Energy Metabolism, Liver And Kidney Function in Adolescent Marathon Runners
Mar 21, 2022
ali.ma@wecistanche.com
Natthapon Traiperm, et al
* Department of Sport Science, Medical Section, University of Innsbruck, Innsbruck, Austria.
* Department of Applied Science and Engineering, Khon Kaen University, Nong Khai Campus, Nong Khai, Thailand
ABSTRACT
Background
To study parameters of energy metabolism, liver and kidney function in adolescent runners completing a standard 42-2-km marathon run.
Design
Observational field study.
Materials and methods
Fifty adolescents (30 healthy males and 20 healthy females) aged between 13 and 17 years participated in the study. All participants underwent routine medical screening. Blood samples were taken before, at the end, and 24 h after a competitive marathon to investigate parameters of metabolism, liver, and kidney function.
Results
Forty-seven runners completed the race with a mean finishing time of 4 h 57 min 24 s (range: 3 h 17 min 09 s to 6 h 14 min 01 s). None of the participants experienced an adverse medical event during or postmarathon. Findings indicate predominant lipid oxidation during and postmarathon, signs of minor hepatic injury, and only transiently reduced kidney function caused by marathon running in adolescents.
Conclusion
The observed findings are very similar to those reported in healthy adults. There is no evidence of liver or kidney injury in adolescent runners participating in a standard marathon run.
Keywords: Adolescents, biochemical parameters, metabolism, running.
Cistanche can improve liver and kidney function
Click to Cistanches for kidney disease
Introduction
Over the last decades, marathon running has become increasingly popular even in the age group below 18 years. Therefore, it is not surprising that thousands of young marathoners participated in the Los Angeles Marathon, and from 1982 to 2005, nearly 300 young runners completed the Twin Cities Marathon with finishing times ranging from 2:53:00 to 6:10:00. The youngest participant in these data sets was 7 years old [1]. No severe emergencies occurred, and none have required intravenous fluids or hospitalization [1]. Nonetheless, deleterious effects of prolonged strenuous exercise, such as electrolyte abnormalities, rhabdomyolysis, acute myocardial infarction, and sudden cardiac death, were reported in adult runners [2]. For young runners (age < 18), data are very limited making risk assessment difficult. Recently, two studies have been published on adolescent marathon runners [3,4]. The main results from these investigations were that markers of myocardial injury (i.e. troponin T and I) are elevated immediately after a marathon race but return to baseline 24 h after finishing [3]. Moreover, slight changes in plasma electrolyte levels were reported without any cases of hyper- or hyponatremia immediately after finishing a marathon [4]. Due to the transient nature of these changes, these authors concluded that increases in cardiac markers may be a physiological rather than a pathological response and that well-trained and educated adolescent runners are not at risk of developing clinically signifificant electrolyte or hematological changes [3,4].
Besides the effects of marathon running on the heart and fluid homeostasis, the degree of potential organ damages, that is of the liver and kidney subsequent to rhabdomyolysis, has been rarely studied and is nearly unknown for young participants [2]. McCullough et al. [2] found that in adults, approximately 40% of marathon runners experienced a transient rise in serum creatinine that met the criteria for acute kidney injury. This increase, however, resolved within 24 h [2]. In adolescents performing a half-marathon, Tian et al. [5] reported mild declines in renal function that persisted for 24 h after the race. The authors concluded that in adolescent runners, normalization of renal function might be delayed when compared to adults and that further studies are needed to establish reference ranges for this population [5]. With respect to parameters of liver function, increased values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (c-GT), lactate dehydrogenase, and alkaline phosphatase (ALP) after marathon or ultra-marathon running were reported implying some damage to the skeletal muscle and hepatic cells [6,7]. However, all these changes were reported for adult marathon runners, and even though it might be assumed that adolescent runners would behave similarly, no data verifying such assumptions exist to date. Therefore, the goal of this study was to investigate the effects of recreational marathon running on parameters of metabolism, liver, and kidney function in a large sample of young male and female adolescent runners. We hypothesized that similar to adult marathon runners renal and liver function would be impaired immediately after the marathon but would at least partly recover during 24 h after the run.
