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Immediate Effects of Aerobic Exercise on Plasma/Serum Zinc Levels

A Meta-analysis


Author Information
Medicine & Science in Sports & Exercise: April 2016 - Volume 48 - Issue 4 - p 726-733
doi: 10.1249/MSS.0000000000000805


Exercise training is an established preventative and management strategy for obesity and related chronic diseases, such as type 2 diabetes mellitus (DM) and cardiovascular diseases (13). The therapeutic effects of exercise have been attributed to improvements in insulin sensitivity, favorable changes in body composition, fat oxidation, and storage in muscles (20). In addition to the benefits induced by physical activity, exercise also can effect changes in nutritional status (24), with implications for the physiological adaptations of exercise. For example, the provision of dietary protein in conjunction with resistance exercise can substantially stimulate the rate of muscle protein synthesis in skeletal muscles (65).

Zinc is involved in numerous metabolic roles, including energy metabolism, immunity, and antioxidative effects. The majority of zinc within the musculoskeletal system is found as part of protein complexes; zinc provides structural stability and enzymatic activities of metalloenzymes, such as lactate dehydrogenase, superoxide dismutases and carbonic anhydrase (55). Under zinc-depleted conditions, reductions in cardiorespiratory function and muscle endurance during exercise were observed; lowered activities of carbonic anhydrase in erythrocytes and lactate dehydrogenase within skeletal muscles, induced by suboptimal zinc status, are suggested to contribute to the decline in cardiorespiratory function during exercise (43).

Current literature suggests that zinc ions can modulate cellular signalling pathways with effects on redox activity and insulin sensitivity; in particular, the functions of cellular zinc transporters play a role in maintaining optimal signalling capacity (33). For example, the loss in expression of a specific zinc transporter, Zrt, Irt-like protein 7 (ZIP7, SLC39A7), in muscle cells induces the downregulation of glycolysis and glycogen synthesis (49). We recently reported a relationship between ZIP7 gene expression and physical activity level in healthy adults, which supports the notion of interaction between mediators of zinc homeostasis and energy metabolism during exercise (10).

Zinc losses during exercise, in particular through sweat, have been well documented (17,27). In addition to systemic zinc losses, cellular disruption as a result of muscular contraction also can lead to the release of zinc ions and zinc-containing proteins into the circulation (9). The initial observations of lower serum zinc concentrations in some groups of athletes, when compared with physically inactive individuals, posed the possibility for suboptimal zinc status in individuals who are physically active (43). Although inadequate zinc intake may partially account for suboptimal zinc status, factors directly related to exercise also contribute to altered zinc metabolism. Multiple factors appear to influence the distribution of zinc in the body, contributing to conflicting results reported for changes in circulating and tissue zinc concentration as a result of exercise. Hence, the present article aims to summarize the current literature on the immediate effects of aerobic exercise on zinc concentrations in blood, sweat, and urine in healthy participants; where possible, meta-analysis will be used to quantify the effects of exercise on zinc status.


Search strategy

A literature search was conducted of PubMed, Web of Science, Scopus, and SportDiscus electronic databases up to December 20, 2014, using the search strategies: (zinc and exercis* or athlet*) and (serum or plasma zinc and physical activity) (see Table, Supplemental Digital Content 1, full search strategy used in Pubmed for systematic literature review, Studies were restricted to human investigations published in English. Reference lists of retrieved studies were inspected for additional relevant articles. The PRISMA flowchart describing the studies identified from the search strategy is shown in Figure 1 (41). Inclusion criteria and methods of the analysis were specified in advance and registered with PROSPERO register at (CRD42014015442).

PRISMA flow diagram of study selection.

Study eligibility criteria

Before–after trials, baseline data from randomised controlled trials and longitudinal studies published in peer-reviewed journals were eligible provided they reported on measurements in indices of zinc status (zinc concentration measured in serum/plasma, red blood cells [RBC], urine, or sweat) after an aerobic exercise bout. Any aerobic exercise, such as running or cycling, in laboratory, field, or competition setting, was included in the selection criteria. Other modes of exercise, such as resistance training, high-intensity interval bouts, and electrically stimulated muscle actions, were excluded. Participants of any age, who were apparently healthy, that is, not diagnosed with any major illness or health conditions, were considered. Literature reviews on the topic were excluded. The title and abstract of each study identified in the search were screened to determine the study’s eligibility for full review. The full report was retrieved if the study potentially or definitely investigated acute changes in the measures of zinc status after an aerobic exercise bout. Two investigators (AC and SS) independently reviewed each full report to determine if the study met the inclusion criteria.

