Funding Body: FWF-Austrian Science Fund, Project No. P18610

http://www.fwf.ac.at/de/abstracts/abstract.asp?L=D&PROJ=P18610

Project Homepage: www.ironcells.com

Duration: 2006-2009

Principal Investigator:

Karl-Heinz Wagner

Project group:

Oliver Neubauer, PhD student, project assistance, finished June 2009
Stefanie Reichhold, PhD student, finished April 2009
Anna Chalopek, finished 2007
Norbert Kern, Master student, finished 2008
Marlies Meisel, Master student, finished 2008
Lucas Nics, Master student, finished 2008

Cooperation partner:

Prof. Sigfried Knasmüller, Institut für Krebsforschung, Medizinische Universität Wien
Prof. Daniel König und Prof. Aloys Berg, Abteilung für Rehabilitative und Präventive Sportmedizin, Medizinische Universitätsklinik Freiburg (D)
Prof. Haber und Mag. Jerzy Mondrzyk, Universitätsklinik für Innere Medizin IV, Klinische Abteilung für Pulmologie, AKH Wien
Ass. Dr. Zeibig, Alpentherme Bad Hofgastein

Short description: Physical activity, especially endurance exercise performed at moderate intensities, exerts a number of beneficial effects. However, there is an apparent paradox regarding the risks of exercise-induced oxidative and genomic stress. Increasing evidence indicates that extraordinary prolonged, intense or unaccustomed physical exercise increases the generation of free radicals and other reactive oxygen species. The hypothesized exercise-induced imbalance between oxidants and antioxidants has been linked to muscular fatigue and damage, inflammatory and other systemic stress responses elicited by vigorous exercise (similar to the acute-phase immune response) and decreased physical performance/regeneration up to muscular overtraining symptoms. Furthermore, the current understanding of this topic provides little information whether exercise-induced formation of free radicals can result in potent harmful effects that might offset the beneficial outcomes imparted by physical training.

Moreover, the interaction and influence of environmental factors and lifestyle, including exercise, on the genome, pose without doubt future challenges not only in exercise and nutritional sciences. Currently, there are no data on long-distance triathlons and genomic stability. Does an (ultra-) endurance exercise induce DNA damage, as this is well known after surgeries, shocks, burns or other serious body impairments? And if yes, how long do the body’s repair and regeneration mechanisms need to counteract this stress reaction?

Research on this topic is of particular importance in terms of a risk assessment, since there is a further increasing interest in physical activity including more extreme challenges in sports such as marathon and triathlon events (e.g. documented by the rapidly growing number of participants in the Ironman Austria – from 124 in 1998 to more than 2000 in 2004). However, comprehensive data on long-distance triathlons as a more and more popular type of endurance exercise with new sophisticated biomarkers are missing. Beyond, due the potential involvement of oxidative and genomic stress such as in the pathologies of arteriosclerosis or cancer and age related processes, research in this field will be of high value for the exploration of certain degenerative diseases states as well as aging. Concerning exercise physiology and biochemistry as well as biomedical research in general, Ironman triathletes provide a unique model for studying the response of physiological regulatory mechanisms to stress.

For all these reasons, the purpose of our research work is to investigate the effects of an Ironman triathlon (3,8 km swim, 180 km bike, 42 km run) on genomic stability, antioxidant related factors, highly sophisticated markers of oxidative stress/damage as well as on parameters of muscular and inflammatory stress responses and signal transduction that are associated with an oxidant-/antioxidant-imbalance.

Outcome: 
We quantified the resolution of recovery up to 19 days (including 5 blood samplings) after the Ironman triathlon and thus longer than any other study that investigated divergent stress effects following ultra-endurance exercise in 42 healthy, male Ironman competitors. With our study we have gained a thorough insight into oxidative, muscular, cardiac, inflammatory and immuno-endocrine stress responses as well as genome stability.

There was a significant systemic inflammatory response that subsided rapidly, most likely due to counter-regulatory mechanisms and returned to baseline three weeks after the event. Similar results were observed for biomarkers of myocardial stress.

On the other side, despite temporary rises in most (but not all) oxidative stress markers, there were no indications of sustained oxidative stress after the Ironman race since they returned to baseline five days after the event. At the same time parameters for the total antioxidative plasma capacity increased as response to the exercise.