Materials and methods
Following approval by the Khon Kaen University Ethics Committee for Human Research, 30 adolescent healthy males and 20 healthy females aged between 13 and 17 years and their parents gave written informed consent for participation in the study. Participants underwent a routine physical examination comprising medical and athletic training history, cardiorespiratory examination including electrocardiogram (ECG) records, neurological and orthopedic examinations. None of the participants showed any abnormal ECG signs. Additionally, all participants performed submaximal exercise testing to estimate maximum oxygen consumption according to Astrand et al. [8]. Each runner had an approximate mean training load of 40 km per week. Baseline characteristics are given in Table 1. All participants ran the marathon at an individual pace conforming to their running ability. They were free to stop whenever they felt overexerted.
Blood samples were taken in the early morning 2 days before the marathon race, immediately after the race, and 24 h after the race, that is at the same time as the prerace sample. On each day, 10 mL of blood was taken from the antecubital vein by the medical technician. Specimens were immediately centrifuged and were transported on dry ice to the laboratory at Srinakarin hospital, Faculty of Medical and Faculty of Associated Medical Science, Khon Kaen University. The marathon began at 04:15 am on 23 January 2011. Fluids were freely available at 22 drink stations including first aid tents, and six sport drink stations (electrolyte drink; Sponsor, Thailand) along the way. For a detailed description of the race, see Traiperm et al. [3,4].
The Automate Chemistry Cobas 6000 analyzers (Roche Diagnostics 9115, Hague Road, PO Box 50457, Indianapolis, IN 46250-0457, USA) was used to determine levels of hemoglobin, hematocrit, glucose, uric acid, creatinine, total, indirect and direct bilirubin, cholesterol, ALP, ALT, AST, and serum urea nitrogen (BUN). Due to financial restrictions, creatine kinase and myoglobin levels (Automate Chemistry Cobas 6000 analyzer, see above) were available solely in a subsample of 37 participants (male: n = 19; female, n = 18; age: 15.7 +-1.4 years; weight: 53.7 +-10.0 kg; height: 166.1 +-9.8 cm). Plasma volume changes were calculated according to Dill & Costill and Gillen et al. [9,10]. Glomerular fifiltration rate (GFR) was estimated using the formula: GFR = height (cm) 9 constant/serum creatinine (mg/dL). For female adolescents (>12 years), the constant was set at 055 and for male adolescents at 070 [11].
Statistical analysis was performed using SPSS statistical software package version 19.0 (SPSS, Inc., Chicago, Illinois, USA). ANOVA for repeated measures and post hoc Student’s t-tests were used to evaluate changes of biomarkers between baseline and postrace values (immediately and 24 h after the race). Correlation analyses (Pearson) were applied to examine relations between changes of myoglobin and CK with changes in liver and kidney parameters. Stepwise multiple linear regression analysis was used to predict race performance by selected explanatory variables. A P value of < 005 was considered signifificant. All values are expressed as means - SD.
Reporting of the study conforms to the STROBE statement along with references to the STROBE statement and the broader EQUA-TOR guidelines (Simera et al. January 2010 issue of EJCI).
Results
Male runners were on average 16-7 years and female runners 14-7 years old. Sexual maturation may therefore be comparable between boys and girls. To our knowledge, all girls were menstruating. Running training of about 40 km per week was part of sports instructions at school and was the same for all participants; however, running experience differed largely between runners (Table 1).
Forty-seven adolescent runners completed the race. On the race day, the ambient air temperature was 16.6 °C to 24.5 °C, and relative humidity during the race was 45% to 82%. The mean finishing time was 4 h 57 min 24 s (range: 3 h 17 min 09 s to 6 h 14 min 01 s). No participant experienced an adverse medical event requiring medical attention during or after the race.