Data extraction and quality assessment of selected study

Data from all selected studies were extracted by two investigators (AC and SS), and any differences were resolved by discussion. The data extraction worksheet included descriptive information, such as the study authors, year of publication, the number and sex of participants. Training status of participants (untrained, moderately trained or athletic) was extracted according to the authors’ description of population group. The duration, intensity, and mode of exercise were detailed in the data extraction worksheet. Primary outcomes extracted were measures of zinc status (plasma or serum, urinary, sweat and RBC zinc concentrations) immediately after exercise compared with baseline values. Plasma and serum concentrations were grouped to represent systemic zinc concentration. The term “serum” will be used to refer to both serum and plasma in this report. Estimations from figures were used where numerical zinc concentrations could not be found in the included reports. P values for paired t-test comparing serum zinc concentration immediately after exercise with baseline values were also recorded. In studies where multiple exercise testings were reported within one population group, the results from the initial intervention were taken. In longitudinal or interventional studies, only baseline data reporting the acute effects of exercise bouts were included. Units were converted to International System of Units measures, where applicable and measures of variability were recorded as SE. The quality of the selected studies was assessed using the American Dietetic Association’s Quality Criteria Checklist for Primary Research (1). The completion of this checklist provides one of three quality rating categories (positive, neutral, or negative), determined by how individual studies addressed validity issues regarding selection bias, inclusion and exclusion of study participants, generalizability of results, data collection, and analysis. The majority of the included studies were rated as neutral because they addressed some issues regarding study validity. A positive quality rating indicates that the article resolved most of the study validity issues, whereas a negative quality rating represents that these issues were not addressed.

Statistical analysis

Meta-analyses of serum zinc concentration were carried out on selected studies using the Comprehensive Meta-Analysis package, version 2 (Biostat, Englewood, NJ; The primary outcome measure was analyzed by the mean difference of serum zinc concentration between baseline (preexercise) and immediately after exercise values, and the P value from the corresponding paired t-test. Where P values of the paired t-test were given within a range, the average was taken, that is, P = 0.03 was taken for the range of 0.01 < P < 0.05. A funnel plot of SE by differences in mean was generated for the main outcome to assess publication bias. Secondary analyses were conducted by grouping the comparisons by the study population’s training status (untrained, moderately trained, or athletic), mode of exercise (running, cycling, or “other”), and exercise intensity (maximal or submaximal). Random-effects models were used for the meta-analyses due to the large variation in study design among selected studies. Sensitivity analyses were conducted to determine the impact of individual or groups of comparisons within the included studies. Mixed-effects metaregression using method of moments was performed to examine the relationships between the change in serum zinc concentrations immediately after exercise and age of study population or intensity of exercise.


Study characteristics of systematic literature review

The electronic database searches provided 3698 citations after removing duplicates. After initial review of all abstracts, 3330 studies were excluded because they did not fit the inclusion criteria. The full texts of the remaining studies were retrieved and examined. Of the 368 full texts retrieved, 45 studies were relevant to the present systematic literature review. The detailed study selection process is shown in Figure 1.

The characteristics of studies included in the systematic literature review are described (see Table, Supplemental Digital Content 2, characteristics of included studies for systematic review, The majority of included studies were before–after studies reporting on the effects of a single acute exercise bout (2–5,7,8,16–18,21–23,26,28,36,38,39,46,50,52,53,56,58,67,68). Multiple exercise bouts were included in four studies (27,59,62,66) which aimed to examine the effects of different exercise conditions on measures of zinc status. The primary outcomes for the remaining studies were the effects of an exercise bout longitudinally (6,15) or after specific interventions, for example, exercise training or nutritional supplementation (11,12,19,29,31,35,37,40,45,51,54,57,60,61). Included studies reported on one or more of the following zinc outcomes: serum (40 studies), urinary (seven studies), sweat (eight studies), and RBC (three studies). All included studies scored neutral in the quality assessment, with the exception of one study (68) scoring a positive rating and another study (29) which scored a negative rating.

The number of participants (n = 727) in the included studies for the systematic literature review ranged from n = 5 to 38, with a median of 10 participants. The majority of the participants were men (n = 627), with the exception of four comparisons (7,17,18,62), which were exclusively women (n = 66) and two comparisons (8,21), which did not differentiate between sexes (n = 34 in total, n = 6 females). When grouped according to their training status, the included participants were distributed into the categories of untrained (n = 282), moderately trained (n = 175), or athletic (n = 270). The majority of the included studies used running (n = 16) or cycling (n = 20) as their exercise mode. Participants exercised maximally to exhaustion under laboratory or field test conditions in 16 of the 45 studies (2,3,6,12,15,22,29,31,38,45,51,56–58,67,68). In the remaining studies, which used submaximal testing protocols, participants performed the exercise for 10–160 min at 50%–90% of V˙O2max.