Addressing a further new issue in the field of sport sciences, we have investigated the effects on genome stability in the course of an exercise bout of such duration. Crucially, by applying diverse sophisticated analytical methods to examine DNA modulations, we observed that there was no long-lasting DNA damage following an Ironman triathlon.

Taken together, the results of the project show that extreme endurance exercise did not attenuate the athletes´ biochemical health status persistently. However, this stress compatibility and ability for regeneration is very much dependent on the trainings status and an appropriate nutritional behaviour before and during the race. 

ISI Publications:

1. König D, Neubauer O, Nics L, Kern N, Berg A, Bisse E, Wagner K-H (2007). Biomarkers of exercise-induced myocardial stress in relation to inflammatory and oxidative stress. Exerc Immunol Rev. 13:15-36 (IF = 4.4, Sport Science, Rank: 1/72), view article

2. Neubauer O, König D, Wagner K-H (2008). Recovery after an Ironman Triathlon: Sustained Inflammatory Responses and Muscular Stress. Eur J Appl Physiol. 104 (3): 417-426 (IF = 1.8, Sport Science, Rank: /72) view article

3. Neubauer O, König D, Kern N, Nics L, Wagner K-H (2008). No Indications of Persistent Oxidative Stress in Response to an Ironman Triathlon. Med Sci Sports Exerc. 40 (12):2119-2128 (IF = 2.9 Sport Science, Rank: 13/72) view article

4. Reichhold S, Neubauer O, Ehrlich V, Knasmüller S, Wagner K-H (2008). No acute and persistent DNA damage after an Ironman Triathlon. Cancer Epidemiol Biomarkers Prev. 17: 1913-1919 (IF = 4.6, Public, Environmental & Occupational Health, Rank: 6/100) view article

5. Neubauer O, Reichhold S, Nersesyan A, König D, Wagner K-H (2008): Exercise-induced DNA damage: Is there a relationship with inflammatory responses? Exerc Immunol Rev. 14:51-72 (IF = 4.4, Sport Science, Rank: 1/72) view article

6. Reichhold S, Neubauer O, Stadlmayr B, Valentini J, Hoelzl C, Ferk F, Knasmüller S, Wagner K-H (2009). DNA damage in response to an Ironman Triathlon. Free Rad Res. In press, (IF = 2.925, Biochemistry Rank: 111/263) view article

7. Reichhold S., Neubauer O., Bulmer A., Knasmüller S., Wagner K-H. (2009): Endurance exercise and DNA stability: Is there a link to duration and intensity. Mut. Res. Rev.  in press, in press, (IF = 7.5, Toxicology Rank: 3/73) view article

8. Wagner KH, Reichhold S, Hölzl C, Knasmüller S, Nics L, Meisel M, Neubauer O. (2010): Well-trained, healthy triathletes experience no adverse health risks regarding oxidative stress and DNA damage by participating in an ultra-endurance event. Toxicology. 278(2):211-216.

9. Neubauer O, Reichhold S, Nics L, Hoelzl C, Valentini J, Stadlmayr B, Knasmüller S, Wagner KH. (2010): Antioxidant responses to an acute ultra-endurance exercise: impact on DNA stability and indications for an increased need for nutritive antioxidants in the early recovery phase. Br J Nutr. 104(8):1129-1138.

10. Wagner KH, Reichhold S, Neubauer O. (2010): Impact of endurance and ultraendurance exercise on DNA damage. Ann N Y Acad Sci. 1229:115-231.

Non  ISI Publications:

1. Neubauer O (2006). Eisenmänner als ´Modelle´ für Stressresistenz. Triathlon Sonderausgabe Ironman Austria:38 (an introduction of the FWF-funded research project conducted at the Ironman Austria 2006)

2. Neubauer O (2007). Eiserner Widerstand. Triathlon Training 4:59-61 (first general study results regarding the stress responses after an Ironman race and regulatory mechanisms.

3. Neubauer O, Reichhold S, Wagner K-H (2008): Biochemische, physiologische und molekularbiologische Stressreaktionen nach einem Ironman-Triathlon. Ernährung aktuell 3:1-4 (brief summary on the main findings of the FWF-funded research project conducted at the Ironman Austria 2006)

From the project we had 6 invited lectures, 4 non invited lectures and 8 poster presentations at international scientific meetings. Stefanie Reichhold was awarded at one of the meetings with the poster prize. 

The project finished December 2008.