Effect of eight weeks high intensity aerobic exercise on C-reactive protein levels in obese middle-aged men

Document Type: Original Article


MS in exercise physiology, The General Education Department of kohgiluyeh and boyer-ahmad Province, Iran


Introduction: C-reactive protein (CRP) is a marker of chronic systemic inflammation frequently used in cardiovascular disease risk assessment. The aim of this study was to investigate CRP concentrations in middle-aged men after 8 weeks high intensity aerobic exercise.
Material & Methods: Twenty two sedentary obese middle-aged men (aged: 46.4 ± 2.3 years and body mass index (BMI): 32.8 ± 2.0 kg/m2; ± SD) volunteered to participate in this study. The subjects were randomly assigned to training group (n=11) or control group (n=11). The training group performed high intensity aerobic training 3 days a week for 8 weeks at an intensity corresponding to 75-80% individual maximum oxygen consumption for 45 min.
Results: The results showed that the body weight, BMI, body fat percent and WHR were decreased and VO2max was increased in the training group compared to the control group (P<0.05). After 8 weeks, the training group resulted in a significant decrease (58.7 %) in the CRP in compared with the control group.
Conclusions: The results suggest high intensity aerobic exercise improves body composition and decreases CRP concentrations in obese middle-aged men.


In summary, resistance training–induced change in body composition decreases CRP concentrations in obese middle-aged men.



Obesity is a public health problem and can be classified as a world epidemic that leads to an elevation in medical costs. Obesity and overweight have been shown to increase the risk of several well-known co-morbidities such as cardiovascular disease. Obesity is characterized by excess energy intake resulting in an expansion of adipose tissue depots, visceral adiposity, hypertrophy, hyperplasia, and adipocyte dysfunction (1). In obese individuals there are marked increases in the secretion of pro-inflammatory adipokines including C-reactive protein (CRP), IL-6 and TNF-α, and decreased production of anti-inflammatory adipokines such as adiponectin. This change in adipokine balance is a key component of pathogenic metabolic and immune responses and has impacts on angiogenesis, blood pressure and lipid metabolism, all of which are linked with cardiovascular disease (2,3).

One of the most commonly measured markers of inflammation in clinical settings is CRP (4,5). Plasma levels of CRP have been reported to be a strong independent predictor of risk of future myocardial infarction, stroke, peripheral arterial disease, and vascular death among individuals without known cardiovascular disease (4). Given the apparent importance of CRP among other inflammatory markers in the development of cardiovascular disease morbidity and mortality, it is critical to determine those factors that may help to lower and maintain optimal levels of CRP (6).

It is documented that physical activity has a role in preventing cardiovascular disease (7), mediated, in part, by changes in inflammation. Recently, great attention has been focused on the response of inflammation to physical exercise. Several studies have not provided support for exercise intervention-induced reductions in CRP in adults (6,8).

A recent review, although concluding that assessing body composition distribution may assist in interpreting the effectiveness of interventions in improving circulating inflammatory markers in obese adults (9), does not provide enough evidence about the effect of physical exercise on reducing CRP levels. In contrast, other studies concluded that habitual physical exercise results in lower levels of CRP (8,10). Therefore, evidence about the impact of physical exercise on controlling the inflammation process is not clear, thus the aim of this study was to investigate CRP concentrations in middle-aged men after 8 weeks high intensity aerobic exercise.


Material & methods


Twenty two sedentary obese middle-aged men (aged: 46.4 ± 2.3 years and body mass index (BMI): 32.8 ± 2.0 kg/m2; ± SD) volunteered to participate in this study. All the subjects were asked to complete a personal health and medical history questionnaire, which served as a screening tool. The subjects were given both verbal and written instructions outlining the experimental procedure, and written informed consent was obtained. Our participants were not engaged in any systematic exercise programs at least 6 months before the study, none of them had any disease or had been consuming any drugs that could affect bone metabolism. The subjects were randomly assigned to one of the training group (n=11) or control group (n=11). The study was approved by the Yasuj branch, Islamic Azad University Ethics Committee.


