Creatine supplementation can improve impact control in high-intensity interval training.

OBJECTIVES: This study aimed to investigate the effects of creatine (Cr) supplementation on biomechanical parameters related to shock attenuation during a session of high-intensity interval training (HIIT). METHODS: A single-blinded, placebo-controlled, crossover design was adopted to test eight male elite soccer players during HIIT sessions under two conditions: after placebo supplementation and after Cr supplementation. HIIT test sessions consisted of an intermittent test (five bouts of running) with a constant load applied until exhaustion was reached. The vertical component of ground reaction force and electromyography data were recorded by Gaitway and Lynx-EMG Systems, respectively. Heart rate, rated perceived exertion (Borg's Scale) and lactate concentration information were also obtained. RESULTS: Cr supplementation did not affect heart rate, rated perceived exertion, and lactate concentration. Decreased values of magnitude of the first peak of the vertical component of ground reaction force (17.2-24.2%) and impulse of the first 50 ms (Imp50; 34.3%) were observed for Cr, but higher values of time to reach the first peak were detected for Cr compared with placebo. Significant modifications in muscle activation were also observed, mainly in the pre-activation phase, and changes were observed in intermediary bouts. CONCLUSIONS: Cr supplementation has the potential to influence biomechanical parameters related to impact control during a single session of HIIT based on running. In particular, the findings of the current study indicate possible improvements in shock attenuation and a safer practice of HIIT under Cr supplementation.

Acute exercise does not impair renal function in nondialysis chronic kidney disease patients regardless of disease stage.

Exercise has been overlooked as a potential therapy in chronic kidney disease (CKD), mainly because of a lack of understanding on its safety aspects. Notably, there are no data on renal function after exercise in CKD considering its stages. We investigated the acute effects of a 30-min moderate-intensity aerobic exercise bout on glomerular filtration rate (GFR) and albuminuria in 22 nondialysis CKD patients divided into: CKD stages 1 and 2 (CKD1-2) and CKD stages 3 and 4 (CKD3-4). Eleven body mass index-, age-, and sex-matched healthy individuals served as control (CON). Blood and urine samples were collected before, immediately after, and up to 90 min postexercise for creatinine and albumin assessments. GFR was determined by creatinine clearance (GFRCr-Cl). All CKD patients had significantly lower peak oxygen uptake than CON. CKD1-2 and CKD3-4 had increasingly higher serum creatinine than CON (9.6 ± 2.6, 25.6 ± 1.01, and 7.5 ± 1.4 mg/l, respectively); however, no within-group changes in serum or urinary creatinine were observed across time. GFRCr-Cl was decreased in CKD1-2 and CKD3-4 compared with CON (91 ± 17 ml·min-1·1.73 m-2; 34 ± 15 ml·min-1·1.73 m-2; 122 ± 20 ml·min-1·1.73 m-2, respectively). Most importantly, exercise did not affect GFRCr-Cl in none of the groups across time. Albuminuria was significantly higher in CKD3-4 (297 ± 284 µg/min) than in CON (5.4 ± 1.4 µg/min), but no within-group changes were observed after exercise. In conclusion, a single 30-min moderate-intensity aerobic exercise bout does not impair renal function in nondialysis CKD patients, regardless of disease stage, supporting the notion that exercise training can be safe in this disease.

Protein metabolism and physical training: any need for amino acid supplementation?

Muscle mass is the major deposit of protein molecules with dynamic turnover between net protein synthesis and degradation. In human subjects, invasive and non-invasive techniques have been applied to determine their skeletal muscle catabolism of amino acids at rest, during and after different forms of physical exercise and training. The aim of this review is to analyse the turnover flux and the relative oxidation rate of different types of muscle proteins after one bout of exercise as well as after resistance and endurance condition of training. Protein feeding in athletes appears to be a crucial nutrition necessity to promote the maintenance of muscle mass and its adaptation to the need imposed by the imposed technical requirements. In resting human individuals, there commended protein daily allowance is about 0.8 g (dry weight) kg−body weight per 24 h knowing that humans are unable to accumulate protein stores in muscle tissues. Nevertheless, practical feeding recommendations related to regular exercise practice are proposed to athletes by different bodies in order to foster their skills and performance. This review will examine the results obtained under endurance and resistance type of exercise while consuming single or repeated doses of various ingestions of protein products (full meat, essential amino acids, specific amino acids and derivatives, vegetarian food). From the scientific literature, it appears that healthy athletes(and heavy workers) should have a common diet of 1.25 g kg−24 h to compensate the exercise training muscle protein degradation and their resyn thesis within the following hours. A nitrogen-balance assay would berecommended to avoid any excessive intake of protein. Eventually, a daily equilibrated food intake would beof primer importance versus inadequate absorption of some specific by-products.

