Creatine supplementation and exercise performance: an update

Creatine, a natural nutrient found in animal foods, is alleged to be an effective nutritional ergogenic aid to enhance sport or exercise performance. Research suggests that oral creatine monohydrate supplementation may increase total muscle creatine [TCr], including both free creatine [FCr] and phosphocreatine [PCr]. Some, but not all, studies suggest that creatine supplementation may enhance performance in high-intensity, short-term exercise tasks that are dependent primarily on PCr (i.e., < 30 seconds), particularly laboratory tests involving repeated exercise bouts with limited recovery time between repetitions; additional corroborative research is needed regarding its ergogenic potential in actual field exercise performance tasks dependent on PCr. Creatine supplementation has not consistently been shown to enhance performance in exercise tasks dependent on anaerobic glycolysis, but additional laboratory and field research is merited. Additionally, creatine supplementation has not been shown to enhance performance in exercise tasks dependent on aerobic glycolysis, but additional research is warranted, particularly on the effect of chronic supplementation as an aid to training for improvement in competitive performance. Short-term creatine supplementation appears to increase body mass in males, although the initial increase is most likely water. Chronic creatine supplementation, in conjunction with physical training involving resistance exercise, may increase lean body mass. However, confirmatory research data are needed. Creatine supplementation up to 8 weeks has not been associated with major health risks, but the safety of more prolonged creatine supplementation has not been established. Creatine is currently legal and its use by athletes is not construed as doping.     

Effect of creatine supplementation on sprint exercise performance and muscle metabolism

The aim of the present study was to examine the effect of creatine supplementation (CrS) on sprint exercise performance and skeletal muscle anaerobic metabolism during and after sprint exercise. Eight active, untrained men performed a 20-s maximal sprint on an air-braked cycle ergometer after 5 days of CrS [30 g creatine (Cr) + 30 g dextrose per day] or placebo (30 g dextrose per day). The trials were separated by 4 wk, and a double-blind crossover design was used. Muscle and blood samples were obtained at rest, immediately after exercise, and after 2 min of passive recovery. CrS increased the muscle total Cr content (9.5 +/- 2.0%, P < 0.05, mean +/- SE); however, 20-s sprint performance was not improved by CrS. Similarly, the magnitude of the degradation or accumulation of muscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate, lactate, and glycogen) and plasma metabolites (e.g. , lactate, hypoxanthine, and ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These data demonstrated that CrS increased muscle total Cr content, but the increase did not induce an improved sprint exercise performance or alterations in anaerobic muscle metabolism.     

Prognostic factors for musculoskeletal sickness absence and return to work among welders and metal workers

The effect of creatine loading on endurance capacity and sprint performance was investigated in elite cyclists according to a double-blind cross-over study design. Subjects (n = 12) underwent on 3 occasions and separated by 5 week wash-out periods, a 2 h 30 min standardized endurance protocol on their own race bicycle, which was mounted on an electromagnetically braked roller-system, whereupon they cycled to exhaustion at their predetermined 4 mmol lactate threshold. Immediately thereafter they performed 5 maximal 10 second sprints, separated by 2 min recovery intervals, on a Monark bicycle ergometer at 6 kg resistance on the flywheel. Before the exercise test, subjects were either creatine loaded (C: 25 g creatine monohydrate/day, 5 days) or were creatine loaded plus ingested creatine during the exercise test (CC: 5 g/h), or received placebo (P). Compared with P, C but not CC increased (p<0.05) peak and mean sprint power output by 8-9% for all 5 sprints. Endurance time to exhaustion was not affected by either C or CC. It is concluded that creatine loading improves intermittent sprint capacity at the end of endurance exercise to fatigue. This ergogenic action is counteracted by high dose creatine intake during exercise.     

Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle

Interest in creatine (Cr) as a nutritional supplement and ergogenic aid for athletes has surged over recent years. After cellular uptake, Cr is phosphorylated to phosphocreatine (PCr) by the creatine kinase (CK) reaction using ATP. At subcellular sites with high energy requirements, e.g. at the myofibrillar apparatus during muscle contraction, CK catalyzes the transphosphorylation of PCr to ADP to regenerate ATP, thus preventing a depletion of ATP levels. PCr is thus available as an immediate energy source, serving not only as an energy buffer but also as an energy transport vehicle. Ingestion of creatine increases intramuscular Cr, as well as PCr concentrations, and leads to exercise enhancement, especially in sprint performance. Additional benefits of Cr supplementation have also been noticed for high-intensity long-endurance tasks, e.g. shortening of recovery periods after physical exercise. The present article summarizes recent findings on the influence of Cr supplementation on energy metabolism, and introduces the Cr transporter protein (CreaT), responsible for uptake of Cr into cells, as one of the key-players for the multi-faceted regulation of cellular Cr homeostasis. Furthermore, it is suggested that patients with disturbances in Cr metabolism or with different neuro-muscular diseases may benefit from Cr supplementation as an adjuvant therapy to relieve or delay the onset of symptoms. Although it is still unclear how Cr biosynthesis and transport are regulated in health and disease, so far there are no reports of harmful side effects of Cr loading in humans. However, in this study, we report that chronic Cr supplementation in rats down-regulates in vivo the expression of the CreaT. In addition, we describe the presence of CreaT isoforms most likely generated by alternative splicing.     

Caffeine counteracts the ergogenic action of muscle creatine loading

This study aimed to compare the effects of oral creatine (Cr) supplementation with creatine supplementation in combination with caffeine (Cr+C) on muscle phosphocreatine (PCr) level and performance in healthy male volunteers (n = 9). Before and after 6 days of placebo, Cr (0.5 g x kg-1 x day-1), or Cr (0.5 g x kg-1 x day-1) + C (5 mg x kg-1 x day-1) supplementation, 31P-nuclear magnetic resonance spectroscopy of the gastrocnemius muscle and a maximal intermittent exercise fatigue test of the knee extensors on an isokinetic dynamometer were performed. The exercise consisted of three consecutive maximal isometric contractions and three interval series of 90, 80, and 50 maximal voluntary contractions performed with a rest interval of 2 min between the series. Muscle ATP concentration remained constant over the three experimental conditions. Cr and Cr+C increased (P < 0.05) muscle PCr concentration by 4-6%. Dynamic torque production, however, was increased by 10-23% (P < 0.05) by Cr but was not changed by Cr+C. Torque improvement during Cr was most prominent immediately after the 2-min rest between the exercise bouts. The data show that Cr supplementation elevates muscle PCr concentration and markedly improves performance during intense intermittent exercise. This ergogenic effect, however, is completely eliminated by caffeine intake.     

Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers

In a double-blind and randomized manner, 18 male and female junior competitive swimmers supplemented their diets with 21 g.day-1 of creatine monohydrate (Cr) or a maltodextrin placebo (P) for 9 days during training. Prior to and following supplementation, subjects performed three 100-m freestyle sprint swims (long course) with 60 s rest/recovery between heats. In addition, subjects performed three 20-s arm ergometer maximal-effort sprint tests in the prone position with 60 s rest/recovery between sprint tests. Significant differences were observed among swim times, with Cr subjects swimming significantly faster than P subjects following supplementation in Heat 1 and significantly decreasing swim time in the second 100-m sprint. There was also some evidence that cumulative time to perform the three 100-m swims was decreased in the Cr group. Results indicate that 9 days of Cr supplementation during swim training may provide some ergogenic value to competitive junior swimmers during repetitive sprint performance.     

Efficacy of nutritional supplements used by athletes

Findings on the efficacy of nutritional supplements used by athletes are reviewed. Many athletes have turned away from anabolic steroids and toward nutritional supplements in the hope of gaining a competitive edge without threatening their health. Athletes may require slightly more protein than sedentary people do to maintain positive nitrogen balance, but it is dubious whether extra dietary protein will help someone to achieve athletic goals. Purified amino acids have become a popular if expensive form of protein supplementation; there is no scientific evidence, however, to support their use. Excessive protein supplementation can lead to dehydration, gout, liver and kidney damage, calcium loss, and gastrointestinal effects. Supplementation with vitamins and minerals in excess of recommended daily allowances appears to have no effect on muscle mass or athletic performance. Other substances touted as having ergogenic properties are carnitine, cobamamide, growth hormone releasers, octacosanol, and ginseng; again, there is no reliable scientific evidence to support claims that products containing these compounds have ergogenic potential, and heavy supplementation may lead to adverse effects. Nutritional supplements are promoted through unsubstantiated claims by magazine advertisements, health food stores, coaches, and other sources. The FDA considers nutritional supplements to be foodstuffs, not drugs, and therefore has not required that they be proved safe and effective. Dosage guidelines are inadequate, and quality control is poor. The FDA has begun to revise regulations governing labeling and health claims for these products. There is little if any evidence that nutritional supplements have ergogenic effects in athletes consuming a balanced diet, and some products have the potential for harm.     

Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons

OBJECTIVE: This study was undertaken to investigate the influence of oral supplementation with creatine monohydrate on muscular performance during repeated sets of high-intensity resistance exercise. SUBJECTS/DESIGN: Fourteen active men were randomly assigned in a double-blind fashion to either a creatine group (n = 7) or a placebo group (n = 7). Both groups performed a bench press exercise protocol (5 sets to failure using each subject's predetermined 10-repetition maximum) and a jump squat exercise protocol (5 sets of 10 repetitions using 30% of each subject's 1-repetition maximum squat) on three different occasions (T1, T2, and T3) separated by 6 days. INTERVENTION: Before T1, both groups received no supplementation. From T1 to T2, both groups ingested placebo capsules. From T2 to T3, the creatine group ingested 25 g creatine monohydrate per day, and the placebo group ingested an equivalent amount of placebo. MAIN OUTCOME MEASURES: Total repetitions for each set of bench presses and peak power output for each set of jump squats were determined. Other measures included assessment of diet, body mass, skinfold thickness, and preexercise and 5-minute postexercise lactate concentrations. RESULTS: Lifting performance was not altered for either exercise protocol after ingestion of the placebos. Creatine supplementation resulted in a significant improvement in peak power output during all 5 sets of jump squats and a significant improvement in repetitions during all 5 sets of bench presses. After creatine supplementation, postexercise lactate concentrations were significantly higher after the bench press but not the jump squat. A significant increase in body mass of 1.4 kg (range = 0.0 to 2.7 kg) was observed after creatine ingestion. CONCLUSION: One week of creatine supplementation (25 g/day) enhances muscular performance during repeated sets of bench press and jump squat exercise.     

Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase

1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.     

The role of intravenous amiodarone in the management of cardiac arrhythmias

PURPOSE: To review the electropharmacology, clinical applications, side effects, and hemodynamic profile of intravenous amiodarone. DATA SOURCES: The MEDLINE database was searched for English-language material, including reports of clinical trials and in vivo studies, review articles, and abstracts presented at national symposia, that was published between 1985 and 1996. Bibliographies of textbooks and articles were also examined. STUDY SELECTION: Studies that reported on the efficacy, toxicity, and hemodynamic profile of intravenous amiodarone and studies that examined the pharmacologic behavior of intravenous amiodarone in laboratory models were reviewed. DATA EXTRACTION: Study design and quality and relevant data on efficacy of suppression and treatment of arrhythmias with oral and intravenous amiodarone therapy, the reported mechanisms of antiarrhythmic effect, and hemodynamic changes seen with therapy were analyzed. DATA SYNTHESIS: Amiodarone is a unique antiarrhythmic agent that is now available in oral and intravenous forms in the United States. The use of intravenous amiodarone in the short-term treatment of life-threatening or hemodynamically unstable rhythm disturbances has generated much interest. Amiodarone has many electropharmacologic actions, some of which differ between the oral and intravenous forms. The wide clinical application of amiodarone includes treatment and prevention of supraventricular and ventricular arrhythmias and arrhythmias related to myocardial infarction. Intravenous amiodarone is effective for supraventricular and ventricular arrhythmias that are resistant to other antiarrhythmic agents. The effectiveness of intravenous amiodarone as short-term treatment also suggests that the drug has an important role in protocols of advanced cardiac life support. Intravenous amiodarone seems to have an overall favorable hemodynamic profile and does not produce many of the unwanted long-term side effects associated with oral therapy. CONCLUSION: Intravenous amiodarone shows much promise for the short-term treatment of unstable arrhythmias. Its favorable hemodynamic effects and minimal short-term side effects make it an attractive option in the management of cardiac arrhythmias.     

