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1.  Characteristics, changes and influence of body composition during a 4486 km transcontinental ultramarathon: results from the Transeurope Footrace mobile whole body MRI-project 
BMC Medicine  2013;11:122.
Background
Almost nothing is known about the medical aspects of runners doing a transcontinental ultramarathon over several weeks. The results of differentiated measurements of changes in body composition during the Transeurope Footrace 2009 using a mobile whole body magnetic resonance (MR) imager are presented and the proposed influence of visceral and somatic adipose and lean tissue distribution on performance tested.
Methods
22 participants were randomly selected for the repeated MR measurements (intervals: 800 km) with a 1.5 Tesla MR scanner mounted on a mobile unit during the 64-stage 4,486 km ultramarathon. A standardized and validated MRI protocol was used: T1 weighted turbo spin echo sequence, echo time 12 ms, repetition time 490 ms, slice thickness 10 mm, slice distance 10 mm (breath holding examinations). For topographic tissue segmentation and mapping a modified fuzzy c-means algorithm was used. A semi-automatic post-processing of whole body MRI data sets allows reliable analysis of the following body tissue compartments: Total body volume (TV), total somatic (TSV) and total visceral volume (TVV), total adipose (TAT) and total lean tissue (TLT), somatic (SLT) and visceral lean tissue (VLT), somatic (SAT) and visceral adipose tissue (VAT) and somatic adipose soft tissue (SAST). Specific volume changes were tested on significance. Tests on difference and relationship regarding prerace and race performance and non-finishing were done using statistical software SPSS.
Results
Total, somatic and visceral volumes showed a significant decrease throughout the race. Adipose tissue showed a significant decrease compared to the start at all measurement times for TAT, SAST and VAT. Lean adipose tissues decreased until the end of the race, but not significantly. The mean relative volume changes of the different tissue compartments at the last measurement compared to the start were: TV −9.5% (SE 1.5%), TSV −9.4% (SE 1.5%), TVV −10.0% (SE 1.4%), TAT −41.3% (SE 2.3%), SAST −48.7% (SE 2.8%), VAT −64.5% (SE 4.6%), intraabdominal adipose tissue (IAAT) −67.3% (SE 4.3%), mediastinal adopose tissue (MAT) −41.5% (SE 7.1%), TLT −1.2% (SE 1.0%), SLT −1.4% (SE 1.1%). Before the start and during the early phase of the Transeurope Footrace 2009, the non-finisher group had a significantly higher percentage volume of TVV, TAT, SAST and VAT compared to the finisher group. VAT correlates significantly with prerace training volume and intensity one year before the race and with 50 km- and 24 hour-race records. Neither prerace body composition nor specific tissue compartment volume changes showed a significant relationship to performance in the last two thirds of the Transeurope Footrace 2009.
Conclusions
With this mobile MRI field study the complex changes in body composition during a multistage ultramarathon could be demonstrated in detail in a new and differentiated way. Participants lost more than half of their adipose tissue. Even lean tissue volume (mainly skeletal muscle tissue) decreased due to the unpreventable chronic negative energy balance during the race. VAT has the fastest and highest decrease compared to SAST and lean tissue compartments during the race. It seems to be the most sensitive morphometric parameter regarding the risk of non-finishing a transcontinental footrace and shows a direct relationship to prerace-performance. However, body volume or body mass and, therefore, fat volume has no correlation with total race performances of ultra-athletes finishing a 4,500 km multistage race.
doi:10.1186/1741-7015-11-122
PMCID: PMC3668188  PMID: 23657091
Magnetic resonance imaging; MRI; Body mass; Body volume; Body composition; Running; Marathon; Ultramarathon; Performance; Adipose tissue; Body fat; Lean tissue; Visceral; Somatic; Topography; Segmentation; Mapping
2.  Born to run. Studying the limits of human performance 
BMC Medicine  2012;10:76.
It is recognised that regular physical activity and a high level of fitness are powerful predictors of positive health outcomes. There is a long and rich history of significant feats of human endurance with some, for example, the death of the first marathon runner, Pheidippides, associated with negative health outcomes.
Early studies on endurance running used X-ray and interview techniques to evaluate competitors and comment on performance. Since then, comparatively few studies have looked at runners competing in distances longer than a marathon. Those that have, tend to show significant musculoskeletal injuries and a remarkable level of adaptation to this endurance load.
The TransEurope Footrace Project followed ultra-endurance runners aiming to complete 4,500 Km of running in 64 days across Europe. This pioneering study will assess the impact of extreme endurance on human physiology; analysing musculoskeletal and other tissue/organ injuries, and the body's potential ability to adapt to extreme physiological stress. The results will be of interest not only to endurance runners, but to anyone interested in the limits of human performance.
Please see related article: http://www.biomedcentral.com/1741-7015/10/78
doi:10.1186/1741-7015-10-76
PMCID: PMC3409846  PMID: 22812408
Physical inactivity; ultra-marathon; endurance; runners; musculoskeletal; nutrition; hydration; race; Trans-Continental
3.  Substantial and reversible brain gray matter reduction but no acute brain lesions in ultramarathon runners: experience from the TransEurope-FootRace Project 
BMC Medicine  2012;10:170.
Background
During the extremely challenging 4,487 km ultramarathon TransEurope-FootRace 2009, runners showed considerable reduction of body weight. The effects of this endurance run on brain volume changes but also possible formation of brain edema or new lesions were explored by repeated magnetic resonance imaging (MRI) studies.
Methods
A total of 15 runners signed an informed consent to participate in this study of planned brain scans before, twice during, and about 8 months after the race. Because of dropouts, global gray matter volume analysis could only be performed in ten runners covering three timepoints, and in seven runners who also had a follow-up scan. Scanning was performed on three identical 1.5 T Siemens MAGNETOM Avanto scanners, two of them located at our university. The third MRI scanner with identical sequence parameters was a mobile MRI unit escorting the runners. Volumetric 3D datasets were acquired using a magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence. Additionally, diffusion-weighted (DWI) and fluid attenuated inversion recovery (FLAIR) imaging was performed.
