TY - JOUR
AU - Lehnhard, Robert, A
AB - Abstract Context Supplementing with fruits high in anthocyanins to reduce exercise-induced oxidative stress and inflammation has produced mixed results. Objective This systematic review and meta-analysis aims to discuss the impact of whole fruits high in anthocyanins, including processing methods and the type and amount of fruit, on inflammation and oxidative stress. Data Sources PICOS reporting guidelines and a customized coding scheme were used to search 5 databases (SPORTDiscus, Science Direct, Web of Science [BIOSIS], Medline [Pubmed], and the Cochrane Collaboration) with additional cross-referencing selection. Data Extraction A random-effects meta-analysis was used to measure effects of the fruit supplements with 3 statistics; the QTotal value based on a χ2 distribution, τ2 value, and I2 value were used to determine homogeneity of variances on 22 studies (out of 807). Outliers were identified using a relative residual value. Results A small significant negative summary effect across the sum of all inflammatory marker outcomes (P < 0.001) and a moderate negative effect for the sum of all oxidative stress marker outcomes (P = 0.036) were found. Moderator analyses did not reveal significant (P > 0.05) differences between subgrouping variables. Conclusions Results indicate that consumption of whole fruit high in anthocyanins can be beneficial for reducing inflammation and oxidative stress. fruit, performance, supplements INTRODUCTION Regular, moderate-intensity physical activity has been shown to have numerous health benefits, including lowering the relative risk for developing many chronic diseases, such as type 2 diabetes and cardiovascular disease. Chronic or unaccustomed high-intensity exercise can create notably high levels of reactive oxygen species, resulting in substantial damage to muscle cells.1,2 This type of physical stress may not allow the body’s natural antioxidant pathways to adapt to the large increase in production of reactive oxygen species created with strenuous exercise, leading to high levels of muscle tissue damage, including damage to DNA strands following a single bout of unfamiliar work or chronic levels of high-intensity work with little rest.2–4 The lack of adaptation creates an imbalance between pro-oxidants and antioxidants, making them more susceptible to oxidative stress and subsequent elevated inflammatory cytokines, with potential for systemic damage that reaches beyond the working muscle itself.5,6 The most common pharmacological treatment of inflammation caused by oxidative stress is nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen.7 The possible harm associated with chronic use of nonsteroidal anti-inflammatory drugs has necessitated research for a more viable and safer alternative. Common nonpharmacological options investigated include those found to occur naturally in foods, such as fruits and vegetables. There are > 5000 individual phytochemicals in fruits and vegetables.8 The 5 major categories are phenolics, carotenoids, alkaloids, nitrogen-containing compounds, and organosulfur compounds. Phenolics, which is the largest group of phytochemicals, are divided into 5 subcategories: phenolic acids, stilbenes, coumarins, tannins, and flavonoids. One major class of flavonoids is anthocyanins.9,10 Anthocyanins are a type of polyphenol that produce natural pigments in foods responsible for the colors blue, purple, red, and orange.11 Many fruits containing anthocyanins have been found to have the ability to scavenge reactive oxygen species and inhibit lipid peroxidation and chelate metal ions,12–15 thus reducing the risk for various diseases associated with oxidative stress.16–19 Although much research has focused on certain components or extracts of fruits and vegetables, such as anthocyanins, it is difficult to be certain of the specific mechanism of action when examining whole foods. Research investigating the effects of whole fruits containing anthocyanins on exercise-induced inflammation and oxidative stress has had varying results.20–40 Potential contributing factors to the level of effectiveness of supplementing with whole fruits containing anthocyanin may stem from the wide variety of anthocyanin concentrations found in the supplements, the frequency of supplementation, the varying synergistic relationships between other phytochemicals and nutrients that may occur within the whole fruit itself, as well as the method of preparation for the fruit delivery. Despite the varied results and lack of specific recommendations for effectiveness of anthocyanin-rich fruit-based supplements, many sports teams and competitive athletes are currently supplementing with whole fruit–based beverages, such as juice concentrates. Clear recommendations for the intake of such drinks may greatly impact not only the success of athletic performance but also the lowering of systemic oxidative stress and inflammation caused by chronic disease. With these positive benefits in mind, the aim of this systematic review and meta-analysis is to address 3 key research questions: 1) What impact do supplemented whole fruits containing anthocyanins have on reducing exercise-induced oxidative stress and inflammation in trained and untrained individuals? 2) What amount (mg) of total daily anthocyanins from whole fruit has the greatest impact on reducing exercise-induced oxidative stress and inflammation in trained and untrained individuals? 3) What type of fruit and fruit processing has the greatest impact on reducing exercise-induced oxidative stress and inflammation in trained and untrained individuals? METHOD Search strategies and inclusion criteria A comprehensive literature search strategy was created using PICOS reporting guidelines (Table 1) along with a customized coding scheme developed by Brown et al.41 The coding scheme was divided into 3 broad categories—intervention characteristics, sample characteristics, and study characteristics—and broken down into combinations of keywords from 5 categories: research design, exercise intervention, fruit intervention, oxidative stress measures, and inflammation measures. Key terms (Figure 1) from each category were combined to locate all relevant literature using SPORTDiscus, Science Direct, Web of Science (BIOSIS), Medline (Pubmed), and the Cochrane Collaboration from June 2016 to June 2018. Articles were selected first by screening titles, followed by reviewing abstracts for inclusion criteria, and finally retrieving full-text articles for screening. From the selected abstracts, only studies meeting the following criteria were included in the study: 1) Exercise was the independent variable used to induce oxidative stress and inflammation; 2) Participants were provided a supplement derived from a whole fruit high in anthocyanins and not an extract only (supplements with additional whole fruit or 100% fruit juice for palatability were included); 3) Biological measures were used to assess oxidative stress and inflammation (excluding subjective evaluation of muscle damage via perceived level of pain and muscle soreness); 4) The interventions were performed on humans; 5) The research was published from 1 January 2000 to 25 June 2018; and (6) The research was published in English. Table 1 PICOS criteria for inclusion and exclusion of studies Parameter Inclusion Exclusion Participants Adults aged 18–65 y Aged <18 y Intervention Exercise intervention, supplementation with whole fruit high in anthocyanins (various processing allowed) No exercise intervention, supplements with extracts of other fruits or ingredients other than for palatability Comparison Placebo or pre/post, same group comparison None Outcomes Change in biological oxidative stress and/or inflammatory markers Change in nonbiological markers, such as visual analog pain scale, or none Study design Experimental, quasi-experimental, English language, published 2000–2018 Reviews, abstracts, editorials, non-English language Parameter Inclusion Exclusion Participants Adults aged 18–65 y Aged <18 y Intervention Exercise intervention, supplementation with whole fruit high in anthocyanins (various processing allowed) No exercise intervention, supplements with extracts of other fruits or ingredients other than for palatability Comparison Placebo or pre/post, same group comparison None Outcomes Change in biological oxidative stress and/or inflammatory markers Change in nonbiological markers, such as visual analog pain scale, or none Study design Experimental, quasi-experimental, English language, published 2000–2018 Reviews, abstracts, editorials, non-English language View Large Table 1 PICOS criteria for inclusion and exclusion of studies Parameter Inclusion Exclusion Participants Adults aged 18–65 y Aged <18 y Intervention Exercise intervention, supplementation with whole fruit high in anthocyanins (various processing allowed) No exercise intervention, supplements with extracts of other fruits or ingredients other than for palatability Comparison Placebo or pre/post, same group comparison None Outcomes Change in biological oxidative stress and/or inflammatory markers Change in nonbiological markers, such as visual analog pain scale, or none Study design Experimental, quasi-experimental, English language, published 2000–2018 Reviews, abstracts, editorials, non-English language Parameter Inclusion Exclusion Participants Adults aged 18–65 y Aged <18 y Intervention Exercise intervention, supplementation with whole fruit high in anthocyanins (various processing allowed) No exercise intervention, supplements with extracts of other fruits or ingredients other than for palatability Comparison Placebo or pre/post, same group comparison None Outcomes Change in biological oxidative stress and/or inflammatory markers Change in nonbiological markers, such as visual analog pain scale, or none Study design Experimental, quasi-experimental, English language, published 2000–2018 Reviews, abstracts, editorials, non-English language View Large Figure 1 View largeDownload slide Flow diagram of the literature search process. Figure 1 View largeDownload slide Flow diagram of the literature search process. Coding and data extraction Two researchers independently extracted information (moderators) using standardized coding forms that included 3 categories: methodological characteristics, sample characteristics, and study characteristics. Methodological characteristics provided information concerning how research was conducted/controlled, sample characteristics provided information related to participant demographic variables, and study characteristics provided information related to quality. Authors of papers (n = 6) were contacted when information was missing or vague. If the author(s) did not respond to initial requests within 2 weeks, a follow-up email was sent (n = 3). Papers were excluded if authors did not respond within 1 month (n = 1). To aid subgroup analyses, studies were coded separately by 2 authors using processes designed to develop and refine coding sheets.41 Methodological characteristics were coded according to research design (experimental or quasi-experimental), intervention duration (<2 wk, 2–6 wk, or >6 wk), exercise type (aerobic or anaerobic), exercise stress protocol (<60 min or >60 min), fruit type (wild blueberries, blueberries, tart cherries, strawberries, bilberries, black current, or other–list), fruit processing method (fresh frozen, fresh whole, freeze dried, juice concentrate or other–list), fruit delivery (single bolus, single daily, multiple bolus, or multiple daily), fruit dosage (specific to body weight, general calculation, or no calculation), and amount of total anthocyanins daily (yes–amount, or no). Sample characteristics included participant sex (male, female, or combined), participant training status (trained or untrained), and geographical location (list). Study characteristics included funding (list), inflammation measure objective reporting (yes or no), oxidative stress measure objective reporting (yes or no), and publication status (published or unpublished). Effect size calculations Comprehensive Meta-Analysis version 2 software (Biostat Inc, Englewood, NJ, USA) was used to compute all effect sizes.42 Hedges’s g was used for a random-effects model to measure the effects of the fruit on oxidative stress and inflammation.43 The statistical assumption supporting a random-effects model suggests that there will be within-study error (sampling error) and between-study variance. To provide more accurate estimates of sample size, standardized mean differences were adjusted by the inverse weight of the variance to prevent inflation of study weights. Standards in meta-analytic literature