Aerobic exercise improves oxidant-antioxidant balance in patients with rheumatoid arthritis
INTRODUCTION
Rheumatoid arthritis (RA) is a systemic autoimmune disorder which is characterized by chronic inflammation mainly affecting the joints and dysregulated oxidative metabolism is a significant mechanism playing a major role in the pathophysiology of the disease. Most RA studies focusing on oxidative metabolism have reported that the oxidant levels are increased in rheumatic patients indicating that RA patients are subjected to oxidative stress1,2,3). Therefore, RA treatment strategies should aim to alter the inflammatory and oxidative pathways to recover as close as possible the normal physiological states.
A growing number of clinical studies have shown that exercise is beneficial for RA patients. It is well known that exercise has beneficial effects on the physical parameters of RA, including pain, fatigue, quality of life, aerobic capacity and muscle strength without inducing any structural damage4,5,6). A wide range of types of exercise, including strengthening and aerobic exercises, are concluded to be safe without any adverse effects on RA5, 7).
Although aerobic exercise improves the functional parameters of RA, its effects on the pathophysiology of the disease remain to be elucidated. The aim of this study was to investigate the effects of an acute bout of moderate aerobic exercise on the plasma oxidant and antioxidant profiles of RA patients. The hypothesis of this study is that aerobic exercise alters the oxidative status and exerts beneficial effects on the pathophysiology of the disease.
SUBJECTS AND METHODS
The study design was approved by Gazi University Clinical Researches Ethics Committee and is registered with the number 275-13.07.2011.
Subjects
Sixteen RA patients diagnosed according to the American College of Rheumatology (ACR) criteria8)and 10 age-matched healthy volunteers participated in this study. All of the RA patients were on synthetic disease modifying anti-rheumatic drugs (DMARD) therapy, and they had been in remission for at least 3 months before entry into the study. Patients with metabolic or cardiovascular disorders were excluded. Patients who had received steroid therapy (any dose or any form) in the previous 3 months were also excluded. Those smoking tobacco or with excessive alcohol consumption in the previous 12 months were also excluded. The eligibility criteria are listed in Table 1.
Eligibility criteria for inclusion in the study
All of the participants were assessed for eligibility after a detailed explanation about the study and all gave signed their informed consent. They were instructed not to exercise and not to take any drugs except their routine medications the day before the test.
Methods
On the test day, the participants were assessed for the descriptive parameters of age, sex, height, body weight, resting heart rate and blood pressure. Prior to the exercise, they completed the Turkish version of the International Physical Activity Questionnaire (IPAQ)9) which assesses individual’s weekly physical activity levels and allows evaluation of metabolic equivalents of tasks (METs).
The aerobic exercise protocol was carried out on a treadmill at a submaximal intensity for 30 minutes. Exercise intensity was determined individually for each participant, with the aim of eliciting 60–75% of the calculated maximal heart rate (220-age)7) . Heart rate was monitored by a polar telemeter during the test. The testing included 3 minutes warm-up and 2 minutes cool-down and the treadmill speed was adjusted to elicit the target heart rate of each participant during the test. Venous blood samples were obtained from the antecubital vein prior to baseline, immediately after, and 24 hours after the exercise. All the participants performed the test in the afternoon and 24-hour blood samples were drawn the next day at about the same time in the afternoon. The blood samples were centrifuged at 3,500 rpm for 10 minutes and stored at −80 °C until the analyses.
Malondialdehyde (MDA) as an indicator of lipid peroxidation (an indicator of oxidant state) and total sulfhydrile groups (RSH), as an indicator of antioxidant state, were measured using Kurtel’s spectrophotometric method10).
Statistical analyses were performed using SPSS Version 15.0. Friedman’s non-parametric test was used to analyze the plasma levels of oxidants and antioxidants. In the case of significant results, Wilcoxon’s test was used for further analysis. The comparison of the groups were performed using the Mann-Whitney U test. The results are expressed as mean±SD, and statistical significance was accepted for values of p<0.05.
RESULTS
The baseline characteristics of the study patients and healthy controls are given in Table 2. The groups did not differ with age, height or physical activity levels (Table 3). However, patients had greater body weight than the healthy controls (p<0.05).
