significantly different from pre-exercise value in the gymnasts group only

Table 1. Changes in the cellular components of the immune system. WBC and lymphocyte subpopulations (cells/µl) following exercise in gymnasts and untrained girls (46).


Table 2. Immunoglobulin levels pre-exercise, immediately post-exercise among gymnasts (46).

Exercise and the Immune System – Focusing on the Effect of Exercise on Neutrophil Functions 151

chemokine IL-8, and the activated complement component(C5a) (49). These chemokines attach to their specific receptors, fMLP-R (N- formyl-Met-Leu-Phe), IL-8-R (CXCR1 and CXCR2), and C5aR, which belong to the seven-transmembrane helix surface receptor family ("serpentine receptors") that transduces signals downstream the cytoskeleton by coupling to heterotrimeric G-proteins (51). Once the signal has been triggered, rapid cytoskeletal rearrangement and chemotaxis take place. "Target" chemoattractants (fMLP, C5a) function primarily through a common signal-transduction pathway by stimulating p38 MAPK, whereas "host" intermediary chemoattractants (IL-8, LTB4) primarily function via the PI3K/Akt pathway (52). The surface density of the chemotactic receptor (C5aR), which serves as a representative model of receptor availability, was not affected 24 h after exercise. Moreover, the integrin CD11b/CD18, which represent one of the main receptors for neutrophil adhesiveness and crucial for normal chemotaxis, was also unaffected by exercise. Therefore, the chemotactic defect is not dependent on the specific receptor of activation, or on its specific pathway of transduction. We could speculate that the chemotactic impairment was related to a common defect at the membrane level, leading to decreased receptor availability or to other factors yet to be elucidated. For achieving appropriate chemotactic responses, an intact cytoskeleton structures are necessary (53,54). Continuous reorganization of the cytoskeleton is required for efficient F-actin polymerization and polarization. Both are important steps in the skeletal rearrangement during migration (55). Consequently, we studied the neutrophil F-actin neutrophil polarization and polymerization (49). Following fMLP stimulation, the cell undergoes sequential morphological changes from round to elongated geometrical forms (figure 2A). These changes reflect the cell activation and the ability to migrate against the chemotactic gradients toward the target (49,53). Using the green phalloidin test we found no correlation between the chemotactic defect and the ability to polymerize F-actin, indicating that the reduction in chemotaxis following exercise was not a result of the F-actin dysfunction. Despite the fact that positive correlation between chemotaxis and F-actin polymerization usually occurs, a lack of correlation in certain

To elucidate other cell skeletal responses to aerobic exercise, we studied the neutrophil

Indeed, the neutrophil polarization was significantly decreased 24 h following aerobic exercise. This change also correlated with the decrease in chemotactic activity (r= 0.945; P=

Since the neutrophil bactericidal activity and the oxidative burst were found to be normal, it seems that the signal transduction pathways are not affected following 30 min of intense aerobic exercise. Rather, it seems that aerobic exercise causes a skeletal impairment, and this eventually could leads to a reduction of the chemotactic activity. Most probably the impaired chemotaxis event, following a short bout of submaximal exercise, occurred at the effectors' machinery level, rather than at the level of the neutrophil membrane receptors. Others found no change in chemotaxis 24 h after a graded exercise to exhaustion (56). Giraldo et. al. reported increased chemotaxis immediately after moderate (45 min of 55% VO2max) and intense (1 hr of 70% VO2max) aerobic exercise that returned to basal values after 24 h (57). These discrepancies are probably related to differences in the type, intensity, and duration of exercise, timing of blood sampling, or use of different

polarization, known to be in tight correlation with the chemotactic activity.

conditions has been reported (55).

0.001) (figure 2B) (49,50).

laboratory assays.


\*0.05 compared with basal values (before vs. following exercise).

0.05 compared with control group (trained vs. untrained).

Table 3. Effect of exercise on neutrophil count and neutrophil functions (mean+SD), Preexercise (basal), immediate post-exercise and 24 h post-exercise (47).

A consistent decrease of neutrophil migration was detected 24 h post-exercise in trained and untrained subjects, children and adults, male and female (47-50). The following studies focused on the recovery time of the impaired neutrophil chemotaxis, using various chemoattractans. We also aimed to learn about the possible mechanisms involved in the post exercise-associated chemotactic defect. We found that the transient impairment shown in the chemotactic activity 24 h post-exercise, returned to normal after 48 h (Figure 1) (49).

Fig. 1. Kinetics of the neutrophil chemotactic activity in 16 athletes; Pre-exercise, immediately post-exercise and 24 h post-exercise. The chemotaxis was induced by the chemoattractant: fMLP (1 µM), IL-8 (10 nM), or C5a (10 nM). Random migration was conducted in the presence of medium M199. The results were expressed as the number of migrating cells per field (mean±SE) (49).

Looking at the response of the neutrophil specific membrane receptors to the different chemoattractants, we repeatedly found reduction of the chemotaxis following intense exercise, regardless of the chemoattractant used, including Formylated peptides (fMLP), the

**Neutrophils (cells/µl) trained** 2710 ± 349 3554 ± 692 3126 ± 498

**untrained** 

**trained untrained** 

**trained untrained** 

**trained untrained** 

**trained untrained** 

Table 3. Effect of exercise on neutrophil count and neutrophil functions (mean+SD), Pre-

Fig. 1. Kinetics of the neutrophil chemotactic activity in 16 athletes; Pre-exercise, immediately post-exercise and 24 h post-exercise. The chemotaxis was induced by the chemoattractant: fMLP (1 µM), IL-8 (10 nM), or C5a (10 nM). Random migration was conducted in the presence of medium M199. The results were expressed as the number of

Looking at the response of the neutrophil specific membrane receptors to the different chemoattractants, we repeatedly found reduction of the chemotaxis following intense exercise, regardless of the chemoattractant used, including Formylated peptides (fMLP), the

A consistent decrease of neutrophil migration was detected 24 h post-exercise in trained and untrained subjects, children and adults, male and female (47-50). The following studies focused on the recovery time of the impaired neutrophil chemotaxis, using various chemoattractans. We also aimed to learn about the possible mechanisms involved in the post exercise-associated chemotactic defect. We found that the transient impairment shown in the chemotactic activity 24 h post-exercise, returned to normal after 48 h

**(Basal)** 

58 ± 11 47 ± 7

0.8 ± 0.3 # 1.1 ± 0.1

0.7 ± 0.2 # 1.0 ± 0.1

5.7 ± 0.4 5.1 ± 0.7

3.4 ± 1.9 4.1 ± 1.3 **Postexercise** 

> 55 ± 13 52 ± 15

0.8 ± 0.2 # 1.1 ± 0.l

0.8 ± 0.1 # 1.0 ± 0.02

4.4 ± 1.0 \* 4.7 ± 1.3

3.2 ± 1.3 3.3 ± 0.5

**untrained** 3570 ± 1000 4658 ± 1184 3490 ± 805

**24 h postexercise** 

> 36 ± 11 \* 42 ± 8 \*

0.8 ± 0.1 # 1.0 ± 0.2

0.8 ± 0.2 0.9 ± 0.2

4.8 ± 1.0 \* 4.9 ± 1.2

2.6 ± 1.3 3.7 ± 0.6

**Pre-exercise** 

**Chemotaxis (cells /field) trained** 

\*0.05 compared with basal values (before vs. following exercise). 0.05 compared with control group (trained vs. untrained).

exercise (basal), immediate post-exercise and 24 h post-exercise (47).

**Killing (log decrease of colonies) with** 

**Killing (log decrease of colonies) with** 

**Superoxide production (nmol 02-/106 PMNs/min) with PMA stimulation** 

**Superoxide production (nmol 02-/106 PMNs/min) with fMLP stimulation** 

migrating cells per field (mean±SE) (49).

**autologous serum** 

**homologous serum** 

(Figure 1) (49).

chemokine IL-8, and the activated complement component(C5a) (49). These chemokines attach to their specific receptors, fMLP-R (N- formyl-Met-Leu-Phe), IL-8-R (CXCR1 and CXCR2), and C5aR, which belong to the seven-transmembrane helix surface receptor family ("serpentine receptors") that transduces signals downstream the cytoskeleton by coupling to heterotrimeric G-proteins (51). Once the signal has been triggered, rapid cytoskeletal rearrangement and chemotaxis take place. "Target" chemoattractants (fMLP, C5a) function primarily through a common signal-transduction pathway by stimulating p38 MAPK, whereas "host" intermediary chemoattractants (IL-8, LTB4) primarily function via the PI3K/Akt pathway (52). The surface density of the chemotactic receptor (C5aR), which serves as a representative model of receptor availability, was not affected 24 h after exercise. Moreover, the integrin CD11b/CD18, which represent one of the main receptors for neutrophil adhesiveness and crucial for normal chemotaxis, was also unaffected by exercise. Therefore, the chemotactic defect is not dependent on the specific receptor of activation, or on its specific pathway of transduction. We could speculate that the chemotactic impairment was related to a common defect at the membrane level, leading to decreased receptor availability or to other factors yet to be elucidated. For achieving appropriate chemotactic responses, an intact cytoskeleton structures are necessary (53,54). Continuous reorganization of the cytoskeleton is required for efficient F-actin polymerization and polarization. Both are important steps in the skeletal rearrangement during migration (55). Consequently, we studied the neutrophil F-actin neutrophil polarization and polymerization (49). Following fMLP stimulation, the cell undergoes sequential morphological changes from round to elongated geometrical forms (figure 2A). These changes reflect the cell activation and the ability to migrate against the chemotactic gradients toward the target (49,53). Using the green phalloidin test we found no correlation between the chemotactic defect and the ability to polymerize F-actin, indicating that the reduction in chemotaxis following exercise was not a result of the F-actin dysfunction. Despite the fact that positive correlation between chemotaxis and F-actin polymerization usually occurs, a lack of correlation in certain conditions has been reported (55).

To elucidate other cell skeletal responses to aerobic exercise, we studied the neutrophil polarization, known to be in tight correlation with the chemotactic activity.

Indeed, the neutrophil polarization was significantly decreased 24 h following aerobic exercise. This change also correlated with the decrease in chemotactic activity (r= 0.945; P= 0.001) (figure 2B) (49,50).

Since the neutrophil bactericidal activity and the oxidative burst were found to be normal, it seems that the signal transduction pathways are not affected following 30 min of intense aerobic exercise. Rather, it seems that aerobic exercise causes a skeletal impairment, and this eventually could leads to a reduction of the chemotactic activity. Most probably the impaired chemotaxis event, following a short bout of submaximal exercise, occurred at the effectors' machinery level, rather than at the level of the neutrophil membrane receptors. Others found no change in chemotaxis 24 h after a graded exercise to exhaustion (56). Giraldo et. al. reported increased chemotaxis immediately after moderate (45 min of 55% VO2max) and intense (1 hr of 70% VO2max) aerobic exercise that returned to basal values after 24 h (57). These discrepancies are probably related to differences in the type, intensity, and duration of exercise, timing of blood sampling, or use of different laboratory assays.

Exercise and the Immune System – Focusing on the Effect of Exercise on Neutrophil Functions 153

complex antioxidant mechanisms including enzymatic (e.g. superoxide dismutase, glutathione peroxidase, catalase) and non-enzymatic antioxidants (e.g., vitamin E (VE), vitamin C, beta-carotene). VE is the most important lipid-soluble antioxidant due to its abundance in cell and mitochondrial membranes and its ability to act directly on ROS and stop lipid peroxidation. This antioxidant is known to decrease the exercise-induced oxidative stress (69-71) and has been shown to protect against exercise-induced muscle damage (70). Neutrophils play a dual role in exercise-induced oxidative damage. On the one hand, they contribute to ROS formation during intense or prolonged exercise; on the other hand, intense exercise can produce oxidative damage within neutrophils. VE has an important role as anti-oxidant and an important role in maintaining normal neutrophil function. Chemotaxis, adherence, and phagocytic capacities of neutrophils were shown to be

Our research focused on the phagocytic immune response to exercise, showing prevention of the impairments by vitamin E supplementation. The results of chemotaxis and polarization are shown in Figure 3, representing the mean +/- SEM of 7 trained men preand post-exercise, before and after 28 days of daily VE supplementation (74). We can see that daily supplementation of 800 IU d-alpha tocopheryl succinate, indeed corrected the

A relatively small number of studies have dealt with the effect of VE on neutrophil functions following exercise. To the best of our knowledge, there are no studies addressing the effect of VE on exercise-induced impaired chemotaxis. However, a beneficial effect of VE on chemotaxis was shown in other populations, such as healthy elderly men and women and elderly women with coronary heart disease or major depressive disorder (72,73). Improvement in chemotactic ability after VE supplementation was also found in rats with

Fig. 3. A. Correction of the defective neutrophil chemotactic activity (observed 24 h postexercise) by vitamin E supplementation. B. Correction of the defective neutrophil polarization (observed 24 h post-exercise) by vitamin E supplementation (74).

reduced in VE deficiency, improving after antioxidant treatment (65,72,73).

defective neutrophil chemotaxis and polarization observed 24 hr post-exercise.

VE deficiency and in periparturient dairy cows (75,76).

Fig. 2. Neutrophil polarization. A. The cell shape changes that occur following fMLPstimulation. Three different cell shapes were recorded: non-activated - round cells (R), partially activated - intermediate cells (I), and fully activated - polarized cells (P). B. Analysis of the cells' morphological changes following fMLP-stimulation, in 11 athletes, before and after effort (mean±SE) (49).

#### **5. Therapeutic approach to exercise-induced immune suppression**

Dietary and drug intervention have been reported to boost performance in athletes (58). They could block the transient immune changes, to prevent the oxidative stress and the inflammation induced by prolonged, intense exercise or excessive training. Some supplements as flavonoids were reported to benefit the immune system (59). In endurance events, iron and mineral supplements, together with antioxidant vitamins, help to prevent muscle damage (60). Carbohydrates enhance muscle glycogen stores. Glutamine and aminoacid supplementation did not prove to be beneficial (61).

Vitamin E (VE) and vitamin C, as antioxidants, play an important role in protecting the cells and muscles from damage (62-65). It is well-established that exercise exerts imbalance on the oxidative state by increasing Reactive Oxygen Species (ROS) and decreasing the level of antioxidants (63). As previously shown, intense or prolonged exercise can adversely affect the function of the immune system. It was found that submaximal aerobic activity (1h swim at 75-80% of VO2max) could produce oxidative damage within the neutrophils (64), which lose the appropriate antioxidant defense mechanisms, leading to a defective chemotactic ability (65). This impairment could rise from the increased levels of ROS and lipid peroxidation; both potentially could damage neutrophil function. The enhanced production of ROS, mainly by mitochondria, is associated with excessive oxidation of lipids, proteins, and nucleic acids, causing damage to cell membranes and to the physiological function of proteins and DNA (66-68). To defend themselves from ROS induced damage, cells contain

Fig. 2. Neutrophil polarization. A. The cell shape changes that occur following fMLPstimulation. Three different cell shapes were recorded: non-activated - round cells (R), partially activated - intermediate cells (I), and fully activated - polarized cells (P).

**5. Therapeutic approach to exercise-induced immune suppression** 

aminoacid supplementation did not prove to be beneficial (61).

before and after effort (mean±SE) (49).

A

B

B. Analysis of the cells' morphological changes following fMLP-stimulation, in 11 athletes,

Dietary and drug intervention have been reported to boost performance in athletes (58). They could block the transient immune changes, to prevent the oxidative stress and the inflammation induced by prolonged, intense exercise or excessive training. Some supplements as flavonoids were reported to benefit the immune system (59). In endurance events, iron and mineral supplements, together with antioxidant vitamins, help to prevent muscle damage (60). Carbohydrates enhance muscle glycogen stores. Glutamine and

Vitamin E (VE) and vitamin C, as antioxidants, play an important role in protecting the cells and muscles from damage (62-65). It is well-established that exercise exerts imbalance on the oxidative state by increasing Reactive Oxygen Species (ROS) and decreasing the level of antioxidants (63). As previously shown, intense or prolonged exercise can adversely affect the function of the immune system. It was found that submaximal aerobic activity (1h swim at 75-80% of VO2max) could produce oxidative damage within the neutrophils (64), which lose the appropriate antioxidant defense mechanisms, leading to a defective chemotactic ability (65). This impairment could rise from the increased levels of ROS and lipid peroxidation; both potentially could damage neutrophil function. The enhanced production of ROS, mainly by mitochondria, is associated with excessive oxidation of lipids, proteins, and nucleic acids, causing damage to cell membranes and to the physiological function of proteins and DNA (66-68). To defend themselves from ROS induced damage, cells contain complex antioxidant mechanisms including enzymatic (e.g. superoxide dismutase, glutathione peroxidase, catalase) and non-enzymatic antioxidants (e.g., vitamin E (VE), vitamin C, beta-carotene). VE is the most important lipid-soluble antioxidant due to its abundance in cell and mitochondrial membranes and its ability to act directly on ROS and stop lipid peroxidation. This antioxidant is known to decrease the exercise-induced oxidative stress (69-71) and has been shown to protect against exercise-induced muscle damage (70). Neutrophils play a dual role in exercise-induced oxidative damage. On the one hand, they contribute to ROS formation during intense or prolonged exercise; on the other hand, intense exercise can produce oxidative damage within neutrophils. VE has an important role as anti-oxidant and an important role in maintaining normal neutrophil function. Chemotaxis, adherence, and phagocytic capacities of neutrophils were shown to be reduced in VE deficiency, improving after antioxidant treatment (65,72,73).

Our research focused on the phagocytic immune response to exercise, showing prevention of the impairments by vitamin E supplementation. The results of chemotaxis and polarization are shown in Figure 3, representing the mean +/- SEM of 7 trained men preand post-exercise, before and after 28 days of daily VE supplementation (74). We can see that daily supplementation of 800 IU d-alpha tocopheryl succinate, indeed corrected the defective neutrophil chemotaxis and polarization observed 24 hr post-exercise.

A relatively small number of studies have dealt with the effect of VE on neutrophil functions following exercise. To the best of our knowledge, there are no studies addressing the effect of VE on exercise-induced impaired chemotaxis. However, a beneficial effect of VE on chemotaxis was shown in other populations, such as healthy elderly men and women and elderly women with coronary heart disease or major depressive disorder (72,73). Improvement in chemotactic ability after VE supplementation was also found in rats with VE deficiency and in periparturient dairy cows (75,76).

Fig. 3. A. Correction of the defective neutrophil chemotactic activity (observed 24 h postexercise) by vitamin E supplementation. B. Correction of the defective neutrophil polarization (observed 24 h post-exercise) by vitamin E supplementation (74).

Exercise and the Immune System – Focusing on the Effect of Exercise on Neutrophil Functions 155

[12] Boxer LA, Blackwood RA. Leukocyte disorders: quantitative and qualitative disorders

[13] Dinauer MC. Disorders of neutrophil function: an overview. Methods Mol Biol, 412:489-

[14] Mackinnon LT. Chronic exercise training effects on immune function. Med Sci Sports

[15] Friman G, Wesslén L. Special feature for the Olympics: effects of exercise on the

[16] Peters EM, Bateman ED. Ultramarathon running and URTI. South African Med J,

[19] Fitzgerald L. Overtraining increases the susceptibility to infection. Int J Sport Med,

[20] Pedersen BK, Ullum H. NK-cell response to physical activity. Possible mechanisms of

[21] Baron RD, Hutch MH, Kleeman K, Maccromac JN. Aseptic meningitis among members

[22] Morse LJ, Bryan JA, Murle JP. The Holly Cross College Football team Hepatitis

[23] Nieman DC, Johanssen LM, Lee JW, Arabatzis K. Infectious episodes in runners before and after the Los Angeles Marathon. J Sports Med Phys Fitness, 30:316-328, 1990 [24] Nieman DC. Prolonged aerobic exercise, immune response and risk of infection. In:

[25] Cox AG, Gleeson M, Pyne DB, Callister R, Hopkings WG, Fricker PA. Clinical and

[26] Suzuki K, Nakaji S, Yamada M, Totsuka M, Sato K, Sugawara K. Systemic

[27] Cox AJ, Pyne DB, Saunders PU, Callister R, Gleeson M. Cytokine responses to treadmill running in healthy and illness-prone athletes. Med Sci Sports Med, 39:1918-1926, 2007 [28] Bishop NC, Gleeson M. Acute and chronic effects of exercise on markers of mucosal

[29] Blanin AK, Robson PJ, Walsh NP, Clark AM, Glennon L, Gleeson M. The effect of

[30] Allgrove JE, Gomes E, Hough J, Gleeson M. Effects of exercise intensity on saliva

[32] Eichner ER. Infectious mononucleosis-recognising the condition, 'reactivating' the

[33] Friman G, Wesslén L, Karjalainen J, Rolf C. Infectious and lymphocytic myocarditis:

protein and electrolyte secretion. Int J Sports Med, 19:547-552, 1998

[31] Sharp JCM. Viruses and the Athlete. Br J Sport Med, 23:47-48, 1989

patient. Physician Sports Med, 24:49-54, 1996

laboratory evaluation of upper respiratory symptoms in elite athletes. Clin J Sports

inflammatory response to exhaustive exercise. Cytokine kinetics. Exerc Immunol

exercising to exhaustion at different intensities on saliva immunoglobulin A,

antimicrobial proteins and markers of stress in active men. J Sports Sci, 26:653-661, 2008

epidemiology and factors relevant to sports medicine. Scand J Med Sci Sports,

[17] Nieman DC. Immune response to heavy exertion. J Appl Physiol, 82:1385-94, 1997 [18] Lehmann M. Foster C, Keul J. Overtraining in endurance athletes: a brief review. Med

immune system: infections and exercise in high-performance athletes. Immunol

of the neutrophil, Part 2. Pediatr Rev, 17:47–50, 1996

Exerc, 32(7 Suppl):S369-376, 2000

Sci Sport Exerc, 25:854-862, 1993

outbreak. JAJA, 219:706-708, 1972

action. Med Sci Sports Exerc, 26:140-146, 1994

immunity. Front Biosci, 14:4444-4456, 2009

of high school football team. JAMA, 248:1724-1727, 1982

Exercise and Immune Function, CRC Press, pp.143-161, 1996

Cell Biol, 78:510-522, 2000

64:583-584, 1983

Suppl 1:S5-8, 1991

Med, 18: 438-445, 2008

Rev, 8:6-48, 2002

5:269-278, 1995

504, 2007

Of note is that recent reports have emphasized that ROS production, through the reversible oxidation of thiol groups, has also important physiological influences on gene transcription and protein synthesis, as part of the adaptive processes that occurs after exercise. High dose antioxidant supplementation may interfere with these processes. Cooper's Group reported gene reorganization after intense exercise (77, 78).

