Oxidative stress and COPD: the effect of oral antioxidants on skeletal muscle fatigue
Matthew J Rossman, H Jonathan Groot, Van Reese, Jia Zhao, Markus Amann, Russell S Richardson, Matthew J Rossman, H Jonathan Groot, Van Reese, Jia Zhao, Markus Amann, Russell S Richardson
Abstract
Purpose: Oxidative stress may contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). This study sought to determine the effect of an acute oral antioxidant cocktail (AOC, vitamins C and E, and alpha-lipoic acid) on skeletal muscle function during dynamic quadriceps exercise in COPD.
Methods: Ten patients with COPD performed knee extensor exercise to exhaustion and isotime trials after either the AOC or placebo (PL). Pre- to postexercise changes in quadriceps maximal voluntary contractions and potentiated twitch forces (Q(tw,pot)) quantified quadriceps fatigue.
Results: Under PL conditions, the plasma electron paramagnetic resonance (EPR) spectroscopy signal was inversely correlated with the forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC), an index of lung dysfunction (r = -0.61, P = 0.02), and maximal voluntary contraction force (r = -0.56, P = 0.04). AOC consumption increased plasma ascorbate levels (10.1 ± 2.2 to 24.1 ± 3.8 μg · mL(-1), P < 0.05) and attenuated the area under the curve of the EPR spectroscopy free radical signal (11.6 ± 3.7 to 4.8 ± 2.2 AU, P < 0.05), but it did not alter the endurance time or quadriceps fatigue. The ability of the AOC to decrease the EPR spectroscopy signal, however, was prominent in those with high basal free radicals (n = 5, PL, 19.7 ± 5.8, to AOC, 5.8 ± 4.5 AU; P < 0.05) with minimal effects in those with low levels (n = 5, PL, 1.6 ± 0.5, to AOC, 3.4 ± 1.1 AU).
Discussion: These data document a relation between directly measured free radicals and lung dysfunction and the ability of the AOC to decrease oxidative stress in COPD. Acute amelioration of free radicals, however, does not appear to affect dynamic quadriceps exercise performance.
Figures
![Figure 1. Relationships between the forced expiratory…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3947987/bin/nihms-556280-f0001.jpg)
![Figure 2. Resting antioxidant and oxidant status…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3947987/bin/nihms-556280-f0002.jpg)
Figure 3. Endurance time to exhaustion and…
Figure 3. Endurance time to exhaustion and end-exercise quadriceps fatigue assessed following constant-load knee extensor…
Figure 4. Physiological responses to constant workload…
Figure 4. Physiological responses to constant workload isotime knee extensor exercise matched for intensity (23±3…
Figure 5. Individual chang es in the…
Figure 5. Individual chang es in the α-Phenyl- tert -butylnitrone (PBN) spin adduct area under…
- Ascorbate attenuates cycling exercise-induced neuromuscular fatigue but fails to improve exertional dyspnea and exercise tolerance in COPD.Hureau TJ, Weavil JC, Sidhu SK, Thurston TS, Reese VR, Zhao J, Nelson AD, Birgenheier NM, Richardson RS, Amann M. Hureau TJ, et al. J Appl Physiol (1985). 2021 Jan 1;130(1):69-79. doi: 10.1152/japplphysiol.00611.2020. Epub 2020 Nov 5. J Appl Physiol (1985). 2021. PMID: 33151775 Free PMC article.
- Ascorbate infusion increases skeletal muscle fatigue resistance in patients with chronic obstructive pulmonary disease.Rossman MJ, Garten RS, Groot HJ, Reese V, Zhao J, Amann M, Richardson RS. Rossman MJ, et al. Am J Physiol Regul Integr Comp Physiol. 2013 Nov 15;305(10):R1163-70. doi: 10.1152/ajpregu.00360.2013. Epub 2013 Sep 25. Am J Physiol Regul Integr Comp Physiol. 2013. PMID: 24068051 Free PMC article.
- Quadriceps and respiratory muscle fatigue following high-intensity cycling in COPD patients.Bachasson D, Wuyam B, Pepin JL, Tamisier R, Levy P, Verges S. Bachasson D, et al. PLoS One. 2013 Dec 6;8(12):e83432. doi: 10.1371/journal.pone.0083432. eCollection 2013. PLoS One. 2013. PMID: 24324843 Free PMC article.
- Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary disease?Koechlin C, Couillard A, Simar D, Cristol JP, Bellet H, Hayot M, Prefaut C. Koechlin C, et al. Am J Respir Crit Care Med. 2004 May 1;169(9):1022-7. doi: 10.1164/rccm.200310-1465OC. Epub 2004 Mar 4. Am J Respir Crit Care Med. 2004. PMID: 15001462 Clinical Trial.
