Iron Supplementation Effects on Redox Status following Aseptic Skeletal Muscle Trauma in Adults and Children

Chariklia K Deli, Ioannis G Fatouros, Vassilis Paschalis, Athanasios Tsiokanos, Kalliopi Georgakouli, Athanasios Zalavras, Alexandra Avloniti, Yiannis Koutedakis, Athanasios Z Jamurtas, Chariklia K Deli, Ioannis G Fatouros, Vassilis Paschalis, Athanasios Tsiokanos, Kalliopi Georgakouli, Athanasios Zalavras, Alexandra Avloniti, Yiannis Koutedakis, Athanasios Z Jamurtas

Abstract

Exercise-induced skeletal muscle microtrauma is characterized by loss of muscle cell integrity, marked aseptic inflammatory response, and oxidative stress. We examined if iron supplementation would alter redox status after eccentric exercise. In a randomized, double blind crossover study, that was conducted in two cycles, healthy adults (n = 14) and children (n = 11) received daily either 37 mg of elemental iron or placebo for 3 weeks prior to and up to 72 h after an acute eccentric exercise bout. Blood was drawn at baseline, before exercise, and 72 h after exercise for the assessment of iron status, creatine kinase activity (CK), and redox status. Iron supplementation at rest increased iron concentration and transferrin saturation (p < 0.01). In adults, CK activity increased at 72 h after exercise, while no changes occurred in children. Iron supplementation increased TBARS at 72 h after exercise in both adults and children; no changes occurred under placebo condition. Eccentric exercise decreased bilirubin concentration at 72 h in all groups. Iron supplementation can alter redox responses after muscle-damaging exercise in both adults and children. This could be of great importance not only for healthy exercising individuals, but also in clinical conditions which are characterized by skeletal muscle injury and inflammation, yet iron supplementation is crucial for maintaining iron homeostasis. This study was registered at Clinicaltrials.gov Identifier: NCT02374619.

Conflict of interest statement

The authors declare that there is no conflict of interests regarding the publication of this paper.

Figures

Figure 1
Figure 1
Experimental design of the study. Arrows indicate the time points of creatine kinase and oxidative stress indices assessment.
Figure 2
Figure 2
CK after eccentric exercise in adults and children. Mean (±SEM) creatine kinase activity (CK), in adults under iron (■) and placebo supplementation (□) and in children under iron (●) and placebo supplementation (○). 1Different from preexercise in the same group. 2Different between adults and children at the same time point.
Figure 3
Figure 3
Plasma antioxidants after eccentric exercise in adults and children. Mean (±SEM) bilirubin (a), uric acid (b), and TAC (c) in adults under iron (■) and placebo supplementation (□) and in children under iron (●) and placebo supplementation (○). 2Different between adults and children at the same time point. 3Different from preexercise in all groups.
Figure 4
Figure 4
Erythrocytes' antioxidants after eccentric exercise in adults and children. Mean (±SEM) catalase (a) and GSH (b), in adults under iron (■) and placebo supplementation (□) and in children under iron (●) and placebo supplementation (○). 2Different between adults and children at the same time point.
Figure 5
Figure 5
Protein and lipid oxidation after eccentric exercise in adults and children. Mean (±SEM) protein carbonyls (PC) (a) and TBARS (b), in adults under iron (■) and placebo supplementation (□) and in children under iron (●) and placebo supplementation (○). 1Different from preexercise in iron condition.
Figure 6
Figure 6
Study results and possible mechanisms triggered after iron-mediated exercise-induced aseptic muscle trauma.

References

    1. Al-Majid S., Waters H. The biological mechanisms of cancer-related skeletal muscle wasting: the role of progressive resistance exercise. Biological Research for Nursing. 2008;10(1):7–20. doi: 10.1177/1099800408317345.