Serum zinc concentrations immediately after exercise—meta-analysis

Sufficient data were available for meta-analysis from 34 studies (2–8,11,12,15,16,18,19,21–23,28,29,31,35,37,38,40,45,46,51,52,54,59–61,66–68), providing 46 comparisons of different population groups (n = 550) to explore the acute effects of exercise on serum zinc concentration. A number of studies (2,7,15,19,29,38,54,59,66) examined the effects of exercise on two or more population groups stratified by their training status or sex, allowing for multiple comparisons within the meta-analysis.

The overall meta-analysis of all included studies revealed an increase in serum zinc concentration immediately after exercise (0.45 ± 0.12 μmol·L−1, P < 0.001, Fig. 2; mean ± SE), with a high degree of statistical heterogeneity (I2 = 82%). Two comparisons from one study (7) were significantly different from other comparisons and hence were identified as outliers in the present analysis. When the outlying comparisons were omitted from analysis, the increase in serum zinc concentration after exercise remained significant (0.40 ± 0.12 μmol·L−1, P = 0.001; see Figure, Supplemental Digital Content 3, forest plot of overall analysis with two outlying comparisons removed, No other significant impact from an individual or group of studies was observed. The funnel plot of SE by difference in means indicated some evidence of publication bias for studies with small sample size (see Figure, Supplemental Digital Content 4, funnel plot of overall meta-analysis, The classic fail-safe N was 427, which represents the number of additional studies required to bring the overall P value to greater than 0.05.

Forest plot from overall meta-analysis determining the difference of serum zinc concentration between baseline (preexercise) levels and immediately after exercise.

Secondary analyses were conducted by stratifying the comparisons by exercise intensity, mode, and training status of study population. Serum zinc concentration was higher after exercising maximally (0.77 ± 0.20 μmol·L−1, P < 0.001, Table 1; see Figure, Supplemental Digital Content 5, forest plot of meta-analysis stratified by exercise intensity,; however, the significant effect was not observed after submaximal exercise (0.27 ± 0.14 μmol·L−1, P = 0.066). When comparisons were separated by the mode of exercise, running significantly increased serum zinc concentrations (0.71 ± 0.26 μmol·L−1, P = 0.006; see Figure, Supplemental Digital Content 6, forest plot of meta-analysis stratified by mode of exercise, This effect remained significant when the outlying comparisons were omitted (0.51 ± 0.24 μmol·L−1, P = 0.035). No significant changes in serum zinc concentration were observed after cycling or other exercise bouts. When comparisons were separated into training status of the studied population, there was a substantial increase in serum zinc concentration immediately after exercise for those classified in the untrained category (0.65 ± 0.19 μmol·L−1, P = 0.001; see Figure, Supplemental Digital Content 7, forest plot of meta-analysis stratified by training status of study participants,, but no significant effect in the moderately trained or athletic groups. The effect of exercise on the untrained group remained significant after the removal of outliers (0.53 ± 0.18 μmol·L−1, P = 0.004). Metaregression models revealed no significant relationship between change in serum zinc concentration and mean age of participants or submaximal exercise intensity immediately after exercise (see Figure, Supplemental Digital Content 8, metaregression plots of age and intensity of submaximal exercise on changes in serum zinc concentration immediately after exercise,

Secondary analyses of the change in serum zinc concentrations immediately after exercise when grouped by exercise intensity, modality, and training status.

Other outcomes (urinary, sweat, and RBC zinc concentrations)

Meta-analyses were unable to be conducted for the other measures of zinc status (urinary, sweat, and RBC zinc) due to inability to resolve the different units of variables used in the identified studies within the systematic literature review. Three studies reported significant increases in urinary zinc excretion after exercise (3,23,36), whereas four other studies reported no significant change (2,8,60,61). RBC zinc concentrations have been reported to decrease significantly immediately after exercise (18,50,52). Although eight studies (5,15,17,27,53,60,61,67) reported sweat zinc loss during exercise, no baseline values were measured and hence comparisons between resting and exercise conditions were not available.


The current review and meta-analysis, which aimed to quantify changes in zinc homeostasis after an aerobic exercise bout, revealed an increase of 0.45 μmol·L−1 in serum zinc concentration immediately after exercise. Secondary analyses showed that changes in serum zinc are influenced by exercise intensity, the mode of exercise and the participants’ training status. Higher increase in serum zinc concentration is observed in studies that used maximal exercise testing (0.77 μmol·L−1); conversely, submaximal exercise sessions failed to induce significant changes in serum zinc concentration. Similarly, although running causes substantial increase in serum zinc concentration, cycling and other aerobic exercise did not elicit similar responses, possibly due to the differences in the size of muscles that are recruited for the activity (47). Muscular contractions and the demand for energy by exercise present as challenges to the multiple homeostatic systems of the body (25). The present report suggests that exercise sessions that use larger muscle groups at higher intensity induce the greatest disturbance to whole-body zinc homeostasis.