signifies the Hedges’s g analysis to prevent overestimation of an effect size value when sample sizes include < 20 studies.44,45 Descriptive measures, such as means, standard deviations, and sample sizes and P values were analyzed by comprehensive meta-analysis to calculate effect sizes. Each study contributed 1 effect size calculation to the overall analysis for the comprehensive meta-analysis. Heterogeneity of variance The assessment of homogeneity of variance was completed using 3 statistics; the QTotal (QT) value that is based on a χ2 (χ2) distribution, tau-square (τ2) value and I-square (I2) value. All 3 statistics (QT,χ2, τ2) were used to interpret heterogeneity of variance. When the QT statistic is significant, then a procedure is used to conduct subgroup (moderator) analyses by compartmentalizing variance into QBETWEEN (QB) and QWITHIN (QW) values. Significant QB values (P < 0.05) would need a statistical technique, such as a t test or analysis of variance, to determine group differences.45 The τ2 statistic provides an estimate of total variance between studies, with larger values reflecting the proportion of variance that can be attributed to real differences between studies in a random-effects model. When there is a small number of studies per subgroup (n < 5), as occurred in this review, τ2 can be imprecise, so a pooled estimate of variance was used for all calculations.46 The I2 statistic represents the ratio of excess dispersion to total dispersion and can be interpreted as the overlap of confidence intervals (CIs) explaining low (25%), moderate (50%) and high (75%) values of the total variance attributed to covariates.47 Larger values of I2 require techniques (ie, moderator analysis or meta-regression) to provide explanations.46,47 Research indicates that smaller sample sizes increase the likelihood that assumptions will be violated when using a random-effects model because error can be overestimated.45 A conservative alpha level (α < 0.01) was established to prevent type I errors when interpreting results from the moderator analysis. Outlier analysis and publication bias A relative residual value (Z > ±1.96) was used to identify outliers, which, if present, were analyzed by using a “one study removed” technique that is available with the Comprehensive Meta-Analysis version 2 software. Criteria for outlier inclusion was a large residual value that did not influence significant (P < 0.01) effect sizes (Hedges’s g) and remained within the 95%CI. Publication bias was analyzed through visual inspection of a funnel plot, a fail-safe N calculation,48 and a trim-and-fill procedure.49,50 Funnel plots provide a visual representation of studies according to standard error (y-axis) and effect size (x-axis), with symmetrical distributions being indicative of a lack of publication bias. Fail-safe N calculations are based on the number of studies needed to nullify significant effects.48 The trim-and-fill procedure is an iterative statistical process that adds/removes studies to balance an asymmetrical funnel plot and provide an unbiased estimate of effect size (k).49,50 RESULTS Literature search and coding The literature search identified 791 studies from database searches, and an additional 16 studies were identified from reference lists of previously published literature. A total of 560 of the 791 papers were unique (approximately 71%) after duplicates were removed, and the screening process (review of titles and abstracts) removed an additional 489 of those 560 papers (approximately 87%) for failure to meet inclusion criteria. Seventy-six of the 560 (approximately 14%) full-text articles were retrieved and screened, and after review 54 of the 76 articles (approximately 71%) were eliminated, leaving 22 articles (approximately 29%) to be included. Studies removed after full-text screening were eliminated due to the following: 1) not using exercise as a means to induce oxidative stress or inflammation; 2) not using whole fruit or whole fruit derivatives for the intervention (extracts or added ingredients other than fruit such as protein or ergogenic aids); 3) using participants with health conditions known to influence oxidative stress and/or inflammation; and 4) using subjective measures to indicate oxidative stress and/or inflammation (perceived level of muscle soreness or visual analog scale for pain). Figure 1 provides an overview of the literature search process. Demographic and descriptive information for studies included in the current investigation is provided in Table 2.11,12,22,24–35,41,51–57 Overall, there were 22 studies with 22 independent samples included between the years 2010 and 2017 with 366 participants (48 females and 318 males) from 7 countries ranging in age from 18 to 57 years. Eleven papers (50%) used an experimental design, and no studies were located in unpublished sources. One paper that was included did not provide the necessary information; therefore, the lead author was contacted and provided the requested information within the 1-month response period. One disagreement was identified during the coding process and was considered to be an interpretive error. Both reviewers discussed the interpretive error and agreed on the final category to be assigned, resulting in 100% agreement. There was high inter-rater reliability agreement (κ = 0.995). Table 2 provides a summary of the methodological, sample, and study coding characteristics and moderators. Table 2 Study characteristics Reference Sample Intervention Study Population: no. and sex, training status Location and study design Study duration Fruit and processing method Fruit intervention Control Total daily anthocyanin amount Exercise intervention, intervention duration Biochemical measures and schedule Ammar et al (2016)51 9 M, trained TN: Q <2 wk Pomegranate, FFJ MD; 3×–250 mL + 500 mL single bolus 1 h before exercise test Same NRa Olympic lifts (snatch, clean and jerk, squat)–5 sets of each exercise, 2 sets of 3 reps at 85% of 1RM and 3 sets of reps at 90% of 1RM I: 3 min, 48 h, rest post exercise Ammar et al (2017)52 9 M, trained TN: Q <2 wk Pomegranate, FFJ MD; 3×–250 mL + 500 mL single bolus 1 h before exercise test Same NRa Olympic lifts (snatch, clean and jerk, squat)–5 sets of each exercise, 2 sets of 3 reps at 85% of 1RM and 3 sets of reps at 90% of 1RM OS: 3 min, 48 h, rest- post exercise Bell et al (2014)20 16 M, trained UK: E <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 546 mg High-intensity cycling intervals, >60 min I, OS: pre-post exercise trials 1, 3 3 Bell et al (2015)21 16 M, trained UK: E <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 552 mg High-intensity cycling intervals, >60 min I, OS: pre, immediate, 1 h, 3 h, 5 h, 48 h, 72 h post exercise Bell et al (2016)57 16 M, trained UK: E 2–6 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 264.6 mg 20-m sprint, agility drills, KE, <60 min I, OS: pre, immediately, 1 h, 3 h, 5 h, 48 h, 72 h post exercise Bloedon et al (2015)40 8 M, untrained US: Q >6 wk Wild blueberry, FFP SD; 300g Same 26 mg 1-h treadmill brisk walk–70% VO, >60 min I, OS: pre, immediately, 30 min, 1 h, 3 h, 6 h post exercise Bowtell et al (2011)22 10 M, trained UK: Q <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Same 547 mg Single-leg KE MVC, <60 min I, OS: pre, immediately, 24 h, 48 h post exercise Carvalho-Peixoto et al (2015)24 14 M, trained BR: Q <2 wk Acai, FDJ SD; 300 mL Same 27.6 mg Treadmill run–90% VO2, >60 min OS: pre, immediately post exercise Fuster-Muñoz et al (2016)25 20 M, trained ES: E 2–6 wk Pomegranate, FJ SD; 200 mL Placebo juiceb 11.71 mg Endurance training program (minimum criteria >1 h–3×/wk), >60 min I, OS: post exercise Goncalves et al (2011)53 10 M, trained BR: Q 2–6 wk Grape, JC SD; 300 mL Same NR Triathlon training–30-km cycling, 7-km run, 2-km swim/d, >60 min OS: post exercise Howatson et al (2010)26 13 M, 7 F, trained UK: E <2 wk Tart cherry, FFJ MD; 2×–8oz Placebo juice 80 mg Marathon race, >60 min I, OS: pre, immediate, 24h, 48h post exercise Hutchison et al (2016)27 6 M, 18 F, untrained US: E <2 wk Black currant, FFJ MD; 2×–16 oz Placebo juice 369 mg Eccentric KE (3 × 10 sets @ 115% 1RM), <60 min I: pre, 24 h, 48 h, 96 h post exercise Levers et al (2015)28 23 M, trained US: E < 2 wk Tart cherry, FDC SD; 480 mg Placebo (RF capsule) 40 mg Isokinetic MVC (10 × 10 sets @ 70% 1RM back squat) <60 min I, OS: pre, 1 h, 24 h, 48 h post exercise Levers et al (2016)29 18 M, 9 F, trained US: E <2 wk Tart cherry, FDC SD; 480 mg Placebo (RF capsule) 66 mg Half marathon race, >60 min I, OS: pre, 1 h, 24 h, 48 h-post exercise Mazani et al (2014)54 14 M, trained IR: E 2–6 wk Pomegranate, JC SD; 240 mL Placebo juice NR Treadmill run to exhaustion @70% max heart rate I, OS: pre, 14 d post supplement, immediately post exercise McAnulty et al (2011)55 25 M, trained US: Q 2–6 wk Blueberries, FW SD; 250 g + 375 g single bolus before exercise test Same NR 2.5-h treadmill run–72% VO2, >60 min I, OS: pre, immediate, 1 h post exercise McCormick et al (2016)30 9 M, trained US: Q <2 wk Tart cherry, JC MD; 1×–30 mL + 100 mL water + 1×–60 mL + 200 mL water Same 825.3 mg Swim-based power tests, >60 min I, OS: day 6 pre-post exercise, day 7, 12 h post exercise McLeay et al (2012)31 10 F, trained NZ: Q <2 wk Blueberry, FFS MD; 3×–200g + 50g banana +200 mL apple juice-1 d, SD-2 d Same 96.6–289.8 mg 300 eccentric KE, <60 min I, OS: 12 h, 36 h, 60 h post exercise Petrovic et al (2016)32 15 M, 17 F, trained RS: Q 2–6 wk Chokeberry, JC SD; 100 mL Same 43.6 mg Handball preseason training, >60 min OS: post exercise Pilaczynska-Szczesniak et al (2005)33 19 M, trained PL: E 2–6 wk Chokeberry, JC MD; 3×–50 mL Placebo juice 3 450 mg 2000-m rowing exercise test, <60 min OS: pre, 1 min, 24 h post exercise Silvestre et al (2014)34 6 M, trained BR: Q 2–6 wk Grape, JC MD; 2×–300 mL Same 6 660 mg Triathlon training–100-km cycling, 6-km run, 1.5-km swim, >60 min OS: prefasting, immediately, 1 h post exercise Toscano et al (2015)35 11 M, 4 F, trained BR: E 2–6 wk Grape, JC MD; 2×–10 mL/kg/d Placebo juice 68 mgc Anaerobic threshold, treadmill exhaustion test, >60 min I, OS: pre, 14 d, 28 d post exercise Reference Sample Intervention Study Population: no. and sex, training status Location and study design Study duration Fruit and processing method Fruit intervention Control Total daily anthocyanin amount Exercise intervention, intervention duration Biochemical measures and schedule Ammar et al (2016)51 9 M, trained TN: Q <2 wk Pomegranate, FFJ MD; 3×–250 mL + 500 mL single bolus 1 h before exercise test Same NRa Olympic lifts (snatch, clean and jerk, squat)–5 sets of each exercise, 2 sets of 3 reps at 85% of 1RM and 3 sets of reps at 90% of 1RM I: 3 min, 48 h, rest post exercise Ammar et al (2017)52 9 M, trained TN: Q <2 wk Pomegranate, FFJ MD; 3×–250 mL + 500 mL single bolus 1 h before exercise test Same NRa Olympic lifts (snatch, clean and jerk, squat)–5 sets of each exercise, 2 sets of 3 reps at 85% of 1RM and 3 sets of reps at 90% of 1RM OS: 3 min, 48 h, rest- post exercise Bell et al (2014)20 16 M, trained UK: E <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 546 mg High-intensity cycling intervals, >60 min I, OS: pre-post exercise trials 1, 3 3 Bell et al (2015)21 16 M, trained UK: E <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 552 mg High-intensity cycling intervals, >60 min I, OS: pre, immediate, 1 h, 3 h, 5 h, 48 h, 72 h post exercise Bell et al (2016)57 16 M, trained UK: E 2–6 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 264.6 mg 20-m sprint, agility drills, KE, <60 min I, OS: pre, immediately, 1 h, 3 h, 5 h, 48 h, 72 h post exercise Bloedon et al (2015)40 8 M, untrained US: Q >6 wk Wild blueberry, FFP SD; 300g Same 26 mg 1-h treadmill brisk walk–70% VO, >60 min I, OS: pre, immediately, 30 min, 1 h, 3 h, 6 h post exercise Bowtell et al (2011)22 10 M, trained UK: Q <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Same 547 mg Single-leg KE MVC, <60 min I, OS: pre, immediately, 24 h, 48 h post exercise Carvalho-Peixoto et al (2015)24 14 M, trained BR: Q <2 wk Acai, FDJ SD; 300 mL Same 27.6 mg Treadmill run–90% VO2, >60 min OS: pre, immediately post exercise Fuster-Muñoz et al (2016)25 20 M, trained ES: E 2–6 wk Pomegranate, FJ SD; 200 mL Placebo juiceb 11.71 mg Endurance training program (minimum criteria >1 h–3×/wk), >60 min I, OS: post exercise Goncalves et al (2011)53 10 M, trained BR: Q 2–6 wk Grape, JC SD; 300 mL Same NR Triathlon training–30-km cycling, 7-km run, 2-km swim/d, >60 min OS: post exercise Howatson et al (2010)26 13 M, 7 F, trained UK: E <2 wk Tart cherry, FFJ MD; 2×–8oz Placebo juice 80 mg Marathon race, >60 min I, OS: pre, immediate, 24h, 48h post exercise Hutchison et al (2016)27 6 M, 18 F, untrained US: E <2 wk Black currant, FFJ MD; 2×–16 oz Placebo juice 369 mg Eccentric KE (3 × 10 sets @ 115% 1RM), <60 min I: pre, 24 h, 48 h, 96 h post exercise Levers et al (2015)28 23 M, trained US: E < 2 wk Tart cherry, FDC SD; 480 mg Placebo (RF capsule) 40 mg Isokinetic MVC (10 × 10 sets @ 70% 1RM back squat) <60 min I, OS: pre, 1 h, 24 h, 48 h post exercise Levers et al (2016)29 18 M, 9 F, trained US: E <2 wk Tart cherry, FDC SD; 480 mg Placebo (RF capsule) 66 mg Half marathon race, >60 min I, OS: pre, 1 h, 24 h, 48 h-post exercise Mazani et al (2014)54 14 M, trained IR: E 2–6 wk Pomegranate, JC SD; 240 mL Placebo juice NR Treadmill run to exhaustion @70% max heart rate I, OS: pre, 14 d post supplement, immediately post exercise McAnulty et al (2011)55 25 M, trained US: Q 2–6 wk Blueberries, FW SD; 250 g + 375 g single bolus before exercise test Same NR 2.5-h treadmill run–72% VO2, >60 min I, OS: pre, immediate, 1 h post exercise McCormick et al (2016)30 9 M, trained US: Q <2 wk Tart cherry, JC MD; 1×–30 mL + 100 mL water + 1×–60 mL + 200 mL water Same 825.3 mg Swim-based power tests, >60 min I, OS: day 6 pre-post exercise, day 7, 12 h post exercise McLeay et al (2012)31 10 F, trained NZ: Q <2 wk Blueberry, FFS MD; 3×–200g + 50g banana +200 mL apple juice-1 d, SD-2 d Same 96.6–289.8 mg 300 eccentric KE, <60 min I, OS: 12 h, 36 h, 60 h post exercise Petrovic et al (2016)32 15 M, 17 F, trained RS: Q 2–6 wk Chokeberry, JC SD; 100 mL Same 43.6 mg Handball preseason training, >60 min OS: post exercise Pilaczynska-Szczesniak et al (2005)33 19 M, trained PL: E 2–6 wk Chokeberry, JC MD; 3×–50 mL Placebo juice 3 450 mg 2000-m rowing exercise test, <60 min OS: pre, 1 min, 24 h post exercise Silvestre et al (2014)34 6 M, trained BR: Q 2–6 wk Grape, JC MD; 2×–300 mL Same 6 660 mg Triathlon training–100-km cycling, 6-km run, 1.5-km swim, >60 min OS: prefasting, immediately, 1 h post exercise Toscano et al (2015)35 11 M, 4 F, trained BR: E 2–6 wk Grape, JC MD; 2×–10 mL/kg/d Placebo juice 68 mgc Anaerobic threshold, treadmill exhaustion test, >60 min I, OS: pre, 14 d, 28 d post exercise Abbreviations: BR, Brazil; E, experimental; ES, Spain; F, females; FDC, freeze-dried capsule; FDJ, freeze-dried juice; FFJ, fresh frozen juice; FFP, fresh frozen puree; FFS, fresh frozen smoothie; FJ, fresh juice; FW, fresh whole; I, inflammation; IR, Iran; JC, juice concentrate; KE, knee extensors; M, males; MD, multiple daily; MVC, maximum voluntary contraction; NR, not reported, NZ, New Zealand; OS, oxidative stress; PL, Poland; Q, quasi; RF, rice flour; RM, rep Mmx; RS, Serbia; SD, single daily; TN, Tunisia; UK, United Kingdom; US, United States; VO2, maximum rate of oxygen consumption a Anthocyanins not tested, but each 500 mL contained 2.56 g of total polyphenol, 1.08 g of orthodiphenols, 292.59 mg of flavonoids, and 46.75 mg of flavonols. b Not reported third group of 50% diluted pomegranate juice. c Provided participant BMI measurements. From this a fruit dosage calculation was estimated and created for a 65-kg person (68 mg anthocyanin/65 kg person). View Large Table 2 Study characteristics Reference Sample Intervention Study Population: no. and sex, training status Location and study design Study duration Fruit and processing method Fruit intervention Control Total daily anthocyanin amount Exercise intervention, intervention duration Biochemical measures and schedule Ammar et al (2016)51 9 M, trained TN: Q <2 wk Pomegranate, FFJ MD; 3×–250 mL + 500 mL single bolus 1 h before exercise test Same NRa Olympic lifts (snatch, clean and jerk, squat)–5 sets of each exercise, 2 sets of 3 reps at 85% of 1RM and 3 sets of reps at 90% of 1RM I: 3 min, 48 h, rest post exercise Ammar et al (2017)52 9 M, trained TN: Q <2 wk Pomegranate, FFJ MD; 3×–250 mL + 500 mL single bolus 1 h before exercise test Same NRa Olympic lifts (snatch, clean and jerk, squat)–5 sets of each exercise, 2 sets of 3 reps at 85% of 1RM and 3 sets of reps at 90% of 1RM OS: 3 min, 48 h, rest- post exercise Bell et al (2014)20 16 M, trained UK: E <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 546 mg High-intensity cycling intervals, >60 min I, OS: pre-post exercise trials 1, 3 3 Bell et al (2015)21 16 M, trained UK: E <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 552 mg High-intensity cycling intervals, >60 min I, OS: pre, immediate, 1 h, 3 h, 5 h, 48 h, 72 h post exercise Bell et al (2016)57 16 M, trained UK: E 2–6 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 264.6 mg 20-m sprint, agility drills, KE, <60 min I, OS: pre, immediately, 1 h, 3 h, 5 h, 48 h, 72 h post exercise Bloedon et al (2015)40 8 M, untrained US: Q >6 wk Wild blueberry, FFP SD; 300g Same 26 mg 1-h treadmill brisk walk–70% VO, >60 min I, OS: pre, immediately, 30 min, 1 h, 3 h, 6 h post exercise Bowtell et al (2011)22 10 M, trained UK: Q <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Same 547 mg Single-leg KE MVC, <60 min I, OS: pre, immediately, 24 h, 48 h post exercise Carvalho-Peixoto et al (2015)24 14 M, trained BR: Q <2 wk Acai, FDJ SD; 300 mL Same 27.6 mg Treadmill run–90% VO2, >60 min OS: pre, immediately post exercise Fuster-Muñoz et al (2016)25 20 M, trained ES: E 2–6 wk Pomegranate, FJ SD; 200 mL Placebo juiceb 11.71 mg Endurance training program (minimum criteria >1 h–3×/wk), >60 min I, OS: post exercise Goncalves et al (2011)53 10 M, trained BR: Q 2–6 wk Grape, JC SD; 300 mL Same NR Triathlon training–30-km cycling, 7-km run, 2-km swim/d, >60 min OS: post exercise Howatson et al (2010)26 13 M, 7 F, trained UK: E <2 wk Tart cherry, FFJ MD; 2×–8oz Placebo juice 80 mg Marathon race, >60 min I, OS: pre, immediate, 24h, 48h post exercise Hutchison et al (2016)27 6 M, 18 F, untrained US: E <2 wk Black currant, FFJ MD; 2×–16 oz Placebo juice 369 mg Eccentric KE (3 × 10 sets @ 115% 1RM), <60 min I: pre, 24 h, 48 h, 96 h post exercise Levers et al (2015)28 23 M, trained US: E < 2 wk Tart cherry, FDC SD; 480 mg Placebo (RF capsule) 40 mg Isokinetic MVC (10 × 10 sets @ 70% 1RM back squat) <60 min I, OS: pre, 1 h, 24 h, 48 h post exercise Levers et al (2016)29 18 M, 9 F, trained US: E <2 wk Tart cherry, FDC SD; 480 mg Placebo (RF capsule) 66 mg Half marathon race, >60 min I, OS: pre, 1 h, 24 h, 48 h-post exercise Mazani et al (2014)54 14 M, trained IR: E 2–6 wk Pomegranate, JC SD; 240 mL Placebo juice NR Treadmill run to exhaustion @70% max heart rate I, OS: pre, 14 d post supplement, immediately post exercise McAnulty et al (2011)55 25 M, trained US: Q 2–6 wk Blueberries, FW SD; 250 g + 375 g single bolus before exercise test Same NR 2.5-h treadmill run–72% VO2, >60 min I, OS: pre, immediate, 1 h post exercise McCormick et al (2016)30 9 M, trained US: Q <2 wk Tart cherry, JC MD; 1×–30 mL + 100 mL water + 1×–60 mL + 200 mL water Same 825.3 mg Swim-based power tests, >60 min I, OS: day 6 pre-post exercise, day 7, 12 h post exercise McLeay et al (2012)31 10 F, trained NZ: Q <2 wk Blueberry, FFS MD; 3×–200g + 50g banana +200 mL apple juice-1 d, SD-2 d Same 96.6–289.8 mg 300 eccentric KE, <60 min I, OS: 12 h, 36 h, 60 h post exercise Petrovic et al (2016)32 15 M, 17 F, trained RS: Q 2–6 wk Chokeberry, JC SD; 100 mL Same 43.6 mg Handball preseason training, >60 min OS: post exercise Pilaczynska-Szczesniak et al (2005)33 19 M, trained PL: E 2–6 wk Chokeberry, JC MD; 3×–50 mL Placebo juice 3 450 mg 2000-m rowing exercise test, <60 min OS: pre, 1 min, 24 h post exercise Silvestre et al (2014)34 6 M, trained BR: Q 2–6 wk Grape, JC MD; 2×–300 mL Same 6 660 mg Triathlon training–100-km cycling, 6-km run, 1.5-km swim, >60 min OS: prefasting, immediately, 1 h post exercise Toscano et al (2015)35 11 M, 4 F, trained BR: E 2–6 wk Grape, JC MD; 2×–10 mL/kg/d Placebo juice 68 mgc Anaerobic threshold, treadmill exhaustion test, >60 min I, OS: pre, 14 d, 28 d post exercise Reference Sample Intervention Study Population: no. and sex, training status Location and study design Study duration Fruit and processing method Fruit intervention Control Total daily anthocyanin amount Exercise intervention, intervention duration Biochemical measures and schedule Ammar et al (2016)51 9 M, trained TN: Q <2 wk Pomegranate, FFJ MD; 3×–250 mL + 500 mL single bolus 1 h before exercise test Same NRa Olympic lifts (snatch, clean and jerk, squat)–5 sets of each exercise, 2 sets of 3 reps at 85% of 1RM and 3 sets of reps at 90% of 1RM I: 3 min, 48 h, rest post exercise Ammar et al (2017)52 9 M, trained TN: Q <2 wk Pomegranate, FFJ MD; 3×–250 mL + 500 mL single bolus 1 h before exercise test Same NRa Olympic lifts (snatch, clean and jerk, squat)–5 sets of each exercise, 2 sets of 3 reps at 85% of 1RM and 3 sets of reps at 90% of 1RM OS: 3 min, 48 h, rest- post exercise Bell et al (2014)20 16 M, trained UK: E <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 546 mg High-intensity cycling intervals, >60 min I, OS: pre-post exercise trials 1, 3 3 Bell et al (2015)21 16 M, trained UK: E <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 552 mg High-intensity cycling intervals, >60 min I, OS: pre, immediate, 1 h, 3 h, 5 h, 48 h, 72 h post exercise Bell et al (2016)57 16 M, trained UK: E 2–6 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Placebo juice 264.6 mg 20-m sprint, agility drills, KE, <60 min I, OS: pre, immediately, 1 h, 3 h, 5 h, 48 h, 72 h post exercise Bloedon et al (2015)40 8 M, untrained US: Q >6 wk Wild blueberry, FFP SD; 300g Same 26 mg 1-h treadmill brisk walk–70% VO, >60 min I, OS: pre, immediately, 30 min, 1 h, 3 h, 6 h post exercise Bowtell et al (2011)22 10 M, trained UK: Q <2 wk Tart cherry, JC MD; 2×–30 mL + 100 mL water Same 547 mg Single-leg KE MVC, <60 min I, OS: pre, immediately, 24 h, 48 h post exercise Carvalho-Peixoto et al (2015)24 14 M, trained BR: Q <2 wk Acai, FDJ SD; 300 mL Same 27.6 mg Treadmill run–90% VO2, >60 min OS: pre, immediately post exercise Fuster-Muñoz et al (2016)25 20 M, trained ES: E 2–6 wk Pomegranate, FJ SD; 200 mL Placebo juiceb 11.71 mg Endurance training program (minimum criteria >1 h–3×/wk), >60 min I, OS: post exercise Goncalves et al (2011)53 10 M, trained BR: Q 2–6 wk Grape, JC SD; 300 mL Same NR Triathlon training–30-km cycling, 7-km run, 2-km swim/d, >60 min OS: post exercise Howatson et al (2010)26 13 M, 7 F, trained UK: E <2 wk Tart cherry, FFJ MD; 2×–8oz Placebo juice 80 mg Marathon race, >60 min I, OS: pre, immediate, 24h, 48h post exercise Hutchison et al (2016)27 6 M, 18 F, untrained US: E <2 wk Black currant, FFJ MD; 2×–16 oz Placebo juice 369 mg Eccentric KE (3 × 10 sets @ 115% 1RM), <60 min I: pre, 24 h, 48 h, 96 h post exercise Levers et al (2015)28 23 M, trained US: E < 2 wk Tart cherry, FDC SD; 480 mg Placebo (RF capsule) 40 mg Isokinetic MVC (10 × 10 sets @ 70% 1RM back squat) <60 min I, OS: pre, 1 h, 24 h, 48 h post exercise Levers et al (2016)29 18 M, 9 F, trained US: E <2 wk Tart cherry, FDC SD; 480 mg Placebo (RF capsule) 66 mg Half marathon race, >60 min I, OS: pre, 1 h, 24 h, 48 h-post exercise Mazani et al (2014)54 14 M, trained IR: E 2–6 wk Pomegranate, JC SD; 240 mL Placebo juice NR Treadmill run to exhaustion @70% max heart rate I, OS: pre, 14 d post supplement, immediately post exercise McAnulty et al (2011)55 25 M, trained US: Q 2–6 wk Blueberries, FW SD; 250 g + 375 g single bolus before exercise test Same NR 2.5-h treadmill run–72% VO2, >60 min I, OS: pre, immediate, 1 h post exercise McCormick et al (2016)30 9 M, trained US: Q <2 wk Tart cherry, JC MD; 1×–30 mL + 100 mL water + 1×–60 mL + 200 mL water Same 825.3 mg Swim-based power tests, >60 min I, OS: day 6 pre-post exercise, day 7, 12 h post exercise McLeay et al (2012)31 10 F, trained NZ: Q <2 wk Blueberry, FFS MD; 3×–200g + 50g banana +200 mL apple juice-1 d, SD-2 d Same 96.6–289.8 mg 300 eccentric KE, <60 min I, OS: 12 h, 36 h, 60 h post exercise Petrovic et al (2016)32 15 M, 17 F, trained RS: Q 2–6 wk Chokeberry, JC SD; 100 mL Same 43.6 mg Handball preseason training, >60 min OS: post exercise Pilaczynska-Szczesniak et al (2005)33 19 M, trained PL: E 2–6 wk Chokeberry, JC MD; 3×–50 mL Placebo juice 3 450 mg 2000-m rowing exercise test, <60 min OS: pre, 1 min, 24 h post exercise Silvestre et al (2014)34 6 M, trained BR: Q 2–6 wk Grape, JC MD; 2×–300 mL Same 6 660 mg Triathlon training–100-km cycling, 6-km run, 1.5-km swim, >60 min OS: prefasting, immediately, 1 h post exercise Toscano et al (2015)35 11 M, 4 F, trained BR: E 2–6 wk Grape, JC MD; 2×–10 mL/kg/d Placebo juice 68 mgc Anaerobic threshold, treadmill exhaustion test, >60 min I, OS: pre, 14 d, 28 d post exercise Abbreviations: BR, Brazil; E, experimental; ES, Spain; F, females; FDC, freeze-dried capsule; FDJ, freeze-dried juice; FFJ, fresh frozen juice; FFP, fresh frozen puree; FFS, fresh frozen smoothie; FJ, fresh