In recent years, it has been reported that regular physical activity can have beneficial role in cancer's prevention and therapy (79,80). There is evidence of a protective effect of physical activity on colon and postmenopausal breast cancer (81). Further, it is also mounting that physical activity reduces risks of lung tumor metastases (82). It has been reported that exercise prevent the loss of muscle mass and functional capacity in chronic deteriorating conditions, beyond the beneficial psychological effects, which certainly improve the quality of life (83-85).

Athletes are not immunocompromised by clinical definition, but could suffer from transitory, persistent immunosuppression, eventually leading to subclinical or clinical diseases. Recovery time is imperative in elite athletes involved in intense training and competitions. The temporary, sometimes multiple, mild impairments of the immune system could change into a chronic more severe immune dysfunction.

The approach should be multidisciplinary, including all care givers as sport medicine physicians, physiologists, immunologists, physiotherapists, nutritionists, psychologists and coaches. To achieve the main goals, an integrated model with programmed activities and clear guidelines for any specific type of sport is imperative. Recommendations should be directed to elite athletes and recreational sports, for sedentary individuals, for moderate and well trained subjects. The target is to maintain the balance of the immune system for the health of the athlete and his optimal performance.

#### **6. References**


Of note is that recent reports have emphasized that ROS production, through the reversible oxidation of thiol groups, has also important physiological influences on gene transcription and protein synthesis, as part of the adaptive processes that occurs after exercise. High dose antioxidant supplementation may interfere with these processes. Cooper's Group reported

In recent years, it has been reported that regular physical activity can have beneficial role in cancer's prevention and therapy (79,80). There is evidence of a protective effect of physical activity on colon and postmenopausal breast cancer (81). Further, it is also mounting that physical activity reduces risks of lung tumor metastases (82). It has been reported that exercise prevent the loss of muscle mass and functional capacity in chronic deteriorating conditions, beyond the beneficial psychological effects, which certainly improve the quality of life (83-85). Athletes are not immunocompromised by clinical definition, but could suffer from transitory, persistent immunosuppression, eventually leading to subclinical or clinical diseases. Recovery time is imperative in elite athletes involved in intense training and competitions. The temporary, sometimes multiple, mild impairments of the immune system

The approach should be multidisciplinary, including all care givers as sport medicine physicians, physiologists, immunologists, physiotherapists, nutritionists, psychologists and coaches. To achieve the main goals, an integrated model with programmed activities and clear guidelines for any specific type of sport is imperative. Recommendations should be directed to elite athletes and recreational sports, for sedentary individuals, for moderate and well trained subjects. The target is to maintain the balance of the immune system for the

[2] Cowles WN. Fatigue as a contributory cause of pneumonia. Boston Med Surg J, 179:555,

[3] Baetjer AM. The effect of muscular fatigue upon resistance. Physiol Rev, 12:453-468, 1932 [4] Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC, Fleshner M,

[6] Buettner P, Mosig S, Lechtermann A, Funke H, Mooren FC. Exercise affects the gene expression profiles of human white blood cells. J Appl Physiol 102: 26-36, 2007 [7] Nieman DC, Nehlsen-Cannarella SL. The immune response to exercise. Sem Hematol,

[8] Lamm ME. Current concepts in mucosal immunity. How epithelial transport of IgA antibodies relates to host defense. Am J Physiol, 274:G614-G617, 1998 [9] Gleeson M, Pyne DB. Special feature for the Olympics: effects of exercise in the immune system: exercise effect on mucosal immunity. Immunol Cell Biol, 78:536-544, 2000 [10] Mackinnon LT. Exercise and resistance to infectious diseases. In: Bahrke, Drews,

[11] Wolach B, Baehner RL, Boxer LA. Review: clinical and laboratory approach to the management of neutrophil dysfunction. Isr J Med Sci, 18:897-916, 1982

Wentworth (Ed.), Advances in Exercise Immunology. Champaign, IL, pp. 1-26,1999

Green C, Pedersen BK, Hoffman-Goetz L, Rogers CJ, Northoff H, Abbasi A, Simon P. Part one: Immune function and exercise. Exercise Immunol Rev, 17:6-63, 2011 [5] Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol,

gene reorganization after intense exercise (77, 78).

could change into a chronic more severe immune dysfunction.

[1] Larrabee RC, Leukocytosis after violent exercise. J Med Res, 7:76-82, 1902

health of the athlete and his optimal performance.

**6. References** 

1918

98:1154-1162, 2005

31:166-179, 1994


Exercise and the Immune System – Focusing on the Effect of Exercise on Neutrophil Functions 157

[51] Prossnitz ER, Gilbert TL, Chiang S, Campbell JJ, Qin S, Newman W, Sklar LA, Ye RD.

[52] Schraufstatter IU, Chung J, Burger M. IL-8 activates endothelial cell CXCR1 and CXCR2

[53] Chodniewicz D, Zhelev DV. Novel pathways of F-actin polymerization in the human

[54] Weiner OD, Servant G, M. D. Welch MD, Mitchison TJ, Sedat JW, Bourne HR. Spatial

[55] Howard TH, Meyer WH. Chemotactic peptide modulation of actin assembly and

[56] Hack V, Strobel G, Rau JP, Weicker H. The effect of maximal exercise on the activity of

[57] Giraldo E, Garcia JJ, Hinchado MD, Ortega E. Exercise intensity-dependent changes in

[58] Walsh NP, Gleeson M, Pyne DB, Nieman DC, Dhabhar FS, Shephard RJ, Oliver SJ,

[59] Nieman DC. Quercetin's bioactive effects in human athletes. Curr Topic Nutraceut Res,

[60] Jackson MJ. Redox regulation of adaptive responses in skeletal muscle to contractile

[61] Gleeeson M. Dosing and efficacy of glutamine supplementation in human exercise and

[62] Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV,

[63] Finaud J, Scislowski V, Lac G, Durand D, Vidalin H, Robert A, Filaire E. Antioxidant

[64] Ferrer, MD, Tauler, P, Sureda, A, Tur, JA and Pons, A. Antioxidant regulatory mechanisms in neutrophils and lymphocytes after intense exercise. J Sports Sci 27: 49-58, 2009 [65] Baehner RL, Boxer LA. Role of membrane vitamin E and cytoplasmic glutathione in the

[66] Powers, SK, Lennon SL. Analysis of cellular responses to free radicals: Focus on exercise

[67] Sachdev S, Davies KJ. Production, detection and adaptive responses to free radicals in

[68] Finaud J. Lac G, Filaire E. Oxidate stress: relationship with exercise and training Sports

locomotion in neutrophils. J Cell Biol, 98:1265–1271, 1984.

cytokine balance. Neuroimmunomodulation, 16:237-244, 2009

activity. Free Radical Biology& Medicine, 47:1267-1275, 2009

American Journal of Clinical Nutrition, 87:142-149, 2008

Journal of Pediatric Hematology/Oncology, 1:71-16, 1979

and skeletal muscle. Proc Nutr Soc, 58:1025-1033, 1999

exercise. Free Radic biol Med. 44:215-223, 2008

Med, 36:327-358, 2006

2247, 1999

1:75–81, 1999

8:33-44, 2010

280:L1094–L1103, 2001

neutrophil. Blood, 102:2251–2258, 2003

Exercise Immunol Rev, 17: 64-103, 2011

sport training. J Nutr, 138: 2045S-2049S, 2008

season. Int J Sports Med, 27:87-93, 2006

Multiple activation steps of the N-formyl- peptide receptor. Biochemistry, 38:2240–

through Rho and Rac signaling pathways. Am J Physiol Lung Cell Mol Physiol,

control of actin polymerization during neutrophil chemotaxis. Nature Cell Biol,

neutrophil granulocytes in highly trained athletes in a moderate training period. European journal of applied physiology and occupational physiology, 65:520-524, 1992

the inflammatory response in sedentary women: role of neuroendocrine parameters in the neutrophil phagocytic process and the pro-/anti-inflammatory

Bermon S, Kajeniene A. Position statement. Part two: Maintaining immune health.

Sastre J, Viña J. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance.

status and oxidative stress in professional rugby players: evolution throughout a

regulation of phagocytic functions of neutrophils and monocytes. American


[34] Russell WR. Poliomyelitis, the paralytic stage and the effect of physical activity on the

[35] Gautmanitan BG, Ghason JL, Lerner AM. Augmentation of the virulence of murine coxsackie virus B3 myocardiopathy by exercise. J Exp Med, 131:1121-1125, 1970 [36] Ortega E. Neuroendocrine mediators in the modulation of phagocytosis by exercise:

[37] Shephard RJ. Adhesion molecules, catecholamines and leucocyte redistribution during

[38] Aoi W, Naito Y, Takanami Y, Kawai Y, Sakuma K, Ichikawa H, Yoshida N, Yoshikawa

[39] Soppi E, Varjo J, Eskola J, Laitinen LA. Effect of strenuous physical stress on circulating

[40] Gabriel H, Schwarz L, Born P, Kindermann W. Differential mobilization of leucocyte

[41] Nieman DC, Henson DA, Sampson CS, Herring JL, Stulles J, Conley M, Stone MH,

[42] Busse WW, Anderson CL, Hanson PG, Folts JD. The effect of exercise in the granulocyte

[43] Hooper S, Mackinnon LT, Howard A, Gordon RD, Bachmann AW. Markers for

[44] Pizza FX, Mitchell JB Davis BH, Starling RD, Holtz RW, Bigelow N . Exercise-induced

[45] Shinkai S, Shore S, Shek PN, Shephard RJ. Acute exercise and immune function.

[46] Eliakim A, Wolach B, Kodesh E, Gavrieli R, Radnay J, Ben-Tovim T, Yarom Y, Falk B.

[47] Wolach B, Eliakim A, Gavrieli R, Kodesh E, Yarom Y, Schlesinger M, Falk B Aspects of

[48] Wolach B, Falk B, Gavrieli R, Kodesh E, Eliakim A. Neutrophil function response to

[49] Wolach B, Gavrieli R, Ben-Dror SG, Zigel L, Eliakim A, Falk B. Transient decrease of

[50] Gavrieli R, Ashlagi-Amiri T, Eliakim A, Nemet D, Zigel L, Berger-Achituv S, Falk B,

T. Oxidative stress and delayed onset muscle damage after exercise. Free Radic Biol

lymphocyte number and function before and after training. J Clin Lab Immunol,

and lymphocyte subpopulations into the circulation during endurance exercise.

Buttersworth DE, Davis JM. The acute immune response to exhaustive resistance

response to isoproterenol in the trained athlete and unconditioned individual. J

monitoring overtraining and recovery in elite swimmers. Med Sci Sports Exerc,

muscle damage: Effect on circulating leukocyte and lymphocyte subsets. Med Sci

Relationship between lymphocyte activity and changes in subset counts. Int J

Cellular and humoral immune response to exercise among gymnasts and

leukocyte function and the complement system following aerobic exercise in young

aerobic and anaerobic exercise in female judoka and untrained subjects. Br J Sports

neutrophil chemotaxis following aerobic exercise. Med Sci Sports Exerc, 37:949-954,

Wolach B. The effect of aerobic exercise on neutrophil functions. Med Sci Sports

physiological implications. Exerc Immunol Rev, 9:70–93, 2003

and following exercise. Sports Med, 33:261–284, 2003

severity of paralysis. Br Med J, 1:465-471, 1949

Med, 37:480–487, 2004

Eur J Appl Physiol, 65:529-534, 1992

exercise. Int J Sports Med, 16:322-328, 1995

Allergy Clin Immunol, 65:358-364, 1980

untrained girls. Int J Sports Med, 18:208–212, 1997

female gymnasts. Scand J Med Sci Sports, 8:91–97, 1998

Sports Exerc, 27:363-370, 1995

Sports Med, 13:452-461, 1992

Med, 34:23–28, 2000

Exerc, 40:1623-1628, 2008

2005

8:43-46, 1982

27:106-112 1995


**9** 

Xiaolin Yang

*Finland* 

**Physical Activity, Physical** 

**Fitness and Metabolic Syndrome** 

*LIKES-Research Center for Sport and Health Sciences, Jyväskylä,* 

The metabolic syndrome is recognized as one of the leading worldwide health problems, which is a constellation of metabolic risk factors that is associated with increased risk for developing cardiovascular disease, type 2 diabetes mellitus and myocardial infarction. Clustered metabolic risk factors include abdominal obesity, dyslipidemia, elevated blood pressure, glucose intolerance, and insulin resistance, as standardized by the international criteria [1]. Evidence from observational epidemiological studies indicates that the metabolic risk factors begin early in life [2,3]. Childhood overweight and obesity are closely associated with insulin resistance, in which result the development of metabolic syndrome. The overall prevalence of metabolic syndrome can be identified in children and adolescents. Obesity and insulin resistance may develop the metabolic syndrome during the early years of life and throughout in adulthood. In Finland, the prevalence of metabolic syndrome has

The benefits of physical activity and physical fitness on the health of the general population have been attested beyond dispute [6]. There is overwhelming evidence that participation in regular, moderate-intensity physical activity may be a preventive intervention of the metabolic syndrome and that activity of greater intensity may provide even greater benefit [7]. Remarkably, supervised exercise training in either aerobic exercise or resistance training may be an effective adjunctive treatment and produce significant functional benefits for individuals with the metabolic syndrome [8]. Physical activity and exercise are thus uniquely positioned to improve physical and psychosocial health and function by reducing the clustered metabolic risk and, in turn, by delaying or avoiding the onset of diabetes and cardiovascular diseases. However, most of the studies have been cross-sectional, but a few

The aim of this chapter is to outline physical activity and fitness to prevent or reduce the prevalence or incidence of metabolic syndrome among youth and adults. I start with the definition of physical activity, cardiorespiratory fitness and muscular strength and proceed to a discussion of the role of physical activity and fitness on the metabolic syndrome. I will discuss the importance of physical activity and fitness as their primary sources of health information that affect the metabolic syndrome in both youth and adults. Special emphasis is given to the use of long-term physical activity as a possible means of effectively reducing

**1. Introduction** 

have been longitudinal.

the prevalence of metabolic syndrome.

increased dramatically over the past decades [4,5].


## **Physical Activity, Physical Fitness and Metabolic Syndrome**

Xiaolin Yang

*LIKES-Research Center for Sport and Health Sciences, Jyväskylä, Finland* 

### **1. Introduction**

158 An International Perspective on Topics in Sports Medicine and Sports Injury

[69] Silva LA, Pinho CA, Silveira PC, Tuon T, De Souza CT, Dal-Pizzol F, Pinho RA.

[70] Bloomer RJ, Goldfarb AH, McKenzie MJ. Oxidative stress response to aerobic exercise:

[71] Williams SL, Strobel NA, Lexis LA, Coombes JS. Antioxidant requirements of endurance athletes: implications for health. Nutrition Reviews, 64:93-108, 2006 [72] De la Fuente M, Ferrández MD, Burgos MS, Soler A, Prieto A, Miquel J. Immune

[73] De la Fuente M, Hernanz A, Guayerbas N, Victor VM, Arnalich F. Vitamin E ingestion

[74] Gavrieli R, Berger-Achituv S, Ashlagi-Amiri T, Zigel L, Nemet D, Eliakim A, Falk B, and

[75] Harris RE, Boxer LA, Baehner RL. Consequences of vitamin-E deficiency on the

[76] Politis I, Hidiroglou N, White JH, Gilmore JA, Williams SN, Scherf H, Frigg M. Effects of

[78] Connolly PH, Caiozzo VJ, Zaldivar F, Nemet D, Larson J, Hung S, Heck JD, Hatfield

[79] Ben-Eliyahu S, Page GG, Schleifer SJ. Stress, NK cells, and cancer: Still a promissory

[80] Mc Tiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer,

[81] Friedenreitch CM, Gregory J, Kopciuk KA, Mackey JR, Courneya KS. Prospective cohort

[82] Davis JM, Kohut ML, Jackson DA, Colbert LH, Mayer EP, Ghaffar A. Exercise effects on

[83] Speck RM, Courneya KS, Masse LC, Duval S, Schmitz KH. An update of controlled

[84] Hoffman-Goetz L, Husted J. Exercise and Cancer. Do the biology and epidemiology

[85] World Cancer Research Fund. Food, Nutrition, Physical Activity and the prevention of

Journal of Physiology and Pharmacology, 76:373-380, 1998

Aerobic Exercise. Submitted for publication.

mononuclear cells. J Appl Physiol, 97:1461-1469, 2004

correspond? Exercise Immunology Rev, 1: 81-96, 1995

Cancer: a Global Perspective. Washington DC, AICR, 2007

note. Brain Behav Immun, Review 21:881-887, 2007

Sciences, 60:51-57, 2010

Research, 42:272-280, 2008

55:338-343, 1980

104:236-243, 2008

8:205-211, 2008

1954-1962, 2009

Am J Physiol, 274:R1454-1459, 1998

Cancer Surviv, 4:87-100, 2010

38:1098-1105, 2006

Vitamin E supplementation decreases muscular and oxidative damage but not inflammatory response induced by eccentric contraction. Journal of Physiological

comparison of antioxidant supplements. Medicine & Science in Sports & Exercise,

function in aged women is improved by ingestion of vitamins C and E. Canadian

improves several immune functions in elderly men and women. Free Radical

Wolach B. Vitamin E Prevents Neutrophil Impairment after a Single Bout of Intense

phagocytic and oxidative functions of the rat polymorphonuclear leukocyte. Blood,

vitamin E on mammary and blood leukocyte function, with emphasis on chemotaxis, in periparturient dairy cows. American Journal of Veterinary Research, 57:468-471, 1996 [77] Cooper DM, Radom-Aizik S, Zaldivar F, Leu SY, Galassetti P. Effects of 30 min of

aerobic exercise on gene expression and in human neutrophils. J Appl Physiol,

GW, Cooper DM. Effects of exercise on gene expression in human peripheral blood

study of lifetime physical activity and breast cancer survival. Int J Cancer, 124:

lung tumor metastases and in vitro alveolar macrophage antitumor cytotoxicity.

physical activity trials in cancer survivors: a systematic review and meta-analysis. J

The metabolic syndrome is recognized as one of the leading worldwide health problems, which is a constellation of metabolic risk factors that is associated with increased risk for developing cardiovascular disease, type 2 diabetes mellitus and myocardial infarction. Clustered metabolic risk factors include abdominal obesity, dyslipidemia, elevated blood pressure, glucose intolerance, and insulin resistance, as standardized by the international criteria [1]. Evidence from observational epidemiological studies indicates that the metabolic risk factors begin early in life [2,3]. Childhood overweight and obesity are closely associated with insulin resistance, in which result the development of metabolic syndrome. The overall prevalence of metabolic syndrome can be identified in children and adolescents. Obesity and insulin resistance may develop the metabolic syndrome during the early years of life and throughout in adulthood. In Finland, the prevalence of metabolic syndrome has increased dramatically over the past decades [4,5].

The benefits of physical activity and physical fitness on the health of the general population have been attested beyond dispute [6]. There is overwhelming evidence that participation in regular, moderate-intensity physical activity may be a preventive intervention of the metabolic syndrome and that activity of greater intensity may provide even greater benefit [7]. Remarkably, supervised exercise training in either aerobic exercise or resistance training may be an effective adjunctive treatment and produce significant functional benefits for individuals with the metabolic syndrome [8]. Physical activity and exercise are thus uniquely positioned to improve physical and psychosocial health and function by reducing the clustered metabolic risk and, in turn, by delaying or avoiding the onset of diabetes and cardiovascular diseases. However, most of the studies have been cross-sectional, but a few have been longitudinal.

The aim of this chapter is to outline physical activity and fitness to prevent or reduce the prevalence or incidence of metabolic syndrome among youth and adults. I start with the definition of physical activity, cardiorespiratory fitness and muscular strength and proceed to a discussion of the role of physical activity and fitness on the metabolic syndrome. I will discuss the importance of physical activity and fitness as their primary sources of health information that affect the metabolic syndrome in both youth and adults. Special emphasis is given to the use of long-term physical activity as a possible means of effectively reducing the prevalence of metabolic syndrome.

