Encyclopedia
Please note this is a comparison between Version 1 by Christos Rahiotis and Version 2 by Amina Yu.
Salivary glands are exocrine organs that produce a large amount of fluid. Through the saliva, electrolytes and other substances are transferred from the inner of the glands to the oral cavity. The mean volume of the fluid is estimated to be 750 mL/day, which almost represents 20% of the overall plasma volume. Apart from the major salivary glands (2–5 mL/min), saliva is also secreted by several minor glands at a rate of 0.5 mL/min.
- oral health
- saliva
- sports dentistry
- physical exercise
- sports medicine
1. Introduction
Salivary glands are stimulated by parasympathetic cholinergic nerves and sympathetic adrenergic nerves [1][4]. Parasympathetic stimulation increases regional blood flow and saliva, consisting of low organic and inorganic components [2][5]. Sympathetic stimulation results in the saliva of low volume, containing high levels of K+ and proteins [3][6]. The autonomous nervous system regulates salivary secretion. Catecholamines might also play a role in the secretion of electrolytes and proteins [4][7]. During exercise, hormone response analysis can provide valuable information regarding training stress, adaptation, dehydration and exercise performance [5][8].
Saliva comprises 99% water and 1% organic and inorganic constituents [6][7][9,10]. Although saliva’s organic and inorganic components are usually present in low concertation, compared with the serum, some proteins such as a-amylase are synthesized in the glands and presented in higher levels [8][9][10][11,12,13]. Other organic components, which can be detected in the saliva are vitamin C, maltase, urea, uric acid, albumin, mucin, creatinine, amino acids, lactase and hormones such as testosterone, cortisol, etc. Moreover, amounts of CO2 are presented and so are immunoglobulins such as IgA, IgG, IgM [11][14].
2. Salivary Secretion
Parasympathetic and sympathetic neural systems regulate saliva secretion. Each one has a different effect on its secretion. When the sympathetic neural system stimulates saliva secretion, it consists more of proteins such as α-amylase and cystatin. When the parasympathetic system stimulates saliva secretion, its volume is mainly increased [12][80]. Physical exercise seems to increase the salivary flow rate and protein (e.g., amylase, lysozyme and MUC5B) secretion [13][81]. The decreased saliva flow may influence the concentration of the saliva substances, such as the metabolites [14][55]. S-IgA’s protective role is dependent on its secretion rate [15][54].
It has been reported that in healthy individuals, unstimulated saliva is secreted at rest at the rate of 0.30–0.65 mL/min, whereas stimulated saliva flows at a rate of 1.5–6.0 mL/min [16][82]. Saliva flow rate increases during exercise to a secretion rate of 0.78–0.94 and decreases after recovery [17][18][19][73,74,75]. Under the physical exercise, as the flow rate of the saliva increases, the concertation of Na+ and HCO3 is raised. Na+, Ca2+, Cl−, HCO3 and proteins increase, whereas K+ shows little change [16][82]. Following the physical activity, the increase in salivary proteins may be associated with adrenergic activity [20][83]. Increased plasma catecholamines may also cause an a-amylase increase during exercise [21][84]. Salivary and serum cortisol increase linearly with the intensity of exercise [22][85]. Secretion of S-type cystatins and cystatin C is also increased by physical exercise [23][39].
Exercise, performed in normoxia and hypoxia, did not affect saliva flow rate or a-amylase concentrations. On the other hand, acute hypoxia increases mean saliva flow rate, both at rest and after exercise and a decrease in mean saliva K+ concentration, at rest and after exercise [23][39]. In addition, food consumption during the exercise increases saliva’s flow rate and the secretion of specific proteins, as lysozyme and α-amylase, but not s-IgA secretion [24][76].
3. Lysozyme and Lactoferrin
Lysozyme and lactoferrin are the main saliva’s antimicrobial proteins. Lysozyme and lactoferrin act synergistically to augment immunity [25][45]. Lysozyme breaks down the polysaccharide wall of their cell, thus facilitating the destruction of mainly gram-positive bacteria [26][86]. Furthermore, exercise activates neutrophils, potentially causing the release of lysozyme and lactoferrin into the saliva [27][28][87,88]. The lysozyme concentration in the saliva and its secretion rate is negatively influenced by psychological stress [29][89]. Lactoferrin has anti-inflammatory and anti-microbial roles, preventing bacterial growth by sequestering ferric iron from the bacteria and directly interacting and damaging bacterial membranes [30][31][90,91].