juice; FW, fresh whole; I, inflammation; IR, Iran; JC, juice concentrate; KE, knee extensors; M, males; MD, multiple daily; MVC, maximum voluntary contraction; NR, not reported, NZ, New Zealand; OS, oxidative stress; PL, Poland; Q, quasi; RF, rice flour; RM, rep Mmx; RS, Serbia; SD, single daily; TN, Tunisia; UK, United Kingdom; US, United States; VO2, maximum rate of oxygen consumption a Anthocyanins not tested, but each 500 mL contained 2.56 g of total polyphenol, 1.08 g of orthodiphenols, 292.59 mg of flavonoids, and 46.75 mg of flavonols. b Not reported third group of 50% diluted pomegranate juice. c Provided participant BMI measurements. From this a fruit dosage calculation was estimated and created for a 65-kg person (68 mg anthocyanin/65 kg person). View Large Outliers and publication bias Studies evaluating oxidative stress outcomes (includes all oxidative stress markers) contained 3 outliers (Mazani et al,54,z = 2.00; Bell et al,20,z = −2.20; Bowtell et al,22,z = −3.08), and for inflammation outcomes (includes all inflammation markers), there were 2 outliers (Hutchison et al,27,z = −2.01; McAnulty et al,55z = −2.00). Sensitivity analyses (one study removed) were performed with comprehensive meta-analysis, and the results determined that there would have been a potential decrease in both inflammation (g = +0.085) and oxidative stress (g = +0.079) if outliers were retained, with results remaining significant for both inflammation (P < 0.001) and oxidative stress (P = 0.036), and within the 95%CI. Therefore, the decision was made to have all 5 studies remain in both analyses. Publication bias was not likely in either set of outcomes because the funnel plots were symmetrically distributed, the trim-and-fill procedures did not adjust values by adding studies to the right side of the distribution, and the fail-safe N calculations were 37 for oxidative stress and 66 for inflammation to nullify the treatment effects. Random-effects model The summary effect across inflammation outcomes by group (k) was a significant small negative effect (k = 16; g = −0.469; 95%CI, −0.687 to −0.252; Z = −4.23; P < 0.001). A small negative effect (k = 20; g = −0.319; 95%CI, −0.616 to −0.021; Z = −2.10; P = 0.036) was found for exercise-induced oxidative stress outcomes. Negative effect sizes were interpreted as treatment/experimental groups/conditions producing stronger results. Studies evaluating oxidative stress had a significant heterogeneous distribution (QTotal = 40.31; P < 0.05) with a moderate degree of variability (I2 = 52.87) that could be explained by moderator analyses. Inflammation outcomes had a homogeneous distribution (QTotal = 11.34; P > 0.05). Larger scores of variability are indicative of analyses that potentially explain the variability, whereas smaller scores can be attributed to random error. Figure 220–22,25–31,35,40,51,54,55,57 (inflammation) and Figure 320–22,24–26,28–35,40,52–55,57 (oxidative stress) provide information and basic statistics on studies in each analysis. Figure 2 View largeDownload slide Summary for the association between consumption of fruits high in anthocyanins and inflammation outcomes. Figure 2 View largeDownload slide Summary for the association between consumption of fruits high in anthocyanins and inflammation outcomes. Figure 3 View largeDownload slide Summary for the association between consumption of fruits high in anthocyanins and oxidative stress outcomes. Figure 3 View largeDownload slide Summary for the association between consumption of fruits high in anthocyanins and oxidative stress outcomes. Outcome analyses There were only 5 inflammation outcomes that could be interpreted from the analysis. Outcomes ranged from small to moderate negative effect sizes with only interleukin 6 (k = 11; g = −0.75; P = 0.002) showing a significant and moderate effect. Additional inflammation outcomes that had small to moderate negative effect sizes included highly sensitive C-reactive protein (k = 7; g = −0.44; P = 0.009) and tumor necrosis factor alpha (k = 6; g = −0.45; P = 0.018). Inflammation outcomes measures of variability were small except for interleukin 6, which had a significant heterogeneous distribution (QTotal = 28.05; P < 0.05). Oxidative stress outcome treatment effect sizes ranged from small to large, with the largest moderate and large effect sizes for malondialdehyde (k = 5; g = −0.65; P < 0.001) and protein carbonyls (k = 4; g = −1.61; P = 0.045), respectively. Table 3 provides an overview of the inflammation and oxidative stress outcomes. Table 3 Outcome analyses for inflammation and oxidative stress Biological marker Effect size statistics Null test (2-tail) Heterogeneity statistics Publication bias k g SE S2 95%CI Z P value Q τ2 I2 Fail-safe N Inflammation outcomes  CRP 3 −0.331 0.255 0.065 −0.831 to 0.168 −1.299 0.194 1.055 0.000 0.000 0  hsCRP 7 −0.438 0.167 0.028 −0.765 to −0.110 −2.620 0.009* 2.729 0.000 0.000 4  INF-y 1 −0.327 0.382 0.146 −1.077 to 0.422 −0.856 0.392 0.000 0.000 0.000 0  IL-1β 5 0.081 0.201 0.040 −0.312 to 0.474 0.402 0.688 4.131 0.006 3.162 0  IL-1ra 1 −0.948 0.474 0.225 −1.878 to −0.019 −1.999 0.046* 0.000 0.000 0.000 0  IL-6 11 −0.748 0.236 0.056 −1.212 to −0.285 −3.165 0.002* 28.076 0.390 64.382 65  IL-8 6 −0.201 0.175 0.031 −0.543 to 0.142 −1.148 0.251 0.847 0.000 0.000 0  IL-10 1 −2.410 0.532 0.283 −3.453 to −1.367 −4.528 0.000** 0.000 0.000 0.000 0  IL-13 1 −0.635 0.390 0.152 −1.398 to 0.129 −1.630 0.103 0.000 0.000 0.000 0  sE Selectin 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000 0  TNF-α 6 −0.446 0.189 0.036 −0.816 to −0.076 −2.362 0.018* 5.341 0.014 6.392 4  Ceruloplasmin 1 −0.337 0.383 0.147 −1.088 to 0.415 −0.878 0.380 0.000 0.000 0.000 0  MMP2 1 −0.434 0.074 0.140 −1.168 to 0.299 −1.160 0.246 0.000 0.000 0.000 0  MMP9 1 −0.660 0.380 0.144 −1.144 to 0.084 −1.739 0.082 0.000 0.000 0.000 0 Oxidative stress outcomes  5-OUMU 1 0.363 0.435 0.189 −1.216 to 0.490 −0.834 0.404 0.000 0.000 0.000 0  8-OH-DG 1 −0.161 0.429 0.184 −1.002 to 0.680 −0.376 0.707 0.000 0.000 0.000 0  AGP 1 −0.434 0.415 0.172 −1.247 to 0.378 −1.048 0.295 0.000 0.000 0.000 0  DCF 1 −0.608 0.444 0.198 −1.479 to 0.264 −1.367 0.172 0.000 0.000 0.000 0  Comet 1 0.447 0.437 0.191 −0.409 to 1.303 1.022 0.307 0.000 0.000 0.000 0  MDA 5 −0.653 0.187 0.035 −1.020 to −0.286 −3.488 0.000** 2.503 0.000 0.000 3  LOOH 3 −0.679 0.571 0.326 −1.798 to 0.439 −1.190 0.234 7.463 0.713 73.199 1  Nt 3 −0.001 0.233 0.054 −0.458 to 0.456 −0.004 0.996 1.098 0.000 0.000 0  PC 4 −1.607 0.802 0.644 −3.179 to −0.035 −2.003 0.045* 24.389 2.020 87.699 16  UA 5 −0.118 0.414 0.171 −0.929 to 0.694 −0.284 0.776 16.524 0.649 75.793 0  CAT 2 0.172 0.350 0.123 −0.514 to 0.859 0.492 0.623 0.093 0.000 0.000 0  GPx 5 0.276 0.374 0.140 −0.458 to 1.009 0.736 0.462 13.706 0.492 70.815 0  SOD 6 0.056 0.258 0.066 −0.449 to 0.561 0.218 0.828 10.684 0.210 53.201 0  TAC 2 0.494 0.299 9.089 −0.091 to 1.080 1.655 0.098 11.346 1.846 91.186 0  TBARS 6 −0.271 0.206 0.042 −0.674 to 0.132 −1.319 0.187 6.182 0.048 19.119 0 Biological marker Effect size statistics Null test (2-tail) Heterogeneity statistics Publication bias k g SE S2 95%CI Z P value Q τ2 I2 Fail-safe N Inflammation outcomes  CRP 3 −0.331 0.255 0.065 −0.831 to 0.168 −1.299 0.194 1.055 0.000 0.000 0  hsCRP 7 −0.438 0.167 0.028 −0.765 to −0.110 −2.620 0.009* 2.729 0.000 0.000 4  INF-y 1 −0.327 0.382 0.146 −1.077 to 0.422 −0.856 0.392 0.000 0.000 0.000 0  IL-1β 5 0.081 0.201 0.040 −0.312 to 0.474 0.402 0.688 4.131 0.006 3.162 0  IL-1ra 1 −0.948 0.474 0.225 −1.878 to −0.019 −1.999 0.046* 0.000 0.000 0.000 0  IL-6 11 −0.748 0.236 0.056 −1.212 to −0.285 −3.165 0.002* 28.076 0.390 64.382 65  IL-8 6 −0.201 0.175 0.031 −0.543 to 0.142 −1.148 0.251 0.847 0.000 0.000 0  IL-10 1 −2.410 0.532 0.283 −3.453 to −1.367 −4.528 0.000** 0.000 0.000 0.000 0  IL-13 1 −0.635 0.390 0.152 −1.398 to 0.129 −1.630 0.103 0.000 0.000 0.000 0  sE Selectin 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000 0  TNF-α 6 −0.446 0.189 0.036 −0.816 to −0.076 −2.362 0.018* 5.341 0.014 6.392 4  Ceruloplasmin 1 −0.337 0.383 0.147 −1.088 to 0.415 −0.878 0.380 0.000 0.000 0.000 0  MMP2 1 −0.434 0.074 0.140 −1.168 to 0.299 −1.160 0.246 0.000 0.000 0.000 0  MMP9 1 −0.660 0.380 0.144 −1.144 to 0.084 −1.739 0.082 0.000 0.000 0.000 0 Oxidative stress outcomes  5-OUMU 1 0.363 0.435 0.189 −1.216 to 0.490 −0.834 0.404 0.000 0.000 0.000 0  8-OH-DG 1 −0.161 0.429 0.184 −1.002 to 0.680 −0.376 0.707 0.000 0.000 0.000 0  AGP 1 −0.434 0.415 0.172 −1.247 to 0.378 −1.048 0.295 0.000 0.000 0.000 0  DCF 1 −0.608 0.444 0.198 −1.479 to 0.264 −1.367 0.172 0.000 0.000 0.000 0  Comet 1 0.447 0.437 0.191 −0.409 to 1.303 1.022 0.307 0.000 0.000 0.000 0  MDA 5 −0.653 0.187 0.035 −1.020 to −0.286 −3.488 0.000** 2.503 0.000 0.000 3  LOOH 3 −0.679 0.571 0.326 −1.798 to 0.439 −1.190 0.234 7.463 0.713 73.199 1  Nt 3 −0.001 0.233 0.054 −0.458 to 0.456 −0.004 0.996 1.098 0.000 0.000 0  PC 4 −1.607 0.802 0.644 −3.179 to −0.035 −2.003 0.045* 24.389 2.020 87.699 16  UA 5 −0.118 0.414 0.171 −0.929 to 0.694 −0.284 0.776 16.524 0.649 75.793 0  CAT 2 0.172 0.350 0.123 −0.514 to 0.859 0.492 0.623 0.093 0.000 0.000 0  GPx 5 0.276 0.374 0.140 −0.458 to 1.009 0.736 0.462 13.706 0.492 70.815 0  SOD 6 0.056 0.258 0.066 −0.449 to 0.561 0.218 0.828 10.684 0.210 53.201 0  TAC 2 0.494 0.299 9.089 −0.091 to 1.080 1.655 0.098 11.346 1.846 91.186 0  TBARS 6 −0.271 0.206 0.042 −0.674 to 0.132 −1.319 0.187 6.182 0.048 19.119 0 In this table, g is the effect size (Hedges’s g); I2 is the total variance explained by moderator; k is the number of effect sizes; S2 is the variance; SE is the standard error; Z is the test of null hypothesis, Q is used to determine heterogeneity; and τ2 indicates between-study variance in the random-effects model. * P < 0.05, **P < 0.001. Abbreviations: AGP, alpha-l- acid- glycoprotein; CAT, catalase; CI, confidence interval; Comet, comet assay (single-cell gel electrophoresis); CRP, C-reactive protein; DCF, carboxy-dihydro-2', 7'-dicholorohydrofluorescein diacetate; GPx, glutathione peroxidase; hsCRP, highly sensitive C-reactive protein; INF-y, interferon gamma; IL-1β, interleukin 1 beta; IL-1ra, interleukin 1 receptor antagonist; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; IL-13, interleukin 13; LOOH, lipid hydroperoxides; MDA malondialdehyde; MMP2, matrix metalloproteinases 2; MMP9, matrix metalloproteinases 9; Nt, nitrotyrosine; PC, protein carbonyls; SOD, superoxide dismutase; TAC, total antioxidant capacity; TBARS, hiobarbituric acid species; TNF-α, tumor necrosis factor alpha; 5-OUMU, 5-hydroxymethyl-2'-deoxyuridine; 8-OH-DG, 8-hydroxy-2-deoxy guanosine; UA, uric acid. View Large Table 3 Outcome analyses for inflammation and oxidative stress Biological marker Effect size statistics Null test (2-tail) Heterogeneity statistics Publication bias k g SE S2 95%CI Z P value Q τ2 I2 Fail-safe N Inflammation outcomes  CRP 3 −0.331 0.255 0.065 −0.831 to 0.168 −1.299 0.194 1.055 0.000 0.000 0  hsCRP 7 −0.438 0.167 0.028 −0.765 to −0.110 −2.620 0.009* 2.729 0.000 0.000 4  INF-y 1 −0.327 0.382 0.146 −1.077 to 0.422 −0.856 0.392 0.000 0.000 0.000 0  IL-1β 5 0.081 0.201 0.040 −0.312 to 0.474 0.402 0.688 4.131 0.006 3.162 0  IL-1ra 1 −0.948 0.474 0.225 −1.878 to −0.019 −1.999 0.046* 0.000 0.000 0.000 0  IL-6 11 −0.748 0.236 0.056 −1.212 to −0.285 −3.165 0.002* 28.076 0.390 64.382 65  IL-8 6 −0.201 0.175 0.031 −0.543 to 0.142 −1.148 0.251 0.847 0.000 0.000 0  IL-10 1 −2.410 0.532 0.283 −3.453 to −1.367 −4.528 0.000** 0.000 0.000 0.000 0  IL-13 1 −0.635 0.390 0.152 −1.398 to 0.129 −1.630 0.103 0.000 0.000 0.000 0  sE Selectin 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000 0  TNF-α 6 −0.446 0.189 0.036 −0.816 to −0.076 −2.362 0.018* 5.341 0.014 6.392 4  Ceruloplasmin 1 −0.337 0.383 0.147 −1.088 to 0.415 −0.878 0.380 0.000 0.000 0.000 0  MMP2 1 −0.434 0.074 0.140 −1.168 to 0.299 −1.160 0.246 0.000 0.000 0.000 0  MMP9 1 −0.660 0.380 0.144 −1.144 to 0.084 −1.739 0.082 0.000 0.000 0.000 0 Oxidative stress outcomes  5-OUMU 1 0.363 0.435 0.189 −1.216 to 0.490 −0.834 0.404 0.000 0.000 0.000 0  8-OH-DG 1 −0.161 0.429 0.184 −1.002 to 0.680 −0.376 0.707 0.000 0.000 0.000 0  AGP 1 −0.434 0.415 0.172 −1.247 to 0.378 −1.048 0.295 0.000 0.000 0.000 0  DCF 1 −0.608 0.444 0.198 −1.479 to 0.264 −1.367 0.172 0.000 0.000 0.000 0  Comet 1 0.447 0.437 0.191 −0.409 to 1.303 1.022 0.307 0.000 0.000 0.000 0  MDA 5 −0.653 0.187 0.035 −1.020 to −0.286 −3.488 0.000** 2.503 0.000 0.000 3  LOOH 3 −0.679 0.571 0.326 −1.798 to 0.439 −1.190 0.234 7.463 0.713 73.199 1  Nt 3 −0.001 0.233 0.054 −0.458 to 0.456 −0.004 0.996 1.098 0.000 0.000 0  PC 4 −1.607 0.802 0.644 −3.179 to −0.035 −2.003 0.045* 24.389 2.020 87.699 16  UA 5 −0.118 0.414 0.171 −0.929 to 0.694 −0.284 0.776 16.524 0.649 