Physical Activity, Physical Fitness and Metabolic Syndrome 161

Sports Occupation

Household/Caregiving Transportation Conditioning

Time spent sitting

Heart rate monitoring

Telephone

Pedometer Accelerometer

12-minutes run 1-mile walk

Handgrip Chin ups Push ups Sit / Curl ups

Bench (30 cm high) step

Waist girth / waist-to-hip ratio Body mass index (kg/m2)

Skinfolds (biceps, triceps, abdomen, suprailium, subscapula and thigh)

Leisure/Recreation activities

*Physical activity* Children and adolescents Adults

Interview Face to face Face to fact

Physical fitness Laboratory Epidemiologic

Bioelectrical impedance analysis

Table 1. Main assessment of physical activity and physical fitness

Flexibility Leighton flexometer Sit-and-reach flexometer

Association of Clinical Endocrinologists criteria requires the presence of abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women) and at least two of the following abnormalities: fasting plasma glucose ≥ 5.6 mmol/L (100mg/dL), systolic/diastolic blood pressure ≥130/85mmHg or medication, triglycerides ≥1.7 mmol/L (150 mg/dL) or medication. The International Diabetes Federation criteria includes the presence of abdominal obesity (waist circumference ≥ 94 cm in men and ≥ 80 cm in women) and ≥ 2 of the following four indicators: fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL), triglycerides ≥ 1.7 mmol/L (150 mg/dL), high-density lipoprotein cholesterol < 40 mg/dL (1.03 mmol/L) in men and < 50 mg/dL (1.29 mmol/L) in women, and systolic/diastolic blood pressure ≥130/85 mmHg or treatment for hypertension. The National Cholesterol Education Program Adult Treatment Panel III criteria includes the presence of at least three of the following: waist circumference ≥ 102 cm in men and ≥ 88 cm in women, triglycerides ≥ 150 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL in men and < 50 mg/dL in women, systolic/diastolic blood pressure ≥130/85 mm Hg or use of medication for hypertension, and fasting plasma glucose ≥ 5.6 mmol/L (100

treadmill or cycle ergometer

Underwater weighing Near infrared

Dynomometer Cable tensiometer Load cells Strain gauges

Organized sport Non-organized sport Commuting to school Leisure activities Time spent sitting

Questionnaire Physical activity at school

Instrument Heart rate monitoring Pedometer Accelerometer

Cardiorespiratory Maximum oxygen uptake on

Body composition

Muscular strength and endurance

mg/dL) or medication.

## **2. Rationale of physical activity and fitness in the prevention of metabolic syndrome**

## **2.1 Definitions**

The terms 'physical activity', 'exercise' and 'physical fitness' have been described in detail by Caspersen et al. [9]. Although these terms are related and have similar meanings, they aren't identical in meaning. Physical activity is defined as any bodily movement produced by skeletal muscles that result in energy expenditure. Exercise is a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermedicate objective the improvement or maintenance of physical fitness. Physical fitness is a set of attributes that are either health-related (i.e. cardiorespiratory endurance, muscular strength and endurance, body composition, and flexibility) or skill-related (i.e. agility, balance, coordination, speed, power, and reaction time). Physical fitness is also referred to almost exclusively as cardiorespiratory fitness (also called cardiovascular fitness or maximal aerobic power), which relates very closely to maximal capacity for oxygen consumption. An important distinction between physical activity and fitness is the intraindividual day-to-day variability; physical activity will undoubtedly vary on a daily basis, whereas cardiorespiratory fitness will remain relatively static, taking time to change. This variability will impact on the ability to measure these two quantities and consequently will influence the ability to demonstrate their relationship with metabolic outcomes. In this chapter physical activity will be used as a generic term, whereas cardiorespiratory fitness and muscular strength will be used in their specific meanings. Based on previous studies of assessments of physical activity and physical fitness, the main methods of these standard measures have been summarized and presented in Table 1.

The term 'metabolic syndrome' is generally defined as the clustering risk factors associated with medical disorders that increase the risk of developing atherosclerotic and insulin resistance, i.e. elevated levels of central adiposity, hypertension, dyslipidemia, impaired glucose metabolism, and a low level of high-density lipoprotein cholesterol [10]. Table 2 summarizes five international criteria in the following: World Health Organization [11], European Group for the Study of Insulin Resistance [12], American College of Endocrinology/American Association of Clinical Endocrinologists [13], International Diabetes Federation [14], and National Cholesterol Education Program Adult Treatment Panel III [10].

The World Health Organization criteria requires the presence of impaired glucose tolerance, impaired fasting glucose, type 2 diabetes, and insulin resistance in top quartile of nondiabetic population and at least two of the following: waist:hip ratio > 0.9 in men and > 0.85 in women, serum triglycerides ≥ 1.7 mmol/L, systolic/diastolic blood pressure ≥ 140/90 mmHg or medication, high-density lipoprotein cholesterol ≤ 0.9 mmol/L in men and ≤ 1.0 mmol/L in women, and microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g. The European Group for the Study of Insulin Resistance criteria includes the presence of hyperinsulinemia (defined as nondiabetic subjects having fasting insulin level in the highest quartile) and at least two of the following abnormalities: fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dL), triglycerides > 2.0 mmol/L, high-density lipoprotein cholesterol < 1.0 mmol/L or medication, systolic/diastolic blood pressure ≥ 140/90 mmHg or current use of antihypertensive medication, and waist circumference ≥ 94 cm in men and ≥ 80 cm in women. The American College of Endocrinology/American

The terms 'physical activity', 'exercise' and 'physical fitness' have been described in detail by Caspersen et al. [9]. Although these terms are related and have similar meanings, they aren't identical in meaning. Physical activity is defined as any bodily movement produced by skeletal muscles that result in energy expenditure. Exercise is a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermedicate objective the improvement or maintenance of physical fitness. Physical fitness is a set of attributes that are either health-related (i.e. cardiorespiratory endurance, muscular strength and endurance, body composition, and flexibility) or skill-related (i.e. agility, balance, coordination, speed, power, and reaction time). Physical fitness is also referred to almost exclusively as cardiorespiratory fitness (also called cardiovascular fitness or maximal aerobic power), which relates very closely to maximal capacity for oxygen consumption. An important distinction between physical activity and fitness is the intraindividual day-to-day variability; physical activity will undoubtedly vary on a daily basis, whereas cardiorespiratory fitness will remain relatively static, taking time to change. This variability will impact on the ability to measure these two quantities and consequently will influence the ability to demonstrate their relationship with metabolic outcomes. In this chapter physical activity will be used as a generic term, whereas cardiorespiratory fitness and muscular strength will be used in their specific meanings. Based on previous studies of assessments of physical activity and physical fitness, the main methods of these standard

The term 'metabolic syndrome' is generally defined as the clustering risk factors associated with medical disorders that increase the risk of developing atherosclerotic and insulin resistance, i.e. elevated levels of central adiposity, hypertension, dyslipidemia, impaired glucose metabolism, and a low level of high-density lipoprotein cholesterol [10]. Table 2 summarizes five international criteria in the following: World Health Organization [11], European Group for the Study of Insulin Resistance [12], American College of Endocrinology/American Association of Clinical Endocrinologists [13], International Diabetes Federation [14], and National Cholesterol Education Program Adult Treatment

The World Health Organization criteria requires the presence of impaired glucose tolerance, impaired fasting glucose, type 2 diabetes, and insulin resistance in top quartile of nondiabetic population and at least two of the following: waist:hip ratio > 0.9 in men and > 0.85 in women, serum triglycerides ≥ 1.7 mmol/L, systolic/diastolic blood pressure ≥ 140/90 mmHg or medication, high-density lipoprotein cholesterol ≤ 0.9 mmol/L in men and ≤ 1.0 mmol/L in women, and microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g. The European Group for the Study of Insulin Resistance criteria includes the presence of hyperinsulinemia (defined as nondiabetic subjects having fasting insulin level in the highest quartile) and at least two of the following abnormalities: fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dL), triglycerides > 2.0 mmol/L, high-density lipoprotein cholesterol < 1.0 mmol/L or medication, systolic/diastolic blood pressure ≥ 140/90 mmHg or current use of antihypertensive medication, and waist circumference ≥ 94 cm in men and ≥ 80 cm in women. The American College of Endocrinology/American

**2. Rationale of physical activity and fitness in the prevention of metabolic** 

measures have been summarized and presented in Table 1.

**syndrome 2.1 Definitions** 

Panel III [10].


Table 1. Main assessment of physical activity and physical fitness

Association of Clinical Endocrinologists criteria requires the presence of abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women) and at least two of the following abnormalities: fasting plasma glucose ≥ 5.6 mmol/L (100mg/dL), systolic/diastolic blood pressure ≥130/85mmHg or medication, triglycerides ≥1.7 mmol/L (150 mg/dL) or medication. The International Diabetes Federation criteria includes the presence of abdominal obesity (waist circumference ≥ 94 cm in men and ≥ 80 cm in women) and ≥ 2 of the following four indicators: fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL), triglycerides ≥ 1.7 mmol/L (150 mg/dL), high-density lipoprotein cholesterol < 40 mg/dL (1.03 mmol/L) in men and < 50 mg/dL (1.29 mmol/L) in women, and systolic/diastolic blood pressure ≥130/85 mmHg or treatment for hypertension. The National Cholesterol Education Program Adult Treatment Panel III criteria includes the presence of at least three of the following: waist circumference ≥ 102 cm in men and ≥ 88 cm in women, triglycerides ≥ 150 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL in men and < 50 mg/dL in women, systolic/diastolic blood pressure ≥130/85 mm Hg or use of medication for hypertension, and fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL) or medication.

Physical Activity, Physical Fitness and Metabolic Syndrome 163

National Cholesterol Education Program Adult Treatment Panel III criteria. The two definitions similarly classified approximately 93% in 3601 American adults aged ≥ 20 years [15], 85% in 2182 Finnish young adults aged 24–39 years [4], and only about 16% in 5047

In general, leisure-time physical activity and aerobic exercise may provide an advantage in helping reducing the metabolic syndrome in middle-aged and elderly population. The potential mechanisms are often proposed by which physical activity and fitness can reduce the risk of the metabolic syndrome in response to insulin resistance and abdominal obesity. From a psychosocial standpoint, physical activity and fitness have a beneficial effect that can improve psychosocial well-being, leading to better mood, higher self-efficacy and stronger social motives for exercise [17,18]. Participation in regular physical activity or aerobic exercise is an effective way to establish lifelong habits for reducing the increased risk of insulin resistance and obesity. Individuals who want to maintain physical abilities may have better awareness of other health-related habits such as diet, smoking and sedentary lifestyle, all of which have been found to be related to the risk for the metabolic syndrome [19,20]. Increased physical activity and fitness may also lead to enhanced overall cardiovascular function and muscular endurance which, in turn, delay the onset or help prevent the development of metabolic syndrome. These psychosocial effects may then interact with biological processes that may result in reduction of subclinical inflammation involving cytokines derived from adipose tissue and modulation of various adipocytokines that lead to reduce the prevalence of metabolic syndrome [21]. The benefit of increased and maintained physical activity and physical fitness may be directly or indirectly associated

However, the relationship between physical activity or physical fitness and the metabolic syndrome may also be bidirectional. The prevalence of metabolic syndrome may lead to declining levels of physical activity and fitness as symptoms of metabolic syndrome may increase sedentary lifestyle, unhealthy diet, low energy level and lack of exercise and physical activity. Therefore, the precise mechanisms underlying the effect of physical

activity and fitness on the metabolic syndrome still need further clarification.

**3. Effect of physical activity and fitness on metabolic syndrome in adults** 

A number of cross-sectional epidemiological studies have been conducted to examine the effect of leisure-time physical activity and cardiorespiratory fitness on the metabolic syndrome in adult population over the last decade. Several studies have only focused on the association in men. An English cohort of 711 employed middle-aged men demonstrated a dose-relationship between both leisure-time physical activity and cardiorespiratory fitness and the clustering of the metabolic syndrome including fasting glucose, triglycerides, highdensity lipoprotein cholesterol, blood pressure, and body mass index [22]. Men with higher physical activity, as defined by a physical activity index, were found to be less likely to have the metabolic syndrome when compared with the inactive ones. The age-adjusted odds ratios and their 95% confidence intervals for having the clustering of metabolic syndrome were 0.56 (0.33-0.96) for occasional/light physical activity, 0.37 (0.19-0.71) for moderate/moderately vigorous physical activity, and 0.12 (0.03-0.50) for vigorous physical activity. Men with moderate to high levels of the fitness were also found to be less likely to

Swedish adults aged 46–68 years [16].

with reduced incidence of the metabolic syndrome.

**2.2 Systemic mechanisms** 


WHO, World Health Organization, EGIR, European Group for the Study of Insulin Resistance; ACE/AACE, American College of Endocrinology/American Association of Clinical Endocrinologists; IDF, International Diabetes Federation; NCEP-ATP III, National Cholesterol Education Program- Adult Treatment Panel III; IGT, impaired glucose tolerance; IFG, impaired fasting glucose, T2D, type 2 diabetes; WHR, waist:hip ratio; BMI, body mass index; UAER, urinary albumin excretion ratio; ACR, albumin:creatinine ratio.

1)High risk: family history of type 2 or gestational diabetes, known cardiovascular disease, polycystic ovary syndrome, physically inactive lifestyle, >40 years of age, and ethnic populations at high risk for type 2 diabetes. M = male, F = female.

Table 2. Metabolic syndrome definitions and diagnosis issued by international criteria

It has been noted that these definitions overlap but differ in the points of emphasis of the components. Using the above definitions of the metabolic syndrome, there are quantitatively significant differences in sample sizes, age groups and rates of healthy participants as well. For example, the International Diabetes Federation definition identifies a high degree of overlap among the participants with the metabolic syndrome using the National Cholesterol Education Program Adult Treatment Panel III criteria. The two definitions similarly classified approximately 93% in 3601 American adults aged ≥ 20 years [15], 85% in 2182 Finnish young adults aged 24–39 years [4], and only about 16% in 5047 Swedish adults aged 46–68 years [16].

#### **2.2 Systemic mechanisms**

162 An International Perspective on Topics in Sports Medicine and Sports Injury

(2003)

High risk1), WC > 102 cm (M) or > 88 cm (F)

(150 mg/dL)

or

< 40 mg/dL (M)

< 50 mg/dL (F)

≥ 130/85 mmHg or medication

≥ 5.6 mmol/L (100 mg/dL)

IDF (2006) NCEP-ATP III

WC ≥ 94 cm (M) or ≥ 80 cm (F), and WC with ethnicity specific values, or BMI > 30 kg/m2

≥102 cm (M)

≥ 1.7 mmol/l (150 mg/dL) or medication

< 40 mg/dL (1.03 mmol/L)

< 50 mg/dL (1.29 mmol/L)

≥ 130/85 mmHg or medication

≥ 5.6 mmol/L (100 mg/dL)

(M) or

(F)

(2005)

or ≥ 88 cm (F)

or

≥ 150 mg/dL

<40 mg/dL (M)

<50 mg/dL (F)

≥130/85 mmHg or medication

≥5.6 mmol/L (100 mg/dL) or medication

WHO (1999) EGIR (1999) ACE/AACE

Insulin resistance in top quartile of non-diabetic population

Other criteria plus ≥ 2 of the following:

or ≥ 80 cm (F)

Triglyceride ≥ 1.7 mmol/L ≥ 2.0 mmol/L ≥ 1.7 mmol/L

≥ 94 cm (M)

< 1.0 mmol/L or medication

≥ 140/90 mmHg or medication

(110 mg/dL)

WHO, World Health Organization, EGIR, European Group for the Study of Insulin Resistance; ACE/AACE, American College of Endocrinology/American Association of Clinical Endocrinologists; IDF, International Diabetes Federation; NCEP-ATP III, National Cholesterol Education Program- Adult Treatment Panel III; IGT, impaired glucose tolerance; IFG, impaired fasting glucose, T2D, type 2 diabetes; WHR, waist:hip ratio; BMI, body mass index; UAER, urinary albumin excretion ratio; ACR,

1)High risk: family history of type 2 or gestational diabetes, known cardiovascular disease, polycystic ovary syndrome, physically inactive lifestyle, >40 years of age, and ethnic populations at high risk for

Table 2. Metabolic syndrome definitions and diagnosis issued by international criteria

It has been noted that these definitions overlap but differ in the points of emphasis of the components. Using the above definitions of the metabolic syndrome, there are quantitatively significant differences in sample sizes, age groups and rates of healthy participants as well. For example, the International Diabetes Federation definition identifies a high degree of overlap among the participants with the metabolic syndrome using the

IGT, IFG, T2D, insulin resistance in top quartile of non-diabetic population

WHR > 0.9(M), or >0.85 (F); or BMI > 30 kg/m2

≤ 0.9 mmol/L (M)

≤ 1.0 mmol/L (F) or medication

or medication

Glucose ≥ 6.1 mmol/L

or ACR ≥ 30 mg/g

or

Blood pressure ≥ 140/90 mmHg

Other Microalbuminuria; UAER ≥ 20 µg/min

type 2 diabetes. M = male, F = female.

albumin:creatinine ratio.

Required criteria

Waist circumference (WC)

High-density lipoprotein cholesterol

In general, leisure-time physical activity and aerobic exercise may provide an advantage in helping reducing the metabolic syndrome in middle-aged and elderly population. The potential mechanisms are often proposed by which physical activity and fitness can reduce the risk of the metabolic syndrome in response to insulin resistance and abdominal obesity. From a psychosocial standpoint, physical activity and fitness have a beneficial effect that can improve psychosocial well-being, leading to better mood, higher self-efficacy and stronger social motives for exercise [17,18]. Participation in regular physical activity or aerobic exercise is an effective way to establish lifelong habits for reducing the increased risk of insulin resistance and obesity. Individuals who want to maintain physical abilities may have better awareness of other health-related habits such as diet, smoking and sedentary lifestyle, all of which have been found to be related to the risk for the metabolic syndrome [19,20]. Increased physical activity and fitness may also lead to enhanced overall cardiovascular function and muscular endurance which, in turn, delay the onset or help prevent the development of metabolic syndrome. These psychosocial effects may then interact with biological processes that may result in reduction of subclinical inflammation involving cytokines derived from adipose tissue and modulation of various adipocytokines that lead to reduce the prevalence of metabolic syndrome [21]. The benefit of increased and maintained physical activity and physical fitness may be directly or indirectly associated with reduced incidence of the metabolic syndrome.

However, the relationship between physical activity or physical fitness and the metabolic syndrome may also be bidirectional. The prevalence of metabolic syndrome may lead to declining levels of physical activity and fitness as symptoms of metabolic syndrome may increase sedentary lifestyle, unhealthy diet, low energy level and lack of exercise and physical activity. Therefore, the precise mechanisms underlying the effect of physical activity and fitness on the metabolic syndrome still need further clarification.

## **3. Effect of physical activity and fitness on metabolic syndrome in adults**

A number of cross-sectional epidemiological studies have been conducted to examine the effect of leisure-time physical activity and cardiorespiratory fitness on the metabolic syndrome in adult population over the last decade. Several studies have only focused on the association in men. An English cohort of 711 employed middle-aged men demonstrated a dose-relationship between both leisure-time physical activity and cardiorespiratory fitness and the clustering of the metabolic syndrome including fasting glucose, triglycerides, highdensity lipoprotein cholesterol, blood pressure, and body mass index [22]. Men with higher physical activity, as defined by a physical activity index, were found to be less likely to have the metabolic syndrome when compared with the inactive ones. The age-adjusted odds ratios and their 95% confidence intervals for having the clustering of metabolic syndrome were 0.56 (0.33-0.96) for occasional/light physical activity, 0.37 (0.19-0.71) for moderate/moderately vigorous physical activity, and 0.12 (0.03-0.50) for vigorous physical activity. Men with moderate to high levels of the fitness were also found to be less likely to

Physical Activity, Physical Fitness and Metabolic Syndrome 165

men aged 18–40 years). Among men, the odds ratios for having the metabolic syndrome risk were independently reduced with increases in both total physical activity (OR = 0.65, 95% CI = 0.47–0.90) and sport activity (OR = 0.40, 95% CI = 0.23–0.70). The components of metabolic syndrome such as abdominal circumference, triglycerides and high-density lipoprotein cholesterol also improved with total and sport physical activity. Among women, the associations of types of physical activity, i.e., leisure, sport, work, and total with the metabolic syndrome were marginal. Only high-density lipoprotein cholesterol was increased by both total physical activity (OR = 0.79, 95% CI = 0.63–0.98) and sport physical activity (OR = 0.54, 95% CI = 0.35–0.84) after controlling for age, smoking and body mass index. These differences may be partly explained by race, age and sex hormone differences, varying patterns of fat

Two studies have reported an inverse association between leisure-time physical activity and metabolic syndrome in women. A cohort study [29] of a tri*-*ethnic sample of women (49 African-American, 46 Native-American, and 51 white) aged 40–83 years in the USA demonstrated that the odds ratios and their 95% confidence intervals for having the metabolic syndrome were 0.18 (0.03–0.90) for women in the highest category of moderateintensity physical activity (≥491 MET min/d) compared with those in the lowest category (<216 MET min/d). The odds ratios for having the metabolic syndrome was 0.07 (0.02–0.35) for women in the highest quartile of maximal treadmill duration (>16 minutes) compared with women in the lowest quartile (≤10 minutes). Although the study population is relatively small, the increased physical activity has important implications in the prevention of metabolic syndrome independently of potential confounding variables. Similar results were found in another study [30] of 7 104 US women, which showed that prevalence of the metabolic syndrome was significantly lower across cardiorespiratory fitness quintiles, with the prevalence ranging from 19.0% in the lowest fit quintile to 2.3% in the highest fit quintile. Also, the prevalence of metabolic syndrome in the different age groups for women who achieved a maximal MET level of 11 or higher was one-third to one-fourth that of

Most studies found that physical activity and fitness was related to the metabolic syndrome in both sexes. An early cohort study [31] of 15 537 men and 3 899 women in the adult US population found that the least-fit men had 3.0- and 10.1-fold higher risk factors for the metabolic clusters (elevated systolic blood pressure, serum triglycerides, fasting blood glucose, and central adiposity) compared with moderately-fit and the most-fit men, respectively. Similarly, the least-fit women had 2.7- and 4.9-fold higher risk factors for the metabolic clusters compared with moderately-fit and the most-fit women, respectively. Data from a cohort of 874 healthy Caucasian participants from the Medical Research Council Ely Study indicated that there was a strong and significant inverse association between physical activity energy expenditure and the metabolic syndrome, while the association between cardiorespiratory fitness and the metabolic syndrome was attenuated after adjusting for age, sex, physical activity, and measurement error. However, cardiorespiratory fitness modified the relationship between physical activity and metabolic syndrome [32]. Thus, prevention of

the metabolic syndrome may be most effective in the subset of unfit inactive people.