A number of mechanisms have been suggested to explain the changes in serum zinc after exercise, namely, the release of zinc ions from ruptured myocytes and changes in acid–base balance during exercise. The perturbations in acid–base balance during high-intensity exercise represent a potential factor that influences whole-body zinc homeostasis. Active zinc transport mediated by cellular zinc transporters is proposed to function by the countertransport of hydrogen (H+) and bicarbonate (HCO3) ions (33); therefore the acid–base balance within peripheral tissues and systemic circulation is intrinsically linked to zinc homeostasis. Zinc transporter-mediated movement of zinc between peripheral tissues and systemic circulation may be influenced by the buildup of H+ induced by exercise (32) and changes in the proportion of albumin–zinc complex in systemic circulation (64). Furthermore, it is well established that the appearance of muscle specific proteins, such as creatine kinase, is the result of disruption in muscle cellular structures induced by exercise. The skeletal muscle system represents the majority of body zinc store (55), so the leakage of zinc ions from damaged muscles is likely to be a major contributor to the increase in serum zinc immediately after exercise. This is supported by the substantially larger increase in serum zinc concentration after heavy intensity resistance exercise, which causes greater degree of muscle damage compared to moderate resistance exercise (48).

Although the overall analysis revealed increase in serum zinc levels after aerobic exercise, there is a lack of consistency in some of the comparisons within the meta-analysis. For instance, a statistically significant decrease in serum zinc level was reported immediately after a 40-min step test in a group of healthy participants (21). In another study, no change in serum zinc level was noted after a marathon run (8). The heterogeneity in results between some individual studies and the overall analysis can be attributed to the diverse nature of the exercise sessions and training status of the participants, which were explored as part of the secondary analyses of this meta-analysis.

A number of limitations in study designs have been identified that have implications for future research. Although serum zinc concentration is the recommended zinc biomarker currently, this measure does not reflect zinc status sensitively (42). The accuracy in measuring serum zinc concentration may be further confounded by changes in blood volume during high-intensity aerobic exercise. Some of the studies identified for the current review failed to report serum zinc concentrations adjusted for hemoconcentration that occurs with exercise. Future studies should consider reporting and/or controlling the hydration status of participants, in addition to the use of van Beaumont’s quotient for changes in serum zinc concentrations (63). Furthermore, many studies identified from the present review failed to report dietary zinc intake which has been shown to modulate the fluctuation of zinc between different compartments after exercise. During zinc depletion, the change in plasma zinc concentrations immediately after exercise was smaller than that in zinc sufficient conditions (45). The authors proposed that low dietary zinc intake, which has been shown to impair exercise capacity (43), contributes to the reduction in circulating exchangeable zinc pool that is highlighted by the stress of exercise.

Although the immediate effects of aerobic exercise on serum zinc levels were revealed in the current meta-analysis, the subsequent changes in serum zinc concentrations during recovery from exercise remain unclear. Conflicting results are reported for serum zinc changes in the hours after an aerobic exercise bout. For instance, although increase in serum zinc levels were reported immediately after swimming, significant decline in serum zinc concentration was noted at 1 h after exercise cessation in participants (19). In contrast, no changes were noted at 2 h after the cessation of a maximal running test, despite significant increase in serum zinc levels immediately after exercise (2). Elucidation of the changes in serum zinc levels during exercise recovery will further the understanding of the role of zinc in exercise metabolism.

One of the strengths of the analysis is the inclusion of exercise sessions that are commonly recommended for the prevention and management of chronic diseases. Secondary analysis from the current report shows greater postexercise increase in serum zinc for untrained individuals. Furthermore, significant reductions in resting serum zinc and exchangeable zinc pool were also reported after several weeks of aerobic training in previously inactive individuals (34,51). Therefore, the prescription of exercise training as a treatment strategy may adversely impact on the zinc status of previously inactive patients with chronic diseases, in particular type 2 DM, of which suboptimal zinc status already exists as part of the disease pathology (30). In clinical practice, dietary advice to increase total zinc intake may be beneficial to at-risk populations.

Previous narrative reviews on the effect of exercise on zinc status generally reported conflicting changes in zinc homeostasis after exercise (14,44). To the best of our knowledge, the present article is the first systematic literature review and meta-analysis to reveal immediate increase in serum zinc concentration as a result of aerobic exercise. Currently, there is limited data on how exercise affects other indices of zinc status in humans. Alteration of zinc homeostasis at the cellular level has been shown to affect glucose uptake and metabolism in muscle cells (49), with potential implications for glycemic control and management of type 2 DM. Further research is required to ascertain the long-term effects of exercise on zinc metabolism and potential consequences for dietary zinc requirements, in particular for those who were previously inactive.

Conflicts of Interest and Source of Funding: None declared for all authors. No external funding secured for this study.

The result of the study does not constitute endorsement by American College of Sports Medicine.


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