Results
Average global gray matter volume as well as body weight significantly decreased by 6% during the race. After 8 months, gray matter volume returned to baseline as well as body weight. No new brain lesions were detected by DWI or FLAIR imaging.
Conclusions
Physiological brain volume reduction during aging is less than 0.2% per year. Therefore a volume reduction of about 6% during the 2 months of extreme running appears to be substantial. The reconstitution in global volume measures after 8 months shows the process to be reversible. As possible mechanisms we discuss loss of protein, hypercortisolism and hyponatremia to account for both substantiality and reversibility of gray matter volume reductions. Reversible brain volume reduction during an ultramarathon suggests that extreme running might serve as a model to investigate possible mechanisms of transient brain volume changes. However, despite massive metabolic load, we found no new lesions in trained athletes participating in a multistage ultramarathon.
See related commentary http://www.biomedcentral.com/1741-7015/10/171
doi:10.1186/1741-7015-10-170
PMCID: PMC3566943  PMID: 23259507
body weight; brain volume; catabolism; DWI; lesion; MRI; ultramarathon
4.  Evidence from neuroimaging to explore brain plasticity in humans during an ultra-endurance burden 
BMC Medicine  2012;10:171.
Physical activity, likely through induction of neuroplasticity, is a promising intervention to promote brain health. In athletes it is clear that training can and does, by physiological adaptations, extend the frontiers of performance capacity. The limits of our endurance capacity lie deeply in the human brain, determined by various personal factors yet to be explored. The human brain, with its vast neural connections and its potential for seemingly endless behaviors, constitutes one of the final frontiers of medicine. In a recent study published in BMC Medicine, the TransEurope FootRace Project followed 10 ultra-endurance runners over around 4,500 km across Europe and recorded a large data collection of brain imaging scans. This study indicates that the cerebral atrophy amounting to a reduction of approximately 6% throughout the two months of the race is reversed upon follow-up. While this study will contribute to advances in the limits of human performance on the neurophysiological processes in sports scientists, it will also bring important understanding to clinicians about cerebral atrophy in people who are vulnerable to physical and psychological stress long term.
See related research article http://www.biomedcentral.com/1741-7015/10/170
doi:10.1186/1741-7015-10-171
PMCID: PMC3566949  PMID: 23259535
cerebral atrophy; exercise behavior; fatigue; overload; plasticity; running
5.  Regionally accentuated reversible brain grey matter reduction in ultra marathon runners detected by voxel-based morphometry 
Background
During the 4,487 km ultra marathon TransEurope-FootRace 2009 (TEFR09), runners showed catabolism with considerable reduction of body weight as well as reversible brain volume reduction. We hypothesized that ultra marathon athletes might have developed changes to grey matter (GM) brain morphology due to the burden of extreme physical training. Using voxel-based morphometry (VBM) we undertook a cross sectional study and two longitudinal studies.
Methods
Prior to the start of the race 13 runners volunteered to participate in this study of planned brain scans before, twice during, and 8 months after the race. A group of matched controls was recruited for comparison. Twelve runners were able to participate in the scan before the start of the race and were taken into account for comparison with control persons. Because of drop-outs during the race, VBM could be performed in 10 runners covering the first 3 time points, and in 7 runners who also had the follow-up scan after 8 months. Volumetric 3D datasets were acquired using an MPRAGE sequence. A level of p < 0.05, family-wise corrected for multiple comparisons was the a priori set statistical threshold to infer significant effects from VBM.
Results
Baseline comparison of TEFR09 participants and controls revealed no significant differences regarding GM brain volume. During the race however, VBM revealed GM volume decreases in regionally distributed brain regions. These included the bilateral posterior temporal and occipitoparietal cortices as well as the anterior cingulate and caudate nucleus. After eight months, GM normalized.
Conclusion
Contrary to our hypothesis, we did not observe significant differences between TEFR09 athletes and controls at baseline. If this missing difference is not due to small sample size, extreme physical training obviously does not chronically alter GM.
However, during the race GM volume decreased in brain regions normally associated with visuospatial and language tasks. The reduction of the energy intensive default mode network as a means to conserve energy during catabolism is discussed. The changes were reversible after 8 months.
Despite substantial changes to brain composition during the catabolic stress of an ultra marathon, the observed differences seem to be reversible and adaptive.
doi:10.1186/2052-1847-6-4
PMCID: PMC3896776  PMID: 24438692
Voxel based morphometry; VBM; Catabolism; Plasticity; Brain; Default mode network; MRI; Ultra marathon
6.  The foot in multistage ultra-marathon runners: experience in a cohort study of 22 participants of the Trans Europe Footrace Project with mobile MRI 
BMJ Open  2012;2(3):e001118.
Objectives
67 runners participated in the Trans Europe FootRace 2009 (TEFR09), a 4487 km (2789 mi) multistage ultra-marathon covering the south of Europe (Bari, Italy) to the North Cape. Reports on ultra-marathons are lacking, but the literature reports overuse injuries in athletes, especially to the Achilles tendon (AT), ankle or hind foot. Bone oedema may be related to exposure and is present in fatigue fractures. Therefore, the aim of this study was to determine prospectively if sustained maximal load during an ultra-marathon leads to damage to the foot.
Design and participants
In a cohort study, repeated scanning of the 22 athletes participating in the study was performed before and during (approximately every 1000 km) the race. Using the obtained fat saturated inversion recovery sequence, two experienced readers blinded to the clinical data rated the images regarding foot lesions. Statistical analysis included regression analysis and computation of the inter-rater reliability.
Setting
The TEFR09 course. MRI scanning was performed according to prearranged schedules for every participant, using a mobile 1.5 Tesla MRI unit on a trailer following the race.
