Ethics of genetic testing and research in sport: a position statement from the Australian Institute of Sport.

As Australia's peak high-performance sport agency, the Australian Institute of Sport (AIS) has developed this position statement to address the implications of recent advances in the field of genetics and the ramifications for the health and well-being of athletes. Genetic testing has proven of value in the practice of clinical medicine. There are, however, currently no scientific grounds for the use of genetic testing for athletic performance improvement, sport selection or talent identification. Athletes and coaches should be discouraged from using direct-to-consumer genetic testing because of its lack of validation and replicability and the lack of involvement of a medical practitioner in the process. The transfer of genetic material or genetic modification of cells for performance enhancement is gene doping and should not be used on athletes. There are, however, valid roles for genetic research and the AIS supports genetic research which aims to enhance understanding of athlete susceptibility to injury or illness. Genetic research is only to be conducted after careful consideration of a range of ethical concerns which include the provision of adequate informed consent. The AIS is committed to providing leadership in delivering an ethical framework that protects the well-being of athletes and the integrity of sport, in the rapidly changing world of genomic science.

Butyrylated starch increases colonic butyrate concentration but has limited effects on immunity in healthy physically active individuals.

BACKGROUND: Butyrate delivery to the large bowel may positively modulate commensal microbiota and enhance immunity. OBJECTIVE: To determine the effects of increasing large bowel butyrate concentration through ingestion of butyrylated high amylose maize starch (HAMSB) on faecal biochemistry and microbiota, and markers of immunity in healthy active individuals. DESIGN: Male and female volunteers were assigned randomly to consume either two doses of 20 g HAMSB (n = 23; age 37.9 +/- 7.8 y; mean +/- SD) or a low amylose maize starch (LAMS) (n = 18; age 36.9 = 9.5 y) twice daily for 28 days. Samples were collected on days 0, 10 and 28 for assessment of faecal bacterial groups, faecal biochemistry, serum cytokines and salivary antimicrobial proteins. RESULTS: HAMSB led to relative increases in faecal free (45%; 12-86%; mean; 90% confidence interval; P = 0.02), bound (950%; 563-1564%; P < 0.01) and total butyrate (260%; 174-373%; P < 0.01) and faecal propionate (41%; 12-77%; P = 0.02) from day 0 to day 28 compared to LAMS. HAMSB was also associated with a relative 1.6-fold (1.2- to 2.0-fold; P < 0.01) and 2.5-fold (1.4- to 4.4-fold; P = 0.01) increase in plasma IL-10 and TNF-alpha but did not alter other indices of immunity. There were relative greater increases in faecal P. distasonis (81-fold (28- to 237-fold; P < 0.01) and F. prausnitzii (5.1-fold (2.1- to 12-fold; P < 0.01) in the HAMSB group. CONCLUSIONS: HAMSB supplementation in healthy active individuals promotes the growth of bacteria that may improve bowel health and has only limited effects on plasma cytokines.

Lactobacillus fermentum (PCC®) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes.

BACKGROUND: Probiotics purportedly reduce symptoms of gastrointestinal and upper respiratory-tract illness by modulating commensal microflora. Preventing and reducing symptoms of respiratory and gastrointestinal illness are the primary reason that dietary supplementation with probiotics are becoming increasingly popular with healthy active individuals. There is a paucity of data regarding the effectiveness of probiotics in this cohort. The aim of this study was to evaluate the effectiveness of a probiotic on faecal microbiology, self-reported illness symptoms and immunity in healthy well trained individuals. METHODS: Competitive cyclists (64 males and 35 females; age 35 ± 9 and 36 ± 9 y, VO2max 56 ± 6 and 52 ± 6 ml.kg-1.min-1, mean ± SD) were randomised to either probiotic (minimum 1 × 109 Lactobacillus fermentum (PCC®) per day) or placebo treatment for 11 weeks in a double-blind, randomised, controlled trial. The outcome measures were faecal L. fermentum counts, self-reported symptoms of illness and serum cytokines. RESULTS: Lactobacillus numbers increased 7.7-fold (90% confidence limits 2.1- to 28-fold) more in males on the probiotic, while there was an unclear 2.2-fold (0.2- to 18-fold) increase in females taking the probiotic. The number and duration of mild gastrointestinal symptoms were ~2-fold greater in the probiotic group. However, there was a substantial 0.7 (0.2 to 1.2) of a scale step reduction in the severity of gastrointestinal illness at the mean training load in males, which became more pronounced as training load increased. The load (duration×severity) of lower respiratory illness symptoms was less by a factor of 0.31 (99%CI; 0.07 to 0.96) in males taking the probiotic compared with placebo but increased by a factor of 2.2 (0.41 to 27) in females. Differences in use of cold and flu medication mirrored these symptoms. The observed effects on URTI had too much uncertainty for a decisive outcome. There were clear reductions in the magnitude of acute exercise-induced changes in some cytokines. CONCLUSION: L. fermentum may be a useful nutritional adjunct for healthy exercising males. However, uncertainty in the effects of supplementation on URTI and on symptoms in females needs to be resolved. TRIAL REGISTRATION: The trial was registered in the Australia and New Zealand Clinical Trials Registry (ACTRN12611000006943).

