor necrosis factor-alpha (TNF-alpha) after running 30km. Runners with previously experience in running marathons, with their personal best between 2.5-3h were supplemented for 5 days prior to the 30km race with 4 doses of 5g of creatine and 15g of maltodextrine per day while the control group received the same amount of maltodextrine. Pre-race blood samples were collected immediately before running the 30km, and 24h after the end of the test (the post-race samples). After the test, athletes from the control group presented an increase in plasma CK (4.4-fold), LDH (43%), PGE2 6.6-fold) and TNF-alpha (2.34-fold) concentrations, indicating a high level of cell injury and inflammation. Creatine supplementation attenuated the changes observed for CK (by 19%), PGE2 and TNF-alpha (by 60.9% and 33.7%, respectively, p<0.05) and abolished the increase in LDH plasma concentration observed after running 30km, The athletes did not present any side effects such as cramping, dehydration or diarrhea, neither during the period of supplementation, nor during the 30km race. All the athletes finished the race in a time equivalent to their personal best +/- 5.8%. These results indicate that creatine supplementation reduced cell damage and inflammation after an exhaustive intense race.     

Human skeletal muscle creatine transporter mRNA and protein expression in healthy,young males and females

The present study investigated whether there were any differences between males and females in respect to creatine transporter (CreaT) gene expression and/or total creatine (TCr) content in human vastus lateralis muscle. Skeletal muscle obtained from young healthy male (n = 13, age: 23.2 ± 5.0 years) and female subjects (n = 12, age: 21.7 ± 4.3 years) was analyzed for CreaT mRNA, CreaT protein and TCr content. Total CreaT protein content in the muscle was similar (p > 0.05) between the sexes. Two bands (~ 55 and 73 kDa) of the CreaT protein were detected in all muscle samples. Both the 55 and the 73 kDa bands were present in similar (p > 0.05) amounts in males compared with females. The 73 kDa band was in greater abundance (p < 0.05) than the 55 kDa band, irrespective of gender. In addition, CreaT mRNA expression relative to -actin mRNA and the TCr content (males: 117.8 ± 2.2, females: 125.3 ± 4.3 mmol.kg^–1 dry mass) were also unaffected (p > 0.05) by gender. These data demonstrate that gender does not influence skeletal muscle TCr content and CreaT gene expression in young human subjects.     

Creatine supplementation reduces oxidative stress biomarkers after acute exercise in rats

The objective of this study was to evaluate the effect of creatine supplementation on muscle and plasma markers of oxidative stress after acute aerobic exercise. A total of 64 Wistar rats were divided into two groups: control group (n = 32) and creatine-supplemented group (n = 32). Creatine supplementation consisted of the addition of 2% creatine monohydrate to the diet. After 28 days, the rats performed an acute moderate aerobic exercise bout (1-h swimming with 4% of total body weight load). The animals were killed before (pre) and at 0, 2 and 6 h (n = 8) after acute exercise. As expected, plasma and total muscle creatine concentrations were significantly higher (P < 0.05) in the creatine-supplemented group compared to control. Acute exercise increased plasma thiobarbituric acid reactive species (TBARS) and total lipid hydroperoxide. The same was observed in the soleus and gastrocnemius muscles. Creatine supplementation decreased these markers in plasma (TBARS: pre 6%, 0 h 25%, 2 h 27% and 6 h 20%; plasma total lipid hydroperoxide: pre 38%, 0 h 24%, 2 h 12% and 6 h 20%, % decrease). Also, acute exercise decreased the GSH/GSSG ratio in soleus muscle, which was prevented by creatine supplementation (soleus: pre 8%, 0 h 29%, 2 h 30% and 6 h 44%, % prevention). The results show that creatine supplementation inhibits increased oxidative stress markers in plasma and muscle induced by acute exercise.     