Nitrate supplementation and human exercise performance: too much of a good thing?

PURPOSE OF REVIEW: Ergogenic supplements in sport events are widely used by popular and competitive athletes to enhance performance and reduce oxygen cost. Beetroot juice and nitrate salts have been increasingly used for the past 5-6 years. The present review discusses the scientific background, the efficiency and potential adverse effects of excessive nitrate supplementation. RECENT FINDINGS: There is clear evidence that nitrate from different food ingredients (such as beetroot juice and other vegetables) is converted into nitrite and possibly into nitric oxide, which may promote vasodilation, angiogenesis and mitochondrial biogenesis. The high affinity of nitric oxide towards different enzyme pathways inhibits excessive mitochondrial respiration and, therefore, tissue oxygen consumption. In addition, L-arginine supplements are proposed to stimulate nitric oxide synthesis in the endothelium. On the basis of these biochemical properties, nitrate supplementation has been suggested to athletes to enhance exercise performance. SUMMARY: The recent publications in human individuals based on L-arginine, beetroot juice or nitrate supplementation revealed either a minor positive effect or no systematic effect on exercise performance, especially in trained athletes. Of note, the sugar content of whole beetroot juice might induce a slightly more pronounced effect. Although reasonable intake of nitrate salts (up to 1 g/day) has no detrimental effect on kidney function, the risk and benefit of higher nitrate intake needs to be evaluated to define the optimal range of supplementation.

ß-Alanine supplementation slightly enhances repeated plyometric performance after high-intensity training in humans.

ß-Alanine (BA) supplementation has become an ergogenic aid amongst competitive athletes to augment intramuscular carnosine content, leading to higher buffer capacity and exercise performance. We investigated 27 regularly trained young males and females who were randomly allocated either to placebo (PL) or BA ingestion for 8 weeks. Every single day, BA or PL (4.0-5.6 g day(-1)) supplements were ingested by participants and associated with a strong plyometric high-intensity training (two sessions per week during the 8 weeks). Before and after training, maximal jump heights were recorded during squat jump (SJ) and countermovement jump (CMJ) and an index of fatigue was recorded as a mean height of 45 consecutive CMJ. Blood lactate was measured at rest, after completing the fatigue test and every 5 min thereafter up to 30 min recovery. After plyometric training, SJ and CMJ were increased, respectively, by 8.8 and 6.4 % in PL group and 9.9 and 11.0 % in BA group (p < 0.01, no difference between groups). Blood lactate reached a maximal value of 9.4 ± 1.6 mmol l(-1) in PL group, and 10.3 ± 1.3 mmol l(-1) in BA group, with a slight better performance in the fatigue test (+8.6 %, p ≤ 0.01) for BA group as compared to PL group. To conclude, 2-month ß-alanine supplementation resulted in a slight improvement of explosive force after 45 maximal consecutive jumps in young athletes. However, the practical adequacy of supplementation remains questionable in an active and healthy population.

Nitrate Supplementation, Exercise, and Kidney Function: Are There Detrimental Effects?

PURPOSE: Recently, dietary supplementation with inorganic nitrate (NO3) has been proposed to endurance athletes to increase their performance. However, it has been suggested that an excess of NO3 might be harmful. The present study analyzed the effect of NO3 supplementation on kidney function. METHODS: Thirteen young male subjects performed a 20-min cycling exercise at 85% of the maximal oxygen capacity. Seven days before exercise, the subjects ingested either a placebo (Pl) or 450 mg of potassium nitrate (PN) per day. Venous blood samples and urine collections were collected before and immediately after exercise and after 60 min of recovery. Glomerular filtration rates (GFR) and clearances (Cl) were calculated from serum content and urine output for creatinine (Crn), albumin (Alb), and urea. RESULTS: Under resting conditions, GFR and all clearance measures did not differ between Pl and PN. Immediately after exercise, GFR remained stable in both Pl and PN, whereas Cl-urea decreased significantly (P < 0.05) in Pl (-44%) and PN (-49%). Alb urine outputs were enhanced by 18- to 20-fold in Pl and PN, respectively (P < 0.05). After the recovery period, GFR remained enhanced under Pl conditions, whereas Cl-urea returned to initial values in placebo and nitrate supplementation. Alb output and Cl-Alb remained enhanced under PN conditions. CONCLUSION: These results mainly indicate that dietary nitrate supplementation over a week does not induce any specific kidney function modifications either at rest or during sustained submaximal exercise as compared with Pl.

