Int J Sports Med 2021; 42(05): 441-447
DOI: 10.1055/a-1255-2863
Physiology & Biochemistry

Dietary Cysteine Intake is Associated with Blood Glutathione Levels and Isometric Strength

1   Department of Physical Education and Sport Science at Serres, Aristotle University of Thessaloniki, Greece
,
Panagiotis N. Chatzinikolaou
1   Department of Physical Education and Sport Science at Serres, Aristotle University of Thessaloniki, Greece
2   Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium
,
Flora V. Bousiou
3   Department of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece
,
Vasiliki J. Malliou
3   Department of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece
,
Sousana K. Papadopoulou
4   Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece
,
Panagiota Potsaki
4   Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece
,
Anastasios A. Theodorou
5   Department of Health Sciences, European University Cyprus, Nicosia, Cyprus
,
Antonios Kyparos
1   Department of Physical Education and Sport Science at Serres, Aristotle University of Thessaloniki, Greece
,
Nikos D. Geladas
3   Department of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece
,
Michalis G. Nikolaidis
1   Department of Physical Education and Sport Science at Serres, Aristotle University of Thessaloniki, Greece
,
Vassilis Paschalis
3   Department of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece
› Author Affiliations

Abstract

Glutathione is the most abundant cellular antioxidant and regulates redox homeostasis. Healthy individuals with certain antioxidant inadequacies/deficiencies exhibit impairments in physiological functions. The aim was to investigate whether low levels of dietary cysteine intake are associated with a) lower erythrocyte glutathione, b) increased plasma F2-isoprostanes, and c) impaired muscle function. Towards this aim, we recorded the dietary intake of the three amino acids that synthesize glutathione (i. e., glutamic acid, cysteine, and glycine) in forty-one healthy individuals, and subsequently measured erythrocyte glutathione levels. Maximal isometric strength and fatigue index were also assessed using an electronic handgrip dynamometer. Our findings indicate that dietary cysteine intake was positively correlated with glutathione levels (r=0.765, p<0.001). In addition, glutathione levels were negatively correlated with F2-isoprostanes (r=− 0.311, p=0.048). An interesting finding was that glutathione levels and cysteine intake were positively correlated with maximal handgrip strength (r=0.416, p=0.007 and r=0.343, p=0.028, respectively). In conclusion, glutathione concentration is associated with cysteine intake, while adequate cysteine levels were important for optimal redox status and muscle function. This highlights the importance of proper nutritional intake and biochemical screening with the goal of personalized nutrition.