Exercise training

The training group performed high intensity aerobic training 3 days a week for 8 weeks at an intensity corresponding to 75-80% individual maximum oxygen consumption for 45 min. Each participant wore a heart rate monitor (Beurer, PM70, Germany) to ensure accuracy of the exercise level. The control group was instructed not to change their physical activity and diet.



Anthropometric and body composition measurements

Anthropometric measures including height, body mass, waist circumference and hip circumference were evaluated using standard techniques (11). Body mass index (BMI) and waist/hip ratio (WHR) were calculated. Then, body composition (percentage of total body fat) was assessed by skinfold thickness protocol. Skinfold thickness was measured sequentially, in triceps, suprailiac, and thigh by the same investigator using a skinfold caliper (Harpenden, HSK-BI, British Indicators, West Sussex, UK) and a standard technique (11).


Measurement of VO2max

VO2max was determined by Rockport One-Mile Fitness Walking Test. In this test, an individual walked 1 mile as fast as possible on a track surface. Total time was recorded and HR was obtained in the final minute. VO2max was calculated using formula (11).


Biochemical analyses

Fasted, resting morning blood samples (10 ml) were taken at the same time before and after 8 weeks intervention. All the subjects fasted at least for 12 hours and a fasting blood sample was obtained by venipuncture. Plasma obtained was frozen at ‒22 oC for subsequent analysis. CRP levels were determined via an enzyme-linked immunosorbent assay (ELISA) kits (Monobind, China, Inc). The intra and inter-assay coefficients of variation for hs-CRP were <0.68% and a sensitivity of 0.01 µg/ml.


Statistical analysis

Results were expressed as the mean ± SD and distributions of all variables were assessed for normality. Paired-sample t-test and independent sample t-test were used to evaluate the changes of Plasma CRP levels before and after the intervention. The level of significance in all statistical analyses was set at P≤0.05. Data analyses were performed using SPSS software for windows (version 17, SPSS, Inc., Chicago, IL).



Changes in anthropometric variables

Anthropometric, body composition and physiological characteristics of the subjects at baseline and after training are presented in Table 1. Before the intervention, there were no significant differences in any of variables among the two groups. The results showed that the body weight (5.5%), BMI (5.5%), body fat percent (12.9%) and WHR (2.9%) were decreased and VO2max was increased (12.9%) in the training group compared to the control group (P<0.05).


Table 1. Anthropometric, body composition and physiological characteristics (mean ± SD) of the subjects


Control (mean±SD)


Training (mean±SD)





Height (cm)

174.7 ± 6.0

173.3 ± 4.0

Body mass (Kg)

100.8 ± 9.4

100.7 ± 9.1

98.1 ± 7.0

92.7 ± 5.5*

BMI (Kg/m2)

33.0 ± 2.3

33.2 ± 2.2

32.6 ± 1.9

30.8 ± 1.6*

Body fat (%)

27.7 ± 4.5

27.8 ± 4.5

29.3 ± 4.0

25.5 ± 4.5*


1.0 ± 0.05

1.0 ± 0.05


1.02 ± 0.02

0.99 ± 0.02*

VO2max (ml/kg/min)

36.4 ± 0.9

36.2 ± 0.9


32.4 ± 2.3

36.6 ± 2.8*


P<0.01, pretraining vs. posttraining values.


Changes in biochemical variables

Changes on CRP concentrations at baseline and after 8 weeks high intensity aerobic exercise are presented in Figure 1. Results showed that the training group resulted in a significant decrease (58.7 %) in the CRP in compared with the control group (P<0.05).



Figure 1. Changes on CRP levels after 8 weeks exercise


P<0.01, pretraining vs. posttraining values.



The aim of this study was to investigate CRP concentrations in middle-aged men after 8 weeks high intensity aerobic exercise. Our results showed that CRP concentrations were decreased after the intervention (58.7 %) in compared with the control group.