75.793 0  CAT 2 0.172 0.350 0.123 −0.514 to 0.859 0.492 0.623 0.093 0.000 0.000 0  GPx 5 0.276 0.374 0.140 −0.458 to 1.009 0.736 0.462 13.706 0.492 70.815 0  SOD 6 0.056 0.258 0.066 −0.449 to 0.561 0.218 0.828 10.684 0.210 53.201 0  TAC 2 0.494 0.299 9.089 −0.091 to 1.080 1.655 0.098 11.346 1.846 91.186 0  TBARS 6 −0.271 0.206 0.042 −0.674 to 0.132 −1.319 0.187 6.182 0.048 19.119 0 Biological marker Effect size statistics Null test (2-tail) Heterogeneity statistics Publication bias k g SE S2 95%CI Z P value Q τ2 I2 Fail-safe N Inflammation outcomes  CRP 3 −0.331 0.255 0.065 −0.831 to 0.168 −1.299 0.194 1.055 0.000 0.000 0  hsCRP 7 −0.438 0.167 0.028 −0.765 to −0.110 −2.620 0.009* 2.729 0.000 0.000 4  INF-y 1 −0.327 0.382 0.146 −1.077 to 0.422 −0.856 0.392 0.000 0.000 0.000 0  IL-1β 5 0.081 0.201 0.040 −0.312 to 0.474 0.402 0.688 4.131 0.006 3.162 0  IL-1ra 1 −0.948 0.474 0.225 −1.878 to −0.019 −1.999 0.046* 0.000 0.000 0.000 0  IL-6 11 −0.748 0.236 0.056 −1.212 to −0.285 −3.165 0.002* 28.076 0.390 64.382 65  IL-8 6 −0.201 0.175 0.031 −0.543 to 0.142 −1.148 0.251 0.847 0.000 0.000 0  IL-10 1 −2.410 0.532 0.283 −3.453 to −1.367 −4.528 0.000** 0.000 0.000 0.000 0  IL-13 1 −0.635 0.390 0.152 −1.398 to 0.129 −1.630 0.103 0.000 0.000 0.000 0  sE Selectin 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000 0  TNF-α 6 −0.446 0.189 0.036 −0.816 to −0.076 −2.362 0.018* 5.341 0.014 6.392 4  Ceruloplasmin 1 −0.337 0.383 0.147 −1.088 to 0.415 −0.878 0.380 0.000 0.000 0.000 0  MMP2 1 −0.434 0.074 0.140 −1.168 to 0.299 −1.160 0.246 0.000 0.000 0.000 0  MMP9 1 −0.660 0.380 0.144 −1.144 to 0.084 −1.739 0.082 0.000 0.000 0.000 0 Oxidative stress outcomes  5-OUMU 1 0.363 0.435 0.189 −1.216 to 0.490 −0.834 0.404 0.000 0.000 0.000 0  8-OH-DG 1 −0.161 0.429 0.184 −1.002 to 0.680 −0.376 0.707 0.000 0.000 0.000 0  AGP 1 −0.434 0.415 0.172 −1.247 to 0.378 −1.048 0.295 0.000 0.000 0.000 0  DCF 1 −0.608 0.444 0.198 −1.479 to 0.264 −1.367 0.172 0.000 0.000 0.000 0  Comet 1 0.447 0.437 0.191 −0.409 to 1.303 1.022 0.307 0.000 0.000 0.000 0  MDA 5 −0.653 0.187 0.035 −1.020 to −0.286 −3.488 0.000** 2.503 0.000 0.000 3  LOOH 3 −0.679 0.571 0.326 −1.798 to 0.439 −1.190 0.234 7.463 0.713 73.199 1  Nt 3 −0.001 0.233 0.054 −0.458 to 0.456 −0.004 0.996 1.098 0.000 0.000 0  PC 4 −1.607 0.802 0.644 −3.179 to −0.035 −2.003 0.045* 24.389 2.020 87.699 16  UA 5 −0.118 0.414 0.171 −0.929 to 0.694 −0.284 0.776 16.524 0.649 75.793 0  CAT 2 0.172 0.350 0.123 −0.514 to 0.859 0.492 0.623 0.093 0.000 0.000 0  GPx 5 0.276 0.374 0.140 −0.458 to 1.009 0.736 0.462 13.706 0.492 70.815 0  SOD 6 0.056 0.258 0.066 −0.449 to 0.561 0.218 0.828 10.684 0.210 53.201 0  TAC 2 0.494 0.299 9.089 −0.091 to 1.080 1.655 0.098 11.346 1.846 91.186 0  TBARS 6 −0.271 0.206 0.042 −0.674 to 0.132 −1.319 0.187 6.182 0.048 19.119 0 In this table, g is the effect size (Hedges’s g); I2 is the total variance explained by moderator; k is the number of effect sizes; S2 is the variance; SE is the standard error; Z is the test of null hypothesis, Q is used to determine heterogeneity; and τ2 indicates between-study variance in the random-effects model. * P < 0.05, **P < 0.001. Abbreviations: AGP, alpha-l- acid- glycoprotein; CAT, catalase; CI, confidence interval; Comet, comet assay (single-cell gel electrophoresis); CRP, C-reactive protein; DCF, carboxy-dihydro-2', 7'-dicholorohydrofluorescein diacetate; GPx, glutathione peroxidase; hsCRP, highly sensitive C-reactive protein; INF-y, interferon gamma; IL-1β, interleukin 1 beta; IL-1ra, interleukin 1 receptor antagonist; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; IL-13, interleukin 13; LOOH, lipid hydroperoxides; MDA malondialdehyde; MMP2, matrix metalloproteinases 2; MMP9, matrix metalloproteinases 9; Nt, nitrotyrosine; PC, protein carbonyls; SOD, superoxide dismutase; TAC, total antioxidant capacity; TBARS, hiobarbituric acid species; TNF-α, tumor necrosis factor alpha; 5-OUMU, 5-hydroxymethyl-2'-deoxyuridine; 8-OH-DG, 8-hydroxy-2-deoxy guanosine; UA, uric acid. View Large Moderators analyses A secondary purpose of the current investigation was to analyze the moderating influences of both inflammation and oxidative stress biomarkers. Results suggest that there were no moderating variables for inflammation biomarkers (all markers combined) that related to methodological, sample, and study characteristics. Studies within the subgroups for fruit type (tart cherries: Z = −2.62, P = 0.009), fruit processing (fresh frozen juice: Z = −2.88, P = 0.004; juice concentrate: Z = −2.74; P = 0.006), fruit delivery (multiple daily: Z = −3.35, P < 0.001), research designs (experimental: Z = −3.23, P = 0.001), study durations (< 2 wk: Z = −2.94, P = 0.002; 2–6 wk, Z = −2.92, P = 0.004), total daily anthocyanins (> 100 mg: Z = −3.23, P = 0.001; <100: Z = −2.79, P = 0.005), exercise type (aerobic: Z = −3.45, P = 0.001; anaerobic: Z = −2.48, P = 0.013), exercise time (< 60 min: Z = −3.10, P = 0.002; > 60 min: Z = −2.94, P = 0.003), training status (trained: Z = −3.62, P < 0.001), sex (males: Z = −3.63, P < 0.001), and funding (grant funded: Z = −3.45, P = 0.001) suggested significant effects within each specific subgroup; however, between-subgroup comparisons were inconclusive (Table 4). Results for oxidative stress biomarkers (all markers combined) also indicated that there were no significant differences between moderators (subgrouping variables); however, trends were apparent within groups. Specifically, fruit types (tart cherry: Z = −2.14, P = 0.033), fruit processing (fresh juice: Z = −2.62, P = 0.009), fruit delivery (multiple daily: Z = −3.49, P < 0.001), research design (experimental: Z = −2.04, P = 0.041), study duration (< 2 wk: Z = −2.52, P = 0.012), total daily anthocyanins (>100 mg/d: Z = −2.98, P = 0.003), exercise type (anaerobic: Z = −2.57, P = 0.01), exercise time (>60 min: Z = −2.44, P = 0.015), training status (trained: Z = −2.14, P = 0.032), and funding (grant funded: Z = −2.31, P = 0.021) revealed differences within each subgroup (Table 5). The degree of variability was small to moderate as interpreted by the Q, τ2, and I2 statistics with moderate (I2 > 50) to large (I2 > 70) need to explain study variance. Tables 4 and 5 provide summaries regarding inflammation and oxidative stress moderators. Table 4 Subgroup analyses for inflammation moderators Moderator Effect size statistics Null test (2-tail) Heterogeneity statistics k g SE S2 95%CI Z P value Q τ2 I2 Random effectsa 16 −0.47 0.12 0.01 −0.687 to −0.252 −4.23 0.001* 11.34 0.00 0.00 Fruit 5.84b  Black currant 1 −1.608 0.578 0.334 −2.741 to −0.474 −2.781 0.005* 0.000 0.000 0.000  Blueberry 2 −0.791 0.318 0.101 −1.414 to −0.168 −2.489 0.013* 2.907 0.388 65.597  Grape 1 −0.271 0.411 0.169 −1.077 to 0.535 −0.659 0.510 0.000 0.000 0.000  Pomegranate 3 −0.286 0.240 0.058 −0.756 to 0.184 −1.191 0.234 0.560 0.000 0.000  Tart cherry 8 −0.414 0.158 0.025 −0.724 to −0.105 −2.623 0.009* 2.040 0.000 0.000  Wild blueberry 1 −0.462 0.448 0.200 −1.339 to 0.415 −1.032 0.302 0.000 0.000 0.000 Fruit frocessing 7.62b  Freeze dried 2 −0.149 0.280 0.078 −0.698 to 0.400 −0.532 0.595 0.339 0.000 0.000  Fresh frozen juice 3 −0.801 0.278 0.077 −1.345 to −0.257 −2.884 0.004* 2.626 0.074 23.826  Fresh frozen puree 2 −0.165 0.311 0.097 −0.775 to 0.444 −0.532 0.595 0.188 0.000 0.000  Fresh juice 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000  Fresh whole 1 −1.383 0.471 0.221 −2.305 to −0.460 −2.938 0.003* 0.000 0.000 0.000  Juice concentrate 7 −0.462 0.168 0.028 −0.792 to −0.132 −2.743 0.006* 0.570 0.000 0.000 Fruit delivery 4.65b  Single daily 5 −0.300 0.182 0.033 −0.657 to 0.057 −1.648 0.099 0.948 0.000 0.000  Single daily + single day bolus 1 −1.383 0.471 0.221 −2.305 to −0.460 −2.938 0.003* 0.000 0.000 0.000  Multiple daily 10 −0.490 0.147 0.021 −0.777 to −0.203 −3.345 0.001* 5.745 0.000 0.000 Research design 0.04b  Experimental 10 −0.452 0.140 0.019 −0.726 to −0.179 −3.239 0.001* 6.197 0.000 0.000  Quasi-experimental 6 −0.498 0.183 0.033 −0.857 to −0.140 −2.727 0.006* 5.107 0.004 2.091 Study duration 0.36b  <2 wk 10 −0.419 0.142 0.020 −0.698 to −0.140 −2.943 0.002* 6.980 0.000 0.000  2 − 6 wk 5 −0.563 0.193 0.037 −1.339 to −0.185 −2.920 0.004* 4.002 0.000 0.038  >6 wk 1 −0.462 0.448 0.200 −1.339 to 0.415 −1.032 0.302 0.000 0.000 0.000 Total daily anthocyanins 1.27b  <100 mg/d 8 −0.421 0.151 0.023 −0.717 to −0.125 −2.791 0.005* 6.047 0.000 0.000  >100 mg/d 6 −0.641 0.199 0.039 −1.031 to −0.252 −3.228 0.001* 3.467 0.000 0.000  NA 2 −0.282 0.289 0.084 −0.848 to 0.284 −0.975 0.329 0.559 0.000 0.000 Exercise type 0.17b  Aerobic 9 −0.510 0.148 0.022 −0.799 to −0.220 −3.454 0.001* 5.668 0.000 0.000  Anaerobic 7 −0.417 0.168 0.028 −0.747 to −0.087 −2.476 0.013* 5.504 0.000 0.000 Exercise time 0.41b  <60 min 6 −0.561 0.181 0.033 −0.915 to −0.207 −3.104 0.002* 4.082 0.000 0.000  >60 min 10 −0.414 0.141 0.020 −0.689 to −0.138 −2.944 0.003* 6.848 0.000 0.000 Training Status 1.58b  Trained 14 −0.423 0.117 0.014 −0.652 to −0.194 −3.623 0.000** 7.312 0.000 0.000  Untrained 2 −0.891 0.354 0.125 −1.585 to −0.198 −2.518 0.012* 2.456 0.389 59.281 Sex 0.18b  Female 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000  Male 11 −0.487 0.135 0.018 −0.751 to −0.223 −3.618 0.000** 5.361 0.000 0.000  Combined 4 −0.467 0.220 0.048 −0.898 to −0.036 −2.124 0.034* 5.802 0.185 48.289 Funding 1.36b  Yes 11 −0.460 0.133 0.018 −0.721 to −0.198 −3.449 0.001* 6.176 0.000 0.000  None 1 −0.025 0.449 0.202 −0.905 to 0.855 −0.055 0.956 0.000 0.000 0.000  Not reported 4 −0.607 0.224 0.050 −1.045 to −0.168 −2.711 0.007* 3.807 0.056 21.193 Moderator Effect size statistics Null test (2-tail) Heterogeneity statistics k g SE S2 95%CI Z P value Q τ2 I2 Random effectsa 16 −0.47 0.12 0.01 −0.687 to −0.252 −4.23 0.001* 11.34 0.00 0.00 Fruit 5.84b  Black currant 1 −1.608 0.578 0.334 −2.741 to −0.474 −2.781 0.005* 0.000 0.000 0.000  Blueberry 2 −0.791 0.318 0.101 −1.414 to −0.168 −2.489 0.013* 2.907 0.388 65.597  Grape 1 −0.271 0.411 0.169 −1.077 to 0.535 −0.659 0.510 0.000 0.000 0.000  Pomegranate 3 −0.286 0.240 0.058 −0.756 to 0.184 −1.191 0.234 0.560 0.000 0.000  Tart cherry 8 −0.414 0.158 0.025 −0.724 to −0.105 −2.623 0.009* 2.040 0.000 0.000  Wild blueberry 1 −0.462 0.448 0.200 −1.339 to 0.415 −1.032 0.302 0.000 0.000 0.000 Fruit frocessing 7.62b  Freeze dried 2 −0.149 0.280 0.078 −0.698 to 0.400 −0.532 0.595 0.339 0.000 0.000  Fresh frozen juice 3 −0.801 0.278 0.077 −1.345 to −0.257 −2.884 0.004* 2.626 0.074 23.826  Fresh frozen puree 2 −0.165 0.311 0.097 −0.775 to 0.444 −0.532 0.595 0.188 0.000 0.000  Fresh juice 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000  Fresh whole 1 −1.383 0.471 0.221 −2.305 to −0.460 −2.938 0.003* 0.000 0.000 0.000  Juice concentrate 7 −0.462 0.168 0.028 −0.792 to −0.132 −2.743 0.006* 0.570 0.000 0.000 Fruit delivery 4.65b  Single daily 5 −0.300 0.182 0.033 −0.657 to 0.057 −1.648 0.099 0.948 0.000 0.000  Single daily + single day bolus 1 −1.383 0.471 0.221 −2.305 to −0.460 −2.938 0.003* 0.000 0.000 0.000  Multiple daily 10 −0.490 0.147 0.021 −0.777 to −0.203 −3.345 0.001* 5.745 0.000 0.000 Research design 0.04b  Experimental 10 −0.452 0.140 0.019 −0.726 to −0.179 −3.239 0.001* 6.197 0.000 0.000  Quasi-experimental 6 −0.498 0.183 0.033 −0.857 to −0.140 −2.727 0.006* 5.107 0.004 2.091 Study duration 0.36b  <2 wk 10 −0.419 0.142 0.020 −0.698 to −0.140 −2.943 0.002* 6.980 0.000 0.000  2 − 6 wk 5 −0.563 0.193 0.037 −1.339 to −0.185 −2.920 0.004* 4.002 0.000 0.038  >6 wk 1 −0.462 0.448 0.200 −1.339 to 0.415 −1.032 0.302 0.000 0.000 0.000 Total daily anthocyanins 1.27b  <100 mg/d 8 −0.421 0.151 0.023 −0.717 to −0.125 −2.791 0.005* 6.047 0.000 0.000  >100 mg/d 6 −0.641 0.199 0.039 −1.031 to −0.252 −3.228 0.001* 3.467 0.000 0.000  NA 2 −0.282 0.289 0.084 −0.848 to 0.284 −0.975 0.329 0.559 0.000 0.000 Exercise type 0.17b  Aerobic 9 −0.510 0.148 0.022 −0.799 to −0.220 −3.454 0.001* 5.668 0.000 0.000  Anaerobic 7 −0.417 0.168 0.028 −0.747 to −0.087 −2.476 0.013* 5.504 0.000 0.000 Exercise time 0.41b  <60 min 6 −0.561 0.181 0.033 −0.915 to −0.207 −3.104 0.002* 4.082 0.000 0.000  >60 min 10 −0.414 0.141 0.020 −0.689 to −0.138 −2.944 0.003* 6.848 0.000 0.000 Training Status 1.58b  Trained 14 −0.423 0.117 0.014 −0.652 to −0.194 −3.623 0.000** 7.312 0.000 0.000  Untrained 2 −0.891 0.354 0.125 −1.585 to −0.198 −2.518 0.012* 2.456 0.389 59.281 Sex 0.18b  Female 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000  Male 11 −0.487 0.135 0.018 −0.751 to −0.223 −3.618 0.000** 5.361 0.000 0.000  Combined 4 −0.467 0.220 0.048 −0.898 to −0.036 −2.124 0.034* 5.802 0.185 48.289 Funding 1.36b  Yes 11 −0.460 0.133 0.018 −0.721 to −0.198 −3.449 0.001* 6.176 0.000 0.000  None 1 −0.025 0.449 0.202 −0.905 to 0.855 −0.055 0.956 0.000 0.000 0.000  Not reported 4 −0.607 0.224 0.050 −1.045 to −0.168 −2.711 0.007* 3.807 0.056 21.193 In this table, g is the effect size (Hedges’s g); I2 is the total variance explained by moderator; k is the number of effect sizes; S2 is the variance; SE is the standard error; Z is the test of null hypothesis, Q is used to determine heterogeneity; and τ2 indicates between-study variance in the random-effects model. * P < 0.05, **P < 0.001. Abbreviations: CI, confidence interval; NA, unknown quantity specific to anthocyanins. a Total Q-value used to determine heterogeneity. b Between Q-value used to determine differences between category subgroups (P < 0.05). View Large Table 4 Subgroup analyses for inflammation moderators Moderator Effect size statistics Null test (2-tail) Heterogeneity statistics k g SE S2 95%CI Z P value Q τ2 I2 Random effectsa 16 −0.47 0.12 0.01 −0.687 to −0.252 −4.23 0.001* 11.34 0.00 0.00 Fruit 5.84b  Black currant 1 −1.608 0.578 0.334 −2.741 to −0.474 −2.781 0.005* 0.000 0.000 0.000  Blueberry 2 −0.791 0.318 0.101 −1.414 to −0.168 −2.489 0.013* 2.907 0.388 65.597  Grape 1 −0.271 0.411 0.169 −1.077 to 0.535 −0.659 0.510 0.000 0.000 0.000  Pomegranate 3 −0.286 0.240 0.058 −0.756 to 0.184 −1.191 0.234 0.560 0.000 0.000  Tart cherry 8 −0.414 0.158 0.025 −0.724 to −0.105 −2.623 0.009* 2.040 0.000 0.000  Wild blueberry 1 −0.462 0.448 0.200 −1.339 to 0.415 −1.032 0.302 0.000 0.000 0.000 Fruit frocessing 7.62b  Freeze dried 2 −0.149 0.280 0.078 −0.698 to 0.400 −0.532 0.595 0.339 0.000 0.000  Fresh frozen juice 3 −0.801 0.278 0.077 −1.345 to −0.257 −2.884 0.004* 2.626 0.074 23.826  Fresh frozen puree 2 −0.165 0.311 0.097 −0.775 to 0.444 −0.532 0.595 0.188 0.000 0.000  Fresh juice 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000  Fresh whole 1 −1.383 0.471 0.221 −2.305 to −0.460 −2.938 0.003* 0.000 0.000 0.000  Juice concentrate 7 −0.462 0.168 0.028 −0.792 to −0.132 −2.743 0.006* 0.570 0.000 0.000 Fruit delivery 4.65b  Single daily 5 −0.300 0.182 0.033 −0.657 to 0.057 −1.648 0.099 0.948 0.000 0.000  Single daily + single day bolus 1 −1.383 0.471 0.221 −2.305 to −0.460 −2.938 0.003* 0.000 0.000 0.000  Multiple daily 10 −0.490 0.147 0.021 −0.777 to −0.203 −3.345 0.001* 5.745 0.000 0.000 Research design 0.04b  Experimental 10 −0.452 0.140 0.019 −0.726 to −0.179 −3.239 0.001* 6.197 0.000 0.000  Quasi-experimental 6 −0.498 0.183 0.033 −0.857 to −0.140 −2.727 0.006* 5.107 0.004 2.091 Study duration 0.36b  <2 wk 10 −0.419 0.142 0.020 −0.698 to −0.140 −2.943 0.002* 6.980 0.000 0.000  2 − 6 wk 5 −0.563 0.193 0.037 −1.339 to −0.185 −2.920 0.004* 4.002 0.000 0.038  >6 wk 1 −0.462 0.448 0.200 −1.339 to 0.415 −1.032 0.302 0.000 0.000 0.000 Total daily anthocyanins 1.27b  <100 mg/d 8 −0.421 0.151 0.023 −0.717 to −0.125 −2.791 0.005* 6.047 0.000 0.000  >100 mg/d 6 −0.641 0.199 0.039 −1.031 to −0.252 −3.228 0.001* 3.467 0.000 0.000  NA 2 −0.282 0.289 0.084 −0.848 to 0.284 −0.975 0.329 0.559 0.000 0.000 Exercise type 0.17b  Aerobic 9 −0.510 0.148 0.022 −0.799 to −0.220 −3.454 0.001* 5.668 0.000 0.000  Anaerobic 7 −0.417 0.168 0.028 −0.747 to −0.087 −2.476 0.013* 5.504 0.000 0.000 Exercise time 0.41b  <60 min 6 −0.561 0.181 0.033 −0.915 to −0.207 −3.104 0.002* 4.082 0.000 0.000  >60 min 10 −0.414 0.141 0.020 −0.689 to −0.138 −2.944 0.003* 6.848 0.000 0.000 Training Status 1.58b  Trained 14 −0.423 0.117 0.014 −0.652 to −0.194 −3.623 0.000** 7.312 0.000 0.000  Untrained 2 −0.891 0.354 0.125 −1.585 to −0.198 −2.518 0.012* 2.456 0.389 59.281 Sex 0.18b  Female 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000  Male 11 −0.487 0.135 0.018 −0.751 to −0.223 −3.618 0.000** 5.361 0.000 0.000  Combined 4 −0.467 0.220 0.048 −0.898 to −0.036 −2.124 0.034* 5.802 0.185 48.289 Funding 1.36b  Yes 11 −0.460 0.133 0.018 −0.721 to −0.198 −3.449 0.001* 6.176 0.000 0.000  None 1 −0.025 0.449 0.202 −0.905 to 0.855 −0.055 0.956 0.000 0.000 0.000  Not reported 4 −0.607 0.224 0.050 −1.045 to −0.168 −2.711 0.007* 3.807 0.056 21.193 Moderator Effect size statistics Null test (2-tail) Heterogeneity statistics k g SE S2 95%CI Z P value Q τ2 I2 Random effectsa 16 −0.47 0.12 0.01 −0.687 to −0.252 −4.23 0.001* 11.34 0.00 0.00 Fruit 5.84b  Black currant 1 −1.608 0.578 0.334 −2.741 to −0.474 −2.781 0.005* 0.000 0.000 0.000  Blueberry 2 −0.791 0.318 0.101 −1.414 to −0.168 −2.489 0.013* 2.907 0.388 65.597  Grape 1 −0.271 0.411 0.169 −1.077 to 0.535 −0.659 0.510 0.000 0.000 0.000  Pomegranate 3 −0.286 0.240 0.058 −0.756 to 0.184 −1.191 0.234 0.560 0.000 0.000  Tart cherry 8 −0.414 0.158 0.025 −0.724 to −0.105 −2.623 0.009* 2.040 0.000 0.000  Wild blueberry 1 −0.462 0.448 0.200 −1.339 to 0.415 −1.032 0.302 0.000 0.000 0.000 Fruit frocessing 7.62b  Freeze dried 2 −0.149 0.280 0.078 −0.698 to 0.400 −0.532 0.595 0.339 0.000 0.000  Fresh frozen juice 3 −0.801 0.278 0.077 −1.345 to −0.257 −2.884 0.004* 2.626 0.074 23.826  Fresh frozen puree 2 −0.165 0.311 0.097 −0.775 to 0.444 −0.532 0.595 0.188 0.000 0.000  Fresh juice 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000  Fresh whole 1 −1.383 0.471 0.221 −2.305 to −0.460 −2.938 0.003* 0.000 0.000 0.000  Juice concentrate 7 −0.462 0.168 0.028 −0.792 to −0.132 −2.743 0.006* 0.570 0.000 0.000 Fruit delivery 4.65b  Single daily 5 −0.300 0.182 0.033 −0.657 to 0.057 −1.648 0.099 0.948 0.000 0.000  Single daily + single day bolus 1 −1.383 0.471 0.221 −2.305 to −0.460 −2.938 0.003* 0.000 0.000 0.000  Multiple daily 10 −0.490 0.147 0.021 −0.777 to −0.203 −3.345 0.001* 5.745 0.000 0.000 Research design 0.04b  Experimental 10 −0.452 0.140 0.019 −0.726 to −0.179 −3.239 0.001* 6.197 0.000 0.000  Quasi-experimental 6 −0.498 0.183 0.033 −0.857 to −0.140 −2.727 0.006* 5.107 0.004 2.091 Study duration 0.36b  <2 wk 10 −0.419 0.142 0.020 −0.698 to −0.140 −2.943 0.002* 6.980 0.000 0.000  2 − 6 wk 5 −0.563 0.193 0.037 −1.339 to −0.185 −2.920 0.004* 4.002 0.000 0.038  >6 wk 1 −0.462 0.448 0.200 −1.339 to 0.415 −1.032 0.302 0.000 0.000 0.000 Total daily anthocyanins 1.27b  <100 mg/d 8 −0.421 0.151 0.023 −0.717 to −0.125 −2.791 0.005* 6.047 0.000 0.000  >100 mg/d 6 −0.641 0.199 0.039 −1.031 to −0.252 −3.228 0.001* 3.467 0.000 0.000  NA 2 −0.282 0.289 0.084 −0.848 to 0.284 −0.975 0.329 0.559 0.000 0.000 Exercise type 0.17b  Aerobic 9 −0.510 0.148 0.022 −0.799 to −0.220 −3.454 0.001* 5.668 0.000 0.000  Anaerobic 7 −0.417 0.168 0.028 −0.747 to −0.087 −2.476 0.013* 5.504 0.000 0.000 Exercise time 0.41b  <60 min 6 −0.561 0.181 0.033 −0.915 to −0.207 −3.104 0.002* 4.082 0.000 0.000  >60 min 10 −0.414 0.141 0.020 −0.689 to −0.138 −2.944 0.003* 6.848 0.000 0.000 Training Status 1.58b  Trained 14 −0.423 0.117 0.014 −0.652 to −0.194 −3.623 0.000** 7.312 0.000 0.000  Untrained 2 −0.891 0.354 0.125 −1.585 to −0.198 −2.518 0.012* 2.456 0.389 59.281 Sex 0.18b  Female 1 −0.295 0.431 0.186 −1.139 to 0.550 −0.684 0.494 0.000 0.000 0.000  Male 11 −0.487 0.135 0.018 −0.751 to −0.223 −3.618 0.000** 5.361 0.000 0.000  Combined 4 −0.467 0.220 0.048 −0.898 to −0.036 −2.124 0.034* 5.802 0.185 48.289 Funding 1.36b  Yes 11 −0.460 0.133 0.018 −0.721 to −0.198 −3.449 0.001* 6.176 0.000 0.000  None 1 −0.025 0.449 0.202 −0.905 to 0.855 −0.055 0.956 0.000 0.000 0.000  Not reported 4 −0.607 0.224 0.050 −1.045 to −0.168 −2.711 0.007* 3.807 0.056 21.193 In this table, g is the effect size (Hedges’s g); I2 is the total variance explained by moderator; k is the number of effect sizes; S2 is the variance; SE is the standard error; Z is the test of null hypothesis, Q is used to determine heterogeneity; and τ2 indicates between-study variance in the random-effects model. * P < 0.05, **P < 0.001. Abbreviations: CI, confidence interval; NA, unknown quantity specific to anthocyanins. a Total Q-value used to determine heterogeneity. b Between Q-value used to determine differences between category subgroups (P < 0.05). View Large Table 5 Subgroup analyses for exercise-induced oxidative stress moderators Effect size statistics Null test (2-tail) Heterogeneity statistics k g SE S2 95%CI Z P value Q τ2 I2 Random effectsa 20 −0.32 0.15 0.02 −0.616 to −0.021 −2.10 0.036* 40* 0.24 52.87 Fruit type 2.56b  Acai 1 −0.281 0.373 0.139 −1.011 to 0.449 −0.754 0.451 0.000 0.000 0.000  Blueberry 2 −0.355 0.308 0.095 −0.958 to 0.247 −1.156 0.248 0.094 0.000 0.000  Chokeberry 2 −0.482 0.344 0.118 −1.156 to 0.192 −1.401 0.161 0.976 0.000 0.000  Grape 3 0.253 0.273 0.074 −0.282 to 0.787 0.926 0.355 9.299 0.835 78.493  Pomegranate 3 −0.075 0.258 0.067 −0.580 to 0.431 −0.291 0.771 11.930 0.998 83.236  Tart cherry 8 −0.360 0.168 0.028 −0.690 to 0.030 −2.138 0.033* 21.843 0.493 67.953  Wild blueberry 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Fruit processing 2.29b  Freeze dried 3 −0.038 0.222 0.049 −0.474 to 0.398 −0.170 0.865 0.948 0.000 0.000  Fresh frozen juice 2 −0.208 0.311 0.097 −0.817 to 0.402 −0.688 0.504 1.383 0.074 27.684  Fresh frozen puree 2 −0.335 0.318 0.101 −0.958 to 0.289 −1.051 0.293 0.151 0.000 0.000  Fresh juice 1 −1.233 0.471 0.221 −2.155 to −0.311 −2.620 0.009* 0.000 0.000 0.000  Fresh whole 1 −0.614 0.448 0.201 −1.492 to 0.264 −1.372 0.170 0.000 0.000 0.000  Juice concentrate 11 −0.233 0.149 0.022 −0.524 to 0.059 −1.565 0.118 31.821 0.537 68.574 Fruit delivery 4.68b  Single daily 8 0.125 0.150 0.023 −0.170 to 0.420 0.830 0.407 21.384 0.375 67.266  Single daily + single day bolus 1 −0.262 0.432 0.187 −1.109 to 0.585 −0.607 0.544 0.000 0.000 0.000  Multiple daily 11 −0.516 0.148 0.022 −0.806 to −0.226 −3.490 0.000** 19.017 0.219 47.415 Research design 0.33b  Experimental 10 −0.289 0.141 0.020 −0.565 to −0.012 −2.047 0.041* 24.922 0.354 68.887  Quasi-experimental 10 −0.111 0.149 0.022 −0.403 to 0.182 −0.742 0.458 23.975 0.375 62.461 Study duration 1.73b  <2 wk 10 −0.365 0.144 0.021 −0.648 to −0.082 −2.524 0.012* 21.797 0.302 58.711  2–6 wk 9 −0.067 0.154 0.024 −0.369 to 0.235 −0.434 0.664 25.164 0.461 68.209  >6 wk 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Total daily anthocyanins 4.29b  <100 mg/d 11 −0.151 0.129 0.017 −0.405 to 0.103 −1.167 0.243 19.927 0.183 49.816  >100 mg/d 7 −0.596 0.200 0.040 −0.988 to −0.204 −2.983 0.003* 18.306 0.588 67.223  NA 2 0.422 0.308 0.095 −0.182 to 1.026 1.369 0.171 3.276 0.439 69.478 Exercise type 1.37b  Aerobic 12 −0.061 0.133 0.018 −0.322 to 0.200 −0.460 0.646 34.657 0.460 68.261  Anaerobic 8 −0.412 0.160 0.026 −0.726 to −0.098 −2.571 0.010* 12.162 0.154 42.444 Exercise time 0.03b  <60 min 7 −0.186 0.172 0.029 −0.522 to 0.151 −1.082 0.279 20.934 0.528 71.338  >60 min 13 −0.311 0.128 0.016 −0.562 to 0.061 −2.437 0.015* 19.035 0.125 36.957 Training status 0.33b  Trained 19 −0.225 0.105 0.011 −0.432 to −0.019 −2.139 0.032* 48.948 0.365 63.227  Untrained 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Sex 0.08b  Female 1 −0.451 0.438 0.192 −1.309 to 0.407 −1.031 0.303 0.000 0.000 0.000  Male 15 −0.188 0.121 0.015 −0.426 to −0.049 −1.557 0.119 46.958 0.521 70.186  Combined 4 −0.196 0.214 0.046 −0.616 to 0.224 −0.915 0.360 2.356 0.000 0.000 Funding 0.82b  Yes 15 −0.281 0.122 0.015 −0.520 to −0.042 −2.306 0.021* 41.505 0.441 66.269  None 1 −0.204 0.463 0.215 −1.112 to 0.704 −0.440 0.660 0.000 0.000 0.000  Not reported 4 0.016 0.207 0.043 −0.399 to 0.422 0.076 0.939 6.618 0.209 54.672 Effect size statistics Null test (2-tail) Heterogeneity statistics k g SE S2 95%CI Z P value Q τ2 I2 Random effectsa 20 −0.32 0.15 0.02 −0.616 to −0.021 −2.10 0.036* 40* 0.24 52.87 Fruit type 2.56b  Acai 1 −0.281 0.373 0.139 −1.011 to 0.449 −0.754 0.451 0.000 0.000 0.000  Blueberry 2 −0.355 0.308 0.095 −0.958 to 0.247 −1.156 0.248 0.094 0.000 0.000  Chokeberry 2 −0.482 0.344 0.118 −1.156 to 0.192 −1.401 0.161 0.976 0.000 0.000  Grape 3 0.253 0.273 0.074 −0.282 to 0.787 0.926 0.355 9.299 0.835 78.493  Pomegranate 3 −0.075 0.258 0.067 −0.580 to 0.431 −0.291 0.771 11.930 0.998 83.236  Tart cherry 8 −0.360 0.168 0.028 −0.690 to 0.030 −2.138 0.033* 21.843 0.493 67.953  Wild blueberry 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Fruit processing 2.29b  Freeze dried 3 −0.038 0.222 0.049 −0.474 to 0.398 −0.170 0.865 0.948 0.000 0.000  Fresh frozen juice 2 −0.208 0.311 0.097 −0.817 to 0.402 −0.688 0.504 1.383 0.074 27.684  Fresh frozen puree 2 −0.335 0.318 0.101 −0.958 to 0.289 −1.051 0.293 0.151 0.000 0.000  Fresh juice 1 −1.233 0.471 0.221 −2.155 to −0.311 −2.620 0.009* 0.000 0.000 0.000  Fresh whole 1 −0.614 0.448 0.201 −1.492 to 0.264 −1.372 0.170 0.000 0.000 0.000  Juice concentrate 11 −0.233 0.149 0.022 −0.524 to 0.059 −1.565 0.118 31.821 0.537 68.574 Fruit delivery 4.68b  Single daily 8 0.125 0.150 0.023 −0.170 to 0.420 0.830 0.407 21.384 0.375 67.266  Single daily + single day bolus 1 −0.262 0.432 0.187 −1.109 to 0.585 −0.607 0.544 0.000 0.000 0.000  Multiple daily 11 −0.516 0.148 0.022 −0.806 to −0.226 −3.490 0.000** 19.017 0.219 47.415 Research design 0.33b  Experimental 10 −0.289 