Primary outcome measures
MRI data such as AT diameter, bone or tendon lesions, subcutaneous, plantar fascia or intraosseous oedema.
Results
The 22 study participants did not differ significantly from the total of the 67 TEFR09 runners regarding height, weight and age. The AT diameter increased significantly from 6.8 to 7.8 mm as did intraosseous signal, bone lesions and subcutaneous oedema. However, finishers differed only regarding plantar aponeurosis and subcutaneous oedema from participants aborting the TEFR09. Inter-rater reliability was 0.88–0.98.
Conclusion
Under the extreme stress of the TEFR09, an increase of the AT diameter as well as bone signal are thought to be adaptive since only subcutaneous oedema and plantar fascia oedema were related to abortion of the race.
Trial registration number
University of Ulm, Germany Ethics Committee Number 78/08-UBB/se.
Article summary
Article focus
A study on effects of ultra-marathon running, in this case, the multistage Trans Europe FootRace covering a distance of 4487 km from Bari (Italy) to the North Cape.
Observational cohort study using MRI to look for possible lesions to the foot.
Key messages
During sustained maximal load, AT diameter and bone MRI short τ inversion recovery signal (hinting at subtle oedema) increases. This is thought to be adaptive.
Subcutaneous oedema and plantar fascia signal were related to abortion of the race. These measurements seem to be related to relevant changes leading to discontinuation of the run.
No relevant new foot joint or tendon lesions were detected during the race over 4487 km.
Strengths and limitations of this study
Repeated measurement prospectively during the run was possible only because of the mobile MRI unit used for this research project.
The number of included runners (22) is high compared with other MRI-based studies but may have been too small to detect less frequent lesions.
doi:10.1136/bmjopen-2012-001118
PMCID: PMC3364457  PMID: 22619270
7.  Proton pump inhibition prevents gastrointestinal bleeding in ultramarathon runners: a randomised, double blinded, placebo controlled study 
Background
Ultra‐endurance running is emerging as a popular sport in Western industrialised countries. Gastrointestinal bleeding has been reported to be an adverse effect in these runners.
Objective
To see if the oral administration of a proton pump inhibitor would reduce the incidence of gastrointestinal bleeding in an ultramarathon.
Methods
In a randomised, double blinded, placebo controlled study, a prophylactic regimen of three days of an oral proton pump inhibitor (pantoprazole 20 mg) was tested in healthy athletes participating in the Spartathlon ultramarathon. The incidence of gastrointestinal bleeding was assessed by a stool guaiac test.
Results
Results were obtained for 70 healthy volunteers. The data for 20 of 35 runners in the intervention group and 17 of 35 runners in the placebo group were entered into the final analysis. At the end of the ultramarathon, two subjects in the intervention group and 12 in the placebo group had positive stool guaiac tests (risk difference 0.86; 95% confidence interval 0.45 to 0.96; p  =  0.001).
Conclusion
A short prophylactic regimen of oral proton pump inhibition can successfully decrease the incidence of gastrointestinal bleeding in participants in an ultramarathon.
doi:10.1136/bjsm.2005.024463
PMCID: PMC2577540  PMID: 16556794
stress; gastric disease; running; prevention; proton pump inhibitor
8.  Changes in Copeptin and Bioactive Vasopressin in Runners With and Without Hyponatremia 
Objective
To evaluate changes in both the N-terminal (arginine vasopressin; AVP) and C-terminal (copeptin) fragments of the vasopressin prohormone before, during, and after an ultramarathon race and to assess vasopressin and copeptin concentrations in runners with and without hyponatremia.
Design
Observational study.
Setting
Three trials (2 sodium balance and 1 hyponatremia treatment) in 2 separate approximately 160-km footraces [Western States Endurance Run (WSER) and Javelina Jundred Mile Race (JJ100)].
Participants
Six hyponatremic and 20 normonatremic runners; 19 finishers with 7 completing 100 km.
Main Outcome Measures
Plasma AVP ([AVP]p), copeptin ([copeptin]p), sodium ([Na+]p), and protein (%plasma volume change; %PV) concentrations.
Results
In the WSER Sodium Trial, a 3-fold prerace to postrace increase in both [AVP]p (0.7 ± 0.4 to 2.7 ± 1.9 pg/mL; P < 0.05) and [copeptin]p (10.3 ± 12.5 to 28.2 ± 16.3 pmol/L; nonsignificant) occurred, despite a 2 mEq/L decrease in [Na+]p (138.7 ± 2.3 to 136.7 ± 1.6 mEq/L; NS). A significant correlation was noted between [AVP]p and [copeptin]p postrace (r = 0.82; P < 0.05). In the WSER Treatment Trial, despite the presence of hyponatremia pre-treatment versus posttreatment ([Na+]p = 130.3 vs 133.5 mEq/L, respectively), both [AVP]p (3.2 vs 2.1 pg/mL) and [copeptin]p (22.5 vs 24.9 pmol/L) were well above the detectable levels. A significant correlation was noted between [AVP]p and [copeptin]p 60 minutes after treatment (r = 0.94; P < 0.05). In the JJ100 Sodium Trial, significant correlations were found between [copeptin]p change and %PV change (r = −0.34; P < 0.05) and between [AVP]p change and [Na+]p change (r = 0.39; P < 0.05) but not vice-versa.
Conclusions
[Copeptin]p seems to be a reliable surrogate of stimulated [AVP]p during exercise. Nonosmotic vasopressin stimulation occurs during ultradistance running. [Copeptin]p may better reflect chronic (%PV) vasopressin secretion under conditions of endurance exercise.
doi:10.1097/JSM.0b013e31821a62c2
PMCID: PMC3690462  PMID: 21519298
exercise; ultramarathon; antidiuretic hormone; SIADH
9.  Relationship of Incident Glaucoma versus Physical Activity and Fitness in Male Runners 
Purpose
To assess the dose–response relationship of vigorous physical activity (running distance, km/d) or cardiorespiratory fitness (meters-per-second pace during a 10-km footrace) to the risk for incident glaucoma.