During the race, the body mass of participants decreased from 55.1+-9.5 kg before to 53.4 +- 9.5 kg immediately after the race, and plasma volume increased by 11.0 +- 8.0% and 6.2 +- 8.5% from before to immediately and 24 h postrace, respectively. Changes in body mass were closely related to individual race times in male and female runners as well (Fig. 1). Stepwise multiple regression analysis with race time as the dependent variable and age, body mass, estimated VO2max, and training history as explanatory variables revealed that only individual estimated VO2max was weakly predictive for race performance in males (R2 = 0.2, P = 0.02) and stronger for females (R2 = 0.6, P < 0.01).
Energy metabolism, parameters of liver and kidney function before, immediately, and 24 hours after the marathon are shown in Table 2.
There was a statistically signifificant (P < 0.05) increase in the levels of blood glucose, ALT, AST, BUN, creatinine, and GFR immediately after the race. Twenty-four-hour after the race values had returned towards the baseline, except for ALT and AST. This is also true when these key parameters were corrected for plasma volume changes but the increase of ALT (39.32+- 13.15 U/L), AST (15.04 +- 8.18 U/L), BUN (16.93 +- 4.19 mg/dL), creatinine (1.05 +-0.22 mg/dL) and the decrease of GFR (106.6 +- 20.3) were somewhat more pronounced immediately after the race; whereas 24 h after the run BUN (14.40+-3.32 mg/dL) and GFR (119.2 +-18.5) had returned to baseline, this was not the case for ALT (45.05 +- 24.69 U/L), AST (17.20 +-7.81 U/L) and creatinine (0.92 +- 0.18 mg/dL).
Levels of triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), ALP, total, direct and indirect bilirubin decreased from before to immediately after the run and remained decreased 24 hours after the run with the exception of HDL, total, direct and indirect bilirubin. Differences between sexes are shown in Table 3. Sex differences were found for triglyceride, cholesterol, HDL, AST, ALP, direct bilirubin, blood urea nitrogen, and creatinine values (P < 0.05).
Subsample analysis (n = 37) showed increased values of creatine kinase and myoglobin, immediately and 24 h after the race with no differences between sexes (25702161 U/L before, 688.9 +- 402.3 U/L immediately, and 950.9 +- 917.7 U/L 24 h postmarathon for creatine kinase; 74.6 +- 13。1 lg/L before, 752.2 +- 117.0 lg/L immediately and 379.4+- 63.5 lg/L after 24 h for myoglobin).
Values of ALT, AST, creatinine, and GFR immediately after the race were not signifificantly related to race time indicating similar responses across performance levels.
Changes in CK correlated with changes of ALT (r = 0。746, P < 0.001) and changes of AST and ALT correlated with changes in ALP (r = 0.485, P = 0.001 and r = 0.544, P < 0.001, respectively). Body mass of the participants was positively correlated with creatinine levels measured before the marathon (r = 0.707, P < 0.001).
Discussion
The present study aimed at investigating changes in parameters of metabolism, liver, and kidney functions in adolescent recreational runners completing a standard marathon. To our knowledge, this is the first report on adolescent runners based on a relatively large sample size (n = 47). Most of the changes observed are very similar to those reported previously in adults after prolonged distance running [2,7,12].
Interestingly, VO2max was a better predictor of running performance in females than male runners. However, this finding has to be interpreted with caution because VO2max has been estimated from submaximal testing. Body mass loss was greater in faster runners compared to slower ones, as reported before for adult amateur marathon runners [13]. However, parameters of liver and kidney function immediately after the marathon was similar in runners of different performance levels.
Parameters of metabolism indicate a large contribution of lipid oxidation to energy supply during marathon running. The increase in creatine kinase and myoglobin levels postmarathon suggests a rather slight degree of exertional rhabdomyolysis with no clinically relevant impairment of liver and kidney function [14].