Attitudes of medical students, clinicians and sports scientists towards exercise counselling.

We compared the amount of exercise undertaken by medical students, clinicians, and sport scientists with the National Australian Physical Activity (NAPA) Guidelines. A second aim was to compare attitudes to exercise counselling as preventive medicine between university- and clinic-based professionals. The research setting was a university medical school and a sports science sports medicine centre. A 20-item questionnaire was completed by 216 individuals (131 medical students, 43 clinicians and 37 sports scientists). Self-reported physical activity habits, exercise counselling practices and attitudes towards preventive medicine were assessed. The physical activity undertaken by most respondents (70%) met NAPA Guidelines. General practitioners had significantly lower compliance rates with NAPA Guidelines than other professionals. More than half of clinicians and medical students (54%) were less active now compared with levels of activity undertaken prior to graduate training. Most physicians (68%) reported they sometimes discuss physical activity with patients. In contrast, the majority of non-medically qualified respondents (60%) said they never discuss physical activity with their doctor. Most respondents (70%) had positive attitudes to exercise counselling. Sports scientists and respondents who were highly active in childhood had more positive attitudes to exercise counselling than others. Health professionals in this study were more active than the general population, however healthy exercise habits tend to deteriorate after the commencement of medical training. Despite the important role of doctors in health promotion, the degree of exercise counselling to patients is low. Key pointsThe rate of exercise counselling by doctors to patients is lowSports physicians and scientists have substantially more positive attitudes to exercise counselling than clinicians and medical studentsMedical schools have a responsibility to promote physical activity of students and improve training in exercise counselling.

Cytokine gene polymorphisms and risk for upper respiratory symptoms in highly-trained athletes.

Physiological and immunological factors contributing to risk for upper respiratory symptoms (URS) in athletic populations remain under investigation. Single nucleotide changes (polymorphisms) in cytokine genes and alterations in associated gene expression may influence risk for URS in some athletes. The aim of this study was to compare the frequency of cytokine gene polymorphisms in athletes with or without a history of frequent URS. Cytokine gene polymorphisms were determined in samples from five previous investigations of immune function in highly-trained athletes (n=170). Participants were classified into two groups based on their self-reported number of episodes of URS in the preceding 12 months. Athletes were classified as healthy (n=82) if they reported < or =2 episodes of URS in the preceding 12 months. Athletes were classified as illness-prone (n=88) if reporting > or =3 episodes of URS. Polymorphisms in Interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist (IL-1ra), IL-2, IL-4 and Interferon(IFN)-gamma were determined using real-time polymerase chain reaction allelic discrimination assays. The distribution of genotype frequencies between the two groups was compared using a Chi-square test and logistic regression was used to model risk for URS as a function of cytokine gene polymorphisms. There was a tendency for IL-6 (chi2 = 5.0, p = 0.08) and IL-4 (chi2 = 4.8, p = 0.09) genotype frequencies to differ between the groups. The IL-6 high-expression genotype was associated with an increased likelihood of > or =3 URS episodes in a 12 month period (odds ratio (OR): 2.87, 95% confidence interval (CI): 1.10-7.53; p = 0.03). The IL-2 high-expression genotype was associated with a tendency for a decreased likelihood of > or =3 URS episodes in a 12 month period (OR: 0.361, 95% CI: 0.124-1.06; p = 0.06). These data suggest cytokine gene polymorphisms may account in part for differences in risk for URS in highly-trained athletes.