Design
Prospective epidemiologic cohort study.
Methods
Participant-reported, physician-diagnosed incident glaucoma was compared with distance run per week and 10-km footrace performance in a cohort of 29,854 male runners without diabetes followed prospectively for 7.7 yr. The survival analyses were adjusted for age, hypertension, current and past cigarette use, and intakes of meat, fish, fruit, and alcohol.
Results
Two hundred incident glaucoma cases were reported during follow-up. The risk for reported glaucoma decreased 37% per meter-per-second increment in a 10-km race performance (P = 0.005). Relative to the least fit men (i.e., slowest, ≤ 3.5 m/s), the risk for incident-reported glaucoma declined 29% in those who ran 3.6–4.0 m/s (P = 0.06), 54% for those who ran 4.1–4.5 m/s (P = 0.001), 51% for those who ran 4.6–5.0 m/s (P = 0.04), and glaucoma was nonexistent among the 781 men who exceeded 5.0 m/s (P = 0.03). The risk for incident, reported glaucoma decreased 5% per kilometer-per-day run at baseline (P = 0.04), which remained significant when adjusted for the 10-km race performance (5% reduction per kilometer-per-day, P = 0.04), and both body mass index and race performance (P = 0.04). Baseline hypertension was unrelated to the incident glaucoma.
Conclusions
These data provide preliminary evidence that vigorous physical activity may reduce glaucoma risk, which, in the absence of medical record validation, could represent ocular hypertension in addition to frank glaucoma. Additional follow-up with validation is needed to identify the type of glaucoma affected.
doi:10.1249/MSS.0b013e31819e420f
PMCID: PMC2864610  PMID: 19568204
10.  A Multi-Stage Ultra-Endurance Run over 1,200 KM Leads to a Continuous Accumulation of Total Body Water 
We determined whether ultra-runners in a multi-stage ultra- endurance run lose body mass, fat mass, skeletal muscle mass or total body water in a descriptive field study at the ‘Deutschlandlauf’ 2007 a 1,200 km run within 17 consecutive days with 10 male non-professional Caucasian ultra-runners (mean ± SD, 43.8 ± 6.2 years, 73.8 ± 6.0 kg body mass, 1.77 ± 0.05 m body height, BMI 23.3 ± 1.8 kg·m-2). Body mass, fat mass, skeletal muscle mass, lean body mass and percent total body water were determined using bioelectrical impedance analysis and the anthropometric method before the race and after each stage. In addition, urinary specific gravity was measured in order to quantify hydration status. Fat mass (bioelectrical impedance analysis) decreased by 3.9 kg (p < 0.05), skeletal muscle mass (anthropometric method) decreased by 2.0 kg (p < 0.05) whereas percent total body water increased by 6.1 % (p < 0.05) by the end of the race. Ultra-runners in a multi-stage ultra-endurance event over 1,200 km, with 17 consecutive stages, showed a cumulative increase in percent total body water, a decrease in skeletal muscle mass and a decrease in fat mass, depending upon the method used. We presume that the eccentric component of running leads to damage of skeletal muscle, leading to rhabdomyolysis, with impaired renal function.
Key pointsUltra-runners in a multi-stage ultra-endurance run over 1,200 km in 17 consecutive stages suffered a decrease in fat mass, skeletal muscle mass and an increase in total body water, whereas overall body mass showed no change.
PMCID: PMC3761892  PMID: 24149903
Body fat; body mass; dehydration; skeletal muscle mass
11.  Running 338 Kilometres within Five Days has no Effect on Body Mass and Body Fat But Reduces Skeletal Muscle Mass – the Isarrun 2006 
We investigated the change of body composition in ultra- endurance runners during a multi-stage ultra-endurance run, the Isarrun 2006 in Bavaria, Germany, where athletes had to run 338 km within 5 days. Body mass, skin fold thicknesses and circumferences of extremities were measured in 21 well-experienced extreme endurance male runners (mean ± SD, 41.5 ± 6.9 years, 72.6 ± 6.4 kg, 178 ± 5 cm, BMI 23.0 ± 2.0 kg·m-2), who finished mainly within the first half of the ranking, in order to calculate skeletal muscle mass and body fat mass to prove changes after the race. Body mass and calculated fat mass did not change significantly (p>0.05), but, calculated skeletal muscle mass decreased significantly (p<0.05) by 0.63 ± 0.79 kg by the end of the race. The most apparent decline (p<0.01) of the calculated skeletal muscle mass was during the first stage, and no changes were observed during the last 4 stages. We conclude, that a multi- stage ultra-endurance run over 338 km within 5 days leads to no changes of body mass or body fat mass, but a statistically significant decrease of skeletal muscle mass of 0.63 ± 0.79 kg by the end of the race in well-trained and well-experienced ultra-endurance runners. The change of skeletal muscle mass has to be evaluated in further studies at ultra-endurance races with suitable methods to detect changes in hydration status and water metabolism.
Key pointsUltra-runners at the Isarrun 2006 suffered no loss of body mass.Skeletal muscle mass decreased highly significantly during the first stage but no significant changes of skeletal muscle mass were observed during the following 4 stages of the Isarrun 2006.Body fat mass remained stable during the Isarrun 2006.
PMCID: PMC3794477  PMID: 24149470
Body composition; anthropometry; ultra-running; stage race; fat mass; ultra-endurance
12.  The oxygen uptake - work-output relationship of runners during graded cycling exercise: sprinters vs. endurance runners. 