Introducing Critical Appraisal to studies of animal models investigating novel therapies in sepsis

OBJECTIVES: To discuss theoretical and practical aspects relating to the design of animal studies investigating the efficacy of novel therapeutic agents for the treatment of sepsis, and to make explicit the process whereby these studies can be evaluated for the purpose of designing clinical trials in humans. DATA SOURCES: Relevant articles from the pertinent literature were reviewed. STUDY SELECTION: Studies relevant to an evidence-based assessment of clinical studies on therapeutic efficacy, and studies relevant to the design of animal models of sepsis were selected. DATA EXTRACTION: Concepts relevant to an evidence-based assessment of the animal literature were extracted. DATA SYNTHESIS: Articles were reviewed and an evidence-based framework for the assessment of animal studies was developed. In this process, we discuss the steps that are necessary to assess the internal validity of an individual study and review topics relevant to the application of animal data to the design of clinical trials. CONCLUSIONS: The success of clinical trials of sepsis therapies is predicated on the generation and interpretation of sound preclinical data. In this review, we have attempted to outline an evidence-based approach to the assessment of preclinical animal studies evaluating novel therapeutic interventions in sepsis.     

The use of drugs to improve athletic performance

In sports, medical drugs are applied for supposedly ergogenic effects. Forbidden drug use (doping) implies that the drug enhances performance, which is not always the case. Amphetamines are ergogenic particularly during short-term, explosive exercise. Amphetamines exert an ergolytic effect on high-intensity endurance exercise. Caffeine has an ergogenic effect on endurance performance in dosages of 3 to 6 mg/kg. Doping regulations allow a small amount of caffeine intake. Androgenic and anabolic steroids elicit an increase in muscle growth and strength. In females low doses appear to be ergogenic in all sport types. beta 2-adrenergic agonists appear to have a positive effect on strength and muscle growth. The effects on endurance performance are still unknown. Although growth hormone is used in sports, scientific studies show that compared with placebo no difference in strength and muscle volume is observed. Blood doping and administration of erythropoietin are effective in enhancing endurance performance.     

Stimulation of insulin release and potentiation of the insulinotropic action of antidiabetic agents by 1,2,3-tri(methylsuccinyl)glycerol ester in anaesthetized rats

The study was designed to investigate the effect of creatine monohydrate ingestion (20 g daily for 5 days) on performance in 45 s maximal continuous jumping and in all-out treadmill running at 20 km x h(-1), (inclination 5 degrees, duration approximately 60s). The participants were qualified sprinters and jumpers. The effect of creatine was compared with placebo in a double-blind design. Creatine (Cr) supplementation led to a significant enhancement of performance capacity in the jumping test by 7% during the first 15 s and by 12% during the second 15 s of the exercise. The positive effect of Cr supplementation was not observed in the last third of the continuous jumping exercise, when the contribution of anaerobic metabolism was decreasing. The time of intensive running up to exhaustion improved by 13%. The results show that Cr supplementation helps to prolong the time during which the maximal rate of power output could be maintained.     

An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway

PURPOSE: To determine the effects of 28 d of creatine supplementation during training on body composition, strength, sprint performance, and hematological profiles. METHODS: In a double-blind and randomized manner, 25 NCAA division IA football players were matched-paired and assigned to supplement their diet for 28 d during resistance/agility training (8 h x wk[-1]) with a Phosphagen HP (Experimental and Applied Sciences, Golden, CO) placebo (P) containing 99 g x d(-1) of glucose, 3 g x d(-1) of taurine, 1.1 g x d(-1) of disodium phosphate, and 1.2 g x d(-1) of potassium phosphate (P) or Phosphagen HP containing the P with 15.75 g x d(-1) of HPCE pure creatine monohydrate (HP). Before and after supplementation, fasting blood samples were obtained; total body weight, total body water, and body composition were determined; subjects performed a maximal repetition test on the isotonic bench press, squat, and power clean; and subjects performed a cycle ergometer sprint test (12 x 6-s sprints with 30-s rest recovery). RESULTS: Hematological parameters remained within normal clinical limits for active individuals with no side effects reported. Total body weight significantly increased (P < 0.05) in the HP group (P 0.85 +/- 2.2; HP 2.42 +/- 1.4 kg) while no differences were observed in the percentage of total body water. DEXA scanned body mass (P 0.77 +/- 1.8; HP 2.22 +/- 1.5 kg) and fat/bone-free mass (P 1.33 +/- 1.1; HP 2.43 +/- 1.4 kg) were significantly increased in the HP group. Gains in bench press lifting volume (P -5 +/- 134; HP 225 +/- 246 kg), the sum of bench press, squat, and power clean lifting volume (P 1,105 +/- 429; HP 1,558 +/- 645 kg), and total work performed during the first five 6-s sprints was significantly greater in the HP group. CONCLUSION: The addition of creatine to the glucose/taurine/electrolyte supplement promoted greater gains in fat/bone-free mass, isotonic lifting volume, and sprint performance during intense resistance/agility training.     