    1. Tidball J. G., Villalta S. A. Regulatory interactions between muscle and the immune system during muscle regeneration. American Journal of Physiology—Regulatory, Integrative and Comparative Physiology. 2010;298(5):R1173–R1187. doi: 10.1152/ajpregu.00735.2009.
    1. Stavropoulos-Kalinoglou A., Deli C. K., Kitas G. D., Jamurtas A. Z. Muscle wasting in rheumatoid arthritis: the role of oxidative stress. World Journal of Rheumatology. 2014;4(3):44–53. doi: 10.5499/wjr.v4.i3.44.
    1. Fehrenbach E., Schneider M. E. Trauma-induced systemic inflammatory response versus exercise-induced immunomodulatory effects. Sports Medicine. 2006;36(5):373–384. doi: 10.2165/00007256-200636050-00001.
    1. Peake J., Nosaka K., Suzuki K. Characterization of inflammatory responses to eccentric exercise in humans. Exercise Immunology Review. 2005;11:64–85.
    1. Michailidis Y., Karagounis L. G., Terzis G., et al. Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise. The American Journal of Clinical Nutrition. 2013;98(1):233–245. doi: 10.3945/ajcn.112.049163.
    1. Sakelliou A., Fatouros I. G., Athanailidis I., et al. Evidence of a redox-dependent regulation of immune responses to exercise-induced inflammation. Oxidative Medicine and Cellular Longevity. 2016;2016:19. doi: 10.1155/2016/2840643.2840643
    1. Cantini M., Giurisato E., Radu C., et al. Macrophage-secreted myogenic factors: a promising tool for greatly enhancing the proliferative capacity of myoblasts in vitro and in vivo. Neurological Sciences. 2002;23(4):189–194. doi: 10.1007/s100720200060.
    1. Smith C., Kruger M. J., Smith R. M., Myburgh K. H. The inflammatory response to skeletal muscle injury: illuminating complexities. Sports Medicine. 2008;38(11):947–969. doi: 10.2165/00007256-200838110-00005.
    1. Fatouros I. G., Jamurtas A. Z. Insights into the molecular etiology of exercise-induced inflammation: opportunities for optimizing performance. Journal of Inflammation Research. 2016;9:175–186. doi: 10.2147/jir.s114635.
    1. Jamurtas A. Z., Garyfallopoulou A., Theodorou A. A., et al. A single bout of downhill running transiently increases HOMA-IR without altering adipokine response in healthy adult women. European Journal of Applied Physiology. 2013;113(12):2925–2932. doi: 10.1007/s00421-013-2717-5.
    1. Theodorou A. A., Nikolaidis M. G., Paschalis V., et al. No effect of antioxidant supplementation on muscle performance and blood redox status adaptations to eccentric training. American Journal of Clinical Nutrition. 2011;93(6):1373–1383. doi: 10.3945/ajcn.110.009266.
    1. Paschalis V., Nikolaidis M. G., Fatouros I. G., et al. Uniform and prolonged changes in blood oxidative stress after muscle-damaging exercise. In Vivo. 2007;21(5):877–884.
    1. Goldfarb A. H., Bloomer R. J., Mckenzie M. J. Combined antioxidant treatment effects on blood oxidative stress after eccentric exercise. Medicine and Science in Sports and Exercise. 2005;37(2):234–239. doi: 10.1249/.
    1. Gleeson M., Almey J., Brooks S., Cave R., Lewis A., Griffiths H. Haematological and acute-phase responses associated with delayed-onset muscle soreness in humans. European Journal of Applied Physiology and Occupational Physiology. 1995;71(2-3):137–142. doi: 10.1007/BF00854970.
    1. Lee J., Goldfarb A. H., Rescino M. H., Hegde S., Patrick S., Apperson K. Eccentric exercise effect on blood oxidative-stress markers and delayed onset of muscle soreness. Medicine and Science in Sports and Exercise. 2002;34(3):443–448. doi: 10.1097/00005768-200203000-00010.