- Pharmacological and dietary antioxidant therapies for chronic obstructive pulmonary disease.Biswas S, Hwang JW, Kirkham PA, Rahman I. Biswas S, et al. Curr Med Chem. 2013;20(12):1496-530. doi: 10.2174/0929867311320120004. Curr Med Chem. 2013. PMID: 22963552 Review.
- Impaired muscle stem cell function and abnormal myogenesis in acquired myopathies.Deprez A, Orfi Z, Rieger L, Dumont NA. Deprez A, et al. Biosci Rep. 2023 Jan 31;43(1):BSR20220284. doi: 10.1042/BSR20220284. Biosci Rep. 2023. PMID: 36538023 Free PMC article. Review.
- Efficacy of Vitamin C Supplementation on Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.Lei T, Lu T, Yu H, Su X, Zhang C, Zhu L, Yang K, Liu J. Lei T, et al. Int J Chron Obstruct Pulmon Dis. 2022 Sep 10;17:2201-2216. doi: 10.2147/COPD.S368645. eCollection 2022. Int J Chron Obstruct Pulmon Dis. 2022. PMID: 36118282 Free PMC article. Review.
- Impact of acute antioxidant supplementation on vascular function and autonomic nervous system modulation in young adults with PTSD.Weggen JB, Darling AM, Autler AS, Hogwood AC, Decker KP, Imthurn B, Tuzzolo GM, Garten RS. Weggen JB, et al. Am J Physiol Regul Integr Comp Physiol. 2021 Jul 1;321(1):R49-R61. doi: 10.1152/ajpregu.00054.2021. Epub 2021 Jun 2. Am J Physiol Regul Integr Comp Physiol. 2021. PMID: 34075811 Free PMC article.
- Ascorbate attenuates cycling exercise-induced neuromuscular fatigue but fails to improve exertional dyspnea and exercise tolerance in COPD.Hureau TJ, Weavil JC, Sidhu SK, Thurston TS, Reese VR, Zhao J, Nelson AD, Birgenheier NM, Richardson RS, Amann M. Hureau TJ, et al. J Appl Physiol (1985). 2021 Jan 1;130(1):69-79. doi: 10.1152/japplphysiol.00611.2020. Epub 2020 Nov 5. J Appl Physiol (1985). 2021. PMID: 33151775 Free PMC article.
- Antioxidant cocktail following a high-sodium meal does not affect vascular function in young, healthy adult humans: a randomized controlled crossover trial.Smiljanec K, Mbakwe AU, Ramos-Gonzalez M, Pohlig RT, Lennon SL. Smiljanec K, et al. Nutr Res. 2020 Jul;79:13-22. doi: 10.1016/j.nutres.2020.05.011. Epub 2020 May 24. Nutr Res. 2020. PMID: 32610254 Free PMC article. Clinical Trial.
- Controlled Clinical Trial
- Research Support, N.I.H., Extramural
- Administration, Oral
- Aged
- Antioxidants / pharmacology*
- Antioxidants / therapeutic use
- Ascorbic Acid / pharmacology*
- Ascorbic Acid / therapeutic use
- Biomarkers / blood
- Drug Administration Schedule
- Drug Combinations
- Electromyography
- Electron Spin Resonance Spectroscopy
- Exercise Test
- Female
- Free Radicals / blood
- Humans
- Male
- Middle Aged
- Muscle Fatigue / drug effects*
- Oxidative Stress / drug effects*
- Pulmonary Disease, Chronic Obstructive / blood
- Pulmonary Disease, Chronic Obstructive / drug therapy*
- Pulmonary Disease, Chronic Obstructive / physiopathology
- Quadriceps Muscle / drug effects
- Quadriceps Muscle / physiopathology
- Respiratory Function Tests
- Single-Blind Method
- Thioctic Acid / pharmacology*
- Thioctic Acid / therapeutic use
- Treatment Outcome
- Vitamin E / pharmacology*
- Vitamin E / therapeutic use
- Antioxidants
- Biomarkers
- Drug Combinations
- Free Radicals
- Vitamin E
- Thioctic Acid
- Ascorbic Acid
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 3. Endurance time to exhaustion and…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3947987/bin/nihms-556280-f0003.jpg)
![Figure 4. Physiological responses to constant workload…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3947987/bin/nihms-556280-f0004.jpg)
![Figure 5. Individual chang es in the…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3947987/bin/nihms-556280-f0005.jpg)
Source: PubMed