Clinical and laboratory evaluation of upper respiratory symptoms in elite athletes.

OBJECTIVE: To characterize the etiology of upper respiratory symptoms in elite athletes presenting to a sports physician for treatment. DESIGN: Prospective clinical and laboratory investigations. SETTING: Sports medicine clinic. PARTICIPANTS: Seventy elite-level athletes. MAIN OUTCOME MEASUREMENTS: Physician-recorded symptoms and diagnosis; health/training questionnaires; laboratory investigations of respiratory pathogens, white blood cell differential counts, and immune parameters. RESULTS: Physicians characterized 89% of presentations as viral or bacterial upper respiratory tract infection. Only 57% of presentations were associated with an identified pathogen or other laboratory parameters indicative of infection. Demographic information, previous illness, and training history did not distinguish between presentations with or without objective measures of infection. Elevated white blood cell and neutrophil counts and lower vitamin D concentrations partially distinguished infectious episodes. The number of systemic symptoms/behaviors at presentation (cough, headache, earache, fatigue, fever/rigors, myalgia/arthralgia, or cessation of training before clinic attendance) had some predictive value for infection: odds ratio per symptom, 1.23 (90% confidence interval: 0.91 to 1.66); probability of infection, 48% with no symptoms to 77% with 6 symptoms. Laboratory investigation identified allergy in a considerable proportion of the cohort (39%). CONCLUSIONS: The discrepancy between physician and laboratory diagnosed infection in elite athletes highlights the need for consideration of alternate diagnostic options when evaluating upper respiratory symptoms in athletes. A considerable proportion of episodes of respiratory symptoms in athletes were not associated with identification of a respiratory pathogen; other potentially treatable causes of upper respiratory symptoms should be considered, particularly in athletes with recurrent symptoms.

Incidence, etiology, and symptomatology of upper respiratory illness in elite athletes.

PURPOSE: Upper respiratory illness (URI) is the most common medical condition affecting elite athletes. The aims of this study were to identify and evaluate the incidence, pathogenic etiology, and symptomatology of acute URI during a 5-month training and competition period. METHODS: Thirty-two elite and 31 recreationally competitive triathletes and cyclists, and 20 sedentary controls (age range 18.0-34.1 yr) participated in a prospective surveillance study. Nasopharyngeal and throat swabs were collected from subjects presenting with two or more defined upper respiratory symptoms. Swabs were analyzed using microscopy, culture, and PCR testing for typical and atypical respiratory pathogens. The Wisconsin Upper Respiratory Symptom Survey (WURSS-44) was used to assess symptomatology and functional impairment. RESULTS: Thirty-seven URI episodes were reported in 28 subjects. Incidence rate ratios for illness were higher in both the control subjects (1.93, 95% CI: 0.72-5.18) and elite athletes (4.50, 1.91-10.59) than in the recreationally competitive athletes. Infectious agents were identified in only 11 (two control, three recreationally competitive, and six elite) out of 37 illness episodes. Rhinovirus was the most common respiratory pathogen isolated. Symptom and functional impairment severity scores were higher in subjects with an infectious pathogen episode, particularly on illness days 3-4. CONCLUSION: The results confirm a higher rate of URI among elite athletes than recreationally competitive athletes during this training and competition season. However, because pathogens were isolated in fewer than 30% of URI cases, further study is required to uncover the causes of unidentified but symptomatic URI in athletes. Despite the common perception that all URI are infections, physicians should consider both infectious and noninfectious causes when athletes present with symptoms.

Valtrex therapy for Epstein-Barr virus reactivation and upper respiratory symptoms in elite runners.

PURPOSE: The aim of the study was to examine the effectiveness of prophylactic administration of the antiviral agent Valtrex for control of Epstein-Barr virus (EBV) reactivation and upper respiratory symptoms in elite distance runners. METHODS: Twenty elite male distance runners were randomized into a 4-month double-blind, placebo-controlled cross-over trial. Saliva samples were collected weekly and mucosal immune status assessed by measurement of secretory IgA (SIgA) using an enzyme-linked immunosorbent assay (ELISA). EBV reactivation was monitored at the same time by detection of EBV in saliva using a quantitative real-time polymerase chain reaction. The initial EBV status of the runners was determined by detecting EBV antibodies in serum using an ELISA. Upper respiratory symptoms were recorded using self-reporting illness logs. RESULTS: There was no evidence of any marked change in maximal oxygen uptake (P = 0.86), training volume (P = 0.30), or mucosal immunity (P = 0.21) over the study period. Valtrex treatment resulted in an 82% reduction in the detectable EBV load in saliva for EBV seropositive runners compared with the placebo treatment (P = 0.04). The incidence of upper respiratory symptoms was not reduced by Valtrex treatment. CONCLUSIONS: The prophylactic administration of Valtrex reduced EBV reactivation but was not an effective intervention strategy for limiting upper respiratory symptoms in this cohort of elite distance runners. The upper respiratory symptoms in the distance runners could not be directly attributed to infection and may be of a noninfectious inflammatory nature.