An Australian study by Dunstan et al. [33] examined the associations of television viewing and physical activity with the metabolic syndrome in 6 241 adults aged ≥ 35 years. They found that the adjusted odds ratios and their 95% confidence intervals for having the metabolic syndrome were 2.07 (1.49-2.88) in women and 1.48 (0.95-2.31) in men who watched TV for >14 hrs/wk compared with those who watched ≤ 7.0 hrs/wk. Compared

distribution, and differences in types and intensity of physical activity.

women who achieved lower maximal MET levels.

develop the metabolic syndrome when compared with those with unfit. The corresponding age-adjusted odds ratios and 95% confidence intervals were 0.27 (0.15-0.46) in the moderate fitness category and 0.18 (0.09-0.33) in the high fitness category compared to the unfit group. A similar study design and analysis was performed in a Finnish study of 1 069 middle-aged men [23]. Leisure-time physical activity, as measured by metabolic equivalent hours per week (MET h·wk-1), was divided into three levels of intensity: low, moderate and high. The each level was grouped again into three categories from low to high. Men who engaged in moderate-intensity physical activity (<1.0 h·wk-1) were 60% more likely to have the metabolic syndrome than those engaging in physical activity (≥ 3.0 h·wk-1). Men with low fitness (VO2max ≤ 29.1 ml·kg-1·min-1) were approximately seven times more likely to have the metabolic syndrome than those with high fitness (VO2max ≥35.5 ml·kg-1·min-1). The relationships remained significant after adjustment for confounders.

In the Whitehall II study, which assessed a dose-response relationship between leisure-time physical activity and metabolic syndrome in 5 153 Caucasian civil servants (ages 45-68 years) from 20 departments in the London offices, showed that the odds ratios and their 95% confidence intervals for having the metabolic syndrome were 0.52 (0.40–0.67) in vigorous (≥12.5 MET h/wk) activity and 0.78 (0.63–0.96) in moderate (≥24 MET h/wk) activity than in low activity, when controlling for confounders, e.g., age, smoking, alcohol intake, socioeconomic status, and other activity [24]. Katzmarzyk et al. [25] carried out a cohort study of 19 223 men (ages 20–83 years), who were selected randomly from a general population in Canada. Cardiorespiratory fitness was used to classify each subject into two fitness exposure categories. Men with the metabolic syndrome had 1.29-fold higher all-cause mortality and 1.89-fold higher cardiovascular disease (CVD) mortality compared with healthy men. However, the associations were no longer significant after accounting for cardiorespiratory fitness. The relative risks comparing unfit vs. fit men for all-cause mortality was similar in healthy men and men with the metabolic syndrome (2.18 vs. 2.01), whereas the relative risks for CVD mortality for unfit vs. fit men were 3.21 in healthy men and 2.25 in men with the metabolic syndrome. Also, a significant dose-response relationship between cardiorespiratory fitness and mortality was observed in men with the metabolic syndrome. It was concluded that exercise provided a protective effect against the risk of allcause and CVD mortality in healthy men and men with the metabolic syndrome.

Although there is a consistent inverse association between leisure-time physical activity and metabolic syndrome and its components in men, the association is not as consistent in women. For example, results from the Quebec family study (158 men and 198 women aged 20-60 years) found that cardiorespiratory fitness was independently related to the metabolic syndrome among both men and women. Cardiorespiratory fitness was inversely related to plasma insulin only for men, while cardiorespiratory fitness was only positively related to high-density lipoprotein cholesterol for women. However, cardiorespiratory fitness was not independently related to the components of metabolic syndrome in both sexes after accounting for total and abdominal adiposity [26]. As in another Canadian population-based study (6 406 men and 6 475 women aged 18-64 years) [27], the odds ratios and their 95% confidence intervals for having the metabolic syndrome in physically active men was 0.45 (0.29-0.69) than their physically inactive counterparts, after consideration of covariates including age, smoking, alcohol consumption, and income adequacy. The association disappeared in women after adjusting for the covariates. Sex differences were also found for the association of the metabolic syndrome with leisure-time physical activity in the Fels Longitudinal Study [28], investigating a sample of US young adults (249 women and 237

develop the metabolic syndrome when compared with those with unfit. The corresponding age-adjusted odds ratios and 95% confidence intervals were 0.27 (0.15-0.46) in the moderate fitness category and 0.18 (0.09-0.33) in the high fitness category compared to the unfit group. A similar study design and analysis was performed in a Finnish study of 1 069 middle-aged men [23]. Leisure-time physical activity, as measured by metabolic equivalent hours per week (MET h·wk-1), was divided into three levels of intensity: low, moderate and high. The each level was grouped again into three categories from low to high. Men who engaged in moderate-intensity physical activity (<1.0 h·wk-1) were 60% more likely to have the metabolic syndrome than those engaging in physical activity (≥ 3.0 h·wk-1). Men with low fitness (VO2max ≤ 29.1 ml·kg-1·min-1) were approximately seven times more likely to have the metabolic syndrome than those with high fitness (VO2max ≥35.5 ml·kg-1·min-1). The

In the Whitehall II study, which assessed a dose-response relationship between leisure-time physical activity and metabolic syndrome in 5 153 Caucasian civil servants (ages 45-68 years) from 20 departments in the London offices, showed that the odds ratios and their 95% confidence intervals for having the metabolic syndrome were 0.52 (0.40–0.67) in vigorous (≥12.5 MET h/wk) activity and 0.78 (0.63–0.96) in moderate (≥24 MET h/wk) activity than in low activity, when controlling for confounders, e.g., age, smoking, alcohol intake, socioeconomic status, and other activity [24]. Katzmarzyk et al. [25] carried out a cohort study of 19 223 men (ages 20–83 years), who were selected randomly from a general population in Canada. Cardiorespiratory fitness was used to classify each subject into two fitness exposure categories. Men with the metabolic syndrome had 1.29-fold higher all-cause mortality and 1.89-fold higher cardiovascular disease (CVD) mortality compared with healthy men. However, the associations were no longer significant after accounting for cardiorespiratory fitness. The relative risks comparing unfit vs. fit men for all-cause mortality was similar in healthy men and men with the metabolic syndrome (2.18 vs. 2.01), whereas the relative risks for CVD mortality for unfit vs. fit men were 3.21 in healthy men and 2.25 in men with the metabolic syndrome. Also, a significant dose-response relationship between cardiorespiratory fitness and mortality was observed in men with the metabolic syndrome. It was concluded that exercise provided a protective effect against the risk of all-

cause and CVD mortality in healthy men and men with the metabolic syndrome.

Although there is a consistent inverse association between leisure-time physical activity and metabolic syndrome and its components in men, the association is not as consistent in women. For example, results from the Quebec family study (158 men and 198 women aged 20-60 years) found that cardiorespiratory fitness was independently related to the metabolic syndrome among both men and women. Cardiorespiratory fitness was inversely related to plasma insulin only for men, while cardiorespiratory fitness was only positively related to high-density lipoprotein cholesterol for women. However, cardiorespiratory fitness was not independently related to the components of metabolic syndrome in both sexes after accounting for total and abdominal adiposity [26]. As in another Canadian population-based study (6 406 men and 6 475 women aged 18-64 years) [27], the odds ratios and their 95% confidence intervals for having the metabolic syndrome in physically active men was 0.45 (0.29-0.69) than their physically inactive counterparts, after consideration of covariates including age, smoking, alcohol consumption, and income adequacy. The association disappeared in women after adjusting for the covariates. Sex differences were also found for the association of the metabolic syndrome with leisure-time physical activity in the Fels Longitudinal Study [28], investigating a sample of US young adults (249 women and 237

relationships remained significant after adjustment for confounders.

men aged 18–40 years). Among men, the odds ratios for having the metabolic syndrome risk were independently reduced with increases in both total physical activity (OR = 0.65, 95% CI = 0.47–0.90) and sport activity (OR = 0.40, 95% CI = 0.23–0.70). The components of metabolic syndrome such as abdominal circumference, triglycerides and high-density lipoprotein cholesterol also improved with total and sport physical activity. Among women, the associations of types of physical activity, i.e., leisure, sport, work, and total with the metabolic syndrome were marginal. Only high-density lipoprotein cholesterol was increased by both total physical activity (OR = 0.79, 95% CI = 0.63–0.98) and sport physical activity (OR = 0.54, 95% CI = 0.35–0.84) after controlling for age, smoking and body mass index. These differences may be partly explained by race, age and sex hormone differences, varying patterns of fat distribution, and differences in types and intensity of physical activity.

Two studies have reported an inverse association between leisure-time physical activity and metabolic syndrome in women. A cohort study [29] of a tri*-*ethnic sample of women (49 African-American, 46 Native-American, and 51 white) aged 40–83 years in the USA demonstrated that the odds ratios and their 95% confidence intervals for having the metabolic syndrome were 0.18 (0.03–0.90) for women in the highest category of moderateintensity physical activity (≥491 MET min/d) compared with those in the lowest category (<216 MET min/d). The odds ratios for having the metabolic syndrome was 0.07 (0.02–0.35) for women in the highest quartile of maximal treadmill duration (>16 minutes) compared with women in the lowest quartile (≤10 minutes). Although the study population is relatively small, the increased physical activity has important implications in the prevention of metabolic syndrome independently of potential confounding variables. Similar results were found in another study [30] of 7 104 US women, which showed that prevalence of the metabolic syndrome was significantly lower across cardiorespiratory fitness quintiles, with the prevalence ranging from 19.0% in the lowest fit quintile to 2.3% in the highest fit quintile. Also, the prevalence of metabolic syndrome in the different age groups for women who achieved a maximal MET level of 11 or higher was one-third to one-fourth that of women who achieved lower maximal MET levels.

Most studies found that physical activity and fitness was related to the metabolic syndrome in both sexes. An early cohort study [31] of 15 537 men and 3 899 women in the adult US population found that the least-fit men had 3.0- and 10.1-fold higher risk factors for the metabolic clusters (elevated systolic blood pressure, serum triglycerides, fasting blood glucose, and central adiposity) compared with moderately-fit and the most-fit men, respectively. Similarly, the least-fit women had 2.7- and 4.9-fold higher risk factors for the metabolic clusters compared with moderately-fit and the most-fit women, respectively. Data from a cohort of 874 healthy Caucasian participants from the Medical Research Council Ely Study indicated that there was a strong and significant inverse association between physical activity energy expenditure and the metabolic syndrome, while the association between cardiorespiratory fitness and the metabolic syndrome was attenuated after adjusting for age, sex, physical activity, and measurement error. However, cardiorespiratory fitness modified the relationship between physical activity and metabolic syndrome [32]. Thus, prevention of the metabolic syndrome may be most effective in the subset of unfit inactive people.

An Australian study by Dunstan et al. [33] examined the associations of television viewing and physical activity with the metabolic syndrome in 6 241 adults aged ≥ 35 years. They found that the adjusted odds ratios and their 95% confidence intervals for having the metabolic syndrome were 2.07 (1.49-2.88) in women and 1.48 (0.95-2.31) in men who watched TV for >14 hrs/wk compared with those who watched ≤ 7.0 hrs/wk. Compared

Physical Activity, Physical Fitness and Metabolic Syndrome 167

0 to ≤156.24, >156.24 to ≤393.10, >393.10 to ≤736.55, >736.55 to ≤1360.15, and >1360.15 MET·minwk-1) based on the compendium of physical activities for adults [40,41] and (2) a three level categorical measure (inactive, insufficiently active, and met physical activity recommendation) based on the recent physical activity public health recommendation of the American College of Sports Medicine/American Heart Association (ACSM/AHA) [42]. When compared to the no physical activity group, adults with physical activity between 736 and 1360 METminwk-1 were found to be 35% less likely (OR= 0.65, 95% CI = 0.48–0.88) to have the metabolic syndrome using the National Cholesterol education Program-Adult Treatment Panel III criteria, while adults with physical activity between 393–737 METminwk-1 were found to be 30% less likely (OR = 0.70, 95% CI = 0.51–0.96) to have the metabolic syndrome using the World Health Organization criteria. Additionally, adults with physical activity met the ACSM/AHA guidelines were found to be 45% (OR = 0.54, 95% CI = 0.44–0.66 for the World Health Organization criteria) and 39% (OR = 0.61, 95% CI = 0.48– 0.77 for the American College of Endocrinology/American Association of Clinical Endocrinologists criteria) less likely to have the metabolic syndrome compared with those who were inactive. In addition, cardiorespiratory fitness was first measured by using a submaximal treadmill test in both healthy men (n = 692) and women (n = 608) aged 18–49 years in the 1999-2002 NHANES [43]. Participants were divided into low, moderate, and high fitness tertiles based on the age-adjusted VO2max values. It was showed that the odds ratios for having the metabolic syndrome in men but not women were significantly lower in moderate and high fitness categories compared with the low fitness category, after controlling for confounding variables such as age, ethnicity, poverty-income ratio, alcohol consumption, smoking and fat consumption. These inconsistent findings may be caused by different assessments of physical activity and fitness and different criteria of metabolic syndrome in different age and samples. Also, it remains unknown whether menopausal or

Only two studies have addressed the relationship between muscle strength and metabolic syndrome in adult men. An American study followed 8 570 men aged 20–75 years from 1981 to 1989 [44]. Muscular strength score was computed by combining body weight-adjusted one-repetition maximal measures for leg and bench presses and then divided into strength quartile (Q) from Q1 (low strength) to Q4 (high strength). Men with high levels of muscular strength were found to be less likely to have the metabolic syndrome than those with low strength after adjusting for age and smoking. Similar results were found in an average of 6.7 years follow-up study by Jurca et al. [45]. They stated that men with more muscular strength were also less likely to develop the metabolic syndrome, even after adjusting for smoking, alcohol intake, number of baseline metabolic syndrome risk factors, family history of diabetes, hypertension, and premature coronary disease. However, these associations were partially explained by cardiorespiratory fitness. To our knowledge, only one study has explored the combined effects of muscular strength and aerobic fitness on the metabolic syndrome in both Flemish adult men (n =571) and women (n = 448) aged 18–75 years [46]. Muscular strength was evaluated by measuring isometric knee extension and flexion peak torque, using a Biodex System Pro 3 dynamometer. The relationship between muscular strength, aerobic fitness and the metabolic syndrome score was analyzed as continuous variables using a multiple linear regression. The risk of metabolic syndrome was inversely associated with muscular strength, independently of aerobic fitness and other confounding factors in women, whereas the association was attenuated when controlling for aerobic

hormonal status in women contributes to this observation.

with those who were less active (<2.5 hrs/wk), the odds ratios for having the metabolic syndrome were 0.72 (0.58-0.90) in men and 0.53 (0.38-0.74) in women who were active (≥2.5 hrs/wk). Additionally, increased TV viewing time or physical activity was also associated with individual components of the metabolic risk in both sexes. Recently, a Swedish study by Halldin et al. [34] included 3 864 60-year-old men and women in the Stockholm region. The results showed that, compared with the low physical activity group, the odds ratios for having the metabolic syndrome in the high physical activity groups (i.e. intensive regular activity more than 2 times/week, at least 30 min each time) was 0.33 (0.22-0.51) after adjustment for covariates.

Based on a nationally representative population-based sample of US adults aged 20 years and older from the National Health and Nutrition Examination Survey (NHANES), several studies have utilized the NHANES to explore the relationship between leisure-time physical activity and metabolic syndrome. However, the results are inconsistent. Park et al. [35] used a physical activity intensity score to examine the association between physical activity and metabolic syndrome. The score was calculated as a dichotomized variable based on the frequency and intensity of leisure-time physical activity. Participants with the total density rating score > 3.5 were active and those with a total density rating score of ≤ 3.5 were inactive. When compared to the active group, the odds ratios for having the metabolic syndrome were significantly higher (OR = 1.4, 95% CI = 1.0–2.0) among inactive men, but not among inactive women. Similar findings have been reported by Zhu et al. [20], although these participants were grouped into 3 categories: active (score > 15.0), moderately activity (score > 3.6 to 14.9) and inactive (≤ 3.5). Men with the active group were found to be 42% less likely (OR = 0.58, 95% CI = 0.39–0.85) to have the metabolic syndrome compared to those with the inactive group, even after controlling for age, race, education, income levels, and other modifiable factors. In women, the association disappeared after adjusting for the confounders. These finding were also supported by a study reported by DuBose et al. [36]. Leisure-time physical activity was classified as regularly active (≥ 5 d/wk moderate- and/or ≥ 3 d/wk vigorousintensity physical activity), irregularly active (some physical activity), and inactive (no physical activity). Regularly active represented that the participants met the recommendations of the Centres for Disease Control and Prevention and the American College of Sports Medicine [37]. The results indicated that the odd ratios for having the metabolic syndrome were only higher in men with the irregular activity (OR = 1.52, 95% CI = 1.11–1.23) and inactivity (OR = 1.60, 95% CI = 1.18–1.98) groups than those with the regularly active group after adjustment for age, race, smoking status, and educational attainment.

However, to continue to expand this field, the duration of physical activity, in addition to the frequency and intensity of physical activity, is required to examine a more precise measure of physical activity dose. In the study of examining the interaction between time spent in physical activity and sedentary behaviour on the metabolic syndrome [38], participants were asked about their moderate/vigorous intensity physical activity patterns and moderate intensity household activity, designating these activities in minutes per week (min/wk-1) based on frequency, duration, and intensity of each activity. These participants were then grouped into three categories: 0, < 150, and ≥150 min/wk-1 of moderate/vigorous physical activity. However, after adjustment for covariates, the cross-sectional association between physical activity and metabolic syndrome was attenuated for both sexes. In a recent study [39], leisure-time physical activity was measured in two ways: (1) a six-level measure based upon participants reporting no physical activity and quintiles of physical activity (0, >

with those who were less active (<2.5 hrs/wk), the odds ratios for having the metabolic syndrome were 0.72 (0.58-0.90) in men and 0.53 (0.38-0.74) in women who were active (≥2.5 hrs/wk). Additionally, increased TV viewing time or physical activity was also associated with individual components of the metabolic risk in both sexes. Recently, a Swedish study by Halldin et al. [34] included 3 864 60-year-old men and women in the Stockholm region. The results showed that, compared with the low physical activity group, the odds ratios for having the metabolic syndrome in the high physical activity groups (i.e. intensive regular activity more than 2 times/week, at least 30 min each time) was 0.33 (0.22-0.51) after

Based on a nationally representative population-based sample of US adults aged 20 years and older from the National Health and Nutrition Examination Survey (NHANES), several studies have utilized the NHANES to explore the relationship between leisure-time physical activity and metabolic syndrome. However, the results are inconsistent. Park et al. [35] used a physical activity intensity score to examine the association between physical activity and metabolic syndrome. The score was calculated as a dichotomized variable based on the frequency and intensity of leisure-time physical activity. Participants with the total density rating score > 3.5 were active and those with a total density rating score of ≤ 3.5 were inactive. When compared to the active group, the odds ratios for having the metabolic syndrome were significantly higher (OR = 1.4, 95% CI = 1.0–2.0) among inactive men, but not among inactive women. Similar findings have been reported by Zhu et al. [20], although these participants were grouped into 3 categories: active (score > 15.0), moderately activity (score > 3.6 to 14.9) and inactive (≤ 3.5). Men with the active group were found to be 42% less likely (OR = 0.58, 95% CI = 0.39–0.85) to have the metabolic syndrome compared to those with the inactive group, even after controlling for age, race, education, income levels, and other modifiable factors. In women, the association disappeared after adjusting for the confounders. These finding were also supported by a study reported by DuBose et al. [36]. Leisure-time physical activity was classified as regularly active (≥ 5 d/wk moderate- and/or ≥ 3 d/wk vigorousintensity physical activity), irregularly active (some physical activity), and inactive (no physical activity). Regularly active represented that the participants met the recommendations of the Centres for Disease Control and Prevention and the American College of Sports Medicine [37]. The results indicated that the odd ratios for having the metabolic syndrome were only higher in men with the irregular activity (OR = 1.52, 95% CI = 1.11–1.23) and inactivity (OR = 1.60, 95% CI = 1.18–1.98) groups than those with the regularly active group

after adjustment for age, race, smoking status, and educational attainment.