Pathology of Penicillium marneffei. An emerging acquired immunodeficiency syndrome-related pathogen

OBJECTIVE: To summarize current knowledge regarding the opportunistic dimorphic fungal pathogen Penicillium marneffei. Clinical presentation, differential diagnosis, mycology, histopathology, diagnostic serology, in vitro antifungal agent susceptibility testing, and therapy are discussed for human immunodeficiency virus-infected individuals primarily living in Southeast Asia. DATA SOURCES: Critical evaluation of peer-reviewed publications located through an electronic literature database search, supplemented by unpublished observations, were used to prepare this report. STUDY SELECTION: Studies were selected based on either the fungal name Penicillium marneffei, penicilliosis, penicilliosis marneffei, or a combination of these. DATA EXTRACTION: Articles were reviewed with appropriate data being abstracted and then synthesized into the review. DATA SYNTHESIS: Differential diagnostic criteria for tissue diagnosis and laboratory identification of the fungus are detailed. The usefulness of mycoserology and antifungal therapy are evaluated. CONCLUSIONS: Penicillium marneffei is an emerging pathogen, primarily among patients with acquired immunodeficiency syndrome residing in Southeast Asia. Although infection caused by P marneffei is endemic to this portion of the world, cases are being diagnosed and treated involving individuals who have traveled to this region. Penicilliosis marneffei can clinically resemble tuberculosis, molluscum contagiosum, cryptococcosis, and histoplasmosis. The successful treatment of P marneffei infection is dependent on its rapid and accurate diagnosis.     

Educational and behavioral interventions for back pain in primary care

STUDY DESIGN AND OBJECTIVES: A review of the literature was undertaken to identify and summarize randomized trials of educational, cognitive, and behavioral interventions for people with chronic low back pain. SUMMARY OF BACKGROUND DATA: Studies of back schools have varied widely in patient characteristics, back school length and content, and comparison treatment. The available evidence suggests that back schools do not affect long-term outcomes of people with back pain. METHODS: MEDLINE and PsycLIT databases were searched to identify randomized trials of cognitive and behavioral treatments for chronic low back pain. Outcome data were extracted from articles that met the meta-analysis inclusion criteria. RESULTS: The meta-analysis found that cognitive and behavioral treatments were superior to control conditions after treatment on measures of chronic low back pain, pain behavior, and disability. Follow-up comparisons of cognitive and behavioral treatments versus control conditions were not available. This meta-analysis did not find cognitive and behavioral therapies to differ from other active treatments on specific outcome measures, although only a few studies were available for each measure. CONCLUSION: It may be useful to incorporate cognitive-behavioral interventions in primary care settings, but additional research is needed to evaluate their efficacy in improving specific outcomes.     

Strategies to enhance fat utilisation during exercise

Compared with the limited capacity of the human body to store carbohydrate (CHO), endogenous fat depots are large and represent a vast source of fuel for exercise. However, fatty acid (FA) oxidation is limited, especially during intense exercise, and CHO remains the major fuel for oxidative metabolism. In the search for strategies to improve athletic performance, recent interest has focused on several nutritional procedures which may theoretically promote FA oxidation, attenuate the rate of muscle glycogen depletion and improve exercise capacity. In some individuals the ingestion of caffeine improves endurance capacity, but L-carnitine supplementation has no effect on either rates of FA oxidation, muscle glycogen utilisation or performance. Likewise, the ingestion of small amounts of medium-chain triglyceride (MCT) has no major effect on either fat metabolism or exercise performance. On the other hand, in endurance-trained individuals, substrate utilisation during submaximal [60% of peak oxygen uptake (VO2peak)] exercise can be altered substantially by the ingestion of a high fat (60 to 70% of energy intake), low CHO (15 to 20% of energy intake) diet for 7 to 10 days. Adaptation to such a diet, however, does not appear to alter the rate of working muscle glycogen utilisation during prolonged, moderate intensity exercise, nor consistently improve performance. At present, there is insufficient scientific evidence to recommend that athletes either ingest fat, in the form of MCTs, during exercise, or "fat-adapt" in the weeks prior to a major endurance event to improve athletic performance.     