In order to study oxygen consumption (VO2) for a given work load at the exhaustive level of a graded cycling exercise in well-trained runners, a progressive cycle ergometer exercise test was performed on 9 sprinters and 12 endurance runners, all in good national standing; 12 sedentary men served as control subjects. The relationship between VO2 and work-output appeared to be linear in most of the subjects, but a plateau phenomenon was observed in two sprinters and two endurance runners. An upwards curvilinear increase in VO2 was noticed during the last two minutes of exercise in four endurance runners, but not in any of the sprinters. The four endurance runners with this unexpected increase in VO2 had a significantly higher (p < .01) "peak VO2" (mean = 75.3 ml.kg.-1.min.-1) than the rest of the endurance runners (mean = 55.1), and a significantly higher (p < .001) peak VO2 than the sprinters (mean = 46.0). It is concluded that the plateau phenomenon appears in runners during graded cycle ergometry, though rather seldom. It is less clear if the endurance runners showing the upwards curvilinear increase in VO2 possess a better aerobic performance capacity towards the end of progressive exercise. Nevertheless, the linear relationship between VO2 and work load does not appear to be the only one observed in runners during graded exercise.
Images
PMCID: PMC1858825  PMID: 6778544
13.  Changes in blood glucose levels during a 1005-km running race: a case study. 
The blood glucose response of a male ultramarathon runner was monitored throughout a 1005-km race. Before the race the runner had a fasting blood glucose concentration of 5.1 mM. At no stage during the race were his mean blood glucose levels less than 5.8 mM. This was partially attributed to the eating patterns of the athlete, the times at which blood samples were taken, the glycaemic index of food ingested and hyperglycaemia. While there was no evidence of glucosuria, ketones were present in the urine on one day of the event. There were other signs suggesting that at various stages of the event the runner had a metabolic acidosis. Possible reasons for this are discussed.
PMCID: PMC1478971  PMID: 1600460
14.  C reactive protein concentrations during long distance running. 
Long distance runners competing in events ranging from 15 to 88 km showed a distance related acute phase response as indicated by significantly raised serum C reactive protein concentrations. In trained athletes only a small rise in C reactive protein concentrations was seen after races of less than 21 km. After an 88 km ultramarathon concentrations comparable to those found in patients with small myocardial infarctions were detected. Indomethacin did not affect the increases in C reactive protein after the ultramarathon. This study has established serial C reactive protein concentrations for given race distances. These data may help in diagnosing myocardial infarction during long distance running. The acute phase response should be measured in untrained people running shorter distances to provide comparative data for the physically untrained population.
PMCID: PMC1443523  PMID: 6437505
15.  Effects of endurance running and dietary fat on circulating ghrelin and peptide YY 
Ghrelin and peptide YY (PYY) are newly recognized gut peptides involved in appetite regulation. Plasma ghrelin concentrations are elevated in fasting and suppressed following a meal, while PYY concentrations are suppressed in fasting and elevated postprandially. We determine whether ghrelin and PYY are altered by a low-fat, high-carbohydrate (10% fat, 75% carbohydrate) or moderate-fat, moderate-carbohydrate (35% fat, 50% carbohydrate) diet and; whether these peptides are affected by intense endurance running (which is likely to temporarily suppress appetite). Twenty-one endurance-trained runners followed a controlled diet (25% fat) and training regimen for 3 days before consuming the low-fat or isoenergetic moderate-fat diet for another 3 days in random cross-over fashion. On day 7 runners underwent glycogen restoration and then completed a 90-minute pre-loaded 10-km time trial on day 8, following a control breakfast. Blood samples were obtained on days 4 and 7 (fasting), and day 8 (non-fasting) before and after exercise for analysis of ghrelin, PYY, insulin and growth hormone (GH). Insulin, GH, Ghrelin and PYY changed significantly over time (p < 0.0001) but were not influenced by diet. Ghrelin was elevated during fasting (days 4 and 7), while insulin and PYY were suppressed. Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression. These peptides do not appear to be influenced by dietary fat intake.
PMCID: PMC3172724  PMID: 21927572
Exercise-induced anorexia; gut peptides; appetite regulation; hunger; exercise
16.  Effects of Endurance Running and Dietary Fat on Circulating Ghrelin and Peptide YY 
Ghrelin and peptide YY (PYY) are newly recognized gut peptides involved in appetite regulation. Plasma ghrelin concentrations are elevated in fasting and suppressed following a meal, while PYY concentrations are suppressed in fasting and elevated postprandially. We determine whether ghrelin and PYY are altered by a low-fat, high-carbohydrate (10% fat, 75% carbohydrate) or moderate-fat, moderate-carbohydrate (35% fat, 50% carbohydrate) diet and; whether these peptides are affected by intense endurance running (which is likely to temporarily suppress appetite). Twenty-one endurance-trained runners followed a controlled diet (25% fat) and training regimen for 3 days before consuming the low-fat or isoenergetic moderate-fat diet for another 3 days in random cross-over fashion. On day 7 runners underwent glycogen restoration and then completed a 90-minute pre-loaded 10-km time trial on day 8, following a control breakfast. Blood samples were obtained on days 4 and 7 (fasting), and day 8 (non-fasting) before and after exercise for analysis of ghrelin, PYY, insulin and growth hormone (GH). Insulin, GH, Ghrelin and PYY changed significantly over time (p < 0.0001) but were not influenced by diet. Ghrelin was elevated during fasting (days 4 and 7), while insulin and PYY were suppressed. Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression. These peptides do not appear to be influenced by dietary fat intake.
Key pointsThe study presents novel findings which address whether the appetite-stimulating gut peptide ghrelin and the appetite-suppressing peptide PYY are influenced by the fat content of the diet and/or by a bout of intense endurance running.The low-fat, high-carbohydrate pre-exercise regimen compared to moderate-fat, moderate-carbohydrate regimen did not influence circulating plasma ghrelin and PYY concentrationsMost importantly, both gut peptides were elevated following two to two-and-a-half hours of strenuous running which lasted between two and two and a half hours. The noted disruption in the normal inverse relationship between ghrelin and PYY at rest suggests that the interaction of ghrelin and PYY may be at least partially responsible for exercise-induced anorexia which is commonly reported following vigorous endurance exercise.