Lower salivary lactoferrin concentrations were found in elite rowers than in the non-exercising control group over a training season [32][66]. Moreover, lactoferrin concentration in saliva decreased over a competitive training season in basketball players [33][29]. On the other hand, acute running increases lactoferrin and lysozyme expression in both men and women [34][35][27,92].
4. Lactate
Lactate is an essential source of energy for the metabolism of skeletal muscle. Measuring blood lactate concentration provides information regarding changes in glycolysis and the capacity of the anaerobic work [35][92]. Saliva lactate is possibly formed by passive diffusion from salivary glands and blood [36][64]. Blood lactate and saliva lactate are highly correlated, with most kinds of exercise [37][63]. It has been suggested that salivary lactate increases due to an increase in the lactate concentration of the blood, which leads to an increase in the permeability of the blood–saliva barrier during exercise [38][93]. Salivary concentrations of lactate during training have been estimated as lower than those of the lactate of the blood [39][62]. Lactate levels can also be used to assess the possibility of overtraining, as they decrease during intense exercise [40][60]. Lactate levels seem to be independent of individuals’ fitness and alteration in anxiety [41][61].
5. Oral Peroxides–Nitric Oxide
One of the highest value components of the saliva antioxidant system is the enzyme nitric oxide [42][94]. The paramount importance of the salivary antioxidant system is to decompose hydrogen peroxide produced by bacteria. Then, the enzymes inactivate bacterial glycolytic enzymes, thus destroying the oral bacteria [43][95]. Exercise with moderate intensity increases the activity of salivary peroxidase. The lower the training power, the longer the peroxidase remains at the high activity level [44][45][72,96]. Exercise-induced stress also induces the production of salivary nitric oxide [46][97].
Oral peroxide increased only in beginner athletes and not in well-trained athletes and professionals [47][48][71,98]. So, it can be a measure of the adaptation of the subject to intense and heavy exercise. Furthermore, exercise increases saliva uric acid and total antioxidant activity, while the saliva lipid hydroperoxides decrease. Thus, it seems increment in uric acid and total antioxidant activity prevent the lipid hydroperoxides from being generated, making oral peroxide a marker of oxidative stress in saliva [49][70].
6. Salivary A-Amylase (sAA)
Some non-immunological salivary proteins can inhibit bacterial adherence to the oral cavity. One protein is a-amylase, which can bind to several oral bacteria [50][51][52][99,100,101]. Salivary a-amylase is the predominant enzyme in saliva. It is responsible for the degradation of starch and glycogen to maltose and has been used as a sympathetic nervous system activation biomarker [53][102]. Both a-amylase and cortisol of the saliva serve as markers to stress response of exertion [54][18]. However, salivary a-amylase activity is a more sensitive, exercise-induced stress marker than cortisol, as it is produced locally in the salivary glands, controlled by the autonomous nervous system. The cortisol is transported from blood to saliva [55][103]. Beta-adrenergic agonists are capable of stimulating salivary a-amylase release without increasing salivary flow [56][104].
Salivary a-amylase increased in acute exercise and the magnitude depended on exercise intensity [57][58][16,105]. Two hours of moderate exercise seems to lead to enhanced a-amylase activity [59][15]. Salivary a-amylase concentrations predict plasma catecholamine levels, particularly norepinephrine, under various stressful conditions and maybe a more direct endpoint of catecholamine activity [60][20]. Salivary a-amylase responses are quick within one to a few minutes, even faster from blood cortisol levels and it declines rapidly after removing the stress factor [60][61][20,65].