Adaptation of renal function to hypotonic medium in the winter flounder (Pseudopleuronectes americanus)

Summary The kidneys of winter flounders transferred to hypotonic medium were investigated for glomerular and tubular handling of fluid and electrolytes and for the urinary excretion of proteins. Media were sea water (925 mosm·kg^–1) and brackish water (70 mosm·kg^–1).In sea water, the urine was hypertonic to the plasma in 7 fish of this study. Urine flow rate was correlated with the GFR. After adaptation to brackish water a delay of 1 to 3 days was observed until the kidneys switched from fluid retention to the excretion of large amounts of dilute urine. GFR and urine flow rate were increased from 0.61±0.08 to 1.58±0.29 ml·h^–1·kg^–1 and from 0.14±0.02 to 0.68±0.08 ml·h^–1·kg^–1, respectively . With increased filtered load the tubular reabsorption of fluid decreased from 74±2.4% to 45±11.2%. The excretion rates of sodium and potassium were increased due to decreased fractional sodium and potassium reabsorption. The urinary excretion of divalent cations, however, was reduced because the net tubular reabsorption of calcium was increased and the net secretion of magnesium was diminished.Both the urinary total protein concentration and the protein pattern showed no significant change, but the rate of protein excretion was increased from 0.21±0.04 to 0.60±0.05 mg·h^–1·kg^–1. The comparison of protein patterns obtained from urine and serum samples revealed that high molecular weight (HMW) proteins prevail in the serum whereas low molecular weight (LMW) proteins dominate in the urine. The diminished quantity of the HMW-protein fraction in the urine thus may reflect size selectivity of the glomerular filtration barrier for serum proteins also in the winter flounder.Abbreviations BW brackish water - SW sea water - GFR glomerular filtration rate - HMW heigh molecular weight - LMW low molecular weight     

Biochemical consequences of electrical pacing in ischemic-reperfused isolated rat hearts

It is still unclear if performance recovery in postischemic hearts is related to their tissue level of high-energy phosphates before reflow. To test the existence of this link, we monitored performance, metabolism and histological damage in isolated, crystalloid-perfused rat hearts during 20 min of low-flow ischemia (90% coronary flow reduction) and reflow. To prevent interference from different ischemia times and perfusing media compositions, the ischemic ATP level was varied by changing energy demand (electrical pacing at 330 min–1). Under full coronary flow conditions, work output, as well as ATP and phosphocreatine contents were the same in control, spontaneously contracting (n = 23) and paced (n = 21) hearts. During low-flow ischemia, the higher work output (p < 0.0001) in paced hearts decreased their tissue content of ATP, phosphocreatine and total adenylates and purines (p < 0.05), as opposed to maintained values in control hearts. During reflow, the recovery of mechanical performance and O2 uptake was 94 ± 5% and 110 ± 9% (p = NS vs. baseline) in controls, vs. 71 ± 5% and 74 ± 6% in paced hearts (p < 0.004 vs. baseline). The levels of ATP and total adenylates and purines remained constant in control, but were markedly depressed (p < 0.05 vs. baseline) in paced hearts. Phosphocreatine+creatine was the same in both groups. These data, together with the observed lack of creatine kinase leakage and of structural damage, indicate that myocardial recovery during reflow reflects the tissue level of ATP, phosphocreatine and total adenylates and purines during ischemia, regardless of physical cell damage.     

Effects of supplementation with acai (Euterpe oleracea Mart.) berry-based juice blend on the blood antioxidant defence capacity and lipid profile in junior hurdlers. A pilot study

The purpose of this pilot study was to examine whether regular consumption of an acai berry-based juice blend would affect sprint performance and improve blood antioxidant status and lipid profile in junior athletes. Seven junior hurdlers (17.5±1.2 years) taking part in a pre-season conditioning camp were supplemented once a day, for six weeks, with 100 ml of the juice blend. At the start and the end of the camp the athletes performed a 300-m sprint running test on an outdoor track. Blood samples were taken before and immediately after the test and after 1 h of recovery. Blood antioxidant status was evaluated based on activities of antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px], glutathione reductase [GR]), concentrations of non-enzymatic antioxidants (reduced glutathione [GSH], uric acid), total plasma polyphenols, ferric reducing ability of plasma (FRAP), thiobarbituric acid reactive substances (TBARS) and activities of creatine kinase (CK) and lactate dehydrogenase (LDH) as muscle damage markers. In order to evaluate potential health benefits of the acai berry, the post-treatment changes in lipid profile parameters (triglycerides, cholesterol and its fractions) were analysed. Six weeks’ consumption of acai berry-based juice blend had no effect on sprint performance, but it led to a marked increase in the total antioxidant capacity of plasma, attenuation of the exercise-induced muscle damage, and a substantial improvement of serum lipid profile. These findings strongly support the view of the health benefits of supplementation with the acai berry-based juice blend, mainly attributed to its high total polyphenol content and the related high in vivo antioxidant and hypocholesterolaemic activities of this supplement.     