Limitations of serum values to estimate glomerular filtration rate during exercise.

OBJECTIVE: Glomerular filtration rate (GFR) is part of routine medical practice for clinical assessment of kidney function in health and disease conditions, and is determined by measuring the clearance of creatinine (Cl-Crn) or estimated (eGFR) from equations using serum creatinine (Crn) or cystatin C (Cyst C). Crn and Cyst C methods obviate the need for urine collection but their reliability under non-resting conditions is uncertain. This study compared GFR determined by Cl-Crn, Crn and Cyst C methods under the conditions of rest and after exercise. METHODS: Twelve young male subjects performed a 30 min treadmill exercise at 80% of the maximal oxygen capacity. Venous blood samples and urine collections were collected before and after exercise and after recovery period. GFR rates were calculated from serum Crn and Cyst C equations, and Cl-Crn measured from serum and urine Crn output. Albumin was also determined for all samples. RESULTS: Under resting conditions, eGFR from Crn and Cyst C did not differ from Cl-Crn (p=0.39). Immediately after exercise, GFR decreased significantly, regardless of the method, but more so for Cl-Crn (-30.0%; p<0.05) compared with Crn (-18.2%) and Cyst C (-19.8%). After the recovery period, GFR determined by Cl-Crn was returned to initial values whereas Crn and Cyst C remained reduced. Although eGFR methods accurately estimate GFR at rest, those methods underestimated the change in GFR after acute exercise. CONCLUSIONS: These results indicate that exercise-induced changes in GFR should be determined by Cl-Crn method.

Renewed avenues through exercise muscle contractility and inflammatory status.

Physical inactivity leads to the accumulation of visceral fat and, consequently, to the activation of a network of inflammatory pathways which may promote development of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. These conditions belong to the "diseasome of physical inactivity". In contrast, the protective effect of regular exercise against diseases associated with chronic inflammation may to some extent be ascribed to an anti-inflammatory effect. The so called "acute exercise threshold", the complex mixture of several variables involved in exercise, such as type, volume, frequency, and intensity range is capable of inducing positive physiological adaptations and has been specifically addressed in the recent literature. The major concern is related to the level of the threshold: "exercise training shifts from a therapeutic adaptive intervention to one with potential pathological consequences". Nonetheless, if the mechanical stimulus is too weak to disrupt cellular homeostasis, training adaptations will not occur. Answering these questions could present practical applications, especially during inflammatory diseases associated with detrimental muscle effects and could theoretically constitute a "new" therapeutic approach to treat/improve an inflammatory state. This paper aims to describe specific data from the literature regarding the effects of exercise on inflammatory diseases in order to promote a more sophisticated perspective on the anti-inflammatory effects of exercise.

Studies on the safety of creatine supplementation.

Doubtful allegations of adverse effects of creatine supplementation have been released through the press media and through scientific publications. In the present review we have tried to separate the wheat from the chaff by looking for the experimental evidence of any such claims. Anecdotal reports from athletes have appeared on muscle cramp and gastrointestinal complaints during creatine supplementation, but the incidence of these is limited and not necessarily linked to creatine itself. Despite several unproved allegations, liver (enzymes, urea) and kidneys (glomerular filtration urea and albumin excretion rates) show no change in functionality in healthy subjects supplemented with creatine, even during several months, in both young and older populations. The potential effects (production of heterocyclic amines) of mutagenicity and carcinogenicity induced by creatine supplementation have been claimed by a French Sanitary Agency (AFSSA), which might put consumers at risk. Even if there is a slight increase (within the normal range) of urinary methylamine and formaldehyde excretion after a heavy load of creatine (20 g/day) this is without effect on kidney function. The search for the excretion of heterocyclic amines remains a future task to definitively exclude the unproved allegation made by some national agencies. We advise that high-dose (>3-5 g/day) creatine supplementation should not be used by individuals with pre-existing renal disease or those with a potential risk for renal dysfunction (diabetes, hypertension, reduced glomerular filtration rate). A pre-supplementation investigation of kidney function might be considered for reasons of safety, but in normal healthy subjects appears unnecessary.

Effects of a combined essential amino acids/carbohydrate supplementation on muscle mass, architecture and maximal strength following heavy-load training.