7. Salivary Cortisol (S-Cortisol)
Cortisol is the primary glucocorticoid produced by the adrenal cortex that regulates blood glucose homeostasis [61][62][65,106]. It is released in stressful situations and leads to an increase in blood-glycose [63][107]. High salivary cortisol concentrations are related to impaired insulin sensitivity [64][108]. Free cortisol is more increased than salivary cortisol [65][109]. After intensive training, periods with elevated cortisol associated with the mild hypoglycemic state seem to produce an immunosuppressive state and decrease plasma glutamine concentration [66][110]. Cortisol is responsible for 95% of the glucocorticoid activity in the human body [67][111]. The secretion of cortisol due to exercise is not immediate [68][37].
Salivary cortisol is expected to be decreased during non-exercising [69][112]. Low-intensity exercise also reduces the levels of salivary cortisol [69][70][112,113]. During moderate-intensity exercise, its levels remain almost stable [71][72][114,115]. Exercise of high intensity influences the secretory process of the adrenal cortex and starts cortisol releasing in adults and adolescents [73][74][30,116]. Heavy training significantly increases the amount of salivary cortisol immediately after exercise. Endurance exercise produces higher plasma cortisol than acute high-intensity exercise [75][76][79,117]. A Itstudy suggests that salivary cortisol is lower during water than land exercises [77][36]. This contrasts with another research work that indicates that the salivary cortisol concentrations similarly significantly decreased with water exercise and land stretching [78][35]. Physical activity seems to increase the diminished due to poor sleep quality awakening cortisol levels [66][110].
Physical fitness is associated with cortisol secretion during psychological stress [79][80][81][82][83][25,34,118,119,120]. Psychological stress factors can contribute to higher values of cortisol [80][81][34,118]. A relation between salivary cortisol and anxiety has been suggested [82][83][119,120]. Depressive patients before and 10 min after the exercise sessions appear to have significantly decreased levels of salivary-free cortisol [84][85][86][23,24,28]. In addition, physical exercise has been found to decline the rate of cortisol [9][87][12,22]. Salivary cortisol measurements can detect the circadian rhythm of the athletes, assisting in the prevention of overtraining syndrome [88][121].
Carbohydrates during exercise decrease glutamine depletion, cortisol and so the immune activity [89][90][122,123]. On the other hand, a diet with low carbohydrates suppresses immune activity and increases cortisol in plasma [90][123]. In addition, carbohydrate intake during prolonged exercise decreases stress hormones responses [90][123]. According to other studies, carbohydrates did not affect saliva flow rate and s-IgA concentration during a single bout of exercise [91][92][48,51]. However, post-exercise consumption of chocolate milk, which contains carbohydrates, proteins, fluid and electrolytes, is associated with lower saliva-cortisol response and higher saliva flow rate than water [93][94][124,125].
8. Steroids–Testosterone
Steroid hormones detectable in saliva include cortisol, androgens including testosterone and dehydroepiandrosterone (DHEA), estrogens and progesterone and aldosterone. Some serum components can transfer freely through the lipid-rich cell membrane into the salivary gland acinar cells and diffuse into the saliva. However, this mechanism is applied only to some lipid-soluble components such as steroid hormones. Salivary steroids are suggested to provide a more sensitive marker of changes than plasma ones [95][33]., Salivary testosterone (sal-T), in unison with cortisol (sal-C), has been used as a marker of anabolic status [96][97][26,38]. Adrenal glands secrete DHEA. A strong relationship between salivary and plasma DHEA has been reported [98][126]. It has also been suggested as an analog in salivary testosterone measurements to assess exercise response in females [75][79].
Salivary measures of testosterone are a reliable indicator of its plasma concentrations [99][127]. Both testosterone and cortisol can be increased at a significant rate with hypertrophic exercising [100][128]. Salivary testosterone is increased linearly during exercise and reaches its peak after the end of the training [101][32]. Salivary testosterone seems to be a valuable tool to assess the performance of the athletes and their readiness to train at a certain intensity level and assist with the designing of workouts for optimal gains [102][78]. This can be explained as testosterone contributes to neuromuscular performance and the muscles’ long-term development [103][129]. The measurement of steroids of saliva samples throughout a competitive event can provide meaningful data regarding exercise’s psychological and physical stress and highlight overtraining [104][97][21,38].
