A systematic review and meta-analysis of carbohydrate benefits associated with randomized controlled competition-based performance trials

Background Carbohydrate supplements are widely used by athletes as an ergogenic aid before and during sports events. The present systematic review and meta-analysis aimed at synthesizing all available data from randomized controlled trials performed under real-life conditions. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched systematically up to February 2015. Study groups were categorized according to test mode and type of performance measurement. Subgroup analyses were done with reference to exercise duration and range of carbohydrate concentration. Random effects and fixed effect meta-analyses were performed using the Software package by the Cochrane Collaboration Review Manager 5.3. Results Twenty-four randomized controlled trials met the objectives and were included in the present systematic review, 16 of which provided data for meta-analyses. Carbohydrate supplementations were associated with a significantly shorter exercise time in groups performing submaximal exercise followed by a time trial [mean difference −0.9 min (95 % confidence interval −1.7, −0.2), p = 0.02] as compared to controls. Subgroup analysis showed that improvements were specific for studies administering a concentration of carbohydrates between 6 and 8 % [mean difference −1.0 min (95 % confidence interval −1.9, −0.0), p = 0.04]. Concerning groups with submaximal exercise followed by a time trial measuring power accomplished within a fixed time or distance, mean power output was significantly higher following carbohydrate load (mean difference 20.2 W (95 % confidence interval 9.0, 31.5), p = 0.0004]. Likewise, mean power output was significantly increased following carbohydrate intervention in groups with time trial measuring power within a fixed time or distance (mean difference 8.1 W (95 % confidence interval 0.5, 15.7) p = 0.04]. Conclusion Due to the limitations of this systematic review, results can only be applied to a subset of athletes (trained male cyclists). For those, we could observe a potential ergogenic benefit of carbohydrate supplementation especially in a concentration range between 6 and 8 % when exercising longer than 90 min. Electronic supplementary material The online version of this article (doi:10.1186/s12970-016-0139-6) contains supplementary material, which is available to authorized users.


Background
Carbohydrates are one of the two main fuels for sport activities and their importance for optimal sport performance both in training and in competition is generally undisputed among experts [1,2].
Carbohydrates are also used by athletes as an ergogenic aid before and during sport events even when they have repleted carbohydrate reserves. The scientific background of carbohydrates as an ergogenic nutritional supplement has been the subject of numerous investigations with the majority of results indicating a performance-enhancing effect of carbohydrate supplementation shortly before and during a performance bout [3][4][5][6][7][8][9][10].
In some of these studies, subjects were competing in a fasted state. Overnight fasting may probably result in more easily reproducible outcomes due to a more balanced state of metabolism in comparison to a postprandial state [11]. However, athletes intuitively avoid a fasted state before any competition and it is not recommended in the pertinent literature. It has been indicated that during an overnight fast liver glycogen stores are reduced substantially by amounts as high as 80 % [1,2]. Therefore, suboptimal carbohydrate stores are likely to be present when beginning an exercise in a fasted state. Furthermore, many performance studies used time-toexhaustion tests, which asses how long subjects can exercise at a given intensity. Again, this protocol does not always reflect the conditions of a real competition because athletes, at least in elite sports, should either perform as fast as possible for a given distance (e.g., races) or as well as possible within a given time (e.g., team sports). Currell and Jeukendrup [12] assessed various performance protocols and concluded that those in which subjects were asked to complete a fixed distance/amount of work as fast as possible or to accomplish as much work/distance as possible in a given time (i.e. time trails), yielded better results with respect to validity, reliability and sensitivity as compared to time-to-exhaustion protocols [12].
In 2013, a systematic review by Colombani and coworkers [11] addressed all these aspects. Their results suggests that only 11 out of 22 investigations included in the review resulted in a significant improvement of performance following carbohydrate supplementation indicating a high amount of uncertainty concerning the benefits of carbohydrate supplementation in field experiments trying to copy a realistic performance setting.
It was the purpose of the present study to expand the approach by Colombani et al. [11] via an updated literature search in order to yield an extended number of suitable studies so that the systematic review can be combined with a statistical synthesis of the available data using a meta-analytical approach.