Characteristics of the RA patients and healthy controls
Comparison of the physical activity of both groups
Although both groups performed the treadmill walking exercise at similar heart rates, the treadmill walking speed of the RA patients during the exercise was significantly lower than that of the controls (p=0.047). The baseline mean serum MDA level of the patients was higher than that of the control group (p<0.05). Serum MDA levels decreased significantly with exercise in both groups (p<0.05). Although a return toward baseline MDA levels were seen at 24-hour post-exercise in both groups, the increase in MDA was significant only in the control group (p<0.05); serum MDA levels of RA patients remained lower than the baseline even at 24 hours after the exercise (Table 4).
Comparison of mean±SD plasma MDA levels (nmol/ml) in the patients and healthy controls
No difference in serum RSH levels was noted between the groups at any time point. Serum RSH levels increased with exercise in both groups, but the change was not statistically significant (Table 5).
Comparison of plasma RSH levels in the RA patients and control groups (p>0.05)
DISCUSSION
This study demonstrated that a bout of moderate intensity aerobic exercise created an antioxidant environment in patients with RA. Moreover, the exercise had no significant adverse effects on the oxidant-antioxidant balance. Hence, it appears that moderate intensity aerobic exercise is beneficial for general health and is safe with respect to inflammatory status in RA. The results also showed that the patients had lower cardiovascular fitness levels than the healthy controls as indicated by their lower walking speeds at the target heart rates.
The beneficial effects of different exercise types for RA have previously been described4,5,6,7). Although several previous studies have reported a link between exercise and RA, they have generally aimed to assess functional and physical parameters such as aerobic capacity, bone mineral density, pain, fatigue, and quality of life5,6,7, 11). Furthermore, exercise has recently been suggested to alter the pathophysiological pathways; therefore it may improve the symptoms of chronic inflammatory diseases12). However, the effects of acute exercise on the dysregulated oxidative processes and their mechanisms in RA are still unclear.
There are many studies in the medical literature suggesting that a mechanism impaired in RA, and that oxidative metabolism plays a role in its pathophysiology. Oxidant levels were shown to be increased in RA patients exhibiting oxidative stress, indicating their link with the chronic inflammation1, 2). Studies have revealed that the levels of oxidative molecules are increased2, 3); however, antioxidant defenses are insufficient in RA patients. Although a great number of studies of the beneficial effects of exercise in RA are present in the literature, its effects on disease pathophysiology are still unclear. The results of the present study support the view that aerobic exercise can affect the pathophysiology of the disease, as evidenced by the serum MDA analyses.
Current data on the oxidative response to exercise show that it varies with exercise intensity13, 14). It is thought that exhaustive exercise at maximal intensity increases serum oxidant levels causing oxidative stress; however, submaximal exercise generally does not affect the oxidant levels. In our present study, plasma MDA levels decreased in response to acute aerobic exercise at submaximal intensity in both groups. This result is consistent with some other studies15, 16). The small increase observed in the RSH levels is possibly a manifestation of other antioxidant defenses. The most exciting result of our study is that the MDA levels did not return to the baseline levels the next day in the RA patients, as opposed to the healthy individuals. This suggests that aerobic exercise exerts an acute antioxidant effect which is maintained longer in RA patients.
Increased risk of cardiovascular diseases has significant effects on disease morbidity and mortality, and RA patients have 60% increased risk of cardiovascular death compared to the general population17). In this study, the lower treadmill walking speeds of the RA patients at the target heart rate indicate the poor cardiovascular status of these patients and this result is in agreement with the literature. Oxidative stress and overproduction of reactive oxygen species play a major role in atherosclerosis and cardiovascular diseases18). Oxidative stress resulting from chronic inflammation in RA seems to enhance cardiovascular risks, and an integrated therapeutic approach combining anti-inflammatory treatment and aerobic exercise may have beneficial effects on the cardiovascular morbidity and mortality of RA. Hence, aerobic exercise could be a powerful physiotherapy intervention in the non-pharmaceutical management of both the disease and its co-morbidities. Walking, which was chosen as the exercise for our study, is the most popular aerobic exercise as it needs no special equipment and has proven effects on blood markers19).
Our study had several limitations. First, we were able to study only a limited number of patients. However, the number is comparable to similar previous exercise intervention studies20, 21). Second, we measured serum levels; thus, systemic, rather than local effects of acute aerobic exercise were investigated. Further studies to examine synovial samples are also needed to investigate local changes. Finally, we measured only the serum levels of MDA as an oxidative marker, which is the most commonly used indicator of lipid peroxidation. However, MDA has been the most commonly measured parameter of the oxidative state in the most recent exercise metabolism studies13,14,15,16).