Epstein-Barr virus reactivation and upper-respiratory illness in elite swimmers.

PURPOSE: The aim of this study was to investigate the relationships between latent viral shedding of Epstein-Barr virus (EBV) in saliva, upper-respiratory illness, and mucosal immune suppression in a cohort of highly trained swimmers undertaking intensive training. METHODS: Saliva was collected before selected training sessions from 14 elite male swimmers during a 30-d period of intensive training. Prior infection with EBV was determined by EBV antibody serology. Salivary IgA concentrations were measured by enzyme linked immunosorbent assay (ELISA), and EBV viral shedding (EBV-DNA) was detected by polymerase chain reaction (PCR). Symptoms of upper-respiratory illness were recorded daily. RESULTS: Eleven swimmers (79%) were seropositive for prior EBV infection. Seven EBV seropositive swimmers (64%) had EBV-DNA detected during the study period. Upper-respiratory symptoms (URS) were reported in six of seven swimmers in whom EBV-DNA was detected and in three of four swimmers with no EBV-DNA detection. No URS were reported in the EBV seronegative swimmers. There was a statistically significant relationship between EBV serology status and URS (P = 0.027). EBV-DNA was detected in saliva before the appearance of URS. Salivary IgA levels were significantly lower immediately before the URS (P = 0.01) compared with subsequent peak IgA levels and declined to pre-URS levels on average 11 d after the first appearance of URS. CONCLUSIONS: The time course of appearance of EBV-DNA in relation to URS suggests latent viral EBV shedding may be a contributing factor in the URS. The low levels of salivary IgA detected before the URS indicated transient mucosal immune suppression in the study cohort. The viral shedding may alternatively be a reflection of the altered immune control mechanisms that occur in response to intensive exercise and unrelated to the URS.

Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals.

BACKGROUND & AIMS: To examine the effect of supplementation with probiotics on respiratory and gastrointestinal illness in healthy active men and women. METHODS: A randomised double-blind placebo-controlled trial was conducted. Four hundred and sixty five participants (241 males; age 35 ± 12 y (mean ± SD) and 224 females; age 36 ± 12 y) were assigned to one of three groups: Group 1 - Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) 2.0 × 10(9)colony forming units per day, CFU per day, Group 2 - Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07 (NCFM & Bi-07) 5 × 10(9) CFU each per day) or Group 3 - placebo mixed in a drink. RESULTS: The risk of an upper respiratory illness episode was significantly lower in the Bl-04 group (hazard ratio 0.73; 95% confidence interval 0.55-0.95; P = 0.022) compared to placebo. There was no significant difference in illness risk between the NCFM & Bi-07 group (hazard ratio 0.81; 0.62-1.08; P = 0.15) and the placebo group. There was a 0.7 and 0.9 month delay in the median time to an illness episode in the Bl-04 and NCFM & Bi-07 groups respectively compared to placebo (placebo 2.5 months; Bl-04 3.2 months; NCFM & Bi-07 3.4 months). There were insufficient GI illness episodes for analysis. The NCFM & Bi-07 group but not the Bl-04 group undertook significantly more physical activity (8.5%; 6.7%-10%; P < 0.003) than the placebo group. CONCLUSION: The probiotic Bl-04 appears to be a useful nutritional supplement in reducing the risk of URTI in healthy physically-active adults. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: Number ACTRN12611000130965.

Gut Balance, a synbiotic supplement, increases fecal Lactobacillus paracasei but has little effect on immunity in healthy physically active individuals.