Catecholamines in fetal pig plasma and the response to acute hypoxia and chronic fetal decapitation

Summary Dopamine, norepinephrine and epinephrine were measured by radioenzymatic assay in blood plasma samples drawn from the umbilical arteries of 30 anaesthetised Landrace pig fetuses. Just prior to term, the concentrations of dopamine (0.46±0.14 ng·ml^–1) and norepinephrine (1.74±0.60 ng·mg^–1) were lower than earlier in gestation, whereas epinephrine concentrations at term (0.80±0.31 ng·ml^–1) were similar to those at mid-gestation, intervening stages of gestation having higher levels of plasma epinephrine. Fetal hypoxia was induced by clamping the umbilical cord for 2 min and the catecholamines determined in arterial blood samples immediately thereafter, then again 3 min after removal of the clamp. Inconsistent effects of cord clamping on catecholamine levels were seen at 55 days, but thereafter, in all but one instance, the hormone levels were increased. Fetuses near term tended to respond less than fetuses at 75 and 96 days gestation (term=114±1 day). Catecholamines were also present in the circulation of fetuses decapitated at 42 days gestation and studied at 109±1 days. The average concentrations of dopamine (1.12±0.27 ng·ml^–1) and norepinephrine (8.23±3.04 ng·ml^–1) were greater than in intact fetuses, the plasma epinephrine levels being comparable to, or slightly higher than, those in intact fetuses. The results demonstrate that catecholamines are present in the circulation of the intact and decapitated pig fetus and that the actual concentrations and the type of response to umbilical cord clamping are dependent on gestation age.     

Development, validation and application of assays to quantify metrifonate and 2,2-dichlorovinyl dimethylphosphate in human body fluids

Gas chromatographic procedures [GC with electron-capture detection (ECD) and GC–MS] for the quantitative analysis of metrifonate and its active metabolite 2,2-dichlorovinyl dimethylphosphate (DDVP) in human blood and urine were developed, validated, and applied to the analysis of clinical study samples. Analysis of metrifonate involved extraction of acidified blood with ethyl acetate followed by solid-phase clean-up of the organic extract. Acidified urine was extracted with dichloromethane and the residue of evaporated organic phase was reconstituted in toluene. ECD and diethyl analogue of metrifonate internal standard (I.S.) were used for quantitation of metrifonate. The metrifonate lower limit of quantitation (LOQ) was 10.0 μg/l. The DDVP metabolite was chromatographed separately after cyclohexane extraction of acidified blood and urine using d₆-DDVP I.S. and MS detection. The LOQ of DDVP was 1 μg/l. Stability studies have confirmed that the matrix should be acidified prior to storage at −20°C or −80°C to inhibit chemical and enzymatic degradation of the analytes and to avoid overestimation of DDVP concentrations. Metrifonate was found to be stable in acidified human blood after 20 months of storage at −20°C and after 23 months of storage at −80°C. Under these conditions DDVP was found to be stable after 12 months of storage. Both assay procedures were cross-validated by different world-wide laboratories and found to be accurate and robust during analyses of clinical study samples.     

Y chromosome haplogroups of elite Ethiopian endurance runners

Favourable genetic endowment has been proposed as part of the explanation for the success of East African endurance athletes, but no evidence has yet been presented. The Y chromosome haplogroup distribution of elite Ethiopian athletes (n=62) was compared with that of the general Ethiopian population (n=95) and a control group from Arsi (a region producing a disproportionate number of athletes; n=85). Athletes belonged to three groups: marathon runners (M; n=23), 5–km to 10–km runners (5–10K; n=21) and other track and field athletes (TF; n=18). DNA was extracted from buccal swabs and haplogroups were assigned after the typing of binary markers in multiplexed minisequencing reactions. Frequency differences between groups were assessed by using contingency exact tests and showed that Y chromosome haplogroups are not distributed amongst elite Ethiopian endurance runners in the same proportions as in the general population, with statistically significant (P<0.05) differences being found in four of the individual haplogroups. The geographical origins and languages of the athletes and controls suggest that these differences are less likely to be a reflection of population structure and that Y chromosome haplogroups may play a significant role in determining Ethiopian endurance running success.     