In conclusion, moderate aerobic exercise exerts an antioxidant effect lasting over 24 hours, providing additional evidence in support of the importance of exercise in the rehabilitation of RA.
Acknowledgments
This study was financially supported by Gazi University Scientific Research Projects Foundation with the project number 47/2012-07.
REFERENCES
1. Vasanthi P, Nalini G, Rajasekhar G.: Status of oxidative stress in rheumatoid arthritis. Int J Rheum Dis, 2009, 12: 29–33. [PubMed]
2. Kamanlı A, Naziroğlu M, Aydilek N, et al. : Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis. Cell Biochem Funct, 2004, 22: 53–57. [PubMed]
3. Desai PB, Manjunath S, Kadi S, et al. : Oxidative stress and enzymatic antioxidant status in rheumatoid arthritis: a case control study. Eur Rev Med Pharmacol Sci, 2010, 14: 959–967. [PubMed]
4. Harkcom TM, Lampman RM, Banwell BF, et al. : Therapeutic value of graded aerobic exercise training in rheumatoid arthritis. Arthritis Rheum, 1985, 28: 32–39. [PubMed]
5. Strasser B, Leeb G, Strehblow C, et al. : The effects of strength and endurance training in patients with rheumatoid arthritis. Clin Rheumatol, 2011, 30: 623–632. [PubMed]
6. Hurkmans E, van der Giesen FJ, Vliet Vlieland TPM, et al. Dynamic exercise programs (aerobic capacity and/or muscle strength training in patients with rheumatoid arthritis. Cochrane Database of Systematic Reviews, 2009, Issue 4. [PubMed]
7. Baillet A, Zeboulon N, Gossec L, et al. : Efficacy of cardiorespiratory aerobic exercise in rheumatoid arthritis: meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken), 2010, 62: 984–992. [PubMed]
8. Arnett FC, Edworthy SM, Bloch DA, et al. : The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum, 1988, 31: 315–324. [PubMed]
9. Saglam M, Arikan H, Savci S, et al. : International physical activity questionnaire: reliability and validity of the Turkish version. Percept Mot Skills, 2010, 111: 278–284. [PubMed]
10. Kurtel H, Granger DN, Tso P, et al. : Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Physiol, 1992, 263: G573–G578. [PubMed]
11. Kelley GA, Kelley KS, Hootman JM, et al. : Effects of community-deliverable exercise on pain and physical function in adults with arthritis and other rheumatic diseases: a meta-analysis. Arthritis Care Res (Hoboken), 2011, 63: 79–93. [PubMed]
12. Gleeson M, Bishop NC, Stensel DJ, et al. : The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol, 2011, 11: 607–615.[PubMed]
13. Urso ML, Clarkson PM.: Oxidative stress, exercise, and antioxidant supplementation. Toxicology, 2003, 189: 41–54. [PubMed]
14. Banerjee AK, Mandal A, Chanda D, et al. : Oxidant, antioxidant and physical exercise. Mol Cell Biochem, 2003, 253: 307–312. [PubMed]
15. Berzosa C, Gómez-Trullén EM, Piedrafita E, et al. : Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans. Eur J Appl Physiol, 2011, 111: 1127–1133. [PubMed]
16. Leaf DA, Kleinman MT, Hamilton M, et al. : The effect of exercise intensity on lipid peroxidation.Med Sci Sports Exerc, 1997, 29: 1036–1039. [PubMed]
17. Meune C, Touzé E, Trinquart L, et al. : Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies.Rheumatology (Oxford), 2009, 48: 1309–1313. [PubMed]
18. Madamanchi NR, Vendrov A, Runge MS.: Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol, 2005, 25: 29–38. [PubMed]
19. Lee SH, Seo BD, Chung SM.: The effect of walking exercise on physical fitness and serum lipids in obese middle-aged women: pilot study. J Phys Ther Sci, 2013, 25: 1533–1536. [PMC free article][PubMed]
20. Flint-Wagner HG, Lisse J, Lohman TG, et al. : Assessment of a sixteen-week training program on strength, pain, and function in rheumatoid arthritis patients. J Clin Rheumatol, 2009, 15: 165–171.[PubMed]
21. Shojaei EA, Jafari A, Farajov A.: Effect of acute moderate aerobic cycling on systemic inflammatory responses in young untrained men. Sci Sports, 2011, 26: 298–302.
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