Increase in myofibrillar protein accretion can occur in the very early post-exercise period and can be potentiated by ingestion of essential amino acid (EAA). Furthermore, strength exercise induces important disturbances in protein turnover, especially in novice athletes. The purpose of this investigation was to evaluate the effects of an EAA supplementation on muscle mass, architecture and strength in the early stages of a heavy-load training programme. 29 young males trained during 12 weeks. They were divided into a placebo (PLA) (n = 14) group and an EAA group (n = 15). At baseline, daily food intake and nitrogenous balance were assessed with a food questionnaire over 7 days and two 24-h urine collections. The effect of training on muscle mass was assessed by anthropometric techniques. Muscle thickness and pennation angle were recorded by ultrasonography of the gastrocnemius medialis (GM). Maximal strength during squat and bench press exercises were tested on an isokinetic ergometer. Training resulted in significant increase in muscle mass and strength in both PLA and EAA groups. Positive linear regressions were found between nitrogen balance and increase in muscle mass in the PLA group (P < 0.01, r2 = 0.63) and between the initial strength and the increase in muscle strength in the EAA group (P <0.05, r2 = 0.29). EAA ingestion resulted in greater changes in GM muscle architecture. These data indicate that EAA supplementation has a positive effect on muscle hypertrophy and architecture and that such a nutritional intervention seems to be more effective in subject having lower nitrogen balance and/or lower initial strength.

Exploring the therapeutic role of creatine supplementation.

Creatine (Cr) plays a central role in energy provision through a reaction catalyzed by phosphorylcreatine kinase. Furthermore, this amine enhances both gene expression and satellite cell activation involved in hypertrophic response. Recent findings have indicated that Cr supplementation has a therapeutic role in several diseases characterized by atrophic conditions, weakness, and metabolic disturbances (i.e., in the muscle, bone, lung, and brain). Accordingly, there has been an evidence indicating that Cr supplementation is capable of attenuating the degenerative state in some muscle disorders (i.e., Duchenne and inflammatory myopathies), central nervous diseases (i.e., Parkinson's, Huntington's, and Alzheimer's), and bone and metabolic disturbances (i.e., osteoporosis and type II diabetes). In light of this, Cr supplementation could be used as a therapeutic tool for the elderly. The aim of this review is to summarize the main studies conducted in this field and to highlight the scientific and clinical perspectives of this promising therapeutic supplement.

The effect of 5 days of aspartate and asparagine supplementation on glucose transport activity in rat muscle.

The consumption of protein supplements containing amino acids is increasing around the world. Aspartate (Asp) and asparagine (Asn) are amino acids metabolized by skeletal muscle. This metabolism involves biochemical pathways that are involved in increasing Krebs cycle activity via anaplerotic reactions, resulting in higher glutamine concentrations. A connection between amino acid supplementation, glycogen concentration, and glucose uptake has been previously demonstrated. The purpose of this study was to evaluate the effect of Asp and Asn supplementation on glucose uptake in rats using three different glycogen concentrations. The results indicate that Asp and Asn supplementation in rats with high glycogen concentrations (fed state) further increased the glycogen concentration in the muscle, and decreased in vitro 2-deoxyglucose (a glucose analog) uptake by the muscle at maximal insulin concentrations. When animals had a medium glycogen concentration (consumed lard for 3 days), glucose uptake was higher in the supplemented group at sub-maximal insulin concentrations. We conclude that supplementation of Asp and Asn reduced glucose transport in rat muscle only at higher levels of glycogen. The ingestion of lard for 3 days changed the responsiveness and sensitivity to insulin, and that group had higher levels of insulin sensitivity with Asp and Asn supplementation.

Urinary creatine and methylamine excretion following 4 x 5 g x day(-1) or 20 x 1 g x day(-1) of creatine monohydrate for 5 days.