Prothrombin in Normal Human Cerebrospinal Fluid Originates from the Blood

In spite of the fact that prothrombin is produced by cells within the central nervous system, its presence in the cerebrospinal fluid (CSF) has not been investigated. We determined the concentration of prothrombin in CSF with reference to the concentration in plasma in paired samples from 18 normal control patients and 4 patients with relapsing-remitting type of multiple sclerosis (MS). The newly developed ELISA was very specific (no cross-reactivity with thrombin) and sensitive (detection limit—0.7 ng/ml) with an imprecision of CV = 8.3% (intraseries) and 7.0% (interassay). The mean prothrombin concentration in normal CSF was 0.55 mg/l (CV ± 33%, range: 0.28–0.93 mg/l), in normal plasma 121.8 mg/l ± 21%, resulting in a mean CSF/plasma concentration quotient (Q_Proth)—4.5 · 10^–3 (CV ± 35%, range: 2.1–8.3 · 10^–3) corresponding to a mean albumin quotient in this group of subjects of Q_Alb = 5.8 · 10^–3. Due to the Q_Proth and the molecular weight of prothrombin (72 kDa)—similar to that of albumin—we conclude that prothrombin in normal human CSF originates predominantly (>95%) from blood. The enzymatic activity in CSF is conserved. Comparable results obtained in MS patients with only few small MRI lesions suggest that local chronic inflammatory disease of the central nervous system does not influence prothrombin concentration in the CSF if the blood-CSF barrier function is normal.     

Subregional localization of the chromosome 21 loci D21S24 and D21S26 using physical mapping techniques

Summary We were able to refine the chromosomal position of two existing marker loci, using an extended chromosome 21 somatic cell hybrid panel. The locus D21S26 mapped in the region 21q11.2–q21.1, and the locus D21S24 in 21q22.1–q22.2. Physical and genetic analysis indicated that D21S26 is tightly linked to D21S13 and D21S16, two markers previously linked to familial Alzheimer's disease.     

Luteal blood flow increases during the first three weeks of pregnancy in lactating dairy cows

The objectives of this experiment were to characterize luteal blood flow in pregnant and non-pregnant cows and to determine its value for early pregnancy diagnosis. Lactating dairy cows (n = 54), 5.2 ± 0.2 y old (mean ± SEM), average parity 2.4 ± 0.2, and ≥ 6 wk postpartum at the start of the study, were used. The corpus luteum (CL) was examined with transrectal color Doppler ultrasonography (10.0-MHz linear-array transducer) on Days 3, 6, 9, 11, 13, 15, 18, and 21 of the estrus cycle (estrus = Day 0). Artificially inseminated cows (n = 40) were retrospectively classified as pregnant (embryonic heartbeat on Day 25; n = 18), nonpregnant (interestrus interval 15 to 21 d, n = 18), or having an apparent early embryonic loss (interestrus interval >25 d, n = 4). There was a group by time interaction (P < 0.001) for luteal blood flow from Days 3 to 18; it was approximately 1.10 ± 0.08 cm² (mean ± SEM) on Day 3, and increased to approximately 2.00 ± 0.08 cm² on Day 13 (similar among groups). Thereafter, luteal blood flow was numerically (albeit not significantly) greater in pregnant cows, remained constant in those with apparent embryonic loss, and declined (not significantly) between Days 15 and 18 in nonpregnant cows. Luteal blood flow was greater in pregnant than in nonpregnant (P < 0.05) and nonbred cows (P < 0.05, n = 14) on Day 15 (2.50 ± 0.16, 2.01 ± 0.16, and 2.00 ± 0.18 cm², respectively) and on Day 18 (2.40 ± 0.19, 1.45 ± 0.19, and 0.95 ± 0.21 cm²). In cows with apparent early embryonic loss, luteal blood flow was 2.00 ± 0.34 and 2.05 ± 0.39 cm² on Days 15 and 18, which was less (not significantly) than in pregnant cows, but greater (P < 0.05) than in nonbred cows on Day 18. Although mean luteal blood flow was significantly greater in pregnant than nonpregnant (and nonbred) cows on Days 15 and 18, due to substantial variation among cows, it was not an appropriate diagnostic tool for pregnancy status.     