PMCID: PMC3172724  PMID: 21927572
Exercise-induced anorexia,; gut peptides,; appetite regulation,; hunger, exercise.
17.  Incident Diverticular Disease Is Inversely Related to Vigorous Physical Activity 
Purpose
In 1995, the Health Professionals Follow-up Study published an isolated report of lower diverticular disease risk in physically active men, particularly among those who ran. The purpose of this article was to assess whether this finding can be verified among older men and women of the National Runners’ Health Study.
Methods
Survival analyses were applied to incident disease occurring during 7.7 yr of follow-up in 9072 men and 1664 women, representing 84% follow-up of the original ≥ 50-yr-old cohort. In addition to the usual running distance (km/d), 80% of the baseline respondents included 10-km footrace performance times (a measure of cardiorespiratory fitness). Results were adjusted for age, sex, and reported intakes of meat, fish, fruit, and alcohol.
Results
A total of 127 men and 21 women reported clinically diagnosed diverticular disease since baseline. The risk for incident diverticular disease decreased 6.2% per km/d run (P = 0.04). Relative to men and women who ran ≤ 2 km/d, those who ran an average of > 8 km/d had 48% lower risk (P = 0.05). Each meter-per-second increment in the 10-km performance was associated with a 36% risk reduction (P = 0.04). Men and women who ran > 4 m/s had 70% lower risk for diverticular disease than those who ran ≤ 2.8 m/s (P = 0.01), which persisted when adjusted for baseline body mass index (69% risk reduction, P = 0.02) or usual running distance (36% risk reduction, P = 0.03).
Conclusion
These results demonstrate an inverse association between vigorous physical activity and incident diverticular disease among older men and women but are limited by their reliance on self-reported physician diagnosis.
doi:10.1249/MSS.0b013e318192d02d
PMCID: PMC2831405  PMID: 19346983
18.  Effects of Endurance Running and Dietary Fat on Circulating Ghrelin and Peptide YY 
Abstract
Ghrelin and peptide YY (PYY) are newly recognized gut peptides involved in appetite regulation. Plasma ghrelin concentrations are elevated in fasting and suppressed following a meal, while PYY concentrations are suppressed in fasting and elevated postprandially. We determine whether ghrelin and PYY are altered by a low-fat, high-carbohydrate (10% fat, 75% carbohydrate) or moderate-fat, moderate-carbohydrate (35% fat, 50% carbohydrate) diet and; whether these peptides are affected by intense endurance running (which is likely to temporarily suppress appetite). Twenty-one endurance-trained runners followed a controlled diet (25% fat) and training regimen for 3 days before consuming the low-fat or isoenergetic moderate-fat diet for another 3 days in random cross-over fashion. On day 7 runners underwent glycogen restoration and then completed a 90-minute pre-loaded 10-km time trial on day 8, following a control breakfast. Blood samples were obtained on days 4 and 7 (fasting), and day 8 (non-fasting) before and after exercise for analysis of ghrelin, PYY, insulin and growth hormone (GH). Insulin, GH, Ghrelin and PYY changed significantly over time (p < 0.0001) but were not influenced by diet. Ghrelin was elevated during fasting (days 4 and 7), while insulin and PYY were suppressed. Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression. These peptides do not appear to be influenced by dietary fat intake.
Key Points
The study presents novel findings which address whether the appetite-stimulating gut peptide ghrelin and the appetite-suppressing peptide PYY are influenced by the fat content of the diet and/or by a bout of intense endurance running.
The low-fat, high-carbohydrate pre-exercise regimen compared to moderate-fat, moderate-carbohydrate regimen did not influence circulating plasma ghrelin and PYY concentrations
Most importantly, both gut peptides were elevated following two to two-and-a-half hours of strenuous running which lasted between two and two and a half hours. The noted disruption in the normal inverse relationship between ghrelin and PYY at rest suggests that the interaction of ghrelin and PYY may be at least partially responsible for exercise-induced anorexia which is commonly reported following vigorous endurance exercise.
PMCID: PMC3761542
Exercise-induced anorexia,; gut peptides,; appetite regulation,; hunger, exercise.
19.  Effect of Dietary Fat on Serum and Intramyocellular Lipids and Running Performance 
Purpose
This study evaluated whether lowering IMCL stores via 3-d consumption of very-low-fat (LFAT) diet impairs endurance performance relative to a moderate-fat diet (MFAT), and whether such a diet unfavorably alters lipid profiles.
Methods
Twenty-one male and female endurance-trained runners followed a controlled diet and training regimen for 3 d prior to consuming either a LFAT (10% fat) or MFAT (35% fat) isoenergetic diet for another 3 d in random crossover fashion. On day 7, runners followed a glycogen normalization protocol (to equalize glycogen stores) and then underwent performance testing (90-min preload run at 62 ± 1% V̇O2max followed by a 10-km time trial) on the morning of day 8. Muscle biopsies obtained from vastus lateralis before and after performance testing were analyzed for IMCL (via electron microscopy) and glycogen content (via enzymatic methodology).
Results
Despite approximately 30% lower IMCL (0.220 ± 0.032% LFAT, 0.316 ± 0.049% MFAT; P = 0.045) and approximately 22% higher muscle glycogen stores at the start of performance testing (P = 0.10), 10-km performance time was not significantly different following the two diet treatments (43.5 ± 1.4 min LFAT vs 43.7 ± 1.2 min MFAT). However, LFAT produced less favorable lipid profiles (P < 0.01) by increasing fasting triglycerides (baseline = 84.9 ± 8.6; LFAT = 118.7 ± 10.0 mg·dL−1) and the total cholesterol:HDL cholesterol ratio (baseline = 3.42 ± 0.13:1; LFAT = 3.75 ± 0.20:1), whereas MFAT lowered triglycerides (baseline = 97.5 ± 12.2; MFAT = 70.9 ± 7.1 mg·dL−1) and the total cholesterol:HDL cholesterol ratio (baseline = 3.47 ± 0.18:1; MFAT = 3.33 ± 0.14:1).