Lipid oxidation becomes the major source of energy during and after prolonged exercise likely explaining reduced triglyceride levels immediately and 24 h postmarathon [15]. Preferred lipid oxidation along with the rather moderate race times and repeated ingestion of carbohydrate beverages may explain elevated plasma glucose at the end of the marathon which may have prevented hypoglycemia [16]. Total cholesterol, HDL, and LDL levels were all decreased at the end of the marathon and only HDL levels returned to baseline 24 h postmarathon. Thus, the total cholesterol/HDL ratio, which is not affected by changes in plasma volume, was reduced immediately and 24 h after the marathon indicating an increase in HDL and a decrease in LDL levels. These changes reflect the beneficial effects of prolonged exercise on lipid metabolism. Whereas glucose changes did not differ between sexes, changes in plasma lipid levels were more pronounced in female runners likely related to a sex hormone-mediated enhancement of lipid oxidation during prolonged submaximal exercise [17].
Alanine aminotransferase and aspartate aminotransferase as specific markers for hepatic injury [7] were slightly increased after the race, although the upper reference limits of the Srinakarin hospital laboratory (Khon Kaen University) and the normal reference values, according to Colantonio et al. [18], were not exceeded (Fig. 2). Thus, potential hepatic cell injury after the marathon run might well be related to damage of muscle cells but was, if at all, of minor degree. In contrast to the findings of Wu et al. [6], we demonstrated a positive correlation between AST, ALT, and ALP elevations postmarathon suggesting the simultaneous occurrence of slight hepatic cell injury and obstruction in the biliary system. The increased bilirubin levels 24 h after the marathon may be due to the destruction of red blood cells consistent with previous reports [7,19,20].
Increased creatinine levels (Fig. 1) and the reduced GFR immediately after the marathon may suggest a minor decline in renal function. Furthermore, in 3 (6%) of the 47 participants, creatinine levels raised by ≥ 03 mg/dL meeting the Acute Kidney Injury Network definition of acute kidney injury stage 1 [2]. However, these changes were of transient nature because the creatinine values and GFR returned to baseline 24 h after the marathon. These observations are in line with those reported in adult runners [2,21–23]. The time course of changes are similar between sexes, but creatinine levels were higher in males compared to females likely explained by the larger muscle mass of male runners [24] supported by the positive relationship between body mass and creatinine level, r = 0.7+-7, P < 0.001).
At least one important limitation has to be mentioned. Runners were free to perform at their individual pace and to stop for drinking and/or recovering whenever they liked which also might partly explain the large variation in performance. Thus, it cannot be excluded that more competitive circumstances might result in more severe exhaustion and more pronounced changes in parameters examined in the present study.
To the best of our knowledge, this is the first data set on parameters of metabolism, liver, and kidney function in adolescent marathon runners. We demonstrated transient changes of most measured parameters that warrant further investigations. When considering the magnitude of the changes and the fast recovery, one could assume that participation in a single marathon run would not permanently hamper liver or kidney function. Certainly, to strengthen this assumption long-term studies are needed. Finally, it should be mentioned that although the finishing rate in the selected population of adolescent runners was high, the training status in many of the athletes was rather moderate as compared to the final running times.
In conclusion, the observed findings are very similar to those reported in healthy adults. There is no evidence of sustainable liver or kidney injury in healthy and trained adolescent runners participating in a standard marathon run. However, we do not know whether repetitive participation in marathon running will evoke beneficial adaptation or even permanent damage.
Acknowledgments
We thank the Austrian Federal Ministry for Science and Research in the frame of the ASEA-UNINET grant for supporting our research project. We also thank participants from Khon Kaen Sports School and staff from the Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen, Thailand.
Contributions
Traiperm N, Gatterer H and Burtscher M involved in conception, design, analysis, and interpretation of data and drafting of the manuscript; Traiperm N and Pariwat P involved in collection and interpretation of data and revising the manuscript; all authors read and approved the final manuscript submitted.
Cistanche can improve liver and kidney function
References
1 Roberts WO. Can children and adolescents run marathons? Sports Med 2007;37:299–301.
2 McCullough PA, Chinnaiyan KM, Gallagher MJ, Colar JM, Geddes T, Gold JM et al. Changes in renal markers and acute kidney injury after marathon running. Nephrology 2011;16:194–9.
3 Traiperm N, Gatterer H, Wille M, Burtscher M. Cardiac troponins in young marathon runners. Am J Cardiol 2012;110:594–8.