Synbiotic supplements, which contain multiple functional ingredients, may enhance the immune system more than the use of individual ingredients alone. A double blind active controlled parallel trial over a 21 d exercise training period was conducted to evaluate the effect of Gut Balance™, which contains Lactobacillus paracasei subsp. paracasei (L. casei 431®), Bifidobacterium animalis ssp. lactis (BB-12®), Lactobacillus acidophilus (LA-5®), Lactobacillus rhamnosus (LGG®), two prebiotics (raftiline and raftilose) and bovine whey derived lactoferrin and immunoglobulins with acacia gum on fecal microbiota, short chain fatty acids (SCFA), gut permeability, salivary lactoferrin and serum cytokines. All subjects randomized were included in the analysis. There was a 9-fold (1.2-fold to 64-fold; 95% confidence intervals p = 0.03) greater increase in fecal L. paracasei numbers with Gut Balance™ compared with acacia gum supplementation. Gut Balance™ was associated with a 50% (-12% to 72%; p = 0.02) smaller increase in the concentration of serum IL-16 in comparison to acacia gum from pre- to post-study. No substantial effects of either supplement were evident in fecal SCFA concentrations, measures of mucosal immunity or GI permeability. Clinical studies are now required to determine whether Gut Balance™ may exert beneficial GI health effects by increasing the recovery of fecal L. paracasei. Both supplements had little effect on immunity. Twenty two healthy physically active male subjects (mean age = 33.9 ± 6.5y) were randomly allocated to either daily prebiotic or synbiotic supplementation for 21 d. Saliva, blood, urine and fecal samples were collected pre-, mid and post-intervention. Participants recorded patterns of physical activity on a self-reported questionnaire.

4. The use and misuse of performance-enhancing substances in sport.

Doctors need to know if a patient is an athlete subject to drug testing, and to be aware of the legal situation surrounding drugs they prescribe such patients. Antidoping laws generally exist in order to provide a safe and fair environment for participation in sport. These laws should prevent and protect athletes from subjecting themselves to health risks through the use of unsafe, but performance-enhancing drugs. Because of difficulties in proving intent to cheat, the World Anti-Doping Agency enforces a principle of strict liability for positive test results for banned substances. An area of major controversy with respect to liability is the "sports supplement" industry, which is poorly regulated when compared with prescription drugs yet is a potential source of doping violations. Medical practitioners can be found guilty of anti-doping violations if they traffic banned drugs, prescribe these to athletes or otherwise assist athletes in taking banned substances. Medical practitioners are also now required to complete paperwork (therapeutic use exemption forms) to enable athletes to take banned substances which are required on medical grounds for specific illnesses.

Influence of training loads on patterns of illness in elite distance runners.

OBJECTIVE: To investigate relationships between training mileage and intensity, and the type, incidence, severity, and duration of respiratory illness in distance runners, and the impact of illness on submaximal and maximal running performance. DESIGN: A longitudinal observational study of distance runners with serial monitoring of training loads and clinical patterns of illness. SETTING: A 4-month winter training period in the Southern Hemisphere. PARTICIPANTS: A total of 20 highly trained (elite) male middle-distance and distance runners competing at the national and international levels. MAIN OUTCOME MEASURES: Training was quantified by mileage (km), intensity (scale, 1-5), and load (volume x intensity). Symptoms and signs of respiratory illness (type, duration, and severity) were verified by a physician at a weekly review. Performance was monitored by measuring submaximal and maximal oxygen uptake and time to exhaustion on a incremental treadmill test. RESULTS: A majority of subjects (15/20) experienced 1 or more episodes of respiratory illness (mean, 2.5 episodes; range, 1-5), with 79% of symptoms classified as upper respiratory in origin. There were no significant differences in mean weekly mileage (P = 0.43), training intensity (P = 0.85), or training load (P = 0.45) between healthy runners and those affected by illness. Mean weekly (88 +/- 46 km) and mean monthly (373 +/- 163 km) mileages prior to each episode of illness were similar to the overall study means (95.5 +/- 36.4 km and 382 +/- 146 km). There were no substantial relationships between mean weekly training mileage, intensity, or training load and the number of illnesses reported (all r < 0.20). Neither submaximal nor maximal running performance was significantly affected by the presence of illness. CONCLUSIONS: Differences in training mileage, intensity, and load were not associated with the incidence of respiratory illness in highly trained middle-distance and distance runners. Runners with mild illness can be reassured that symptoms will not necessarily impair submaximal and maximal performance.