Conclusion
The results suggest that reducing IMCL via 3-d consumption of a LFAT diet does not impair running performance lasting a little over 2 h (compared with 3-d consumption of a MFAT diet plus 1-d glycogen normalization), but that even short-term consumption of a LFAT diet may unfavorably alter serum lipids, even in healthy, endurance-trained runners.
doi:10.1249/MSS.0b013e318164cb33
PMCID: PMC3182469  PMID: 18408608
SERUM TRIGLYCERIDES; CARDIOVASCULAR DISEASE RISK; TIME TRIAL; FEMALE RUNNERS
20.  Serum Oxidant and Antioxidant Status in Adolescents Undergoing Professional Endurance Sports Training 
This study evaluated the impact of professional training on serum oxidant and antioxidant status in adolescent endurance athletes and compared it with that of untrained individuals. Firstly, serum thiobarbituric-acid-reactive substances (TBARSs), xanthine oxidase (XO), catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) were measured in 67 male runners, cyclists, and untrained adolescents. Seven-day dietary intakes were also assessed. Secondly, for age- and Tanner-stage-matched comparison, 36 out of the 67 subjects (12 for each group) were then selected and investigated. In cyclists, XO, GSH, and CAT were higher as compared with runners and controls. The CAT in runners, but not GSH and XO, was also higher than in controls. TBARS, T-AOC, and SOD did not differ among the study populations. Regarding the inter-individual relationships among serum redox statuses and dietary nutrient intakes, significant correlations were noted in CAT versus carbohydrates, protein, magnesium, and manganese; GSH versus carbohydrates, protein, fat, selenium, zinc, iron, and magnesium; XO versus cholesterol; CAT versus GSH. These findings suggest that the resting blood redox balance in the professional adolescent athletes was well maintained partly by the increase of individual antioxidant in adaptation to chronic exercise.
doi:10.1155/2012/741239
PMCID: PMC3345234  PMID: 22577491
21.  Changes in Running Speeds in a 100 KM Ultra-Marathon Race 
The purpose of this study was to determine if runners who completed a 100 km ultramarathon race in the fastest times changed their running speeds differently compared to those runners who ran an overall slower race. Times were taken from the race results of the 1995 100 km IAU World Challenge in Winschoten, Netherlands. Race times and 10 km split times were analyzed. Runners (n = 67) were divided into groups of ten with the last group consisting of seven runners. The mean running speed for each 10 km segment was calculated using each runner’s 10 km split times. Mean running speed was calculated using each runner’s race time. The first 10 km split time was normalized to 100, with all subsequent times adjusted accordingly. The mean running speed for each group at each 10 km split was then calculated. The faster runners started at a faster running speed, finished the race within 15 % of their starting speed, and maintained their starting speed for longer (approximately 50 km) before slowing. The slower runners showed a greater percentage decrease in their mean running speed, and were unable to maintain their initial pace for as long. It is concluded that the faster runners: 1) ran with fewer changes in speed, 2) started the race at a faster running speed than the slower runners, and 3) were able to maintain their initial speed for a longer distance before slowing.
Key PointsFaster runners in the 100 km race;ran with fewer changes in running speed compared to the slower runners;started the race at a faster running speed than the slower runners;were able to maintain their initial running speed for longer distances than slower runners.
PMCID: PMC3905299  PMID: 24482594
Pacing strategy; peak performance; ultra-endurance
22.  Water and sodium intake habits and status of ultra-endurance runners during a multi-stage ultra-marathon conducted in a hot ambient environment: an observational field based study 
Nutrition Journal  2013;12:13.
Background
Anecdotal evidence suggests ultra-runners may not be consuming sufficient water through foods and fluids to maintenance euhydration, and present sub-optimal sodium intakes, throughout multi-stage ultra-marathon (MSUM) competitions in the heat. Subsequently, the aims were primarily to assess water and sodium intake habits of recreational ultra-runners during a five stage 225 km semi self-sufficient MSUM conducted in a hot ambient environment (Tmax range: 32°C to 40°C); simultaneously to monitor serum sodium concentration, and hydration status using multiple hydration assessment techniques.
Methods
Total daily, pre-stage, during running, and post-stage water and sodium ingestion of ultra-endurance runners (UER, n = 74) and control (CON, n = 12) through foods and fluids were recorded on Stages 1 to 4 by trained dietetic researchers using dietary recall interview technique, and analysed through dietary analysis software. Body mass (BM), hydration status, and serum sodium concentration were determined pre- and post-Stages 1 to 5.
Results
Water (overall mean (SD): total daily 7.7 (1.5) L/day, during running 732 (183) ml/h) and sodium (total daily 3.9 (1.3) g/day, during running 270 (151) mg/L) ingestion did not differ between stages in UER (p < 0.001 vs. CON). Exercise-induced BM loss was 2.4 (1.2)% (p < 0.001). Pre- to post-stage BM gains were observed in 26% of UER along competition. Pre- and post-stage plasma osmolality remained within normal clinical reference range (280 to 303 mOsmol/kg) in the majority of UER (p > 0.05 vs. CON pre-stage). Asymptomatic hyponatraemia (<135 mmol/L) was evident pre- and post-stage in n = 8 UER, corresponding to 42% of sampled participants. Pre- and post-stage urine colour, urine osmolality and urine/plasma osmolality ratio increased (p < 0.001) as competition progressed in UER, with no change in CON. Plasma volume and extra-cellular water increased (p < 0.001) 22.8% and 9.2%, respectively, from pre-Stage 1 to 5 in UER, with no change in CON.