9. Salivary Immunoglobulin A (s-IgA)
Immunoglobulin A (IgA) is the pre-dominant immunoglobulin in the mucosal immune system [105][130]. IgA is produced by long-lived plasma B cells, which are influenced by T cell-generated cytokines [106][131]. It is found in the saliva, intestinal secretions, bronchoalveolar lavage fluid, urine and other mucosal fluids and it is also associated with resistance to specific infections [107][132].
Salivary immunoglobulin A (s-IgA) plays an essential role in immunity as the first line of defense against potential pathogens [108][133]. Older people who follow a daily moderate-intensity exercise program appear to have higher levels of S-IgA, than others of the same age who do not exercise. In addition, moderate to intense exercise can increase the secretion of salivary S-IgA in older adults to improve their immune function [109][52]. S-IgA also presented an increased post-exercise when combined with a high carbonated diet, suggesting that carbohydrates enhance the immune activity during exercise [110][47]. On the contrary, others indicated no effect of carbohydrate ingestion on saliva immunoglobulin concentrations or secretion rates [92][51]. Finally, ita wasstudy demonstrated that a fed or fasted state 2 h before exercise does not influence resting s-IgA [111][31].
As far as the relationship between exercise and s-IgA, the majority of the studies conclude that s-IgA decreases after exercise [34][112][27,134], others report no change [113][114][19,46] and others show increased levels of s-IgA post-exercise [115][116][117][17,43,50]. S-IgA measurement seems to be a good way which shows the over-training [118][119][135,136]. The s-IgA may decrease over prolonged periods of intensive training in elite athletes. This reduction is attributed to neurohormonal factors related to physical and psychological stress during intensive daily exercise [120][49]. In addition, no significant association between changes in s-IgA levels and those in cortisol levels during exercise [120][121][49,56]. Low temperatures, such as in ski races, might depress the activity of secretion of s-IgA [122][57].
High training loads can decrease s-IgA and suppress immune function, as lower concentrations of salivary IgA or chronic salivary IgA deficiencies are associated with an increased frequency of upper respiratory tract infections (URTI) [77][123][36,137]. However, more studies are required to clarify the relationship between the components of the saliva and the incidence of URTI. The coaches can use this information to predict athletes’ immune function to help reduce the risk of upper respiratory tract infection [124][42]. S-IgA fluctuation is seemed to be mirrored by the secretion of salivary free light chains [125][41].
10. Immunoglobulin G (IgG) & Immunoglobulin M (IgM)
All salivary immunoglobulins contribute to mucosal immunity and defense against upper respiratory tract infections. However, only a few studies have evaluated s-IgM and s-IgG, under physical exercise. It seems that s-IgG levels remain unchanged during exercise, while s-IgM levels decrease and are restored within 24 h [58][105].
11. Insulin-like Growth Factor 1 (s-IGF-1)
According to a ystudy in young female volleyball players, free IGF-1 in saliva levels was decreased in well-trained athletes, compared with sedentary groups [126][59]. In contrast, in another study, salivary IGF-1 was increased after exercise, while plasma IGF-1 was not [127][58]. Salivary IGF-1 can be more sensitive. Training is suggested to increase human growth hormone hGh secretion, which is regulated by the hypothalamus. The increase seems to be attributed to insulin-like growth factor I (IGF-I) [128][138].
12. Salivary MicroRNAs
Salivary microRNAs can reflect critical biological processes related to a trauma, such as hypoxia, neurogenesis, axon repair, and cell death. MicroRNAs, expressed from the saliva, seems to be an accurate non-invasive alternative to diagnose a traumatic brain injury due to a concussion [129][130][68,69].
13. Melatonin
Melatonin is a hormone found naturally in the human body, regulating sleep-wake cycles. Physical exercise during the afternoon can decrease melatonin secretion compared to the morning exercise. A non-invasive evaluation of melatonin can be performed [131][67].
14. Uric Acid
The effect of exercise in the concentration of uric acid in saliva has to be further investigated, as the available studies come to opposite conclusions. Aerobic exercise, such as long-distance running, has a significant impact, increasing the concentration of uric acid [49][70]. On the other hand, it seems that explosive physical exercise, such as short sprints, does not significantly influence the concentration of uric acid in saliva [132][133][40,139].