    1. Childs A., Jacobs C., Kaminski T., Halliwell B., Leeuwenburgh C. Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free Radical Biology and Medicine. 2001;31(6):745–753. doi: 10.1016/S0891-5849(01)00640-2.
    1. Close G. L., Ashton T., McArdle A., MacLaren D. P. M. The emerging role of free radicals in delayed onset muscle soreness and contraction-induced muscle injury. Comparative Biochemistry and Physiology—A Molecular and Integrative Physiology. 2005;142(3):257–266. doi: 10.1016/j.cbpa.2005.08.005.
    1. Hellsten Y., Frandsen U., Ørthenblad N., Sjødin B., Richter E. A. Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation. Journal of Physiology. 1997;498(1):239–248. doi: 10.1113/jphysiol.1997.sp021855.
    1. Nikolaidis M. G., Jamurtas A. Z., Paschalis V., Fatouros I. G., Koutedakis Y., Kouretas D. The effect of muscle-damaging exercise on blood and skeletal muscle oxidative stress: magnitude and time-course considerations. Sports Medicine. 2008;38(7):579–606. doi: 10.2165/00007256-200838070-00005.
    1. Khassaf M., McArdle A., Esanu C., et al. Effect of vitamin C supplements on antioxidant defence and stress proteins in human lymphocytes and skeletal muscle. Journal of Physiology. 2003;549(2):645–652. doi: 10.1113/jphysiol.2003.040303.
    1. Ji L. L. Antioxidant signaling in skeletal muscle: a brief review. Experimental Gerontology. 2007;42(7):582–593. doi: 10.1016/j.exger.2007.03.002.
    1. Ji L. L. Modulation of skeletal muscle antioxidant defense by exercise: role of redox signaling. Free Radical Biology & Medicine. 2008;44(2):142–152. doi: 10.1016/j.freeradbiomed.2007.02.031.
    1. Valko M., Leibfritz D., Moncol J., Cronin M. T. D., Mazur M., Telser J. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology. 2007;39(1):44–84. doi: 10.1016/j.biocel.2006.07.001.
    1. Reid M. B., Shoji T., Moody M. R., Entman M. L. Reactive oxygen in sheletal muscle. II. Extracellular release of free radicals. Journal of Applied Physiology. 1992;73(5):1805–1809.
    1. Berdoukas V., Coates T. D., Cabantchik Z. I. Iron and oxidative stress in cardiomyopathy in thalassemia. Free Radical Biology and Medicine. 2015;88:3–9. doi: 10.1016/j.freeradbiomed.2015.07.019.
    1. Coates T. D. Physiology and pathophysiology of iron in hemoglobin-associated diseases. Free Radical Biology and Medicine. 2014;72:23–40. doi: 10.1016/j.freeradbiomed.2014.03.039.
    1. Crichton R. R., Ward R. J. An overview of iron metabolism: molecular and cellular criteria for the selection of iron chelators. Current Medicinal Chemistry. 2003;10(12):997–1004. doi: 10.2174/0929867033457566.
    1. Hood D. A., Kelton R., Nismo M. L. Mitochondrial actaptations to chronic muscle use: effect of iron deficiency. Comparative Biochemistry and Physiology Part A: Physiology. 1992;101(3):597–605. doi: 10.1016/0300-9629(92)90514-q.
    1. Deli C. K., Fatouros I. G., Koutedakis Y., Jamurtas A. Z. Iron supplementation and physical performance. In: Hamlin A. P. M., editor. Current Issues in Sports and Exercise Medicine. InTech; 2013.
    1. Peeling P., Blee T., Goodman C., et al. Effect of iron injections on aerobic-exercise performance of iron-depleted female athletes. International Journal of Sport Nutrition and Exercise Metabolism. 2007;17(3):221–231. doi: 10.1123/ijsnem.17.3.221.
    1. Marginson V., Rowlands A. V., Gleeson N. P., Eston R. G. Comparison of the symptoms of exercise-induced muscle damage after an initial and repeated bout of plyometric exercise in men and boys. Journal of Applied Physiology. 2005;99(3):1174–1181. doi: 10.1152/japplphysiol.01193.2004.