0.141 0.020 −0.565 to −0.012 −2.047 0.041* 24.922 0.354 68.887  Quasi-experimental 10 −0.111 0.149 0.022 −0.403 to 0.182 −0.742 0.458 23.975 0.375 62.461 Study duration 1.73b  <2 wk 10 −0.365 0.144 0.021 −0.648 to −0.082 −2.524 0.012* 21.797 0.302 58.711  2–6 wk 9 −0.067 0.154 0.024 −0.369 to 0.235 −0.434 0.664 25.164 0.461 68.209  >6 wk 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Total daily anthocyanins 4.29b  <100 mg/d 11 −0.151 0.129 0.017 −0.405 to 0.103 −1.167 0.243 19.927 0.183 49.816  >100 mg/d 7 −0.596 0.200 0.040 −0.988 to −0.204 −2.983 0.003* 18.306 0.588 67.223  NA 2 0.422 0.308 0.095 −0.182 to 1.026 1.369 0.171 3.276 0.439 69.478 Exercise type 1.37b  Aerobic 12 −0.061 0.133 0.018 −0.322 to 0.200 −0.460 0.646 34.657 0.460 68.261  Anaerobic 8 −0.412 0.160 0.026 −0.726 to −0.098 −2.571 0.010* 12.162 0.154 42.444 Exercise time 0.03b  <60 min 7 −0.186 0.172 0.029 −0.522 to 0.151 −1.082 0.279 20.934 0.528 71.338  >60 min 13 −0.311 0.128 0.016 −0.562 to 0.061 −2.437 0.015* 19.035 0.125 36.957 Training status 0.33b  Trained 19 −0.225 0.105 0.011 −0.432 to −0.019 −2.139 0.032* 48.948 0.365 63.227  Untrained 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Sex 0.08b  Female 1 −0.451 0.438 0.192 −1.309 to 0.407 −1.031 0.303 0.000 0.000 0.000  Male 15 −0.188 0.121 0.015 −0.426 to −0.049 −1.557 0.119 46.958 0.521 70.186  Combined 4 −0.196 0.214 0.046 −0.616 to 0.224 −0.915 0.360 2.356 0.000 0.000 Funding 0.82b  Yes 15 −0.281 0.122 0.015 −0.520 to −0.042 −2.306 0.021* 41.505 0.441 66.269  None 1 −0.204 0.463 0.215 −1.112 to 0.704 −0.440 0.660 0.000 0.000 0.000  Not reported 4 0.016 0.207 0.043 −0.399 to 0.422 0.076 0.939 6.618 0.209 54.672 In this table, g is the effect size (Hedges’s g); I2 is the total variance explained by moderator; k is the number of effect sizes; S2 is the variance; SE is the standard error; Z is the test of null hypothesis, Q is used to determine heterogeneity; and τ2 indicates between-study variance in the random-effects model. * P < 0.05, **P < 0.001. Abbreviations: CI, confidence interval; NA, unknown quantity specific to anthocyanins. a Total Q value used to determine heterogeneity. b Between Q value used to determine differences between category subgroups (P < 0.05). View Large Table 5 Subgroup analyses for exercise-induced oxidative stress moderators Effect size statistics Null test (2-tail) Heterogeneity statistics k g SE S2 95%CI Z P value Q τ2 I2 Random effectsa 20 −0.32 0.15 0.02 −0.616 to −0.021 −2.10 0.036* 40* 0.24 52.87 Fruit type 2.56b  Acai 1 −0.281 0.373 0.139 −1.011 to 0.449 −0.754 0.451 0.000 0.000 0.000  Blueberry 2 −0.355 0.308 0.095 −0.958 to 0.247 −1.156 0.248 0.094 0.000 0.000  Chokeberry 2 −0.482 0.344 0.118 −1.156 to 0.192 −1.401 0.161 0.976 0.000 0.000  Grape 3 0.253 0.273 0.074 −0.282 to 0.787 0.926 0.355 9.299 0.835 78.493  Pomegranate 3 −0.075 0.258 0.067 −0.580 to 0.431 −0.291 0.771 11.930 0.998 83.236  Tart cherry 8 −0.360 0.168 0.028 −0.690 to 0.030 −2.138 0.033* 21.843 0.493 67.953  Wild blueberry 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Fruit processing 2.29b  Freeze dried 3 −0.038 0.222 0.049 −0.474 to 0.398 −0.170 0.865 0.948 0.000 0.000  Fresh frozen juice 2 −0.208 0.311 0.097 −0.817 to 0.402 −0.688 0.504 1.383 0.074 27.684  Fresh frozen puree 2 −0.335 0.318 0.101 −0.958 to 0.289 −1.051 0.293 0.151 0.000 0.000  Fresh juice 1 −1.233 0.471 0.221 −2.155 to −0.311 −2.620 0.009* 0.000 0.000 0.000  Fresh whole 1 −0.614 0.448 0.201 −1.492 to 0.264 −1.372 0.170 0.000 0.000 0.000  Juice concentrate 11 −0.233 0.149 0.022 −0.524 to 0.059 −1.565 0.118 31.821 0.537 68.574 Fruit delivery 4.68b  Single daily 8 0.125 0.150 0.023 −0.170 to 0.420 0.830 0.407 21.384 0.375 67.266  Single daily + single day bolus 1 −0.262 0.432 0.187 −1.109 to 0.585 −0.607 0.544 0.000 0.000 0.000  Multiple daily 11 −0.516 0.148 0.022 −0.806 to −0.226 −3.490 0.000** 19.017 0.219 47.415 Research design 0.33b  Experimental 10 −0.289 0.141 0.020 −0.565 to −0.012 −2.047 0.041* 24.922 0.354 68.887  Quasi-experimental 10 −0.111 0.149 0.022 −0.403 to 0.182 −0.742 0.458 23.975 0.375 62.461 Study duration 1.73b  <2 wk 10 −0.365 0.144 0.021 −0.648 to −0.082 −2.524 0.012* 21.797 0.302 58.711  2–6 wk 9 −0.067 0.154 0.024 −0.369 to 0.235 −0.434 0.664 25.164 0.461 68.209  >6 wk 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Total daily anthocyanins 4.29b  <100 mg/d 11 −0.151 0.129 0.017 −0.405 to 0.103 −1.167 0.243 19.927 0.183 49.816  >100 mg/d 7 −0.596 0.200 0.040 −0.988 to −0.204 −2.983 0.003* 18.306 0.588 67.223  NA 2 0.422 0.308 0.095 −0.182 to 1.026 1.369 0.171 3.276 0.439 69.478 Exercise type 1.37b  Aerobic 12 −0.061 0.133 0.018 −0.322 to 0.200 −0.460 0.646 34.657 0.460 68.261  Anaerobic 8 −0.412 0.160 0.026 −0.726 to −0.098 −2.571 0.010* 12.162 0.154 42.444 Exercise time 0.03b  <60 min 7 −0.186 0.172 0.029 −0.522 to 0.151 −1.082 0.279 20.934 0.528 71.338  >60 min 13 −0.311 0.128 0.016 −0.562 to 0.061 −2.437 0.015* 19.035 0.125 36.957 Training status 0.33b  Trained 19 −0.225 0.105 0.011 −0.432 to −0.019 −2.139 0.032* 48.948 0.365 63.227  Untrained 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Sex 0.08b  Female 1 −0.451 0.438 0.192 −1.309 to 0.407 −1.031 0.303 0.000 0.000 0.000  Male 15 −0.188 0.121 0.015 −0.426 to −0.049 −1.557 0.119 46.958 0.521 70.186  Combined 4 −0.196 0.214 0.046 −0.616 to 0.224 −0.915 0.360 2.356 0.000 0.000 Funding 0.82b  Yes 15 −0.281 0.122 0.015 −0.520 to −0.042 −2.306 0.021* 41.505 0.441 66.269  None 1 −0.204 0.463 0.215 −1.112 to 0.704 −0.440 0.660 0.000 0.000 0.000  Not reported 4 0.016 0.207 0.043 −0.399 to 0.422 0.076 0.939 6.618 0.209 54.672 Effect size statistics Null test (2-tail) Heterogeneity statistics k g SE S2 95%CI Z P value Q τ2 I2 Random effectsa 20 −0.32 0.15 0.02 −0.616 to −0.021 −2.10 0.036* 40* 0.24 52.87 Fruit type 2.56b  Acai 1 −0.281 0.373 0.139 −1.011 to 0.449 −0.754 0.451 0.000 0.000 0.000  Blueberry 2 −0.355 0.308 0.095 −0.958 to 0.247 −1.156 0.248 0.094 0.000 0.000  Chokeberry 2 −0.482 0.344 0.118 −1.156 to 0.192 −1.401 0.161 0.976 0.000 0.000  Grape 3 0.253 0.273 0.074 −0.282 to 0.787 0.926 0.355 9.299 0.835 78.493  Pomegranate 3 −0.075 0.258 0.067 −0.580 to 0.431 −0.291 0.771 11.930 0.998 83.236  Tart cherry 8 −0.360 0.168 0.028 −0.690 to 0.030 −2.138 0.033* 21.843 0.493 67.953  Wild blueberry 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Fruit processing 2.29b  Freeze dried 3 −0.038 0.222 0.049 −0.474 to 0.398 −0.170 0.865 0.948 0.000 0.000  Fresh frozen juice 2 −0.208 0.311 0.097 −0.817 to 0.402 −0.688 0.504 1.383 0.074 27.684  Fresh frozen puree 2 −0.335 0.318 0.101 −0.958 to 0.289 −1.051 0.293 0.151 0.000 0.000  Fresh juice 1 −1.233 0.471 0.221 −2.155 to −0.311 −2.620 0.009* 0.000 0.000 0.000  Fresh whole 1 −0.614 0.448 0.201 −1.492 to 0.264 −1.372 0.170 0.000 0.000 0.000  Juice concentrate 11 −0.233 0.149 0.022 −0.524 to 0.059 −1.565 0.118 31.821 0.537 68.574 Fruit delivery 4.68b  Single daily 8 0.125 0.150 0.023 −0.170 to 0.420 0.830 0.407 21.384 0.375 67.266  Single daily + single day bolus 1 −0.262 0.432 0.187 −1.109 to 0.585 −0.607 0.544 0.000 0.000 0.000  Multiple daily 11 −0.516 0.148 0.022 −0.806 to −0.226 −3.490 0.000** 19.017 0.219 47.415 Research design 0.33b  Experimental 10 −0.289 0.141 0.020 −0.565 to −0.012 −2.047 0.041* 24.922 0.354 68.887  Quasi-experimental 10 −0.111 0.149 0.022 −0.403 to 0.182 −0.742 0.458 23.975 0.375 62.461 Study duration 1.73b  <2 wk 10 −0.365 0.144 0.021 −0.648 to −0.082 −2.524 0.012* 21.797 0.302 58.711  2–6 wk 9 −0.067 0.154 0.024 −0.369 to 0.235 −0.434 0.664 25.164 0.461 68.209  >6 wk 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Total daily anthocyanins 4.29b  <100 mg/d 11 −0.151 0.129 0.017 −0.405 to 0.103 −1.167 0.243 19.927 0.183 49.816  >100 mg/d 7 −0.596 0.200 0.040 −0.988 to −0.204 −2.983 0.003* 18.306 0.588 67.223  NA 2 0.422 0.308 0.095 −0.182 to 1.026 1.369 0.171 3.276 0.439 69.478 Exercise type 1.37b  Aerobic 12 −0.061 0.133 0.018 −0.322 to 0.200 −0.460 0.646 34.657 0.460 68.261  Anaerobic 8 −0.412 0.160 0.026 −0.726 to −0.098 −2.571 0.010* 12.162 0.154 42.444 Exercise time 0.03b  <60 min 7 −0.186 0.172 0.029 −0.522 to 0.151 −1.082 0.279 20.934 0.528 71.338  >60 min 13 −0.311 0.128 0.016 −0.562 to 0.061 −2.437 0.015* 19.035 0.125 36.957 Training status 0.33b  Trained 19 −0.225 0.105 0.011 −0.432 to −0.019 −2.139 0.032* 48.948 0.365 63.227  Untrained 1 0.149 0.434 0.189 −0.703 to 1.001 0.343 0.732 0.000 0.000 0.000 Sex 0.08b  Female 1 −0.451 0.438 0.192 −1.309 to 0.407 −1.031 0.303 0.000 0.000 0.000  Male 15 −0.188 0.121 0.015 −0.426 to −0.049 −1.557 0.119 46.958 0.521 70.186  Combined 4 −0.196 0.214 0.046 −0.616 to 0.224 −0.915 0.360 2.356 0.000 0.000 Funding 0.82b  Yes 15 −0.281 0.122 0.015 −0.520 to −0.042 −2.306 0.021* 41.505 0.441 66.269  None 1 −0.204 0.463 0.215 −1.112 to 0.704 −0.440 0.660 0.000 0.000 0.000  Not reported 4 0.016 0.207 0.043 −0.399 to 0.422 0.076 0.939 6.618 0.209 54.672 In this table, g is the effect size (Hedges’s g); I2 is the total variance explained by moderator; k is the number of effect sizes; S2 is the variance; SE is the standard error; Z is the test of null hypothesis, Q is used to determine heterogeneity; and τ2 indicates between-study variance in the random-effects model. * P < 0.05, **P < 0.001. Abbreviations: CI, confidence interval; NA, unknown quantity specific to anthocyanins. a Total Q value used to determine heterogeneity. b Between Q value used to determine differences between category subgroups (P < 0.05). View Large DISCUSSION The aim of this systematic review and meta-analysis was to synthesize existing literature addressing the effects of whole fruits containing anthocyanins on reducing exercise-induced oxidative stress and inflammation. Specific questions were the following: 1) What impact do whole fruits containing anthocyanins have on reducing exercise-induced oxidative stress and inflammation? 2) What amount (mg) of total daily anthocyanins from whole fruit has the greatest impact on reducing exercise-induced oxidative stress and inflammation? 3) What type of fruit and fruit processing method has the greatest impact on reducing exercise-induced oxidative stress and inflammation? Inflammation An overall small but significant effect (g = 0.47; k = 16; P < 0.001) was found for reducing overall inflammation in the experimental groups compared with control groups. A reduction in inflammation following anthocyanin-rich whole fruit consumption, regardless of the method used to induce inflammation, has been well documented,21,27,29,55–60 although the effectiveness specific to the type of fruit, fruit dose, and fruit processing method remains unclear. Black currants (P = 0.005), blueberries (P = 0.013), and tart cherries (P = 0.009) displayed the most significant effects on overall inflammatory markers (Table 4). Research using tart cherries as a means to reduce inflammation in sport and exercise has been quite prevalent. Of the 22 studies included in this review, 8 used tart cherries. Eight of the 16 studies that looked at inflammatory markers did so using providing tart cherries as the experimental fruit.21,22,26,28,29,56,57 Despite the wealth of research on tart cherries, the data suggest that blueberries and black currants may offer similar benefits. The limited number of studies meeting the search parameters using blueberries (k = 2) and black currants (k = 1), compared with tart cherries (k = 8) leaves the interpretation of the large effect size seen in blueberries and black currants in question. There is not enough evidence to conclude a strong recommendation of any one fruit over another. In addition, the processing method, dose, and milligrams of daily anthocyanins provided varied within each fruit type. Fruit processing method varied from small to large effect sizes, with fresh frozen juice having a significant (P = 0.004) impact on inflammation with a moderate effect size (k = 3). Fresh whole fruit (in this case blueberries), had a large effect size (−1.383) and significant (P = 0.003) inflammatory protection; however, with only 1 study55 it cannot be concluded that fresh fruit provides the most protection. Juice concentrates were also significantly (P = 0.006) able to reduce inflammation, and in 7 studies, showed a small effect. Given these results, it is unclear what processing method and subsequent delivery method is the most effective for inflammatory protection (Table 4). Often the practicality and ease of use is placed above biological availability when choosing the supplement. To the researchers’ knowledge, exercise intervention studies have not compared 2 different processing methods against a control to determine greater effectiveness within the same study. Another factor that complicates proper dosing protocol