In this study, we examined the effect of two creatine monohydrate supplementation regimes on 24-h urinary creatine and methylamine excretion. Nine male participants completed two trials, separated by 6 weeks. Participants ingested 4 x 5 g x day(-1) creatine monohydrate for 5 days in one trial and 20 x 1 g x day(-1) for 5 days in the other. We collected 24-h urine samples on 2 baseline days (days 1-2), during 5 days of supplementation (days 3-7), and for 2 days post-supplementation (days 8-9). Urine was assayed for creatine using high-performance liquid chromatography and methylamine using gas chromatography. Less creatine was excreted following the 20 x 1 g x day(-1) regime (49.25 +/- 10.53 g) than the 4 x 5 g x day(-1) regime (62.32 +/- 9.36 g) (mean +/- s; P < 0.05). Mean total excretion of methylamine (n = 6) over days 3-7 was 8.61 +/- 7.58 mg and 24.81 +/- 25.76 mg on the 20 x 1 g x day(-1) and 4 x 5 g x day(-1) regimes, respectively (P < 0.05). The lower excretion of creatine using 20 x 1 g x day(-1) doses suggests a greater retention in the body and most probably in the muscle. Lower and more frequent doses of creatine monohydrate appear to further attenuate formation of methylamine.

Nutritional habits of Flemish adolescent sprint athletes.

PURPOSE AND METHODS: To investigate dietary habits of Flemish adolescent track and field athletes using a 7-d weighed-food record. Besides adequacy for growth, development, and physical performance, dietary health aspects were considered. RESULTS: Twenty-nine girls and 31 boys, with minimum 2 yr of track and field training practice, were recruited. All participants had daily breakfast (girls 22.5% +/- 5.5% of total energy intake [TEI]; boys 19.8% +/- 7.3%). Fruit in girls and juices and sports drinks in boys were consumed mostly between meals (girls 21.3% +/- 8.1% of TEI; boys 24.3% +/- 10.1%). Soft drinks contributed considerably to energy intake between meals in both sexes. Protein intake (1.5 +/- 0.3 g . kg-1 . d-1 for both sexes) was within the recommended daily intake (RDI) for strength athletes. Mean daily carbohydrate intake in girls was lower than in boys (girls 5.1 +/- 1.1 g/kg; boys 6.0 +/- 0.9 g/kg), with mono- and disaccharides contributing 26% to TEI in both sexes. Total fat intake was above 30% of TEI in more than half the participants, and only 10 participants had a saturated-fat intake below 10% of TEI. Fiber intake (girls 23.7 +/- 7.9 g; boys 29.1 +/- 11.2 g) was far below the Belgian RDI. Intake of vitamins and minerals were generally low, despite micronutrient supplementation in 37.5% of the participants. CONCLUSION: Few athletes reached all nutrient RDIs. Unhealthy food habits with regard to refined sugars, fat, and micronutrients were observed. These adolescent sprinters should be encouraged to consume more nonsweetened beverages, fruits, and vegetables.

Kinetics of creatine ingested as a food ingredient.

The aim of the present study was to test if the consumption of creatine incorporated in food bars modifies creatine plasma kinetics, erythrocyte retention and loss in urine and in feces when compared with its consumption in the form of an aqueous solution (AS). Seventeen healthy young men ingested 2 g creatine either in the form of AS, or incorporated in a protein (PP)- or in a beta-glucan (BG)-rich food bar. Kinetics of plasma creatine was measured for 8-h duration and urinary excretion for 24 h. Then, the subjects received the same treatment thrice a day for 1 week at the end of which creatine contents were determined in erythrocytes and in feces (n = 4 for feces). The three crossover treatments were interspaced by a 40 +/- 1.2-day wash-out. Absorption of creatine was slowed down by 8-fold in the presence of BG (P < 0.001) and by 4-fold with PP (P < 0.001) whereas the velocity rate constant of elimination and the area under the curve were not modified. Urinary loss of creatine in the first 24 h following ingestion was 15 +/- 1.9% in AS and 14 +/- 2.2% in PP conditions (NS), whereas it was only 8 +/- 1.2% with BG (P = 0.004). Increase in creatine concentration in erythrocyte was similar in whatever form the creatine was ingested. Creatine seems to be totally absorbed since no creatine or creatinine was detectable in feces. No side effects were reported. In conclusion, ingestion of creatine combined with BG facilitates its retention by slowing down its absorption rate and reducing its urinary excretion.

Glomerular filtration rate and albumin excretion after maximal exercise in aging sedentary and active men.