However, to continue to expand this field, the duration of physical activity, in addition to the frequency and intensity of physical activity, is required to examine a more precise measure of physical activity dose. In the study of examining the interaction between time spent in physical activity and sedentary behaviour on the metabolic syndrome [38], participants were asked about their moderate/vigorous intensity physical activity patterns and moderate intensity household activity, designating these activities in minutes per week (min/wk-1) based on frequency, duration, and intensity of each activity. These participants were then grouped into three categories: 0, < 150, and ≥150 min/wk-1 of moderate/vigorous physical activity. However, after adjustment for covariates, the cross-sectional association between physical activity and metabolic syndrome was attenuated for both sexes. In a recent study [39], leisure-time physical activity was measured in two ways: (1) a six-level measure based upon participants reporting no physical activity and quintiles of physical activity (0, >

adjustment for covariates.

0 to ≤156.24, >156.24 to ≤393.10, >393.10 to ≤736.55, >736.55 to ≤1360.15, and >1360.15 MET·minwk-1) based on the compendium of physical activities for adults [40,41] and (2) a three level categorical measure (inactive, insufficiently active, and met physical activity recommendation) based on the recent physical activity public health recommendation of the American College of Sports Medicine/American Heart Association (ACSM/AHA) [42]. When compared to the no physical activity group, adults with physical activity between 736 and 1360 METminwk-1 were found to be 35% less likely (OR= 0.65, 95% CI = 0.48–0.88) to have the metabolic syndrome using the National Cholesterol education Program-Adult Treatment Panel III criteria, while adults with physical activity between 393–737 METminwk-1 were found to be 30% less likely (OR = 0.70, 95% CI = 0.51–0.96) to have the metabolic syndrome using the World Health Organization criteria. Additionally, adults with physical activity met the ACSM/AHA guidelines were found to be 45% (OR = 0.54, 95% CI = 0.44–0.66 for the World Health Organization criteria) and 39% (OR = 0.61, 95% CI = 0.48– 0.77 for the American College of Endocrinology/American Association of Clinical Endocrinologists criteria) less likely to have the metabolic syndrome compared with those who were inactive. In addition, cardiorespiratory fitness was first measured by using a submaximal treadmill test in both healthy men (n = 692) and women (n = 608) aged 18–49 years in the 1999-2002 NHANES [43]. Participants were divided into low, moderate, and high fitness tertiles based on the age-adjusted VO2max values. It was showed that the odds ratios for having the metabolic syndrome in men but not women were significantly lower in moderate and high fitness categories compared with the low fitness category, after controlling for confounding variables such as age, ethnicity, poverty-income ratio, alcohol consumption, smoking and fat consumption. These inconsistent findings may be caused by different assessments of physical activity and fitness and different criteria of metabolic syndrome in different age and samples. Also, it remains unknown whether menopausal or hormonal status in women contributes to this observation.

Only two studies have addressed the relationship between muscle strength and metabolic syndrome in adult men. An American study followed 8 570 men aged 20–75 years from 1981 to 1989 [44]. Muscular strength score was computed by combining body weight-adjusted one-repetition maximal measures for leg and bench presses and then divided into strength quartile (Q) from Q1 (low strength) to Q4 (high strength). Men with high levels of muscular strength were found to be less likely to have the metabolic syndrome than those with low strength after adjusting for age and smoking. Similar results were found in an average of 6.7 years follow-up study by Jurca et al. [45]. They stated that men with more muscular strength were also less likely to develop the metabolic syndrome, even after adjusting for smoking, alcohol intake, number of baseline metabolic syndrome risk factors, family history of diabetes, hypertension, and premature coronary disease. However, these associations were partially explained by cardiorespiratory fitness. To our knowledge, only one study has explored the combined effects of muscular strength and aerobic fitness on the metabolic syndrome in both Flemish adult men (n =571) and women (n = 448) aged 18–75 years [46]. Muscular strength was evaluated by measuring isometric knee extension and flexion peak torque, using a Biodex System Pro 3 dynamometer. The relationship between muscular strength, aerobic fitness and the metabolic syndrome score was analyzed as continuous variables using a multiple linear regression. The risk of metabolic syndrome was inversely associated with muscular strength, independently of aerobic fitness and other confounding factors in women, whereas the association was attenuated when controlling for aerobic

Physical Activity, Physical Fitness and Metabolic Syndrome 169

possibly through different causal pathways. Among more recent studies, findings have been mixed. In a population-based sample of 3 193 10- and 15-year-old youth from three European countries (Estonia, Denmark, and Portugal), Ekelund et al. [66] further found that both cardiorespiratory fitness (OR = 0.33, 95% CI = 0.15–0.75) and objectively measured physical activity (OR = 0.40, 95% CI = 0.18–0.88) were significantly and independently associated with being categorized as having the metabolic syndrome. Relatively small increases in physical activity might significantly reduce the risk of metabolic syndrome in healthy youth. Conversely, Martínez-Gómez et al. [67] did not find the same association between physical activity and metabolic syndrome in 202 adolescents (99 girls) aged 13-17 years after controlling for age, sex and maturation status, and suggested that cardiorespiratory fitness appeared to have a pivotal role in the metabolic syndrome and in

There were only few studies have reported on the effect of diet and physical activity on prevention of the metabolic syndrome in adolescents. For example, Pan and Pratt [68] investigated a sample of 4 450 US adolescents aged 12 to 19 years from the National Health and Nutrition Examination Survey 1999-2002. They reported that although there was not significant relationship between physical activity and the overall prevalence of metabolic syndrome, the differences in some metabolic syndrome components among groups were statistically significant. Adolescents with low physical activity had higher levels of triglycerides and blood pressure than those with moderate or high physical activity. In addition, the prevalence of metabolic syndrome was a 16-fold higher in overweight adolescents (BMI ≥ 95th percentile) compared with their normal weight peers (BMI ≤ 85th percentile). Higher overall healthy eating index and fruit scores were also associated with lower risk of the metabolic syndrome. The authors concluded that unhealthy lifestyle behaviours might be the major underlying cause for the metabolic syndrome in adolescents. The primary means for preventing the metabolic syndrome was needed to engage adolescents in regular physical activity and healthful dietary practices to prevent excessive weight gain. However, these studies have not addressed issues specific to population subgroups or intervention-delivery modalities. In a very recent review of the literature on the relationship between physical activity and metabolic syndrome in youth, Brambilla et al. [50] provided an overview of 11 studies [69–79] on physical activity intervention, focusing on a subsample of obese youth and intervention modalities and concluded that the different physical activity programs, relatively short duration and small sample size of these studies likely contributed to the inconsistent results. Although there were some controversies regarding the risk of insulin resistance, fat mass and body mass index for certain subgroups of children and adolescents with obesity, regular vigorous intensity physical activity on blood pressure and lipid levels did much to alleviate concerns that physical activity programs could have positive effect in these metabolic risk parameters. Furthermore, the authors suggested that the effect of low-intensity physical activity (e.g., playing at home, walking to school, dancing, and downstairs) on the metabolic risk in a large sample of overweight and obese

children and adolescents should be taken into consideration in future study.

To summarize, several studies have shown that metabolic risk factors are readily detectable in children and adolescents because obesity is closely associated with insulin resistance in youth. It seems that physical activity intervention strategies may be most effective in childhood and adolescence before the development of metabolic syndrome. The main question to be asked is whether the positive effects of physical activity seen in adults will

the association of physical activity with the metabolic risk.

fitness in men. Thus, strength training in addition to aerobic exercise may provide additional effects in reducing the prevalence of metabolic syndrome, particularly for women. These findings are inconsistent that may be partially explained by socio-cultural differences of the samples and the methodological issues including different measures, methods of analysis and sample size.

In summary, these findings imply that leisure-time physical activity, cardiorespiratory fitness and muscular strength may be an important determinant of the overall prevalence of metabolic syndrome independent of several other confounding factors. Accumulating evidence suggests that regular physical activity which increases aerobic capacity and cardiovascular fitness and maintain muscular strength has a beneficial effect on the metabolic syndrome. However, the relationship between physical activity and metabolic syndrome is still somewhat controversial, particularly for women. Such studies have varied in assessments of physical activity (subjective vs. objective), cardiorespiratory fitness (ergometer cycle vs. treadmill tests) and muscular strength (1-repetition maximum vs. isometric dynamometry), as well as criteria or risks to define the metabolic syndrome. In addition, the cross-sectional nature of most of these studies does not allow inference of causality. Further studies examining sex differences in the relation between physical activity and metabolic syndrome that address confounding factors such as menopausal status and concurrent medical conditions are needed. A longitudinal study design is also needed to examine the causal relationship between physical activity and metabolic syndrome.

### **4. Effect of physical activity and fitness on metabolic syndrome in children and adolescents**

The beneficial effect of leisure-time physical activity on the metabolic syndrome in children and adolescents has been assessed within the contemporary reviews [47–50]. Froberg and Andersen [47] have authored a review on the linking physical inactivity and low fitness to metabolic disorders including CVD risk factors and obesity in European children. The authors concluded that there was only weak evidence of the association between physical activity or physical fitness and CVD risk factors in children when risk factors were analyzed isolated, but the clustering of risk factors was strongly associated with low physical activity or physical fitness among children. They also stated that participation in regular physical activity was one of the key determinants of lifestyle-related health. Furthermore, the relationship between aerobic fitness, fatness and the metabolic syndrome in children and adolescents was reviewed [48]. It was concluded that the relationship between fatness and the metabolic syndrome remained significant after controlling for fitness, whereas the relationship between fitness and metabolic syndrome disappeared after controlling for fatness. The author also reviewed four studies [51–54] of the combined influence of fatness and fitness on the metabolic syndrome and concluded that fitness attenuated the metabolic syndrome score among fat children and adolescents when they were cross-tabulated into categories (fat-fit, etc.), it might be possible to involve genetics, adipocytokines and mitochondrial function.

A recent review by Steele et al. [49], outlined the evidence from 6 studies [55–60] on objectively measured physical activity (i.e. accelerometer) and 11 studies [51–54, 59–65] on cardiorespiratory fitness, identifying the influence of physical activity and fitness on the clustered metabolic risk in youth. They concluded that physical activity and fitness were separately and independently related to metabolic risk factors in children and adolescents,

fitness in men. Thus, strength training in addition to aerobic exercise may provide additional effects in reducing the prevalence of metabolic syndrome, particularly for women. These findings are inconsistent that may be partially explained by socio-cultural differences of the samples and the methodological issues including different measures,

In summary, these findings imply that leisure-time physical activity, cardiorespiratory fitness and muscular strength may be an important determinant of the overall prevalence of metabolic syndrome independent of several other confounding factors. Accumulating evidence suggests that regular physical activity which increases aerobic capacity and cardiovascular fitness and maintain muscular strength has a beneficial effect on the metabolic syndrome. However, the relationship between physical activity and metabolic syndrome is still somewhat controversial, particularly for women. Such studies have varied in assessments of physical activity (subjective vs. objective), cardiorespiratory fitness (ergometer cycle vs. treadmill tests) and muscular strength (1-repetition maximum vs. isometric dynamometry), as well as criteria or risks to define the metabolic syndrome. In addition, the cross-sectional nature of most of these studies does not allow inference of causality. Further studies examining sex differences in the relation between physical activity and metabolic syndrome that address confounding factors such as menopausal status and concurrent medical conditions are needed. A longitudinal study design is also needed to

examine the causal relationship between physical activity and metabolic syndrome.

**4. Effect of physical activity and fitness on metabolic syndrome in children** 

The beneficial effect of leisure-time physical activity on the metabolic syndrome in children and adolescents has been assessed within the contemporary reviews [47–50]. Froberg and Andersen [47] have authored a review on the linking physical inactivity and low fitness to metabolic disorders including CVD risk factors and obesity in European children. The authors concluded that there was only weak evidence of the association between physical activity or physical fitness and CVD risk factors in children when risk factors were analyzed isolated, but the clustering of risk factors was strongly associated with low physical activity or physical fitness among children. They also stated that participation in regular physical activity was one of the key determinants of lifestyle-related health. Furthermore, the relationship between aerobic fitness, fatness and the metabolic syndrome in children and adolescents was reviewed [48]. It was concluded that the relationship between fatness and the metabolic syndrome remained significant after controlling for fitness, whereas the relationship between fitness and metabolic syndrome disappeared after controlling for fatness. The author also reviewed four studies [51–54] of the combined influence of fatness and fitness on the metabolic syndrome and concluded that fitness attenuated the metabolic syndrome score among fat children and adolescents when they were cross-tabulated into categories (fat-fit, etc.), it might be possible to involve genetics, adipocytokines and

A recent review by Steele et al. [49], outlined the evidence from 6 studies [55–60] on objectively measured physical activity (i.e. accelerometer) and 11 studies [51–54, 59–65] on cardiorespiratory fitness, identifying the influence of physical activity and fitness on the clustered metabolic risk in youth. They concluded that physical activity and fitness were separately and independently related to metabolic risk factors in children and adolescents,

methods of analysis and sample size.

**and adolescents** 

mitochondrial function.

possibly through different causal pathways. Among more recent studies, findings have been mixed. In a population-based sample of 3 193 10- and 15-year-old youth from three European countries (Estonia, Denmark, and Portugal), Ekelund et al. [66] further found that both cardiorespiratory fitness (OR = 0.33, 95% CI = 0.15–0.75) and objectively measured physical activity (OR = 0.40, 95% CI = 0.18–0.88) were significantly and independently associated with being categorized as having the metabolic syndrome. Relatively small increases in physical activity might significantly reduce the risk of metabolic syndrome in healthy youth. Conversely, Martínez-Gómez et al. [67] did not find the same association between physical activity and metabolic syndrome in 202 adolescents (99 girls) aged 13-17 years after controlling for age, sex and maturation status, and suggested that cardiorespiratory fitness appeared to have a pivotal role in the metabolic syndrome and in the association of physical activity with the metabolic risk.

There were only few studies have reported on the effect of diet and physical activity on prevention of the metabolic syndrome in adolescents. For example, Pan and Pratt [68] investigated a sample of 4 450 US adolescents aged 12 to 19 years from the National Health and Nutrition Examination Survey 1999-2002. They reported that although there was not significant relationship between physical activity and the overall prevalence of metabolic syndrome, the differences in some metabolic syndrome components among groups were statistically significant. Adolescents with low physical activity had higher levels of triglycerides and blood pressure than those with moderate or high physical activity. In addition, the prevalence of metabolic syndrome was a 16-fold higher in overweight adolescents (BMI ≥ 95th percentile) compared with their normal weight peers (BMI ≤ 85th percentile). Higher overall healthy eating index and fruit scores were also associated with lower risk of the metabolic syndrome. The authors concluded that unhealthy lifestyle behaviours might be the major underlying cause for the metabolic syndrome in adolescents. The primary means for preventing the metabolic syndrome was needed to engage adolescents in regular physical activity and healthful dietary practices to prevent excessive weight gain.

However, these studies have not addressed issues specific to population subgroups or intervention-delivery modalities. In a very recent review of the literature on the relationship between physical activity and metabolic syndrome in youth, Brambilla et al. [50] provided an overview of 11 studies [69–79] on physical activity intervention, focusing on a subsample of obese youth and intervention modalities and concluded that the different physical activity programs, relatively short duration and small sample size of these studies likely contributed to the inconsistent results. Although there were some controversies regarding the risk of insulin resistance, fat mass and body mass index for certain subgroups of children and adolescents with obesity, regular vigorous intensity physical activity on blood pressure and lipid levels did much to alleviate concerns that physical activity programs could have positive effect in these metabolic risk parameters. Furthermore, the authors suggested that the effect of low-intensity physical activity (e.g., playing at home, walking to school, dancing, and downstairs) on the metabolic risk in a large sample of overweight and obese children and adolescents should be taken into consideration in future study.

To summarize, several studies have shown that metabolic risk factors are readily detectable in children and adolescents because obesity is closely associated with insulin resistance in youth. It seems that physical activity intervention strategies may be most effective in childhood and adolescence before the development of metabolic syndrome. The main question to be asked is whether the positive effects of physical activity seen in adults will

Physical Activity, Physical Fitness and Metabolic Syndrome 171

both the maintenance of physical activity in adulthood and reducing body weight in youth. The path from youth physical activity to adult obesity through youth obesity seemed to be stronger than the path through adult physical activity. However, the level of youth physical activity did not predict adult abdominal obesity in either men or women (Figure 1). The authors concluded that the prevalence of abdominal obesity as defined by waist circumference during adulthood was directly related to adult physical activity and youth overall obesity in both sexes. Youth physical activity had an indirect effect on abdominal obesity through both the maintenance of physical activity in adulthood and reduction in body weight in youth. Participation in and maintaining physical activity from youth into

0.32 (0.18)

0.40 (0.34)

R² = 0.02 (0.02) R² = 0.19 (0.13)

In another study by Yang et al. [83], 1 493 Finnish children and adolescents aged 3 to 18 years were followed over a 21-year period. Participation in sport-club training and competitions were assessed by use of a self-report physical activity questionnaire. Participants were divided into athletes and non-athletes at each measurement point (1980 and 1983), and then classified into four groups: persistent athlete, starter, leaver and nonathlete. A mean score of youth sport was assessed by calculating the average of four consecutive measurements (1980-1989). The metabolic syndrome in adulthood was defined as a categorical variable based on the guidelines of the European Group for the Study of Insulin resistance and as a continuous metabolic syndrome risk score by summing the zscores of individual metabolic variables. The results indicated that the mean score of youth sport across the four time points and covariate variables were simultaneously entered as predictors for the adult metabolic syndrome risk score. Mean youth sport level emerged as a significant predictor of the metabolic syndrome in men (*β* = -0.149, *P* = 0.001) and women (*β* = -0.118, *P* = 0.005). Furthermore, non-athletic males and females had a significantly higher prevalence of the metabolic syndrome in adulthood than persistent athletes (Table 3). The relationships remained significant after adjustment for age and baseline clustered metabolic risk scores. The adds ratios and 95% confidence intervals for non-athletic males and females were 2.94 (1.01–8.99) and 4.04 (1.18–13.85), respectively. After additional adjustment for adult leisure-time physical activity, the trend of the associations was the same but

Fig. 1. Estimadtd parameters (stan dardized solution) in structural equation for males


Adult physical activity

R² = 0.10 (0.03)

Adult waist circumference

adulthood might play an important role in reducing obesity in adulthood.

Youth physical activity

Adult body mass index

(females)

occur in children and adolescents. Most studies have found that objectively measured physical activity and cardiorespiratory fitness are inversely associated with clustered metabolic risk score in children and adolescents, while some have shown that physical activity in adolescents does not result in significantly reduce the prevalence of metabolic syndrome when cardiorespiratory fitness is adjusted for in the analysis. A question which remains unanswered, however, is how much physical activity is needed to prevent the metabolic syndrome and the diseases with which it is associated. Also, the clustered metabolic risk score has been applied in these studies, but no clear definition of the metabolic syndrome has been formally established for either children or adolescents. Attention to these questions with further research is needed.

### **5. Early physical activity and fitness as a predictor of metabolic syndrome in adulthood**

The mechanism behind the relationship between physical activity in childhood and adolescence and adult risk for the metabolic syndrome has been explored. Referring to the model including three possible paths from childhood physical activity to adulthood health presented by Blair et al. [80], one of the hypothetical paths is a direct connection from physical activity or physical fitness in youth to cardiovascular and metabolic health in adult life. In the Cardiovascular Risk in Young Finns Study [19], 961 participants aged 12-18 years from five cities of Finland were included and followed from 1980 to 1983 and 1986. Physical activity was assessed with a standardized questionnaire and then summed a physical activity index from its intensity, frequency and duration. The results showed that the change in physical activity over 6 years was inversely associated with changes in insulin and triglycerides among boys. Among girls, the change in physical activity did not make any independent contribution to the models for serum lipoproteins. It was concluded that participation in regular leisure-time physical activity should be encouraged among adolescents in order to improve coronary risk profiles. Similar observations have been reported in other European studies. In the Amsterdam Growth and Health Study [81], 181 13-year-old Dutch adolescents were followed over a 15 years. The daily physical activity and fitness (both cardiopulmonary and neuromotor fitness) have been measured with six repeated times during the period. They found that daily physical activity was positively related to high-density lipoprotein cholesterol, and inversely to the total cholesterol/highdensity lipoprotein ratio and to the sum of four skinfolds. Additionally, cardiopulmonary fitness was inversely associated with the total cholesterol. Neuromotor fitness was inversely associated with the sum of four skinfolds, and positively to systolic blood pressure. The authors stated that during adolescence and young adulthood both daily physical activity and fitness were related to a healthy coronary heart disease risk profile.

There are two recent studies for extending the Cardiovascular Risk in Young Finns Study. Yang et al. [82] followed 1 319 boys and girls (ages 9–18 years) from five Finnish university towns and their rural surroundings from 1980 to 2001. Leisure-time physical activity was assessed by a short self-report questionnaire. The results indicated that youth physical activity predicted adult physical activity in men (R2 = 0.10) and women (R2 = 0.03), which, in turn, predicted waist circumference in adulthood. Youth body mass index was directly related to waist circumference in adulthood in both sexes. The models were significant explaining 19% of variance of abdominal obesity in men and 13% in women. Also, youth physical activity was indirectly associated with waist circumference in adulthood through

occur in children and adolescents. Most studies have found that objectively measured physical activity and cardiorespiratory fitness are inversely associated with clustered metabolic risk score in children and adolescents, while some have shown that physical activity in adolescents does not result in significantly reduce the prevalence of metabolic syndrome when cardiorespiratory fitness is adjusted for in the analysis. A question which remains unanswered, however, is how much physical activity is needed to prevent the metabolic syndrome and the diseases with which it is associated. Also, the clustered metabolic risk score has been applied in these studies, but no clear definition of the metabolic syndrome has been formally established for either children or adolescents.