for clear effective use stems from the fact that researchers using the same fruit processing method often use different doses and delivery schedules. Consuming the fruit, regardless of type of fruit and method of preparation, multiple times per day (2–3 times/d) resulted in a significant (P = 0.001) reduction of inflammation with a moderate effect. This evidence is in support of previous research findings recommending habitual consumption to maximize protective effects,61,62 in part because of the rapid clearance of anthocyanins, with very little detected in the plasma 6 hours after consumption.63 The strength of the moderate effect documented in 10 studies suggests that, in the future, research participants should consume fruit containing anthocyanins 2–3 times per day. There was a significant (P = 0.003) and strong effect (−1.383) for a single daily dose plus a single day bolus of fresh whole blueberries provided before the onset of exercise. Although, with this being reported by only 1 study,55 it is difficult to say if this is the optimal method; additionally, it is difficult to say if it was the single bolus or the daily dose that impacted inflammatory outcomes. The total milligrams per day of anthocyanins given to participants varied greatly among the 22 studies. Daily intake was categorized into 2 groups (<100 mg/d and > 100 mg/d). Table 2 shows the wide differences in anthocyanin doses, even within the same category. Although some studies indicated which type of anthocyanin the fruit supplementation contained, others listed only total anthocyanins. Both categories showed significant results (P = 0.005, P = 0.001, respectively), although a moderate effect was seen in doses > 100 mg/day (Table 4). Given the variability within doses containing > 100 mg/day, it is difficult to say which dose is the most effective. Previous research has recommended effective doses of anthocyanins for cardiovascular protection at about 150 mg/day,64 whereas > 25 mg/day has been shown to have the potential to reduce the risk of a heart attack by 32%.65 Although the use of fruit-based supplements in sport, particularly tart cherry juice, is growing in popularity, the recommendations for effectiveness are not clear. Research providing clear evidence on proper dose and use of anthocyanin-rich fruit products to improve sports performance by decreasing exercise-induced inflammation is lacking, despite the strong evidence of its ability to reduce vascular inflammation.64,66,67 Oxidative stress A significant (P = 0.036), yet small effect, suggests that anthocyanin-rich fruit consumption may be able to reduce exercise-induced oxidative stress. Although these results showed a small effect, many researchers have reported notable reductions of oxidative stress following anthocyanin consumption, regardless of the means to induce oxidative stress.13,20,22,24–26,31–33,38,53,55,68–71 Effect sizes were small for fruit type and overall oxidative stress, with only tart cherries showing significance (P = 0.033). Again, tart cherries outnumbered all other fruits with 8 of 20 (40%) studies that measured oxidative stress using tart cherry juice; other berry types were included in only 1–3 studies each. A significant (P = 0.009) and large effect was found for fresh juice as a processing method. It should be noted that only 1 of the 20 studies looking at oxidative stress used fresh juice, specifically fresh pomegranate juice.25 Despite the positive results, it cannot be concluded that fresh juice is the best delivery method. Additionally, the practicality of using fresh juice on a yearly basis may not feasible in many regions. Similar to the research on inflammation, providing multiple servings daily showed significant (P < 0.0001) decreases in oxidative stress with a moderate effect size. The 11 studies providing supplementation multiple times a day were from a variety of fruits—pomegranate (k = 1), grape (k = 2), chokeberry (k = 1), tart cherry (k = 6), and blueberry (k = 1)—making it difficult to narrow down the most effective fruit to provide 2–3 times per day. It may be noteworthy that 8 of the 11 studies providing supplementation multiple times per day were using juice concentrate (grape [k = 2], chokeberry [k = 1], tart cherry [(k = 5]). In a category of its own was a study by McAnulty et al55 that used the equivalent of approximately 2 cups of fresh blueberries daily for 6 weeks plus an additional single bolus of approximately 4 cups of fresh blueberries immediately before the exercise intervention (classified as Single Daily + Single Day Bolus). Although the amount of anthocyanins was not directly measured, as indicated by the researchers, fresh blueberries may contain as much as 7.2 mg/g of anthocyanins,72 which may be as high as 1800 mg/day of anthocyanins from the fresh whole blueberries. Much like with the inflammation outcomes, supplements providing > 100 mg/day of anthocyanins significantly (P = 0.003) reduced oxidative stress with a moderate effect size. Anthocyanin dosage appears to yield better results for larger concentrations; however, more research is needed to determine more precise prescriptions and recommendations. The research models used in the above studies varied greatly. Both experimental and quasi-experimental studies equally showed significant (P = 0.001, P = 0.006, respectively) results in decreasing exercise-induced inflammation, although when examining oxidative stress outcomes, only experimental studies demonstrated significant results (P = 0.041), while quasi-experimental studies failed to show significant changes (P = 0.458). Although most diet intervention studies last 6–8 weeks, results showed significant reductions in inflammation (P = 0.002) and oxidative stress (P = 0.012) after only 2 weeks of supplementation.21,22,24,26,27,29,31,56 Although these effects were small for both inflammation and oxidative stress, there was a moderate effect and significant (P = 0.004) reduction in inflammation for the 2–6-week duration. One explanation or the lack of significance in studies longer than 6 weeks may be due to participant fatigue in consuming the supplement as directed. These findings suggest that research examining the effects of sports performance outcomes may be able to detect changes in a shorter time frame. Antioxidant supplements, particularly those derived from fruits high in anthocyanins, have been targeted to all types of athletes and sports. The research has also been widespread in regards to the types of exercise protocols used to induce oxidative stress and inflammation. In these studies, whole fruit supplementation was able to significantly reduce inflammation in both aerobic (P = 0.001) and anaerobic (P = 0.013) exercise interventions with a moderate and small effect size, respectively, regardless of training status. A small but significant effect was found for reducing oxidative stress in anaerobic interventions (P = 0.010), but not for aerobic interventions. Exercise intervention durations less than and greater than 60 minutes were both shown to be positively affected by the whole fruits, with significant (P = 0.002, P = 0.003, respectively) reductions in inflammation, although only durations of > 60 minutes showed significant (P = 0.015) changes in oxidative stress. It is worth noting that, although most of the studies used trained participants (k = 19) for oxidative stress measures, the level of training status varied from recreational to elite athlete, when indicated. This may play a role in the effectiveness of such supplements and warrants further investigation. Together, these data suggest that the type of exercise, duration, and training status may play a major role in how effective consuming these fruits are on oxidative stress and inflammation. The intensity of exercise that describes damage-causing potential and the training level of the participant may be the largest factors when determining outcomes. Differences in sex were not found for oxidative stress outcomes, but only males (P < 0.0001) or the combination of males and females (P = 0.034) were found to have significant reductions in inflammation. It should be noted that 1 study used females only and 4 studies used a combination of males and females, whereas the remaining 11 studies were all conducted on males. The limited data on females may explain the observed differences; therefore it cannot be concluded that fruit-derived anthocyanins are more effective for either males or females in reducing exercise-induced oxidative stress and inflammation. One factor that was not specifically analyzed but may also play a role in the outcomes of these studies is the varied time frames in which the biochemical samples were taken. Most studies obtained a pre or resting sample that was taken before supplementation, whereas others did not. Having a clear baseline, particularly after a washout period, is important to fully understand the impact of the fruit supplement. Most studies used a diet log or food recall, but most did not carry out a washout before supplementation. Biological samples were collected after the various exercise protocols, although the collection time frame varied significantly (Table 1). The data on overall effects on inflammation and oxidative stress were compiled based on these varied collection times. This may have a great impact on clear capture of the effects of the fruit. It is not evident what guidelines there should be for manufacturer in regard to producing an effective product for performance enhancement. Yet, these types of fruits are being marketed to athletes and active individuals with varying recommendations on proper dosage. If an athlete consumes a dose that does not meet the effective criteria, there may be no major consequences, although high levels of anthocyanins, like many antioxidants, may act as pro-oxidants, which could hinder performance. Although the data suggest that doses of anthocyanins > 100 mg/day are more effective at reducing both oxidative stress and inflammation following intense bouts of exercise, the wide variability in doses (264.6–6660 mg/d) within that category makes it difficult to recommend any effective daily dose. Additionally, doses of < 100 mg/day were found to be effective in reducing inflammation following strenuous exercise, although doses showing significant inflammation reduction ranged considerably (43.6–80 mg/d). The varied use of each moderator within and between the studies does not lend to clear recommendations for fruit type, processing method, or dose of daily anthocyanins. Given the search criteria, some excluded articles may have changed the outcomes of the analysis. The wide variability in methods in both the exercise and fruit intervention protocol lends to possible misinterpretation or exclusion for some studies. CONCLUSION This meta-analysis assessed the effect of fruits containing anthocyanins on exercise-induced oxidative stress and inflammation. The results indicate that supplementing with these fruits may contribute to improved sports performance by decreasing oxidative stress and inflammation. With only 22 studies meeting the search criteria, interpretation of the data should be met with measured caution. More research is needed to adequately assess dose–response effects for performance gain. As well, if consideration for ease of use for such supplements is paramount, regardless of the bioavailability and effectiveness of the processing method, standardizations should be studied and met for dosing effectiveness. Based on the results reported here, it appears that for these supplements to be effective an athlete should consume the product 2–3 times daily at a dose containing > 100 mg of anthocyanins. It also appears that trained athletes may receive a greater benefit in use, as sedentary or untrained individuals have more confounding variables. It is also noted that overall it would appear that fresh and fresh frozen juice may have a greater impact than other processing methods. More research should be completed to determine a realistic serving of fresh frozen juices and the ease of use and storage for consumption, as well as how to improve the quality of juice concentrates to meet the standards of fresh frozen juices. Acknowledgments Author contributions. 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TI - Impact of anthocyanin-rich whole fruit consumption on exercise-induced oxidative stress and inflammation: a systematic review and meta-analysis
JF - Nutrition Reviews
DO - 10.1093/nutrit/nuz018
DA - 2019-09-01
UR - https://www.deepdyve.com/lp/oxford-university-press/impact-of-anthocyanin-rich-whole-fruit-consumption-on-exercise-induced-g9XWKbYEeQ
SP - 630
VL - 77
IS - 9
DP - DeepDyve
ER -