Publication History

Received: 11 April 2020

Accepted: 18 August 2020

Article published online:
29 October 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Deponte M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 2013; 1830: 3217-3266 doi:10.1016/j.bbagen.2012.09.018
  • 2 May JM, Qu Z, Morrow JD. Mechanisms of ascorbic acid recycling in human erythrocytes. Biochim Biophys Acta 2001; 1528: 159-166 doi:10.1016/s0304-4165(01)00188-x
  • 3 Deponte M. The incomplete glutathione puzzle: Just guessing at numbers and figures?. Antioxid Redox Signal 2017; 27: 1130-1161 doi:10.1089/ars.2017.7123
  • 4 Taylor CG, Nagy LE, Bray TM. Nutritional and hormonal regulation of glutathione homeostasis. Curr Top Cell Regul 1996; 34: 189-208 doi:10.1016/s0070-2137(96)80007-0
  • 5 Sekhar RV, Patel SG, Guthikonda AP. et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr 2011; 94: 847-853 DOI: 10.3945/ajcn.110.003483.
  • 6 Minich DM, Brown BI. A review of dietary (phyto)nutrients for glutathione support. Nutrients 2019; 11: 2073 doi:10.3390/nu11092073
  • 7 Yin J, Ren W, Yang G. et al. L-Cysteine metabolism and its nutritional implications. Mol Nutr Food Res 2016; 60: 134-146 DOI: 10.1002/mnfr.201500031.
  • 8 Block G, Jensen CD, Morrow JD. et al. The effect of vitamins C and E on biomarkers of oxidative stress depends on baseline level. Free Radic Biol Med 2008; 45: 377-384 DOI: 10.1016/j.freeradbiomed.2008.04.005.
  • 9 Dolopikou CF, Kourtzidis IA, Margaritelis NV. et al. Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. Eur J Nutr 2020; 59: 505-515 DOI: 10.1007/s00394-019-01919-4.
  • 10 Paschalis V, Theodorou AA, Kyparos A. et al. Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation. Eur J Nutr 2016; 55: 45-53 DOI: 10.1007/s00394-014-0821-x.
  • 11 Paschalis V, Theodorou AA, Margaritelis NV. et al. N-acetylcysteine supplementation increases exercise performance and reduces oxidative stress only in individuals with low levels of glutathione. Free Radic Biol Med 2018; 115: 288-297 DOI: 10.1016/j.freeradbiomed.2017.12.007.
  • 12 Traber MG. Vitamin E inadequacy in humans: Causes and consequences. Adv Nutr 2014; 5: 503-514 doi:10.3945/an.114.006254
  • 13 Margaritelis NV, Cobley JN, Paschalis V. et al. Principles for integrating reactive species into in vivo biological processes: Examples from exercise physiology. Cell Signal 2016; 28: 256-271 DOI: 10.1016/j.cellsig.2015.12.011.
  • 14 Margaritelis NV, Paschalis V, Theodorou AA. et al. Antioxidants in Personalized Nutrition and Exercise. Adv Nutr 2018; 9: 813-823 DOI: 10.1093/advances/nmy052.
  • 15 Chen Y, Dong H, Thompson DC. et al. Glutathione defense mechanism in liver injury: Insights from animal models. Food Chem Toxicol 2013; 60: 38-44 DOI: 10.1016/j.fct.2013.07.008.
  • 16 Njalsson R, Ristoff E, Carlsson K. et al. Genotype, enzyme activity, glutathione level, and clinical phenotype in patients with glutathione synthetase deficiency. Hum Genet 2005; 116: 384-389 DOI: 10.1007/s00439-005-1255-6.
  • 17 Shi ZZ, Habib GM, Rhead WJ. et al. Mutations in the glutathione synthetase gene cause 5-oxoprolinuria. Nat Genet 1996; 14: 361-365 DOI: 10.1038/ng1196-361.
  • 18 Jones DP, Park Y, Gletsu-Miller N. et al. Dietary sulfur amino acid effects on fasting plasma cysteine/cystine redox potential in humans. Nutrition 2011; 27: 199-205 DOI: 10.1016/j.nut.2010.01.014.
  • 19 Parcell S. Sulfur in human nutrition and applications in medicine. Altern Med Rev 2002; 7: 22-44
  • 20 Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013; 1830: 3143-3153 doi:10.1016/j.bbagen.2012.09.008
  • 21 Jackson AA, Gibson NR, Lu Y. et al. Synthesis of erythrocyte glutathione in healthy adults consuming the safe amount of dietary protein. Am J Clin Nutr 2004; 80: 101-107 DOI: 10.1093/ajcn/80.1.101.
  • 22 McCarty MF, O’Keefe JH, DiNicolantonio JJ. Dietary glycine is rate-limiting for glutathione synthesis and may have broad potential for health protection. Ochsner J 2018; 18: 81-87
  • 23 Cobley JN, McGlory C, Morton JP. et al. N-Acetylcysteine’s attenuation of fatigue after repeated bouts of intermittent exercise: Practical implications for tournament situations. Int J Sport Nutr Exerc Metab 2011; 21: 451-461 DOI: 10.1123/ijsnem.21.6.451.