**5. Early physical activity and fitness as a predictor of metabolic syndrome in** 

The mechanism behind the relationship between physical activity in childhood and adolescence and adult risk for the metabolic syndrome has been explored. Referring to the model including three possible paths from childhood physical activity to adulthood health presented by Blair et al. [80], one of the hypothetical paths is a direct connection from physical activity or physical fitness in youth to cardiovascular and metabolic health in adult life. In the Cardiovascular Risk in Young Finns Study [19], 961 participants aged 12-18 years from five cities of Finland were included and followed from 1980 to 1983 and 1986. Physical activity was assessed with a standardized questionnaire and then summed a physical activity index from its intensity, frequency and duration. The results showed that the change in physical activity over 6 years was inversely associated with changes in insulin and triglycerides among boys. Among girls, the change in physical activity did not make any independent contribution to the models for serum lipoproteins. It was concluded that participation in regular leisure-time physical activity should be encouraged among adolescents in order to improve coronary risk profiles. Similar observations have been reported in other European studies. In the Amsterdam Growth and Health Study [81], 181 13-year-old Dutch adolescents were followed over a 15 years. The daily physical activity and fitness (both cardiopulmonary and neuromotor fitness) have been measured with six repeated times during the period. They found that daily physical activity was positively related to high-density lipoprotein cholesterol, and inversely to the total cholesterol/highdensity lipoprotein ratio and to the sum of four skinfolds. Additionally, cardiopulmonary fitness was inversely associated with the total cholesterol. Neuromotor fitness was inversely associated with the sum of four skinfolds, and positively to systolic blood pressure. The authors stated that during adolescence and young adulthood both daily physical activity

Attention to these questions with further research is needed.

and fitness were related to a healthy coronary heart disease risk profile.

There are two recent studies for extending the Cardiovascular Risk in Young Finns Study. Yang et al. [82] followed 1 319 boys and girls (ages 9–18 years) from five Finnish university towns and their rural surroundings from 1980 to 2001. Leisure-time physical activity was assessed by a short self-report questionnaire. The results indicated that youth physical activity predicted adult physical activity in men (R2 = 0.10) and women (R2 = 0.03), which, in turn, predicted waist circumference in adulthood. Youth body mass index was directly related to waist circumference in adulthood in both sexes. The models were significant explaining 19% of variance of abdominal obesity in men and 13% in women. Also, youth physical activity was indirectly associated with waist circumference in adulthood through

**adulthood** 

both the maintenance of physical activity in adulthood and reducing body weight in youth. The path from youth physical activity to adult obesity through youth obesity seemed to be stronger than the path through adult physical activity. However, the level of youth physical activity did not predict adult abdominal obesity in either men or women (Figure 1). The authors concluded that the prevalence of abdominal obesity as defined by waist circumference during adulthood was directly related to adult physical activity and youth overall obesity in both sexes. Youth physical activity had an indirect effect on abdominal obesity through both the maintenance of physical activity in adulthood and reduction in body weight in youth. Participation in and maintaining physical activity from youth into adulthood might play an important role in reducing obesity in adulthood.

Fig. 1. Estimadtd parameters (stan dardized solution) in structural equation for males (females)

In another study by Yang et al. [83], 1 493 Finnish children and adolescents aged 3 to 18 years were followed over a 21-year period. Participation in sport-club training and competitions were assessed by use of a self-report physical activity questionnaire. Participants were divided into athletes and non-athletes at each measurement point (1980 and 1983), and then classified into four groups: persistent athlete, starter, leaver and nonathlete. A mean score of youth sport was assessed by calculating the average of four consecutive measurements (1980-1989). The metabolic syndrome in adulthood was defined as a categorical variable based on the guidelines of the European Group for the Study of Insulin resistance and as a continuous metabolic syndrome risk score by summing the zscores of individual metabolic variables. The results indicated that the mean score of youth sport across the four time points and covariate variables were simultaneously entered as predictors for the adult metabolic syndrome risk score. Mean youth sport level emerged as a significant predictor of the metabolic syndrome in men (*β* = -0.149, *P* = 0.001) and women (*β* = -0.118, *P* = 0.005). Furthermore, non-athletic males and females had a significantly higher prevalence of the metabolic syndrome in adulthood than persistent athletes (Table 3). The relationships remained significant after adjustment for age and baseline clustered metabolic risk scores. The adds ratios and 95% confidence intervals for non-athletic males and females were 2.94 (1.01–8.99) and 4.04 (1.18–13.85), respectively. After additional adjustment for adult leisure-time physical activity, the trend of the associations was the same but

Physical Activity, Physical Fitness and Metabolic Syndrome 173

followed over a 28-year period. Physical activity was assessed by means of a sports participation inventory in youth and the Tecumseh community health study questionnaire in adulthood. The results found that sports participation during adolescence was not related to levels of cardiovascular risk factors at 40 years of age. In the Danish Youth and Sport Study [85], 101 adolescents aged 15–19 years were followed over an 8-year period. Physical activity was assessed by a questionnaire including the number of hours per week of sports participation and physical education lessons. Physical fitness in terms of aerobic fitness was calculated asVO2max relative to body weight (ml/min/kg). It was showed that the relationships between the absolute levels of physical fitness and activity in adolescence and the subsequent level of CVD risk factors were generally weak. However, the changes in physical fitness and physical activity were related to the absolute levels of CVD risk factors in young adulthood, especially in men. A subsequent study conducted by the same investigators [86] reported similar results when a physical activity index was constructed from the intensity and duration of the organized and unorganized sports activities. The results showed that the youth sports activities and fitness were not associated with clustered risk in adulthood. The lack of significant associations could be due to methodological limitations such as small samples and assessment of physical activity based on self-reported

minutes spent on sports activities rather than objective measure to physical activity.

changes in physical activity decrease the metabolic risk for different lifespan.

physical activity in association with adulthood metabolic syndrome.

**adulthood** 

Moreover, future study is indicated in distinguishing between active and inactive on the adulthood risk of developing the metabolic syndrome. Future research is also need to develop and evaluate objective measures of physical activity (e.g., pedometers, accelerometers) in youth, define and measure the criteria of metabolic syndrome and clarify whether long-lasting

**6. Effect of change in physical activity and fitness on metabolic syndrome in** 

According to the model [80], the most probable path is from childhood physical activity to adult physical activity and further to adult metabolic health. This supported by the studies on tracking of physical activity [87–90], and also studies on the relationship between physical activity and metabolic syndrome in either youth or adults as has just been mentioned above. Another potential path is physical activity in youth through youth clustered metabolic risk to adult metabolic syndrome. This path is supported by the finding that physical activity and physical fitness correlate negatively with the metabolic risk in youth [49]. Further, metabolic risk variables, especially obesity, likely track rather well from childhood to adulthood [82,91]. Only a few prospective population-based studies have reported long-term physical activity in predicting the prevalence of metabolic syndrome over time and especially of changes in

Laaksonen et al. [92] followed a cohort of 612 middle-aged men in the Kuopio Ischemic Heart Disease Risk Factor Study over a 4-year follow-up period. Leisure-time physical activity was measured by a questionnaire with the dose calculated as MET-minutes per week. Physical activity was then grouped into three levels: low-intensity (< 4.5 METsmin/wk), moderate- and high intensity (≥ 4.5 METs-min/wk) and high-intensity physical activity (≥ 7.5 METs-min/wk). Cardiorespiratory fitness (VO2max, ml·kg-1·min-1) was divided into three levels: low (≤ 28.9), moderate (29.0–35.6) and high (≥ 35.7). Men with moderate and vigorous physical activity were significant lower prevalence of the metabolic syndrome than those with low physical activity. The odds ratios were 0.60 (0.37–0.99) for physical activity ≥ 4.5 METs (>3 h/wk vs. ≤60 min/wk) and 0.48 (0.29–0.77) for physical activity ≥ 7.5

significant difference between persistent athletic and non-athletic males disappeared. Those males who dropped out from organized sport during the 3 years had higher prevalence of the metabolic syndrome compared with persistently athletic counterparts. The difference remained significant after adjustment for age, baseline clustered metabolic risk scores and adult leisure-time physical activity (OR = 4.52, 95% CI = 1.29–15.84).

The mechanisms explaining the relationship between sport participation in youth and the prevalence of metabolic syndrome in adulthood are not well understood. One of the more obvious explanations can be that youth sport may reduce the risk of metabolic syndrome in youth, which then tracks into adulthood. However, the explanation is not clear because adjustment for youth clustered metabolic risk does not change the result. In addition, sustained youth sport seems to predict low prevalence of the metabolic syndrome in adulthood 21 years later independently of adult physical activity. It is possible that participation in organized youth sport may establish lifelong habits for good health that in turn reduces risk for the metabolic syndrome. Participation in sustained youth sport may also lead to improved cardiovascular function and physical fitness that carries over into adulthood. Furthermore, children and adolescents who want to maintain their athletic abilities may have better awareness of other health related habits such as diet, smoking and sedentary lifestyle, all of which have been found to be related to risk for the metabolic syndrome. Finally, selfselection and genetic factors shall be taken into account as possible explanations for the direct relationship between youth sport and adult health. Thus, intensive and sustained participation in youth sport may benefit adult cardiovascular health and prevent the development of metabolic syndrome. Organizers of youth sport may have a significant impact on public health by paying attention to the factors that increase adherence in youth sport.


1) 3-year follow-up youth sport: persistently athlete (did between 1980 and 1983); starter (did not in 1980 but did in 1983); leaver (did in 1980 but did not in 1983); and non-athlete (did in neither 1980 nor 1983). 2) Adjusted for baseline age, smoking, total caloric intake and baseline-clustered risk for metabolic syndrome.

3) Additionally adjusted for adult leisure-time physical activity. \* *p*< 0.05.

Table 3. Odds ratios for the prevalence of metabolic syndrome (European Group for the Study of Insulin Resistance) according to organized youth sport 1) over 3 years in boys and girls

Contrary to the expected beneficial effect, no association between the level of physical activity and the risk of metabolic syndrome was found. In the Leuven Longitudinal Study on Lifestyle, Fitness and Health [84], 166 Belgian adolescent boys aged 13–18 years were

significant difference between persistent athletic and non-athletic males disappeared. Those males who dropped out from organized sport during the 3 years had higher prevalence of the metabolic syndrome compared with persistently athletic counterparts. The difference remained significant after adjustment for age, baseline clustered metabolic risk scores and

The mechanisms explaining the relationship between sport participation in youth and the prevalence of metabolic syndrome in adulthood are not well understood. One of the more obvious explanations can be that youth sport may reduce the risk of metabolic syndrome in youth, which then tracks into adulthood. However, the explanation is not clear because adjustment for youth clustered metabolic risk does not change the result. In addition, sustained youth sport seems to predict low prevalence of the metabolic syndrome in adulthood 21 years later independently of adult physical activity. It is possible that participation in organized youth sport may establish lifelong habits for good health that in turn reduces risk for the metabolic syndrome. Participation in sustained youth sport may also lead to improved cardiovascular function and physical fitness that carries over into adulthood. Furthermore, children and adolescents who want to maintain their athletic abilities may have better awareness of other health related habits such as diet, smoking and sedentary lifestyle, all of which have been found to be related to risk for the metabolic syndrome. Finally, selfselection and genetic factors shall be taken into account as possible explanations for the direct relationship between youth sport and adult health. Thus, intensive and sustained participation in youth sport may benefit adult cardiovascular health and prevent the development of metabolic syndrome. Organizers of youth sport may have a significant impact on public health

adult leisure-time physical activity (OR = 4.52, 95% CI = 1.29–15.84).

by paying attention to the factors that increase adherence in youth sport.

3) Additionally adjusted for adult leisure-time physical activity. \* *p*< 0.05.

Boys

Girls

syndrome.

Group Unadjusted OR (CI) Adjusted OR (CI) 2) Adjusted OR (CI) 3)

Persistent athlete 1.00 1.00 1.00 Starter 1.62 0.45 – 5.80 1.49 0.39 – 5.71 1.55 0.41 – 5.85 Leaver 4.55 1.39 – 14.87\* 4.70 1.31 – 16.91\* 4.52 1.29 – 15.84\* Non-athlete 3.06 1.08 – 8.64\* 2.94 1.01 – 8.99\* 2.72 0.90 – 8.17

Persistent athlete 1.00 1.00 1.00 Starter 1.67 0.38 – 7.27 1.63 0.35 – 7.64 1.66 0.36 – 7.69 Leaver 2.24 0.60 – 8.35 1.98 0.47 – 8.30 1.57 0.38 – 6.44 Non-athlete 3.54 1.08 – 11.55\* 4.04 1.18 – 13.85\* 3.46 1.03 – 11.66\* 1) 3-year follow-up youth sport: persistently athlete (did between 1980 and 1983); starter (did not in 1980 but did in 1983); leaver (did in 1980 but did not in 1983); and non-athlete (did in neither 1980 nor 1983). 2) Adjusted for baseline age, smoking, total caloric intake and baseline-clustered risk for metabolic

Table 3. Odds ratios for the prevalence of metabolic syndrome (European Group for the Study of Insulin Resistance) according to organized youth sport 1) over 3 years in boys and girls

Contrary to the expected beneficial effect, no association between the level of physical activity and the risk of metabolic syndrome was found. In the Leuven Longitudinal Study on Lifestyle, Fitness and Health [84], 166 Belgian adolescent boys aged 13–18 years were followed over a 28-year period. Physical activity was assessed by means of a sports participation inventory in youth and the Tecumseh community health study questionnaire in adulthood. The results found that sports participation during adolescence was not related to levels of cardiovascular risk factors at 40 years of age. In the Danish Youth and Sport Study [85], 101 adolescents aged 15–19 years were followed over an 8-year period. Physical activity was assessed by a questionnaire including the number of hours per week of sports participation and physical education lessons. Physical fitness in terms of aerobic fitness was calculated asVO2max relative to body weight (ml/min/kg). It was showed that the relationships between the absolute levels of physical fitness and activity in adolescence and the subsequent level of CVD risk factors were generally weak. However, the changes in physical fitness and physical activity were related to the absolute levels of CVD risk factors in young adulthood, especially in men. A subsequent study conducted by the same investigators [86] reported similar results when a physical activity index was constructed from the intensity and duration of the organized and unorganized sports activities. The results showed that the youth sports activities and fitness were not associated with clustered risk in adulthood. The lack of significant associations could be due to methodological limitations such as small samples and assessment of physical activity based on self-reported minutes spent on sports activities rather than objective measure to physical activity.

Moreover, future study is indicated in distinguishing between active and inactive on the adulthood risk of developing the metabolic syndrome. Future research is also need to develop and evaluate objective measures of physical activity (e.g., pedometers, accelerometers) in youth, define and measure the criteria of metabolic syndrome and clarify whether long-lasting changes in physical activity decrease the metabolic risk for different lifespan.

#### **6. Effect of change in physical activity and fitness on metabolic syndrome in adulthood**

According to the model [80], the most probable path is from childhood physical activity to adult physical activity and further to adult metabolic health. This supported by the studies on tracking of physical activity [87–90], and also studies on the relationship between physical activity and metabolic syndrome in either youth or adults as has just been mentioned above. Another potential path is physical activity in youth through youth clustered metabolic risk to adult metabolic syndrome. This path is supported by the finding that physical activity and physical fitness correlate negatively with the metabolic risk in youth [49]. Further, metabolic risk variables, especially obesity, likely track rather well from childhood to adulthood [82,91]. Only a few prospective population-based studies have reported long-term physical activity in predicting the prevalence of metabolic syndrome over time and especially of changes in physical activity in association with adulthood metabolic syndrome.

Laaksonen et al. [92] followed a cohort of 612 middle-aged men in the Kuopio Ischemic Heart Disease Risk Factor Study over a 4-year follow-up period. Leisure-time physical activity was measured by a questionnaire with the dose calculated as MET-minutes per week. Physical activity was then grouped into three levels: low-intensity (< 4.5 METsmin/wk), moderate- and high intensity (≥ 4.5 METs-min/wk) and high-intensity physical activity (≥ 7.5 METs-min/wk). Cardiorespiratory fitness (VO2max, ml·kg-1·min-1) was divided into three levels: low (≤ 28.9), moderate (29.0–35.6) and high (≥ 35.7). Men with moderate and vigorous physical activity were significant lower prevalence of the metabolic syndrome than those with low physical activity. The odds ratios were 0.60 (0.37–0.99) for physical activity ≥ 4.5 METs (>3 h/wk vs. ≤60 min/wk) and 0.48 (0.29–0.77) for physical activity ≥ 7.5

Physical Activity, Physical Fitness and Metabolic Syndrome 175

and diabetes (OR = 0.68, 95%CI = 0.52–0.91) over 28 years when adjusted for age and educational attendance. However, these associations were markedly attenuated when

Yang et al. [97] followed six cohorts of 2 060 (961 males) young adults aged 24–39 years in the Young Finns Study. Leisure-time physical activity was assessed using a self-report questionnaire completed in connection with a medical examination at two consecutive measurements in 1992 and 2001. By summing the physical activity items, a physical activity index was formed for both measurement points according to which the participants were divided into tracking groups: persistently active, increasingly active, decreasingly active, and persistently inactive. The prevalence of the metabolic syndrome on all three definitions was significantly lower in men and women who were persistently active during the 9 yr of follow-up compared with persistently inactive ones. In men, the odds ratios and their 95% confidence intervals were 0.23 (0.11–0.49) for the European Group for the Study of Insulin Resistance (EGIR) criteria, 0.54 (0.31–0.93) for the National Cholesterol Education Program-Adult Treatment Panel III (NCEP) criteria, and 0.49 (0.29–0.83) for the International Diabetes Federation (IDF) criteria. In women, the odds ratios were 0.33 (0.12–0.94) for EGIR, 0.21 (0.06–0.67) for NCEP, and 0.27 (0.11–0.63) for IDF. Also, women who were increasingly active were less likely on all definitions to have the metabolic syndrome than their persistently inactive counterparts. The associations remained significant for EGIR (OR = 0.28, 95% CI = 0.09–0.92), NCEP (OR = 0.22, 95% CI = 0.07–0.73), and IDF (OR = 0.42, 95% CI = 0.19–0.94). All of these associations remained significant after adjustment for potential confounders such as age, smoking and education (Table 4). The authors concluded that

> NCEP-ATP III Adjusted OR (CI)

IDF Adjusted OR (CI)

additional adjusted for baseline clustered metabolic risks.

EGIR Adjusted OR (CI) 2)

Persistently inactive 1.00 1.00 1.00

Persistently inactive 1.00 1.00 1.00

Decreasingly active 0.69 0.41 – 1.15 0.99 0.62 – 1.57 1.07 0.69 – 1.65 Increasingly active 0.73 0.30 – 1.79 0.58 0.22 – 1.52 0.48 0.19 – 1.27 Persistently active 0.23 0.11 – 0.49\*\*\* 0.54 0.31 – 0.93\* 0.49 0.29 – 0.83\*\*

Decreasingly active 0.68 0.35 – 1.34 0.65 0.35 – 1.21 0.59 0.33 – 1.05 Increasingly active 0.28 0.09 – 0.92\* 0.22 0.07 – 0.73\* 0.42 0.19 – 0.94\* Persistently active 0.33 0.12 – 0.94\* 0.21 0.06 – 0.67\*\* 0.27 0.11 – 0.63\*\*

EGIR, European Group for the Study of Insulin Resistance; NCEP-ATP III, National Cholesterol

1)Physical activity groups: persistently inactive (inactive both in 1992 and 2001); decreasingly active (change 1992-2001 from active to inactive); increasingly active (change 1992-2001 from inactive to

Table 4. Adjusted odds ratios for three definitions of metabolic syndrome according to

education Program-Adult Treatment Panel III; IDF, International Diabetes Federation.

2) Adjusted for age, smoking and education. \* *p*< 0.05, \*\* *p*<0.01, \*\*\* *p*<0.001.

active); and persistently active (active both 1992 and 2001).

change in physical activity groups 1) over a 9-yr period

Group

Women

Men

METs after adjustment for major confounding variables (age, body mass index, smoking, alcohol, and socioeconomic status) or potentially mediating variables (insulin, glucose, lipids, and blood pressure), especially in high-risk men. Vigorous physical activity had an even stronger inverse association, particularly in unfit men. Men in the highest tertile of cardiorespiratory fitness were 75% less likely to develop the metabolic syndrome than men in the lowest tertile of cardiorespiratory fitness after adjustment for major confounders, but the association was attenuated after adjustment for possible mediating variables. it was included that physical activity and cardiorespiratory fitness predicted directly or indirectly the development of metabolic syndrome.

A randomized controlled trial was used to investigate the effectiveness of supervised aerobic exercise training in 105 participants with the metabolic syndrome before and after 20 weeks [93]. 30.5% (32 participants) of the participants were no longer classified as having the metabolic syndrome following exposure to a standardized 20-week exercise program. It was suggested that aerobic exercise training showed prolonged vigorous exercise programs and reduced substantially in those with the metabolic syndrome. Although limited by lack of a control group, this study supported that the effectiveness of aerobic exercise training could be useful as a treatment strategy in prevention of the metabolic syndrome. In their further study of the impact of cardiorespiratory fitness on the risk of metabolic syndrome, obesity and mortality among 19 173 American men aged 20–83 years, Katzmarzyk et al. [94] reported that the odds ratios and their 95% confidence intervals for having risks of all-cause mortality were 1.11 (0.75-1.17) in normal weight, 1.09 (0.82-1.47) in overweight, and 1.55 (1.14-2.11) in obese men with the metabolic syndrome, compared with normal weight healthy men. The corresponding risks for cardiovascular disease mortality were 2.06 (0.92- 4.63) in normal weight, 1.80 (1.10-2.97) in overweight, and 2.83 (1.70-4.72) in obese men with the metabolic syndrome, compared with normal weight healthy men. However, the risks of all-cause mortality associated with obesity and metabolic syndrome were no longer significant after adjustment for cardiorespiratory fitness, which suggested that these risks were largely explained by overall physical fitness levels.