Infection and atherosclerosis--focus on cytomegalovirus and Chlamydia pneumoniae

BACKGROUND AND OBJECTIVE: Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections. This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (i.e, cytomegalovirus and Chlamydia pneumoniae) in atherogenesis, and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease. DATA SOURCES: English-language clinical studies, abstracts, and review articles pertaining to infectious agents and coronary atherosclerosis. STUDY SELECTION AND DATA EXTRACTION: Relevant seroepidemiologic and pathologic studies and animal models evaluating the role of cytomegalovirus or C. pneumoniae in coronary atherosclerosis. DATA SYNTHESIS: Studies evaluating the possible role of cytomegalovirus and C. pneumoniae in the pathogenesis of atherosclerosis, as well as studies examining the use of antimicrobial and antiviral agents for reduction of cardiovascular events, are reviewed and critiqued. CONCLUSIONS: Current data do not allow us to determine whether infection is a cause or a cofactor of atherosclerosis. These uncertainties can be resolved by larger scale seroepidemiologic, pathologic, and interventional studies. Such efforts will contribute to identifying populations that are appropriate for particular surveillance or specific interventions, such as antibiotics or antiviral therapy.     

Analysis of obstetric complications reported to the National Patient Insurance Association in Finland from 1987 to 1995

OBJECTIVE: To review comparative studies evaluating oral propafenone for restoring sinus rhythm in recent onset atrial fibrillation. DATA SOURCES: A MEDLINE search of the English-language literature (1966 to 1996) along with any referenced articles not identified by MEDLINE. STUDY SELECTION: Because intravenous propafenone is not marketed in Canada, only studies evaluating oral propafenone were included. Studies were selected if they compared oral propafenone with placebo or other antiarrhythmic agents for converting recent onset atrial fibrillation to normal sinus rhythm. DATA SYNTHESIS: Propafenone is often used as a first-line agent for pharmacological cardioversion of atrial fibrillation. In earlier studies, the efficacy of propafenone in restoring sinus rhythm was reported to be low with conversion rates of 6% to 62%. Many of these studies were noncomparative and often included patients with refractory, chronic atrial fibrillation or employed suboptimal doses of propafenone. More recently propafenone has been evaluated in the treatment of recent onset atrial fibrillation by using a single 600 mg oral loading dose. Success rates of 76% at 8 h and 83% at 12 h following the loading dose are reported. The incidence of atrial flutter during active treatment was similar to that with placebo, with the majority exhibiting 2:1 or greater atrioventricular conduction ratios and heart rates 150 beats/min or less. CONCLUSIONS: A single 600 mg oral dose of propafenone is highly effective at restoring sinus rhythm in patients with acute onset atrial fibrillation with few adverse effects. The small studies reviewed cannot lead to definitive conclusions about the safety of propafenone without prior administration of agents for rate control.     

Effect of clenbuterol on athletic performance

Unlike inhaled beta 2-agonists, more studies need to be performed before the action of systemic beta 2-agonists on athletic performance can be assessed accurately. Experiments in animals with oral clenbuterol have shown augmentation in muscle bulk across numerous species, but human studies cannot confirm similar muscle mass enlargement in healthy men. Although the human studies demonstrate the potential for long-acting systemic beta 2-agonists to increase muscle strength in certain muscle fiber types, it is difficult to judge the drugs' effects on overall athletic performance, because athletic skill is more than strength, speed, and endurance. The effect of oral clenbuterol on athletic performance cannot be evaluated from its actions on muscle strength alone. However, as evidence stands now, sports regulatory agencies are correct to ban systemic beta 2-agonists until the following 2 points can be proven: (1) oral forms provide a therapeutic benefit that cannot be obtained with aerosol or inhaled forms; and (2) oral forms do not give any unfair advantage to the competitor in muscle strength, power output, or endurance. Provided they are administered as prescribed, aerosol or inhaled beta-agonists do not impart an unfair advantage or enhance athletic performance and can continue to be used in competition by athletes with EIA.