  • 24 Medved I, Brown MJ, Bjorksten AR. et al. N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. J Appl Physiol (1985) 2004; 97: 1477-1485 DOI: 10.1152/japplphysiol.00371.2004.
  • 25 Margaritelis NV, Paschalis V, Theodorou AA et al. Antioxidant supplementation, redox deficiencies and exercise performance: A falsification design. Free Radic Biol Med 2020; 158: 44–52
  • 26 Matuszczak Y, Farid M, Jones J. et al. Effects of N-acetylcysteine on glutathione oxidation and fatigue during handgrip exercise. Muscle Nerve 2005; 32: 633-638 DOI: 10.1002/mus.20385.
  • 27 Lohman TG, MIlliken LA. ACSM’s Body Composition Assessment. Champaing: Human Kinetics; 2020
  • 28 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817 doi:10.1055/a-1015-3123
  • 29 Papadopoulou SK, Dalatsi VA, Methenitis SK. et al. Nutritional routine of tae kwon do athletes prior to competition: What Is the Impact of Weight Control Practices?. J Am Coll Nutr 2017; 36: 448-454 DOI: 10.1080/07315724.2017.1319305.
  • 30 Papadopoulou SK, Xyla EE, Methenitis S. et al. Nutrition strategies before and during ultra-endurance event: A significant gap between science and practice. Scand J Med Sci Sports 2018; 28: 881-892 DOI: 10.1111/sms.13006.
  • 31 Veskoukis AS, Kyparos A, Paschalis V. et al. Spectrophotometric assays for measuring redox biomarkers in blood. Biomarkers 2016; 21: 208-217 DOI: 10.3109/1354750X.2015.1126648.
  • 32 Pincivero DM, Gear WS, Sterner RL. Assessment of the reliability of high-intensity quadriceps femoris muscle fatigue. Med Sci Sports Exerc 2001; 33: 334-338 doi:10.1097/00005768-200102000-00025
  • 33 Nikolaidis MG, Kyparos A, Vrabas IS. F(2)-isoprostane formation, measurement and interpretation: the role of exercise. Prog Lipid Res 2011; 50: 89-103 doi:10.1016/j.plipres.2010.10.002
  • 34 Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition 2002; 18: 872-879 doi:10.1016/s0899-9007(02)00916-4
  • 35 Ford E, Hughes MN, Wardman P. Kinetics of the reactions of nitrogen dioxide with glutathione, cysteine, and uric acid at physiological pH. Free Radic Biol Med 2002; 32: 1314-1323 doi:10.1016/s0891-5849(02)00850-x
  • 36 Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 2014; 141: 150-159 doi:10.1016/j.pharmthera.2013.09.006
  • 37 Niki E. Role of vitamin E as a lipid-soluble peroxyl radical scavenger: In vitro and in vivo evidence. Free Radic Biol Med 2014; 66: 3-12 doi:10.1016/j.freeradbiomed.2013.03.022
  • 38 Niki E, Traber MG. A history of vitamin E. Ann Nutr Metab 2012; 61: 207-212 doi:10.1159/000343106
  • 39 Traber MG. Vitamin E regulatory mechanisms. Annu Rev Nutr 2007; 27: 347-362 doi:10.1146/annurev.nutr.27.061406.093819
  • 40 Margaritelis NV, Paschalis V, Theodorou AA. et al. Redox basis of exercise physiology. Redox Biol 2020; 101499 DOI: 10.1016/j.redox.2020.101499.
  • 41 Reid MB. Invited Review: redox modulation of skeletal muscle contraction: what we know and what we don’t. J Appl Physiol (1985) 2001; 90: 724-731 doi:10.1152/jappl.2001.90.2.724
  • 42 Moen RJ, Cornea S, Oseid DE. et al. Redox-sensitive residue in the actin-binding interface of myosin. Biochem Biophys Res Commun 2014; 453: 345-349 DOI: 10.1016/j.bbrc.2014.09.072.
  • 43 Murphy RM, Dutka TL, Lamb GD. Hydroxyl radical and glutathione interactions alter calcium sensitivity and maximum force of the contractile apparatus in rat skeletal muscle fibres. J Physiol 2008; 586: 2203-2216 doi:10.1113/jphysiol.2007.150516
  • 44 Mollica JP, Dutka TL, Merry TL. et al. S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans. J Physiol 2012; 590: 1443-1463 DOI: 10.1113/jphysiol.2011.224535.
  • 45 Park Y, Ziegler TR, Gletsu-Miller N. et al. Postprandial cysteine/cystine redox potential in human plasma varies with meal content of sulfur amino acids. J Nutr 2010; 140: 760-765 DOI: 10.3945/jn.109.116764.
  • 46 Di Buono M, Wykes LJ, Ball RO. et al. Total sulfur amino acid requirement in young men as determined by indicator amino acid oxidation with L-[1-13C]phenylalanine. Am J Clin Nutr 2001; 74: 756-760 DOI: 10.1093/ajcn/74.6.756.
  • 47 van de Poll MC, Dejong CH, Soeters PB. Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. J Nutr 2006; 136: 1694S-1700S doi:10.1093/jn/136.6.1694S