In the Medical Research Council Ely Study [95], 605 (249 males) middle-aged adults in England were followed over the past 5.6 years. Physical activity energy expenditure was measured objectively by individually calibrated heart rate against energy expenditure and was then divided into quartiles: < 44 kJ/kgFFM/d, 44-70 kJ/kgFFM/d, 71-100 kJ/kgFFM/d, and > 100 kJ/kgFFM/d. Aerobic fitness was predicted from a submaximal exercise stress test. Physical activity energy expenditure predicted progression toward the metabolic syndrome after adjusting for sex, baseline age, smoking, socioeconomic status, follow-up time, and baseline phenotypes. The associations remained significant after additional adjustment for aerobic fitness. While the relationship between aerobic fitness and metabolic syndrome was attenuated after adjusting for physical activity. In a cohort of the Oslo study, Holme et al. [96] followed 6 410 Norwegian middle-aged men from 1972/3 to 2000 in the city of Oslo. Leisure-time physical activity was measured by a questionnaire to classify men into four groups as follows: sedentary/light (usually reading, watching television or other sedentary occupations at leisure), moderate (walking, bicycling or other forms of physical activity including walking or bicycling to and from the place of work and a Sunday walk totalling at least four hours a week), moderately vigorous (exercise, sports, heavy gardening and similar activities totalling at least 4 hours a week), and vigorous (hard training or competition sports regularly several times a week). Physical activity was a significant predictor of the prevalence of metabolic syndrome (OR = 0.65, 95%CI = 0.54–0.80)

METs after adjustment for major confounding variables (age, body mass index, smoking, alcohol, and socioeconomic status) or potentially mediating variables (insulin, glucose, lipids, and blood pressure), especially in high-risk men. Vigorous physical activity had an even stronger inverse association, particularly in unfit men. Men in the highest tertile of cardiorespiratory fitness were 75% less likely to develop the metabolic syndrome than men in the lowest tertile of cardiorespiratory fitness after adjustment for major confounders, but the association was attenuated after adjustment for possible mediating variables. it was included that physical activity and cardiorespiratory fitness predicted directly or indirectly

A randomized controlled trial was used to investigate the effectiveness of supervised aerobic exercise training in 105 participants with the metabolic syndrome before and after 20 weeks [93]. 30.5% (32 participants) of the participants were no longer classified as having the metabolic syndrome following exposure to a standardized 20-week exercise program. It was suggested that aerobic exercise training showed prolonged vigorous exercise programs and reduced substantially in those with the metabolic syndrome. Although limited by lack of a control group, this study supported that the effectiveness of aerobic exercise training could be useful as a treatment strategy in prevention of the metabolic syndrome. In their further study of the impact of cardiorespiratory fitness on the risk of metabolic syndrome, obesity and mortality among 19 173 American men aged 20–83 years, Katzmarzyk et al. [94] reported that the odds ratios and their 95% confidence intervals for having risks of all-cause mortality were 1.11 (0.75-1.17) in normal weight, 1.09 (0.82-1.47) in overweight, and 1.55 (1.14-2.11) in obese men with the metabolic syndrome, compared with normal weight healthy men. The corresponding risks for cardiovascular disease mortality were 2.06 (0.92- 4.63) in normal weight, 1.80 (1.10-2.97) in overweight, and 2.83 (1.70-4.72) in obese men with the metabolic syndrome, compared with normal weight healthy men. However, the risks of all-cause mortality associated with obesity and metabolic syndrome were no longer significant after adjustment for cardiorespiratory fitness, which suggested that these risks

In the Medical Research Council Ely Study [95], 605 (249 males) middle-aged adults in England were followed over the past 5.6 years. Physical activity energy expenditure was measured objectively by individually calibrated heart rate against energy expenditure and was then divided into quartiles: < 44 kJ/kgFFM/d, 44-70 kJ/kgFFM/d, 71-100 kJ/kgFFM/d, and > 100 kJ/kgFFM/d. Aerobic fitness was predicted from a submaximal exercise stress test. Physical activity energy expenditure predicted progression toward the metabolic syndrome after adjusting for sex, baseline age, smoking, socioeconomic status, follow-up time, and baseline phenotypes. The associations remained significant after additional adjustment for aerobic fitness. While the relationship between aerobic fitness and metabolic syndrome was attenuated after adjusting for physical activity. In a cohort of the Oslo study, Holme et al. [96] followed 6 410 Norwegian middle-aged men from 1972/3 to 2000 in the city of Oslo. Leisure-time physical activity was measured by a questionnaire to classify men into four groups as follows: sedentary/light (usually reading, watching television or other sedentary occupations at leisure), moderate (walking, bicycling or other forms of physical activity including walking or bicycling to and from the place of work and a Sunday walk totalling at least four hours a week), moderately vigorous (exercise, sports, heavy gardening and similar activities totalling at least 4 hours a week), and vigorous (hard training or competition sports regularly several times a week). Physical activity was a significant predictor of the prevalence of metabolic syndrome (OR = 0.65, 95%CI = 0.54–0.80)

the development of metabolic syndrome.

were largely explained by overall physical fitness levels.

and diabetes (OR = 0.68, 95%CI = 0.52–0.91) over 28 years when adjusted for age and educational attendance. However, these associations were markedly attenuated when additional adjusted for baseline clustered metabolic risks.

Yang et al. [97] followed six cohorts of 2 060 (961 males) young adults aged 24–39 years in the Young Finns Study. Leisure-time physical activity was assessed using a self-report questionnaire completed in connection with a medical examination at two consecutive measurements in 1992 and 2001. By summing the physical activity items, a physical activity index was formed for both measurement points according to which the participants were divided into tracking groups: persistently active, increasingly active, decreasingly active, and persistently inactive. The prevalence of the metabolic syndrome on all three definitions was significantly lower in men and women who were persistently active during the 9 yr of follow-up compared with persistently inactive ones. In men, the odds ratios and their 95% confidence intervals were 0.23 (0.11–0.49) for the European Group for the Study of Insulin Resistance (EGIR) criteria, 0.54 (0.31–0.93) for the National Cholesterol Education Program-Adult Treatment Panel III (NCEP) criteria, and 0.49 (0.29–0.83) for the International Diabetes Federation (IDF) criteria. In women, the odds ratios were 0.33 (0.12–0.94) for EGIR, 0.21 (0.06–0.67) for NCEP, and 0.27 (0.11–0.63) for IDF. Also, women who were increasingly active were less likely on all definitions to have the metabolic syndrome than their persistently inactive counterparts. The associations remained significant for EGIR (OR = 0.28, 95% CI = 0.09–0.92), NCEP (OR = 0.22, 95% CI = 0.07–0.73), and IDF (OR = 0.42, 95% CI = 0.19–0.94). All of these associations remained significant after adjustment for potential confounders such as age, smoking and education (Table 4). The authors concluded that


EGIR, European Group for the Study of Insulin Resistance; NCEP-ATP III, National Cholesterol education Program-Adult Treatment Panel III; IDF, International Diabetes Federation.

1)Physical activity groups: persistently inactive (inactive both in 1992 and 2001); decreasingly active (change 1992-2001 from active to inactive); increasingly active (change 1992-2001 from inactive to active); and persistently active (active both 1992 and 2001).

2) Adjusted for age, smoking and education. \* *p*< 0.05, \*\* *p*<0.01, \*\*\* *p*<0.001.

Table 4. Adjusted odds ratios for three definitions of metabolic syndrome according to change in physical activity groups 1) over a 9-yr period

Physical Activity, Physical Fitness and Metabolic Syndrome 177

[2] J.C. Eisenmann, "Secular trends in variables associated with the metabolic syndrome of

[3] M.L. Cruz and M.I. Goran, "The metabolic syndrome in children and adolescents," *Curr.* 

[4] N. Mattsson, T. Rönnemaa, M. Juonala, J.S. Viikari and O.T. Raitakari, "The prevalence of

[5] G. Hu, J. Lindström, P. Jousilahti, M. Peltonen, L. Sjöberg, R. Kaaja, J. Sundvall and J.

[6] C.G. Spain and B.D. Franks, "Healthy people 2010: Physical activity and fitness.

[7] J.R. Churilla and R.F. Zoeller Jr, "Physical activity and the metabolic syndrome: A review of the evidence," *Am. J. Lifestyle Med.* vol. 2, no. 2, pp. 118.–125, Mar/Apr. 2008. [8] S. Carroll and M. Dudfield, "What is the relationship between exercise and metabolic

[9] C. J. Caspersen, K. E. Powell, and G. M. Christenson, "Physical activity, exercise, and

[10] "Third report of the National Cholesterol Education Program (NCEP) Expert Panel on

[11] World Health Organization, "Definition diagnosis and classification of diabetes mellitus

[12] B. Balkau, M.A. Charles, T. Drivsholm, K. Borch-Johnsen, N. Wareham, J.S. Yudkin, R.

Study of Insulin Resistance (EGIR)," *Diabetes Metab*. 28, pp. 364.–376, 2002. [13] S.M. Grundy, J.I. Cleeman, S.R. Daniels, K.A. Donato, R.H. Eckel, B.A. Franklin, D.J.

[14] G. Alberti Sir, P. Zimmet, J. Shaw and S.M. Grundy, "The IDF consensus worldwide

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3full.pdf.

http://www.staff.ncl.ac.uk/philip.home/who\_dmg.pdf.

*Opin Cardiol.* vol. 21, no. 1, pp. 1.–6, Jan. 2006.

definition of the metabolic syndrome," Available at:

Study," *J. Intern. Med*. vol. 261, no. 2, pp. 159.–169, Feb. 2007.

*and Sport Research Digest.* vol. 3, no. 13, pp. 1.–16, Mar. 2001.

*health Rep*. vol. 100, no. 2, pp. 126.–131, Mar-Apr. 1985.

vol. 15, no. 6, pp. 786.–794, Nov-Dec. 2003.

*Diab. Rep*. vol. 4, no.1, pp. 53.–62, Feb. 2004.

836, Mar. 2008.

371.–418, 2004.

5215, Sep. 2002. Available at:

North American children and adolescent: a review and synthesis," *Am. J. Hum. Biol*.

the metabolic syndrome in young adults. The Cardiovascular Risk in Young Finns

Tuomilehto, "The increasing prevalence of metabolic syndrome among Finnish men and women over a decade," *J. Clin. Endocrinol. Metab*. vol. 93, no. 3, pp. 832.–

President's Council Physical Fitness Sport," *President's Council on Physical Fitness* 

abnormalities? A review of the metabolic syndrome," *Sports Med.* vol. 34, no. 6, pp.

physical fitness: definitions and distinctions for health-related research," *Public* 

Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Final report", *National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health*. NIH publication No. 02-

and its complications. Report of a WHO Consultation. Part 1: diagnosis and classification of diabetes mellitus," World Health Organization, Department of Noncommunicable Disease Surveillance, Geneva, 1999. Available at:

Morris, I. Zavaroni, R. van Dam, E. Feskins, R. Gabriel, M. Diet, P. Nilsson and B. Hedblad, "Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. European Group for the

Gordon, R.M. Krauss, P.J. Savage, S.C. Smith Jr, J.A. Spertus and F. Costa, "Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement," *Curr.* 

maintaining a high level of physical activity across the life span might decrease the prevalence of the metabolic syndrome not only in the short term but also in the long term. Individuals should be encouraged to participate in regular physical activity as early as possible to prevent the risk of developing the metabolic syndrome and related adult-onset diabetes and cardiovascular diseases.

## **7. Conclusion**

Outlined in this chapter is a brief overview of leisure-time physical activity, cardiorespiratory fitness and muscular strength which focus is on prevention and intervention of the prevalence of the metabolic syndrome in youth and adulthood. In addition, there is a brief summarizes on maintaining regular physical activity and aerobic exercise over time focused on the metabolic syndrome in adulthood.

It is worth highlighting that regular leisure-time physical activity, endurance training, and strength training are critically important for prevention of the metabolic syndrome and its components in both early life and later life. Evidence is beginning to accumulate in the epidemiological literature which suggests that participation in regular aerobic and strength exercises, particularly when combined with moderate- or vigorous-intensity activity may alter all metabolic risk factors. Leisure-time physical activity is an effective intervention or modulation to improve cardiovascular functional capacity and prevent or delay the development of metabolic syndrome, which in turn maintains health status and reduces the incidence of diabetes and cardiovascular diseases. According to the recommendations of the American College of Sports medicine and the American Heart Association, all adults shall participate in accumulated moderate-intensity physical activity during leisure time for a minimum of 30 minutes or more on 5 days per week or vigorous intensity activity for a minimum of 20 minutes on 3 days per week [42]. It may be that the combination of reductions in energy intake and increases in energy expenditure, through structured exercise and other forms of physical activity, is one of the most effective way to prevent or delay the development of metabolic syndrome over time. This chapter focuses mainly on physical activity and aerobic exercise during leisure time related the prevalence of metabolic syndrome, however there is limited literature relating to specific sport activities, workrelated physical activity, commuting physical activity and household physical activity. Emphasis will be placed on the impact of these activities in the future.

## **8. Acknowledgments**

This study was financially supported by the Academy of Finland (grants no. 77841, 210283, 123621 [L.P.-R.], 121584, 124282), Social Insurance Institution of Finland, Ministry of Education, Turku University Foundation, Special Federal Grants for Turku University Hospital, Research Funds of the University of Helsinki (project no 2106012 [L.P.-R.], Juho Vainio Foundation, Finnish Foundation of Cardiovascular Research, Emil Aaltonen Foundation (M.H.), Finnish Medical Foundation, Finnish Cultural Foundation, Yrjö Jahnsson Foundation, and Signe and Ane Gyllenberg Foundation (M.H.).

## **9. References**

[1] E.S. Ford, "Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence," *Diabetes Care*. vol. 28, no. 7, pp. 1769.–1778, Jul. 2005.

maintaining a high level of physical activity across the life span might decrease the prevalence of the metabolic syndrome not only in the short term but also in the long term. Individuals should be encouraged to participate in regular physical activity as early as possible to prevent the risk of developing the metabolic syndrome and related adult-onset

Outlined in this chapter is a brief overview of leisure-time physical activity, cardiorespiratory fitness and muscular strength which focus is on prevention and intervention of the prevalence of the metabolic syndrome in youth and adulthood. In addition, there is a brief summarizes on maintaining regular physical activity and aerobic

It is worth highlighting that regular leisure-time physical activity, endurance training, and strength training are critically important for prevention of the metabolic syndrome and its components in both early life and later life. Evidence is beginning to accumulate in the epidemiological literature which suggests that participation in regular aerobic and strength exercises, particularly when combined with moderate- or vigorous-intensity activity may alter all metabolic risk factors. Leisure-time physical activity is an effective intervention or modulation to improve cardiovascular functional capacity and prevent or delay the development of metabolic syndrome, which in turn maintains health status and reduces the incidence of diabetes and cardiovascular diseases. According to the recommendations of the American College of Sports medicine and the American Heart Association, all adults shall participate in accumulated moderate-intensity physical activity during leisure time for a minimum of 30 minutes or more on 5 days per week or vigorous intensity activity for a minimum of 20 minutes on 3 days per week [42]. It may be that the combination of reductions in energy intake and increases in energy expenditure, through structured exercise and other forms of physical activity, is one of the most effective way to prevent or delay the development of metabolic syndrome over time. This chapter focuses mainly on physical activity and aerobic exercise during leisure time related the prevalence of metabolic syndrome, however there is limited literature relating to specific sport activities, workrelated physical activity, commuting physical activity and household physical activity.

This study was financially supported by the Academy of Finland (grants no. 77841, 210283, 123621 [L.P.-R.], 121584, 124282), Social Insurance Institution of Finland, Ministry of Education, Turku University Foundation, Special Federal Grants for Turku University Hospital, Research Funds of the University of Helsinki (project no 2106012 [L.P.-R.], Juho Vainio Foundation, Finnish Foundation of Cardiovascular Research, Emil Aaltonen Foundation (M.H.), Finnish Medical Foundation, Finnish Cultural Foundation, Yrjö

[1] E.S. Ford, "Risks for all-cause mortality, cardiovascular disease, and diabetes associated

with the metabolic syndrome: a summary of the evidence," *Diabetes Care*. vol. 28,

exercise over time focused on the metabolic syndrome in adulthood.

Emphasis will be placed on the impact of these activities in the future.

Jahnsson Foundation, and Signe and Ane Gyllenberg Foundation (M.H.).

no. 7, pp. 1769.–1778, Jul. 2005.

diabetes and cardiovascular diseases.

**7. Conclusion** 

**8. Acknowledgments** 

**9. References** 


http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3full.pdf.


Physical Activity, Physical Fitness and Metabolic Syndrome 179

[29] M.L. Irwin, B.E. Ainsworth, E.J. Mayer-Davis, C.L. Addy, R.R. Pate and J.L. Durstine,

[30] S.W. Farrell, Y.J. Cheng and S.N. Blair, "Prevalence of the metabolic syndrome across

[31] M.H. Whaley, J.B. Kampert, H.W. 3rd, Kohl and S.N. Blair, "Physical fitness and

[32] P.W. Franks, U. Ekelund, S. Brage, M.Y. Wong and N.J. Wareham, "Does the association

Australian adults," *Diabetologia*. vol. 48, no. 11, pp. 2254.–2261, Oct. 2005. [34] M. Halldin, M. Rosell, U. de Faire, M.L. Hellenius, "The metabolic syndrome:

[35] Y.W. Park, S. Zhu, L. Palaniappan, S. Heshka, M.R. Carnethon and S.B. Heymsfield,

[37] R.R. Pate, M. Pratt, S.N. Blair, W.L. Haskell, C.A. Macera, C. Bouchard, D. Buchner, W.

[38] E.S. Ford, H.W. 3rd Kohl, A.H. Mokdad, U.A. Ajani, "Sedentary behavior, physical

[39] J.R. Churilla and E.C. Fitzhugh, "Relationship between leisure-time physical activity

[40] B.E. Ainsworth BE, W.L. Haskell, M.C. Whitt, M.L. Irwin, A.M. Swartz, S.J. Strath, W.L.

*Vasc. Dis. Res*. vol. 6, no. 2, pp. 100.–109, Apr. 2009.

1988-1994," *Arch. Intern. Med.* vol. 163, no. 4, pp. 427.–436, Feb. 2003. [36] K.D. DuBose, C.L. Addy, B.E. Ainsworth, G.A. Hand and J.L. Durstine, "The

*Am. J. Hum. Biol*. vol. 19, no. 4, pp. 544.–550, Jul-Aug. 2007.

*Obes. Res*. vol. 10, no. 10, pp. 1030.–1037, Oct. 2002.

*Exerc*. vol. 31, no. 2, pp. 287.–293, Feb. 1999.

May. 2004.

Mar. 2007.

1995.

no. 4, pp. 470.–487, Oct. 2005.

pp. 608.–614, Mar. 2005.

adulthood metabolic syndrome and physical activity: the Fels longitudinal study,"

"Physical activity and the metabolic syndrome in a tri-ethnic sample of women,"

cardiorespiratory fitness levels in women," *Obes. Res*. vol. 12, no. 5, pp. 824.–830,

clustering of risk factors associated with the metabolic syndrome," *Med. Sci. Sports* 

of habitual physical activity with the metabolic syndrome differ by level of cardiorespiratory fitness?" *Diabetes Care*. vol. 27, no. 5, pp. 1187.–1193, May. 2004. [33] D.W. Dunstan, J. Salmon, N. Owen, T. Armstrong, P.Z. Zimmet, T.A. Welborn, A.J.