BACKGROUND: From 30 years onwards there is a linear reduction of renal function of about 0.41% per year. Aging induces progressive impairment of glomeruli leading to an increase in protein excretion. The purpose of the present study was to investigate the effect of maximal exercise on glomerular filtration rate (GFR) and albumin excretion in an aging population. METHODS: This is a cross-sectional study from 213 healthy men, sedentary or endurance-trained, aged 20-30 and 50-80 years submitted to maximal exercise on a cycle ergometer. Blood and urine samples were obtained at rest and after the strenuous exercise. We evaluated the GFR by measuring creatinine clearance and the urine albumin excretion rate. RESULTS: After exercise, the older adults had a lesser reduction in GFR (mean 12%) than the young participants (mean 28%). As compared to those at rest, the increase of postexercise albumin excretion rates was lower in older participants (mean 7-fold) versus the young population (mean 20-fold). It appears that the exercise impact on some renal functions is related to the absolute load imposed on the individuals (r2 = 0.693). CONCLUSION: As far as GFR and urine albumin excretion are concerned, regular endurance training does not induce any signs of potential incipient nephropathy in a healthy aging population.

Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the "normobaric oxygen paradox".

Renal (peritubular) tissue hypoxia is a well-known physiological trigger for erythropoietin (EPO) production. We investigated the effect of rebound relative hypoxia after hyperoxia obtained under normo- and hyperbaric oxygen breathing conditions. A group of 16 healthy volunteers were investigated before and after a period of breathing 100% normobaric oxygen for 2 h and a period of breathing 100% oxygen at 2.5 ATA for 90 min (hyperbaric oxygen). Serum EPO concentration was measured using a radioimmunoassay at various time points during 24-36 h. A 60% increase (P < 0.001) in serum EPO was observed 36 h after normobaric oxygen. In contrast, a 53% decrease in serum EPO was observed at 24 h after hyperbaric oxygen. Those changes were not related to the circadian rhythm of serum EPO of the subjects. These results indicate that a sudden and sustained decrease in tissue oxygen tension, even above hypoxia thresholds (e.g., after a period of normobaric oxygen breathing), may act as a trigger for EPO serum level. This EPO trigger, the "normobaric oxygen paradox," does not appear to be present after hyperbaric oxygen breathing.

Side effects of creatine supplementation in athletes.

CONTEXT: Allegations about side effects of creatine supplementation by athletes have been published in the popular media and scientific publications. PURPOSE: To examine the experimental evidence relating to the physiological effects of creatine supplementation. RESULTS: One of the purported effects of oral creatine supplementation is increased muscle mass. A review of the literature reveals a 1.0% to 2.3% increase in body mass, which is attributed to fat-free mass and, more specifically, to skeletal-muscle mass. Although it is unlikely that water retention can completely explain these changes, increase in muscle-protein synthesis has never been observed after creatine supplementation. Indirect evidence based on mRNA analyses suggests that transcription of certain genes is enhanced. Although the effect of creatine on muscle-protein synthesis seems irrefutable according to advertising, this allegation remains under debate in the scientific literature. The kidneys appear to maintain their functionality in healthy subjects who supplement with creatine, even over several months. CONCLUSION: The authors, however, think that creatine supplementation should not be used by an individual with preexisting renal disease and that risk should be evaluated before and during any supplementation period. Even if there is a slight increase in mutagenic agents (methylamine and formaldehyde) in urine after a heavy load of creatine (20 g/day), their excretion remains within a normal range. No data are currently available regarding the potential production of heterocyclic amines with creatine supplementation. In summary, the major risk for health is probably associated with the purity of commercially available creatine.

Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate.

PURPOSE: It has been claimed that oral creatine supplementation might have potential cytotoxic effects on healthy consumers by increasing the production of methylamine and formaldehyde. Despite this allegation, there has been no scientific evidence obtained in humans to sustain or disprove such a detrimental effect of this widely used ergogenic substance. METHODS: Twenty young healthy men ingested 21 g of creatine monohydrate daily for 14 consecutive days. Venous blood samples and 24-h urine were collected before and after the 14th day of supplementation. Creatine and creatinine were analyzed in plasma and urine, and methylamine, formaldehyde, and formate were determined in 24-h urine samples. RESULTS: Oral creatine supplementation increased plasma creatine content 7.2-fold (P < 0.001) and urine output 141-fold (P < 0.001) with no effect on creatinine levels. Twenty-four-hour urine excretion of methylamine and formaldehyde increased, respectively, 9.2-fold (P = 0.001) and 4.5-fold (P = 0.002) after creatine feeding, with no increase in urinary albumin output (9.78 +/- 1.93 mg x 24 h(-1) before, 6.97 +/- 1.15 mg x 24 h(-1) creatine feeding). CONCLUSION: This investigation shows that short-term, high-dose oral creatine supplementation enhances the excretion of potential cytotoxic compounds, but does not have any detrimental effects on kidney permeability. This provides indirect evidence of the absence of microangiopathy in renal glomeruli.