    1. Gorianovas G., Skurvydas A., Streckis V., Brazaitis M., Kamandulis S., McHugh M. P. Repeated bout effect was more expressed in young adult males than in elderly males and boys. BioMed Research International. 2013;2013:10. doi: 10.1155/2013/218970.218970
    1. Soares J. M. C., Mota P., Duarte J. A., Appell H. J. Children are less susceptible to exercise-induced muscle damage than adults: a preliminary investigation. Pediatric Exercise Science. 1996;8(4):361–367. doi: 10.1123/pes.8.4.361.
    1. Clark S. F. Iron deficiency anemia. Nutrition in Clinical Practice. 2008;23(2):128–141. doi: 10.1177/0884533608314536.
    1. Nikolaidis M. G., Jamurtas A. Z., Paschalis V., et al. Exercise-induced oxidative stress in G6PD-deficient individuals. Medicine and Science in Sports and Exercise. 2006;38(8):1443–1450. doi: 10.1249/01.mss.0000228938.24658.5f.
    1. Nielsen P., Nachtigall D. Iron supplementation in athletes. Current recommendations. Sports Medicine. 1998;26(4):207–216. doi: 10.2165/00007256-199826040-00001.
    1. Lyle R. M., Weaver C. M., Sedlock D. A., Rajaram S., Martin B., Melby C. L. Iron status in exercising women: the effect of oral iron therapy vs increased consumption of muscle foods. American Journal of Clinical Nutrition. 1992;56(6):1049–1055.
    1. Schoene R. B., Escourrou P., Robertson H. T., Nilson K. L., Parsons J. R., Smith N. J. Iron repletion decreases maximal exercise lactate concentrations in female athletes with minimal iron-deficiency anemia. Journal of Laboratory and Clinical Medicine. 1983;102(2):306–312.
    1. Trumbo P., Yates A. A., Schlicker S., Poos M. Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Journal of the American Dietetic Association. 2001;101(3):294–301. doi: 10.1016/s0002-8223(01)00078-5.
    1. Morris N. M., Udry J. R. Validation of a self-administered instrument to assess stage of adolescent development. Journal of Youth and Adolescence. 1980;9(3):271–280. doi: 10.1007/BF02088471.
    1. Deli C. K., Paschalis V., Theodorou A. A., Nikolaidis M. G., Jamurtas A. Z., Koutedakis Y. Isokinetic knee joint evaluation in track and field events. Journal of Strength and Conditioning Research. 2011;25(9):2528–2536. doi: 10.1519/jsc.0b013e3182023a7a.
    1. Coleman L., Coleman J. The measurement of puberty: a review. Journal of Adolescence. 2002;25(5):535–550. doi: 10.1006/jado.2002.0494.
    1. Baltzopoulos V., Brodie D. A. Isokinetic dynamometry. Applications and limitations. Sports Medicine. 1989;8(2):101–116. doi: 10.2165/00007256-198908020-00003.
    1. Nikolaidis M. G., Paschalis V., Giakas G., et al. Decreased blood oxidative stress after repeated muscle-damaging exercise. Medicine & Science in Sports & Exercise. 2007;39(7):1080–1089. doi: 10.1249/mss.0b013e31804ca10c.
    1. Theodorou A. A., Nikolaidis M. G., Paschalis V., et al. Comparison between glucose-6-phosphate dehydrogenase-deficient and normal individuals after eccentric exercise. Medicine and Science in Sports and Exercise. 2010;42(6):1113–1121. doi: 10.1249/MSS.0b013e3181c67ecd.
    1. Deruisseau K. C., Roberts L. M., Kushnick M. R., Evans A. M., Austin K., Haymes E. M. Iron status of young males and females performing weight-training exercise. Medicine and Science in Sports and Exercise. 2004;36(2):241–248. doi: 10.1249/01.mss.0000113483.13339.7b.