How exercise training reduces inflammation and suppresses CRP levels is not well defined. Physical activity is related to several confounders that are independently associated with lower CRP levels. For example, physical activity is inversely related to age, smoking, hypertension, BMI, and WHR, total and non–high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B concentrations, whereas these factors are directly related to CRP concentrations (12). Similarly, physical activity is directly related to the proportion of white participants, education level, insulin sensitivity, alcohol consumption, and fruit and vegetable intake, all factors that are inversely associated with CRP (12). Despite the overlap between factors associated with physical activity and CRP, higher CRP levels persist in more active subjects in most studies even after adjustment.

Hepatic CRP production is stimulated by IL-6 and, to a lesser extent, by IL-1 and TNF-α. Individuals who are obese and/or hyperinsulinemic have increased adipocyte production of inflammatory markers, including CRP, IL-6, and TNF-α (13,14). A multidisciplinary program to reduce body weight in obese women through lifestyle changes, including a low-calorie diet, and increased physical activity, reduced IL-6, IL-18, CRP, and insulin resistance, whereas adiponectin levels increased (15). Adiponectin is a novel adipocytokine with anti-inflammatory and insulinsensitizing properties (16). Evidence also exists that leptin levels are reduced in physically active individuals independent of BMI (17) and that leptin is associated with CRP (18). Moreover, in centrally obese individuals, omental adipocytes produce more IL-6 than do abdominal subcutaneous adipocytes (19). Consequently, physical activity could decrease resting levels of IL-6 and TNF-alpha and, ultimately, CRP production, by reducing obesity and leptin and increasing adiponectin and insulin sensitivity (20). Once again, however, the relationship between increased physical activity and lower CRP persists even after adjusting for BMI, WHR, and fasting insulin concentration (17,21), suggesting that other factors contribute to the exercise-related anti-inflammatory effect.

Some of this effect may be mediated by modification of cytokine production from other sites, besides adipose tissue, such as skeletal muscles (22) and mononuclear cells (23). Exercise training reduces skeletal muscle TNF-alpha, IL-1-beta, and IL-6 expression in patients with heart failure (22). Furthermore, long-term exercise attenuates mononuclear cell production of atherogenic cytokines (IL-1-alpha, TNF-alpha, and interferon gamma) while augmenting the production of atheroprotective cytokines (IL-4, IL-10, and transforming growth factor-beta-1) (23). Thus, these multifocal effects of exercise drive the resting cytokine balance to an “anti-inflammatory” state.

Physical activity may also mitigate inflammation by improving endothelial function. Endothelial cells are known to secrete IL-1 and IL-6, whereas activated endothelial cells can increase the production of ILs and adhesion molecules inducing inflammation (24). Physical training reduces peripheral inflammatory markers associated with endothelial dysfunction, such as soluble intracellular and vascular adhesion molecules, granulocyte-macrophage colony-stimulating factor, and macrophage chemoattractant protein-1 in patients with heart failure (25). Regular physical activity also improves endothelial function preserving nitric oxide availability (26). Although exercise acutely increases oxidative metabolism and thereby induces oxidative stress, there is evidence that long-term physical activity increases antioxidant defenses through the up-regulation of antioxidant enzymes (27). Furthermore, this antioxidant effect of exercise reduces the susceptibility of low-density lipoprotein to oxidation (28), which in turn helps further prevent endothelial injury and inflammation (39,30). In summary, it is likely that exercise training reduces CRP both directly by reducing cytokine production in fat, muscle, and mononuclear cells and indirectly by increasing insulin sensitivity, improving endothelial function, and reducing body weight. Additional research is needed to examine these mechanisms.



In summary, resistance training–induced change in body composition decreases CRP concentrations in obese middle-aged men.


Conflict of interests: There was no conflict of interest among authors.


1. Khan M, Joseph F. Adipose tissue and adipokines: the association with and application of adipokines in obesity. Scientifica 2014; 2014: 328592.

2. Northcott JM, Yeganeh A, Taylor CG, Zahradka P, Wigle JT. Adipokines and the cardiovascular system: mechanisms mediating health and disease. Can J Physiol Pharmacol 2012; 90: 1029-1059.