Cameron, T. Dwyer, D. Jolley, J.E. Shaw and AusDiab Steering Committee, "Associations of TV viewing and physical activity with the metabolic syndrome in

prevalence and association to leisure-time and work-related physical activity in 60 year-old men and women," *Nutr. Metab. Cardiovasc. Dis*. vol. 17, no. 5, pp. 349.–357,

"The metabolic syndrome: Prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey,

relationship between leisure-time physical activity and the metabolic syndrome: an examination of NHANES III, 1988-1994," *Journal of Physical Activity & Health*. vol. 2,

Ettinger, G.W. Heath, A.C. King, et al., "Physical activity and public health. A recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine," *JAMA*. vol. 273, no. 5, pp. 402.–407, Feb.

activity, and the metabolic syndrome among U.S. adults," *Obes. Res*. vol. 13, no. 3,

and metabolic syndrome using varying definitions: 1999-2004 NHANES," *Diab.* 

O'Brien, D.R. Bassett Jr, K.H. Schmitz, P.O. Emplaincourt, D.R. Jacobs Jr and A.S. Leon, "Compendium of physical activities: an update of activity codes and MET intensities," *Med. Sci. Sports Exerc.*, vol. 32, Suppl 9, pp. S498.–S504, Sep. 2000.

http://www.idf.org/webdata/docs/IDF\_Meta\_def\_final.pdf. International Diabetes Federation, 2006.


http://www.idf.org/webdata/docs/IDF\_Meta\_def\_final.pdf. International

[15] E.S. Ford, "Prevalence of the metabolic syndrome defined by the International Diabetes

[16] P.M. Nilsson, G. Engström and B. Hedblad, "The metabolic syndrome and incidence of

[17] S.A. Paluska and T.L. Schwenk, "Physical activity and mental health: current concepts,"

[18] P. Ekkekakis, E.E. Hall and S.J. Petruzzello, "Variation and homogeneity in affective

[19] O.T. Raitakari, K.V. Porkka, S. Taimela, R. Telama, L. Räsänen and J.S. Viikari, "Effects

[20] S. Zhu, M.P. St-Onge, S. Heshka and S.B. Heymsfield, "Lifestyle behaviors associated

[21] L.E. Robinson and T.E. Graham, "Metabolic syndrome, a cardiovascular disease risk

[22] S. Carroll, C.B. Cooke and R.J. Butterly, "Metabolic clustering, physical activity and

[23] T.A. Lakka, D.E. Laaksonen, H.M. Lakka, N. Männikkö, L.K. Niskanen, R. Rauramaa

[24] K.L. Rennie, N. McCarthy, S. Yazdgerdi, M. Marmot and E. Brunner, "Association of the

[25] P.T. Katzmarzyk, T.S. Church and S.N. Blair, "Cardiorespiratory fitness attenuates the

[27] S.E. Brien and P.T. Katzmarzyk, "Physical activity and the metabolic syndrome in Canada," *Appl. Physiol. Nutr. Metab.* vol. 31, no. 1, pp. 40.–47, Feb. 2006. [28] K.E. Remsberg, N.L. Rogers, E.W. Demerath, S.A. Czerwinski, A.C. Choh, M. Lee, W.C.

in men," *Arch. Intern. Med*. vol. 164, no. 10, pp. 1092.–1097, May. 2004. [26] N.G. Boule, C. Bouchard and A. Tremblay, "Physical fitness and the metabolic

*Sports Med*. vol. 29, no. 3, pp. 167.–180, Mar. 2000.

*Epidemiol*. vol. 140, no. 3, pp. 195.–205, Aug. 1994.

*Physiol*. vol. 29, no. 6, pp. 808.–829, Dec. 2004.

*Epidemiol*. vol. 32, no. 4, pp. 600.–606, Aug. 2003.

Federation among adults in the U.S.," *Diabetes Care*. vol. 28, no. 11, pp. 2745.–2749,

cardiovascular disease in non-diabetic subjects--a population-based study comparing three different definitions," *Diabet. Med*. vol. 24, no. 5, pp. 464.–472,

responses to physical activity of varying intensities: an alternative perspective on dose-response based on evolutionary considerations," *J. Sport Sci*. vol. 23, no. 5, pp.

of persistent physical activity and inactivity on coronary risk factors in children and young adults. The Cardiovascular Risk in Young Finns Study". *Am. J.* 

with lower risk of having the metabolic syndrome," *Metabolism*. vol. 53, no. 11, pp.

factor: role of adipocytokines and impact of diet and physical activity," *Can. J. Appl.* 

fitness in nonsmoking, middle-aged men," *Med. Sci. Sports Exerc.* vol. 32, no. 12, pp.

and J.T. Salonen, "Sedentary lifestyle, poor cardiorespiratory fitness, and the metabolic syndrome," *Med. Sci. Sports Exerc*. vol. 35, no. 8, pp. 1279.–1286, Aug.

metabolic syndrome with both vigorous and moderate physical activity," *Int. J.* 

effects of the metabolic syndrome on all-cause and cardiovascular disease mortality

syndrome in adults from the Quebec family study," *Can. J. Appl. Physiol.* vol. 30, no.

Chumlea, S.S. Sun, B. Towne and R.M. Siervogel, "Sex differences in young

Diabetes Federation, 2006.

Nov. 2005.

May. 2007.

477.–500, May. 2005.

1503.–1511, Nov. 2004.

2079.–2086, Dec. 2000.

2, pp. 140.–156, Apr. 2005.

2003.

adulthood metabolic syndrome and physical activity: the Fels longitudinal study," *Am. J. Hum. Biol*. vol. 19, no. 4, pp. 544.–550, Jul-Aug. 2007.


Physical Activity, Physical Fitness and Metabolic Syndrome 181

[55] L.B. Andersen, M. Harro, L.B. Sardinha, K. Froberg, U. Ekelund, S. Brage and S.A.

[56] S. Brage, N. Wedderkopp, U. Ekelund, P.W. Franks, N.J. Wareham, L.B. Andersen and

*Int. J. Obes. Relat. Metab. Disord.* vol. 28, no. 11, pp. 1503.–1508, Nov. 2004. [57] N.F. Butte, M.R. Puyau, A.L. Adolph, F.A. Vohra and I. Zakeri, "Physical activity in

[58] U. Ekelund, S. Brage, P.W. Froberg, M. Harro, S.A. Anderssen, L.B. Sardinha, C.

[59] U. Ekelund, S.A. Anderssen, K. Froberg, L.B. Sardinha, L.B. Andersen, S. Brage and

[61] S.A. Anderssen, A.R. Cooper, C. Riddoch, L.B. Sardinha, M. Harro, S. Brage and L.B.

sex," *Eur. J. Cardiovasc. Prev. Rehabil.* vol. 14, no. 4, pp. 526.–531, Aug. 2007. [62] E. Garcia-Artero, F.B. Ortega, J.R. Ruiz, J.L. Mesa, M. Delgado, M. González-Gross, M.

activity (AVENA study)," *Rev. Esp. Cardiol*. vol. 60, no. 6, pp. 581.–588, 2007. [63] I. Janssen and W.C. Cramp, "Cardiorespiratory fitness is strongly related to the

[64] J.R. Ruiz, F.B. Ortega, N.S. Rizzo, I. Villa, A. Hurtig-Wennlöf, L. Oja and M. Sjöström,

[65] G.Q. Shaibi, M.L. Cruz, G.D. Ball, M.J. Weigensberg, H.A. Kobaissi, G.J. Salem and M.I.

youths," *Med. Sci. Sports Exerc*. vol. 37, no. 6, pp. 922.–928, Jun. 2005. [66] U. Ekelund, S. Anderssen, L.B. Andersen, C.J. Riddoch, L.B. Sardinha, J. Luan, K.

youth heart study," *Diabetologia*. vol. 50, no. 9, pp. 1832.–1840, Jul. 2007. [60] N.S. Rizzo, J.R. Ruiz, A. Hurtig-Wennlof, F.B. Ortega and M. Sjöström, "Relationship of

*Exerc.* vol. 39, no. 8, pp. 1257.–1266, Aug. 2007.

*Med.* vol. 3, no. 12, pp. e488, Dec. 2006.

pp. 299.–304, Jul. 2006.

394, Apr. 2007.

Aug. 2007.

90.–96, Jan. 2009.

2007.

Anderssen, "Physical activity and clustered cardiovascular risk in children: a crosssectional study (The European Youth Heart Study)," *Lancet*. vol. 22, no. 368(9532),

F. Froberg, "Objectively measured physical activity correlates with indices of insulin resistance in Danish children. The European Youth Heart Study (EYHS),"

nonoverweight and overweight Hispanic children and adolescents," *Med. Sci. Sport* 

Riddoch and L.B. Andersen, "TV viewing and physical activity are independently associated with metabolic risk in children: the European Youth Heart Study," *PLoS* 

European Youth Heart Study Group, "Independent associations of physical activity and cardiorespiratory fitness with metabolic risk factors in children: the European

physical activity, fitness, and fatness with clustered metabolic risk in children and adolescents: the European youth heart study," *J. Pediatr*. vol. 150, no. 4, pp. 388.–

Andersen, "Low cardiorespiratory fitness is a strong predictor for clustering of cardiovascular disease risk factors in children independent of country, age and

García-Fuentes, G. Vicente-Rodríguez, A. Gutiérrez and M.J. Castillo, "Lipid and metabolic profiles in adolescents are affected more by physical fitness than physical

metabolic syndrome in adolescents," *Diabetes Care*. vol. 30, no. 8, pp. 2143.–2144,

"High cardiovascular fitness is associated with low metabolic risk score in children: the European Youth Heart Study," *Pediatr. Res*. vol. 61, no. 3, pp. 350.–355, Mar.

Goran, "Cardiovascular fitness and the metabolic syndrome in overweight latino

Froberg and S. Brage, "Prevalence and correlates of the metabolic syndrome in a population-based sample of European youth," *Am. J. Clin. Nutr.* vol. 89, no. 1, pp.


[41] E.T. Howley, "Type of activity: resistance, aerobic and leisure versus occupational

[42] W.L. Haskell, I.M. Lee, R.R. Pate, K.E. Powell, S.N. Blair, B.A. Franklin, C.A. Macera,

[43] S.E. Brien, I. Janssen and P.T. Katzmarzyk, "Cardiorespiratory fitness and metabolic

[44] R. Jurca, M.J. Lamonte, T.S. Church, C.P. Earnest, S.J. Fitzgerald, C.E. Barlow, A.N.

[45] R. Jurca, M.J. Lamonte, C.E. Barlow, J.B. Kampert, T.S. Church and S.N. Blair,

[46] K. Wijndaele, N. Duvigneaud, L. Matton, W. Duquet, M. Thomis, G. Beunen, J. Lefevre

[47] K. Froberg and L.B. Andersen, "Mini review: Physical activity and fitness and its

[48] J.C. Eisenmann, "Aerobic fitness, fatness and the metabolic syndrome in children and adolescents," *Acta Pediatric.* vol. 96, no. 12, pp. 1723.–1729, Oct. 2007. [49] R.M. Steele, S. Brage, K. Corder, N.J. Wareham and U. Ekelund, "Physical activity,

[50] P. Brambilla, G. Pozzobon and A. Pietrobelli, "Physical activity as the main therapeutic

[51] J.C. Eisenmann, P.T. Katzmarzyk, L. Perusse, A. Tremblay, J.P. Despres and C.

[52] J.C. Eisenmann, G.J. Welk, E.E. Wickel and S.N. Blair, "Combined influence of

[53] J.C. Eisenmann, G.J. Welk, M.A. Ihmel and J. Dollman, "Fitness, fatness and

[54] K.D. DuBose, J.C. Eisenmann and J.E. Donnelly, "Aerobic fitness attenuates the

overweight children," *Pediatrics*. vol. 120, no. 5, pp. e1262.–e1268, Nov. 2007.

*Physiol. Nutr. Metab.* vol. 32, no. 1, pp. 143.–147, Feb. 2007.

*Med. Sci. Sports Exerc*. vol. 37, no. 11, pp. 1849.–1855, Nov. 2005.

(discussion S419.–S420).

1301.–1307, Aug. 2004.

2, pp. S34.–S39, Sep. 2005.

vol. 105, no. 1, pp. 342.–351, Jul. 2008.

*Pediatr. Obes*. vol. 2, no. 2, pp. 66.–72, 2007.

*Exerc*. vol. 39, no. 8, pp. 1251.–1256, Aug. 2007.

published online 7 Dec. 2010.

Sep. 2005.

physical activity," *Med. Sci. Sports Exerc.* vol. 33, Suppl 6, pp. S364.–S369, Jun. 2001

G.W. Heath, P.D. Thompson, A. Bauman, American College of Sports Medicine and American Heart Association, "Physical activity and public health: updated recommendation for adults form the American College of Sports medicine and the American Heart Association," *Circulation.* vol. 116, no. 9, pp. 1081.–1093, Aug. 2007.

syndrome: US National Health and Nutrition Examination Survey 1999-2002," *Appl.* 

Jordan, J.B. Kampert and S.N. Blair, "Associations of muscle strength and aerobic fitness with metabolic syndrome in men," *Med. Sci. Sports Exerc*. vol. 36, no. 8, pp.

"Associations of muscle strength with incidence of metabolic syndrome in men,"

and R.M. Philippaerts, "Muscular strength, aerobic fitness, and metabolic syndrome risk in Flemish adults," *Med. Sci. Sports Exerc*. vol. 39, no. 2, pp. 233.–240, Feb. 2007.

relation to cardiovascular disease risk factors in children," *Int. J. Obes*. vol. 29, Suppl

cardiorespiratory fitness, and the metabolic syndrome in youth," *J. Appl. Physiol*.

tool for metabolic syndrome in childhood," *Int. J. Obes*. vol. 35, pp. 16.–28, 2011;

Bouchard, "Aerobic fitness, body mass index and CVD risk factors among adolescents: the Quebec Family Study," *Int. J. Obes*. vol. 29, no. 9, pp. 1077.–1083,

cardiorespiratory fitness and body mass index on cardiovascular disease risk factors among 8–18 year old youth: The Aerobics Center Longitudinal Study," *Int. J.* 

cardiovascular disease risk factors in children and adolescents," *Med. Sci. Sports* 

metabolic syndrome score in normal-weight, at-risk-for-overweight, and


Physical Activity, Physical Fitness and Metabolic Syndrome 183

[80] S.N. Blair, G.G. Clark and K.J. Cureton, "Exercise and fitness in childhood: implications

[81] J.W.R. Twisk, H.C.G. Kemper and W. van Mechelen, "Tracking of activity and fitness

[82] X. Yang, R. Telama, E. Leskinen, K. Mansikkaniemi, J. Viikari and O.T. Raitakari,

[83] X. Yang, R. Telama, M. Hirvensalo, J.S. Viikari and O.T. Raitakari, "Sustained

[84] J. Lefevre, R. Philippaerts, K. Delvaux, M. Thomis, A.L. Claessens, R. Lysens, R. Renson,

[85] H. Hasselstrom, S.E. Hansen, K. Froberg, L.B. Andersen, "Physical fitness and physical

[86] L.B. Andersen, H. Hasselstrøm, V. Grønfeldt, S.E. Hansen and F. Karsten, "The

[88] R.M. Malina, "Adherence to physical activity from childhood to adulthood: a perspective from tracking studies," *Quest*. vol. 53, no. 3, pp. 346.–355, Aug. 2001. [89] T. Temmelin, S. Näyhä, A.P. Hills and M.R. Järvelin, "Adolescent participation in sports and adult physical activity," *Am. J. Prev. Med.* vol. 24, no. 1, pp. 22.–28, Jan. 2003. [90] R. Telama, X. Yang, J. Viikari, I. Välimäki, O. Wanne and O. Raitakari, "Physical activity

[91] Y.B. Cheung, D. Machin, J. Karlberg and K.S. Khoo, "A longitudinal study of pediatric

[92] D.E. Laaksonen, H.M. Lakka, J.T. Salonen, L.K. Niskanen, R. Rauramaa and T.A. Lakka,

[93] P.T. Katzmarzyk, A.S. Leon, J.H. Wilmore, J.S. Skinner, D.C. Rao, T. Rankinen and C.

Press, 1989, pp. 401.–430.

527, Mar. 2007.

vol. 32, no. 8, pp. 1455.–1461, Aug. 2000.

*Obes*. vol. 33, no. 11, pp. 1219.–1226, Sep. 2009.

*Sport Med*. vol. 23, Suppl 1, pp. S27.–S31, May. 2002.

Suppl 1, pp. S32.–S38, May. 2002.

no. 2, pp. 120.–127, Apr. 1999.

no. 3, pp. 267.–273, Apr. 2005.

no. 12, pp. 1316.–1322, Dec. 2004.

1612.–1618, Sep. 2002.

for a lifetime health," In *Perspectives in Exercise Science and Sport Medicine, Vol 2. Youth Exercise and Sport*, C.V. Gisolfi and D.L. Lamb Eds. Indianapolis: Benchmark

and the relationship with cardiovascular disease risk factors," *Med. Sci. Sports Exerc*.

"Testing a model of physical activity and obesity tracking from youth to adulthood: the cardiovascular risk in young Finns study," *Int. J. Obes*. vol. 31, no. 3, pp. 521.–

participation in youth sport decreases metabolic syndrome in adulthood," *Int. J.* 

B. Vanden Eynde, B. Vanreusel and G. Beunen, "Relation between cardiovascular risk factors at adult age, and physical activity during youth and adulthood: the Leuven longitudinal study on lifestyle, fitness and health," *Int. J. Sports Med*. vol. 23,

activity during adolescence as predictors of cardiovascular disease risk in young adulthood. Danish Youth and Sports Study. An eight-year follow-up study," *Int. J.* 

relationship between physical fitness and clustered risk, and tracking of clustered risk from adolescence to young adulthood: eight years follow-up in the Danish Youth and Sport Study," *Int. J. Behav. Nutr. Phys. Act*. vol. 8, no. 1, pp. 6, Mar. 2004. [87] X. Yang, R. Telama, M. Leino and J. Viikari, "Factors explaining the physical activity of

young adults: the importance of early socialization," *Scand. J. Med. Sci. Sports* vol. 9,

from childhood to adulthood – A 21-year tracking study," *Am. J. Prev. Med*. vol. 28,

body mass index values predicted health in middle age," *J. Clin. Epidemiol*. vol. 57,

"Low Levels of Leisure-Time Physical Activity and Cardiorespiratory Fitness Predict Development of the Metabolic Syndrome," *Diabetes Care*. vol. 25, no. 9, pp.

Bouchard, "Targeting the metabolic syndrome with exercise: evidence from the


[67] D. Martinez-Gómez, J.C. Eisenmann, J.M. Moya, S. Gómez-Martínez, A. Marcos and

[68] Y. Pan and C.A. Pratt, "Metabolic syndrome and its association with diet and physical

[69] M.A. Ferguson, B. Gutin, N.A. Le, W. Karp, M. Litaker, M. Humphries, T. Okuyama, S.

[70] H.S. Kang, B. Gutin, P. Barbeau, S. Owens, C.R. Lemmon, J. Allison, M.S. Litaker and

adolescents," *Med. Sci. Sports Exerc*. vol. 34, no. 12, pp. 1920.–1927, Dec. 2002. [71] R.Y. Sung, C.W. Yu, S.K. Chang, S.W. Mo, K.S. Woo and C.W. Lam, "Effects of dietary

[72] J.X. Jiang, X.L. Xia, T. Greiner, G.L. Lian and U. Rosengvist, "A two year family based

[73] D. Nemet, S. Barkan, Y. Epstein, O. Friedland, G. Kowen and A. Eliakim, "Short- and

[74] A.L. Carrel, R.R. Clark, S.E. Peterson, B.A. Nemeth, J. Sullivan and D.B. Allen,

[75] A.A. Meyer, G. Kundt, U. Lenschow, P. Schuff-Werner and W. Kienast, "Improvement

[76] G.Q. Shaibi, M.L. Cruz, G.D. Ball, M.J. Weigensberg, G.J. Salem, N.C. Crespo and M.I.

[78] N.J. Farpour-Lambert, Y. Aggoun, L.M. Marchand, X.E. Martin, F.R. Herrmann and M.

[79] E.C. Murphy, L. Carson, W. Neal, C. Baylis, D. Donley and R. Yeater, "Effects of an

*Pediatr. Adolesc. Med*. vol. 159, no. 10, pp. 963.–968, Oct. 2005.

65, no. 3, pp. 277.–289, Sep. 2009.

Disord. vol. 23, no. 8, pp. 889.–895, Aug. 1999.

*Child*. vol. 86, no. 6. pp. 407.–410, Jun. 2002.

vol. 191, no. 2, pp. 447.–453, Apr. 2007.

54, no. 25, pp. 2396.–2406, Dec. 2009.

1238, Dec. 2005.

2006.

214, Apr. 2009.

e443.–e449, Apr. 2005.

O.L. Veiga, "The role of physical activity and fitness on the metabolic syndrome in adolescents: effect of different scores. The AFINOS Study," *J. Physiol. Biochem*. vol.

activity in US adolescents," *J. Am. Diet Assoc*. vol. 108, no. 2, pp. 276.–286, Feb. 2008.

Riggs and S. Owens, "Effects of exercise training and its cessation on components of the insulin resistance syndrome in obese children," *Int. J. Obes*. Relat. Metab.

N.A. Le, "Physical training improves insulin resistance syndrome markers in obese

intervention and strength training on blood lipid level in obese children," *Arch. Dis.* 

behaviour treatment for obese children," *Arch. Dis. Child.* vol. 90, no. 12, pp. 1235.–

long-term beneficial effects of a combined dietary behavioural- physical activity intervention for the treatment of childhood obesity," *Pediatrics*. vol. 115, no. 4, pp.

"Improvement of fitness, body composition, and insulin sensitivity in overweight children in a school-based exercise program: a randomized, controlled study," *Arch.* 

of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise program," *J. Am. Coll. Cardiol*. vol. 48, no. 9, pp. 1865.–1870, Nov.

Goran, "Effects of resistance training on insulin sensitivity in overweight Latino adolescent males," *Med. Sci. Sports Exerc*. vol. 38, no. 7, pp. 1208.–1215, Jul. 2006. [77] G.A. Kelley and K.S. Kelley, "Aerobic exercise and lipids and lipoproteins in children

and adolescents: a meta-analysis of randomized controlled trials," *Atherosclerosis*.

Beghetti, "Physical activity reduces systemic blood pressure and improves early markers of atherosclerosis in prepubertal obese children," *J. Am. Coll. Cardiol*. vol.

exercise intervention using Dance Dance Revolution on endothelial function and other risk factors in overweight children," *Int. J. Pediatr. Obes*. vol. 4, no. 4, pp. 205.–


**Part 2** 

**Medical Issues in Sports Medicine** 

HERITAGE Family Study," *Med. Sci. Sports Exerc*. vol. 35, no. 10, pp. 1703.–1709, Oct. 2003.