Search strategy
Data of the original search by Colombani et al. [11] were used as starting point. The authors performed a search in "PubMed" up to September 3, 2011 using the following combination of key words: ( In addition to the systematic search of Colombani and coworkers [11] we searched the electronic databases "Embase" as well as the "Cochrane Central Register Of Controlled Trials" up to February, 2016 and expanded the search in "PubMed" starting September 4 th , 2011 to February, 2016 using the same combinations of search terms with the following exceptions: we used "Human" and "Adult <18 to64 years" as further limitations in the database "Embase". Hand search was done using the reference lists of two meta-analyses [7,8], yielding one additional article suitable for this systematic review [13].

Inclusion criteria
In accordance to Colombani et al. [11], the following inclusion criteria were defined: -Randomized, crossover, placebo-controlled and if possible blinded study design. Blinding was not feasible as an absolute criterion, as sometimes the intervention could not be fully masked; -Mean age of the subjects between 18 and 40 years, but no restriction with respect to gender; -A reported VO 2max ≥ 50 mL/kg/min (for an appropriate estimation of subject's fitness level); -Assessment of body mass; -Subjects were tested in the postprandial state (between 2 h and 4 h after ingesting last meal); -Performance test had to be either of a time trial (TT) character or a submaximal exercise followed by a time trial (S + TT); -For studies with carbohydrate intake immediately prior to and/or during exercise, we included only studies with provision of any type of carbohydrates, electrolytes and water but no further components.

Exclusion criteria
-Studies with time-to-exhaustion tests or studies with insufficient methodological information to enable a check of the inclusion criteria were excluded. Furthermore, subgroups were formed in order to address two other research questions:
In the scientific literature, the different mechanisms for ergogenic effects of carbohydrates with respect to short and long lasting physical exercise was explained to be due to different carbohydrate availability. For exercise durations lasting ≤ 90 min there should be sufficient substrate without power loss given the condition of regularly filled glycogen stores [14][15][16]. Therefore we compared exercise durations ≤ and > than 90 min.

Statistical analyses
Data were analyzed using the Review Manager 5.3 software provided by the Cochrane Collaboration (http://tech.cochrane.org/revman). Differences in means were compared for outlining possible differences between carbohydrates and placebo with a fixed-effect meta-analysis using the inverse-variance method. However, when heterogeneity exceeded the level of 50 %, the random-effects model was used. The Cochrane Collaboration suggests to use metaanalyses in order to synthesize evidence from multiple experiments addressing the same research questions. Checking consistency of the results is of major importance in meta-analyses. Statistical heterogeneity in studies is characterized by 95 % CI that show poor overlap. We used the I 2 statistic to detect heterogeneity [17]. If considerable heterogeneity is observed (I 2 ≥ 50 %), fixed-effect models should be avoided, since they underperform in that context. Random effects models provide a more conservative approach yielding better estimates [18].
Descriptive data of included trials are given as mean ± SD. Pooled estimates of the effects size obtained by either comprehensive or subgroup meta-analyses are reported as mean difference together with the 95 % confidence intervals, respectively. P-values < 0.05 were considered to be statistically significant. Moreover, effects sizes are given as standardized mean differences (SMD) for each analysis group as Additional files 1, 2, 3 and 4 (see corresponding Result section).

Literature search
In the original literature search by Colombani et al. [11] performed in the electronic database Pubmed until September 3 rd , 2011, 16,658 articles were identified. Our own updated search for literature yielded 15,105 articles (4,136 articles from PubMed published between September 4 th , 2011 and February, 2016, 2,916 articles from Cochrane Central Register Of Controlled Trials, and 8,053 from Embase, respectively). Articles which contained sufficient information in the title or abstract to identify them as not eligible were discarded, if this was not the case, the full text was consulted. Furthermore, 12 reviews [3-6, 9, 10, 19-24] concerning this topic were hand-searched for eligible studies, however no additional study fulfilling the search criteria was identified. In total, the full text of 205 articles was examined yielding 24 studies that met the inclusion criteria and are displayed in the systematic review (Tables 1  and 2). 16 of these articles provided enough information to allow for a quantitative evaluation. Steps of article search and selection are summarized as a flow chart in Fig. 1.