Supplementation with antioxidants and folinic acid for children with Down’s syndrome: randomised controlled trial

Objectives To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down’s syndrome.Design Randomised controlled trial with two by two factorial design.Setting Children living in the Midlands, Greater London, and the south west of England.Participants 156 infants aged under 7 months with trisomy 21.Intervention Daily oral supplementation with antioxidants (selenium 10 μg, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo.Main outcome measures Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months.Results Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval −2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, −1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results.Conclusions This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down’s syndrome.Trial registration Clinical trials {"type":"clinical-trial","attrs":{"text":"NCT00378456","term_id":"NCT00378456"}}NCT00378456.     

Effects of repeated creatine supplementation on muscle, plasma, and urine creatine levels

The purpose of this case study was to examine the effects of repeated creatine administration on muscle phosphocreatine, plasma creatine, and urine creatine. One male subject (age, 32 years; body mass, 78.4 kg; height, 160 cm; resistance training experience, 15 years) ingested creatine (20 g.d(-1) for 5 days) during 2 bouts separated by a 30-day washout period. Muscle phosphocreatine was measured before and after supplementation. On day 1 of supplementation, blood samples were taken immediately before and hourly for 5 hours following ingestion of 5 g of creatine, and a pharmacokinetic analysis of plasma creatine was conducted. Twenty-four-hour urine collections were conducted before and for 5 days during supplementation. Muscle phosphocreatine increased 45% following the first supplementation bout, decreased 22% during the 30-day washout period, and increased 25% following the second bout. There were no meaningful differences in plasma creatine pharmacokinetic parameters between bouts 1 and 2. Total urine creatine losses during supplementation were 63.2 and 63.4 g during bouts 1 and 2, respectively. The major findings were that (a) a 30-day washout period is insufficient time for muscle phosphocreatine to return to baseline following creatine supplementation but is sufficient time for plasma and urine creatine levels to return to presupplementation values; (b) postsupplementation muscle phosphocreatine levels were similar following bouts 1 and 2 despite 23% higher presupplementation muscle phosphocreatine before bout 2; and (c) the increased muscle phosphocreatine that persisted throughout the 30-day washout period corresponded with maintenance of increased body mass (+2.0 kg). Athletes should be aware that the washout period for muscle creatine to return to baseline levels may be longer than 30 days in some individuals, and this may be accompanied by a persistent increase in body mass.     

Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after myocarditis

The cardioprotective properties of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of dilated cardiomyopathy. Twenty-eight days after immunization of pig cardiac myosin, four groups rats were given 0.2 mg/kg (Q0.2, n = 11), 2 mg/kg (Q2, n = 11) or 20 mg/kg (Q20, n = 11) of quinapril or vehicle (V, n = 15) orally once a day. After 1 month, left ventricular end-diastolic pressure (LVEDP), ±dP/dt, area of myocardial fibrosis, and myocardial mRNA expression of transforming growth factor (TGF)-1, collagen-III and fibronectin were measured. Four of 15 (27%) rats in V and two of 11 (18%) in Q0.2 died. None of the animals in Q2 or Q20 died. The LVEDP was higher and ±dP/dt was lower in V (14.1 ± 2.0 mmHg and +2409 ± 150/–2318 ± 235 mmHg/sec) than in age-matched normal rats (5.0 ± 0.6 mmHg and +6173 ± 191/–7120 ± 74 mmHg/sec; all p < 0.01). After quinapril treatment, LVEDP was decreased and ±dP/dt was increased in a dose-dependent manner (10.8 ± 1.8 mmHg and +3211 ± 307/–2928 ± 390 mmHg/sec in Q0.2, 9.4 ± 1.5 mmHg and +2871 ± 270/–2966 ± 366 mmHg/sec in Q2, and 6.6 ± 1.5 mmHg, and +3569 ± 169/–3960 ± 203 mmHg/sec in Q20). Increased expression levels of TGF-1, collagen-III and fibronectin mRNA in V were reduced in Q20. Quinapril improved survival rate and cardiac function in rats with dilated cardiomyopathy after myocarditis. Furthermore, myocardial fibrosis was regressed and myocardial structure returned to nearly normal in animals treated with quinapril.