Conclusion
Water intake habits of ultra-runners during MSUM conducted in hot ambient conditions appear to be sufficient to maintain baseline euhydration levels. However, fluid over-consumption behaviours were evident along competition, irrespective of running speed and gender. Normonatraemia was observed in the majority of ultra-runners throughout MSUM, despite sodium ingestion under benchmark recommendations.
doi:10.1186/1475-2891-12-13
PMCID: PMC3554439  PMID: 23320854
Water; Drinking; Beverages; Total body water; Dehydration; Euhydration; Hyponatraemia; Carbohydrate
23.  Delayed enhancement of the intraventricular septum following an extraordinary endurance exercise 
BMJ Case Reports  2010;2010:bcr0620103096.
Cardiac fatigue and elevations in cardiac biomarkers have been described following prolonged exertion in endurance athletes. We comprehensively evaluated a highly trained 46-year-old man attempting a North American transcontinental run in a record time of 45 consecutive days. After running 1460 km and ascending over 2600 m, the run was ended prematurely on day 17 following a leg injury; in support of the event, the subject cycled an additional 1580 km. Echocardiography and biomarker analysis performed pre-event and while running revealed no decrement in systolic function and undetectable levels of troponin I and T. Post-event cardiac MRI demonstrated the interval appearance of delayed enhancement of gadolinium at the inferior insertion of the right ventricle and in the interventricular septum—a novel finding that may represent subtle inflammation secondary to a combined exercise and altitude effect.
doi:10.1136/bcr.06.2010.3096
PMCID: PMC3027915  PMID: 22798307
24.  Physiological factors associated with low bone mineral density in female endurance runners 
Objective: To explore potential factors that could be associated with low bone mineral density (BMD) in female endurance runners.
Methods: Fifty two female endurance runners (1500 m to marathon), aged 18–44 years, took part. Body fat percentage, lumbar spine BMD, and femoral neck BMD were measured using the Hologic QDR 4500w bone densitometer. Data on training, menstrual cycle status, osteoporosis, and health related factors were obtained by questionnaire. Dietary variables were assessed from a prospective seven day dietary record of macronutrients and micronutrients.
Results: The mean (SD) lumbar spine and femoral neck BMD were 1.11 (0.11) and 0.89 (0.12) g/cm2 respectively. A backward elimination regression analysis showed that age, body mass, body fat, distance run, magnesium, and zinc intake were the variables significantly associated with BMD. Lumbar spine BMD (g/cm2) = -1.90 + (0.0486 x age (years)) + (0.342 x log mass (kg)) - (0.000861 x age2 (years)) - (0.00128 x distance (km/week)), with an R2 = 30.1% (SEE = 0.089 (95% confidence interval (CI) 0.05 to 0.23); p<0.001). Femoral neck BMD (g/cm2) = -2.51 - (0.00989 x age (years)) + (0.720 x log mass (kg)) + (0.000951 x magnesium (mg/day)) -(0.0289 x zinc (mg/day)) - (0.00821 x body fat (%)) - (0.00226 x distance (km/week)), with an R2 = 50.2% (SEE = 0.100 (95% CI 0.06 to 0.22); p<0.001). The negative association between skeletal BMD and distance run suggested that participants who ran longer distances had a lower BMD of the lumbar spine and femoral neck. Further, the results indicated a positive association between body mass and BMD, and a negative association between body fat and BMD.
Conclusions: The results suggest a negative association between endurance running distance and lumbar spine and femoral neck BMD, with a positive association between body mass and femoral neck and lumbar spine BMD. However, longitudinal studies are required to assess directly the effect of endurance running and body mass on BMD, and to see if the addition of alternative exercise that would increase lean body mass would have a positive effect on BMD and therefore help to prevent osteoporosis.
doi:10.1136/bjsm.37.1.67
PMCID: PMC1724580  PMID: 12547747
25.  Health and Exercise-Related Medical Issues among 1,212 Ultramarathon Runners: Baseline Findings from the Ultrarunners Longitudinal TRAcking (ULTRA) Study 
PLoS ONE  2014;9(1):e83867.
Regular exercise is associated with substantial health benefits; however, little is known about the health impact of extreme levels of exercise. This study examined the prevalence of chronic diseases, health-care utilization, and risk factors for exercise-related injuries among ultramarathon runners. Retrospective, self-reported enrollment data from an ongoing longitudinal observational study of 1,212 active ultramarathon runners were analyzed. The most prevalent chronic medical conditions were allergies/hay fever (25.1%) and exercise-induced asthma (13.0%), but there was a low prevalence of serious medical issues including cancers (4.5%), coronary artery disease (0.7%), seizure disorders (0.7%), diabetes (0.7%), and human immunodeficiency virus (HIV) infection (0.2%). In the year preceding enrollment, most (64.6%) reported an exercise-related injury that resulted in lost training days (median of 14 days), but little nonattendance of work or school due to illness, injury, or exercise-related medical conditions (medians of 0 days for each). The knee was the most common area of exercise-related injury. Prior year incidence of stress fractures was 5.5% with most (44.5%) involving the foot. Ultramarathon runners who sustained exercise-related injuries were younger (p<0.001) and less experienced (p<0.01) than those without injury. Stress fractures were more common (p<0.01) among women than men. We conclude that, compared with the general population, ultramarathon runners appear healthier and report fewer missed work or school days due to illness or injury. Ultramarathon runners have a higher prevalence of asthma and allergies than the general population, and the prevalence of serious medical issues was nontrivial and should be recognized by those providing medical care to these individuals. Ultramarathon runners, compared with shorter distance runners, have a similar annual incidence of exercise-related injuries but higher proportion of stress fractures involving the foot, and it is the younger and less experienced ultramarathoners who appear most at risk for injury.
doi:10.1371/journal.pone.0083867
PMCID: PMC3885517  PMID: 24416176

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