    1. Hinton P. S., Sinclair L. M. Iron supplementation maintains ventilatory threshold and improves energetic efficiency in iron-deficient nonanemic athletes. European Journal of Clinical Nutrition. 2007;61(1):30–39. doi: 10.1038/sj.ejcn.1602479.
    1. Brown S. J., Child R. B., Day S. H., Donnelly A. E. Exercise-induced skeletal muscle damage and adaptation following repeated bouts of eccentric muscle contractions. Journal of Sports Sciences. 1997;15(2):215–222. doi: 10.1080/026404197367498.
    1. Jamurtas A. Z., Fatouros I. G., Buckenmeyer P., et al. Effects of plyometric exercise on muscle soreness and plasma creatine kinase levels and its comparison with eccentric and concentric exercise. Journal of Strength and Conditioning Research. 2000;14(1):68–74.
    1. Chatzinikolaou A., Christoforidis C., Avloniti A., et al. A microcycle of inflammation following a team-handball game. Journal of Strength and Conditioning Research. 2013;28(7):1981–1994.
    1. Chatzinikolaou A., Draganidis D., Avloniti A., et al. The microcycle of inflammation and performance changes after a basketball match. Journal of Sports Sciences. 2014;32(9):870–882. doi: 10.1080/02640414.2013.865251.
    1. Jamurtas A. Z., Theocharis V., Tofas T., et al. Comparison between leg and arm eccentric exercises of the same relative intensity on indices of muscle damage. European Journal of Applied Physiology. 2005;95(2-3):179–185. doi: 10.1007/s00421-005-1345-0.
    1. Webber L. M., Byrnes W. C., Rowland T. W., Foster V. L. Serum creatine kinase activity and delayed onset muscle soreness in prepubescent children: a preliminary study. Pediatric Exercise Science. 1989;1(4):351–359. doi: 10.1123/pes.1.4.351.
    1. Goldfarb A. H., Garten R. S., Cho C., Chee P. D., Chambers L. A. Effects of a fruit/berry/vegetable supplement on muscle function and oxidative stress. Medicine & Science in Sports & Exercise. 2011;43(3):501–508.
    1. Maughan R. J., Donnelly A. E., Gleeson M., Whiting P. H., Walker K. A., Clough P. J. Delayed-onset muscle damage and lipid peroxidation in man after a downhill run. Muscle and Nerve. 1989;12(4):332–336. doi: 10.1002/mus.880120412.
    1. Paltoglou G., Fatouros I. G., Valsamakis G., et al. Antioxidation improves in puberty in normal weight and obese boys, in positive association with exercise-stimulated growth hormone secretion. Pediatric Research. 2015;78(2):158–164. doi: 10.1038/pr.2015.85.
    1. Zalavras A., Fatouros I. G., Deli C. K., et al. Age-related responses in circulating markers of redox status in healthy adolescents and adults during the course of a training macrocycle. Oxidative Medicine and Cellular Longevity. 2015;2015:17. doi: 10.1155/2015/283921.283921
    1. Halliwell B., Gutteridge J. M. C. Free Radicals in Biology and Medicine. 4th. New York, NY, USA: Oxford University Press; 2007.
    1. Pyne D. B., Baker M. S., Smith J. A., Telford R. D., Weidemann M. J. Exercise and the neutrophil oxidative burst: biological and experimental variability. European Journal of Applied Physiology and Occupational Physiology. 1996;74(6):564–571. doi: 10.1007/s004210050116.
    1. Gutteridge J. M. C. Iron promoters of the Fenton reaction and lipid peroxidation can be released from haemoglobin by peroxides. FEBS Letters. 1986;201(2):291–295. doi: 10.1016/0014-5793(86)80626-3.
    1. Balla G., Jacob H. S., Balla J., et al. Ferritin: a cytoprotective antioxidant strategem of endothelium. The Journal of Biological Chemistry. 1992;267(25):18148–18153.