3. Smith MM, Minson CT. Obesity and adipokines: effects on sympathetic overactivity. J Physiol. 2012; 590: 1787-1801.

4. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107: 363-369.

5. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. JAMA 1998; 279: 1477-1482.

6. Kelley GA, Kelley KS. Effects of aerobic exercise on C-reactive protein, body composition, and maximum oxygen consumption in adults: a meta-analysis of randomized controlled trials. Metabolism 2006; 55: 1500-1507.

7. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc 2007; 39: 1423-1434.

8. Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol 2005; 45: 1563-1569.

9. Fedewa MV, Hathaway ED, Ward-Ritacco CL. Effect of exercise training on C reactive protein: a systematic review and meta-analysis of randomised and non-randomised controlled trials. Br J Sports Med 2017; 51: 670-676.

10. Hayashino Y, Jackson JL, Hirata T, Fukumori N, Nakamura F, Fukuhara S, et al. Effects of exercise on C-reactive protein, inflammatory cytokine and adipokine in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Metabolism 2014; 63: 431-440.

11. American Collage of Sport Medicine. Guidelines for exercise testing and prescription. Philadelphia: Lippincott Williams & Wilkins 2005; 57-90.

12. Ford ES. Does exercise reduce inflammation? Physical activity and C-reactive protein among U.S. adults. Epidemiology 2002; 13: 561-568.

13. McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P, et al. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation 2002; 106: 2908-2912.

14. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999; 19: 972-978.

15. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003; 289: 1799-1804.

16. Stefan N, Stumvoll M. Adiponectin-its role in metabolism and beyond. Horm Metab Res 2002; 34: 469-474.

17. Tomaszewski M, Charchar FJ, Przybycin M, Crawford L, Wallace AM, Gosek K, et al. Strikingly low circulating CRP concentrations in ultramarathon runners independent of markers of adiposity: how low can you go? Arterioscler Thromb Vasc Biol 2003; 23: 1640-1644.

18. Shamsuzzaman AS, Winnicki M, Wolk R, Svatikova A, Phillips BG, Davison DE, et al. Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 2004; 109: 2181-2185.

19. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998; 83: 847-850.

20. Mayer-Davis EJ, D’Agostino R Jr., Karter AJ, Haffner SM, Rewers MJ, Saad M, et al. Intensity and amount of physical activity in relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study. JAMA 1998; 279: 669-674.

21. Aronson D, Sheikh-Ahmad M, Avizohar O, Kerner A, Sella R, Bartha P, et al. C-Reactive protein is inversely related to physical fitness in middle-aged subjects. Atherosclerosis 2004; 176: 173-179.

22. Gielen S, Adams V, Mobius-Winkler S, Linke A, Erbs S, Yu J, et al. Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol 2003; 42: 861-868.

23. Smith JK, Dykes R, Douglas JE, Krishnaswamy G, Berk S. Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. JAMA 1999; 281: 1722-1727.

24. Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 1997; 6: 315-325.

25. Adamopoulos S, Parissis J, Kroupis C, Georgiadis M, Karatzas D, Karavolias G, et al. Physical training reduces peripheral markers of inflammation in patients with chronic heart failure. Eur Heart J 2001; 22: 791-797.

26. Taddei S, Galetta F, Virdis A, Ghiadoni L, Salvetti G, Franzoni F, et al. Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation 2000; 101: 2896-2901.

27. Powers SK, Ji LL, Leeuwenburgh C. Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Med Sci Sports Exerc 1999; 31: 987-997.

28. Shern-Brewer R, Santanam N, Wetzstein C, White-Welkley J, Parthasarathy S. Exercise and cardiovascular disease: a new perspective. Arterioscler Thromb Vasc Biol 1998; 18: 1181-1187.

29. Witztum JL. Immunological response to oxidized LDL. Atherosclerosis 1997; 131: S9-S11.

30. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, et al. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 1995; 91: 2488-2496.