4 Traiperm N, Gatterer H, Burtscher M. Plasma electrolyte and hematological changes after marathon running in adolescents. Med Sci Sports Exerc 2013;45:1182–7.
5 Tian Y, Tong TK, Lippi G, Huang C, Shi Q, Nie J. Renal function parameters during early and late recovery periods following an all-out 21-km run in trained adolescent runners. Clin Chem Lab Med 2011;49:993–7.
6 Wu HJ, Chen KT, Shee BW, Chang HC, Huang YJ, Yang RS. Effects of 24 h ultra-marathon on biochemical and hematological parameters. World J Gastroenterol 2004;10:2711–4.
7 Kratz A, Lewandrowski K, Siegel AJ, Chun KY, Flood JG, Van Cott EM, et al. Effects of marathon running on hematologic and biochemical laboratory parameter, including cardiac markers. Am J Clin Pathol 2002;118:856–63.
8 Astrand PO, Rodahl K, Dahl HA, Stromme SB, Textbook of Work Physiology. Windsor, Canada: Human Kinetics; 2003: pp 280–7.
9 Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol 1974;37:247–8.
10 Gillen CM, Lee R, Mack GW, Tomaselli CM, Nishiyasu T, Nadel ER. Plasma volume expansion in humans after a single intense exercise protocol. J Appl Physiol 1991;71:1914–20.
11 Cordeiro VF, Pinheiro DC, Silva GB Jr, Lima JW, Mota RM, Liborio AB et al. Comparative study of cystatin C and serum creatinine in the estimative of glomerular filtration rate in children. Clin Chim Acta 2008;391:46–50.
12 Wells CL, Stern JR, Hecht LH. Hematological changes following a marathon race in male and female runners. Eur J Appl Physiol 1982;48:41–9.
13 Zouhal H, Groussard C, Minter G, Vincent S, Cretual A, GratasDelamarche A et al. Inverse relationship between percentage body weight change and finishing time in 643 forty-two-kilometer marathon runners. Br J Sports Med 2011;45:1101–5.
14 Clarkson PM. Exertional rhabdomyolysis and acute renal failure in marathon runners. Sports Med 2007;37:361–3.
15 Tuominen JA, Ebeling P, Bourey R, Koranyi L, Lamminen A, Rapala J et al. Postmarathon paradox: insulin resistance in the face of glycogen depletion. Am J Physiol 1996;270(2 Pt 1): E336–43.
16 Callow M, Morton A, Guppy M. Marathon fatigue: the role of plasma fatty acids, muscle glycogen, and blood glucose. Eur J Appl Physiol Occup Physiol 1986;55:654–61.
17 Tarnopolsky MA. Sex differences in exercise metabolism and the role of 17-beta estradiol. Med Sci Sports Exerc 2008;40:648–54.
18 Colantonio DA, Kyriakopoulou L, Chan MK, Daly CH, Brinc D, Venner AA et al. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem 2012;58:854–68.
19 Banfi G, Colombini A, Lombardi G, Lubkowska A. Metabolic markers in sports medicine. Adv Clin Chem 2012;56:1–54.
20 Bird SR, Linden M, Hawley JA. Acute changes to biomarkers as a consequence of prolonged strenuous running. Ann Clin Biochem 2014;51:137–50.
21 Neumayr G, Pfister R, Hoertnagl H, Mitterbauer G, Prokop W, Joannidis M. Renal function and plasma volume following ultramarathon cycling. Int J Sports Med 2005;26:2–8.
22 Lippi G, Schena F, Salvagno GL, Tarperi C, Montagnana M, Gelati M et al. Acute variation of estimated glomerular filtration rate following a half-marathon run. Int J Sports Med 2008;29:948–51.
23 Hewing B, Schattke S, Spethmann S, Sanad W, Schroeckh S, Schimke I et al. Cardiac and renal function in a large cohort of amateur marathon runners. Cardiovasc Ultrasound 2015;13:13.
24 Baxmann AC, Ahmed MS, Marques NC, Menon VB, Pereira AB, Kirsztajn GM et al. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol 2008;3:348–54.