    1. Vítek L., Schwertner H. A. The heme catabolic pathway and its protective effects on oxidative stress-mediated diseases. Advances in Clinical Chemistry. 2007;43:1–57. doi: 10.1016/s0065-2423(06)43001-8.
    1. Frazer D. M., Anderson G. J. The regulation of iron transport. BioFactors. 2014;40(2):206–214. doi: 10.1002/biof.1148.
    1. Meneghini R. Iron homeostasis, oxidative stress, and DNA damage. Free Radical Biology & Medicine. 1997;23(5):783–792. doi: 10.1016/s0891-5849(97)00016-6.
    1. Nadadur S. S., Srirama K., Mudipalli A. Iron transport & homeostasis mechanisms: their role in health & disease. Indian Journal of Medical Research. 2008;128(4):533–544.
    1. Anderson C. P., Shen M., Eisenstein R. S., Leibold E. A. Mammalian iron metabolism and its control by iron regulatory proteins. Biochimica et Biophysica Acta—Molecular Cell Research. 2012;1823(9):1468–1483. doi: 10.1016/j.bbamcr.2012.05.010.
    1. Ludwig H., Evstatiev R., Kornek G., et al. Iron metabolism and iron supplementation in cancer patients. Wien Klin Wochenschr. 2015;127(23-24):920–921. doi: 10.1007/s00508-015-0893-5.
    1. Marnett L. J. Lipid peroxidation—DNA damage by malondialdehyde. Mutation Research—Fundamental and Molecular Mechanisms of Mutagenesis. 1999;424(1-2):83–95. doi: 10.1016/s0027-5107(99)00010-x.
    1. Jomova K., Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology. 2011;283(2-3):65–87. doi: 10.1016/j.tox.2011.03.001.
    1. Rowley D., Gutteridge J. M. C., Blake D., Farr M., Halliwell B. Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients. Clinical Science. 1984;66(6):691–695.
    1. Cooper D. M., Nemet D., Galassetti P. Exercise, stress, and inflammation in the growing child: from the bench to the playground. Current Opinion in Pediatrics. 2004;16(3):286–292. doi: 10.1097/01.mop.0000126601.29787.39.
    1. Child R., Brown S., Day S., Donnelly A., Roper H., Saxton J. Changes in indices of antioxidant status, lipid peroxidation and inflammation in human skeletal muscle after eccentric muscle actions. Clinical Science. 1999;96(1):105–115. doi: 10.1042/CS19980146.
    1. Finch C. A., Deubelbeiss K., Cook J. D., et al. Ferrokinetics in man. Medicine. 1970;49(1):17–53.
    1. Beard J. L. Iron biology in immune function, muscle metabolism and neuronal functioning. Journal of Nutrition. 2001;131(2S-2):568S–579S.
    1. Cooper C. E., Vollaard N. B., Choueiri T., Wilson M. T. Exercise, free radicals and oxidative stress. Biochemical Society Transactions. 2002;30(2):280–285. doi: 10.1042/bst0300280.
    1. Ames B. N., Cathcart R., Schwiers E., Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proceedings of the National Academy of Sciences of the United States of America. 1981;78(11):6858–6862. doi: 10.1073/pnas.78.11.6858.
    1. Stocker R., Yamamoto Y., McDonagh A. F., Glazer A. N., Ames B. N. Bilirubin is an antioxidant of possible physiological importance. Science. 1987;235(4792):1043–1046. doi: 10.1126/science.3029864.
    1. Shatat I. F., Abdallah R. T., Sas D. J., Hailpern S. M. Serum uric acid in US adolescents: distribution and relationship to demographic characteristics and cardiovascular risk factors. Pediatric Research. 2012;72(1):95–100. doi: 10.1038/pr.2012.47.
    1. Choi H. K., Liu S., Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the third national health and nutrition examination survey. Arthritis and Rheumatism. 2005;52(1):283–289. doi: 10.1002/art.20761.

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