Types of studies Carbohydrate intervention
Two studies were carboloading interventions, one [25] using a TT as the performance test, the other one [26] a submaximal exercise followed by a TT.
We found one eligible study [27] with a mouth-rinse intervention, the remaining 21 studies compared the effect of a carbohydrate-containing drink versus a noncarbohydrate placebo. In eight of these interventions, the carbohydrate type was not specified with only the total amount of carbohydrate being reported. In the All of the 16 studies provided enough information for a quantitative evaluation used cycling as their exercise mode. For reason of a better comparability, these studies were assigned to one of four different groups as described in the Methods section. Study designs with both time and power outcomes where assigned to all applicable groups. Two articles presented their outcomes as work [13,31], which was converted into power prior to analyses by dividing work by the required time.
Results for group 1 and 3 were subdivided based on the administered carbohydrate concentrations, results for group 2 and 4 were subdivided based on exercise duration.

Exclusion of studies
Two studies tested the advantage of carbohydrates during a running exercise and were not included into one of the four groups because of considerable physiological differences between this and the other types of exercise [28,29]. In addition, the study by Clarke et al. [30] was the only eligible study using a soccer-specific protocol and could therefore not be included in the meta-analysis. Other studies had to  [27], carboloading [25,26]], or presentation of data in an inoperable unit (N/m) [32], or presentation of results only via graphics, respectively [33].

Characteristics of subjects
Subjects were male with the exception of two studies [29,34] enrolling both genders. Sample size varied between seven and 16 volunteers, mean age ranged between 19 and 35 years, and mean VO 2max ranged between 50 and 71 ml/kg body weight/min.

Performance outcomes
For each of the four groups, results of both comprehensive as well as subgroup meta-analyses are given in Figs Group 2 included seven studies [40][41][42][43][44][45][46] with seven interventions in total. Figure 3 summarizes the pooled estimates for effect size obtained by a random effects model due to the considerable heterogeneity between studies (I 2 = 73 %; P = 0.001) (forest plot showing pooled SMD is given as Additional file 2). Average cycling time was faster in subjects ingesting carbohydrates as compared to placebo, however, without being statistically significant [mean difference 2.8 min (95 % CI −7.7, 2.1), p = 0.26]. Subgroup analysis including only studies with an exercise duration shorter than 90 min revealed a marginally higher average cycling time in the carbohydrate groups [mean difference 0.1 min (95 % CI −1.1, 1.2), p = 0.89]. In contrast, subgroup analysis taking into account studies with an exercise duration longer than 90 min resulted in a decreased average cycling time following carbohydrate ingestion when compared to placebo [mean difference −4.6 min (95 % CI −12.4, 3.2), p = 0.25].

Discussion
Based upon the recent systematic review by Colombani et al. [11], it was the purpose of the present study to synthesize all available data from randomized controlled trials investigating the potential ergogenic effects of carbohydrate supplementation via meta-analysis. Due to the inbetween heterogeneity of trials with respect to study design, we decided to evaluate only studies choosing cycling as the mode of exercise. Moreover, four groups of carbohydrate interventions with respect to test and performance measurement were classified in order to achieve a better comparability of results. Taken together, all four groups indicated an improved performance following carbohydrate intervention as compared to placebo with differences being statistically significant in group 1 (submaximal exercise followed by a time trial measuring time needed to cover a fixed distance or a fixed set amount of work), group 3 (submaximal exercise followed by a time trial measuring power (W) accomplished within a fixed time or distance), and group 4 (time trial measuring power (W) accomplished within a fixed time or distance), respectively.

Subgroups duration
Duration of exercise ≤ 90 min did not result in statistically significant differences between carbohydrate interventions and placebo either in group 2 or in group 4. These findings seem to be in contrast with studies reporting an improved performance via carbohydrate mouth rinsing [10,[48][49][50][51][52][53][54]. It has been suggested that oral receptors within the mouth and the digestive tract sense carbohydrates and activate brain regions associated with reward and pleasure which may lead to enhanced performance [5,10,48]. However, most mouth rinse studies were conducted in a fasted state [48,50,52,53] or had other limitations such as lack of or improper randomization [51,54] or uncertain time of last ingested meal [49]. In our systematic review, three studies [27,33,38] with an exercise duration less than 90 min could not be included in either groups 2 or group 4. Beelen et al. [27] demonstrated a non-significant performance decline when testing a carbohydrate mouth rinse. Likewise, Acker-Hewitt et al. [38] did not find a significantly better performance subsequent to a carbohydrate solution when compared to placebo, while El-Sayed et al. [33] could detect an increase in performance capacity. Therefore, it seems premature to finally evaluate the potential benefit of ingesting carbohydrates in short-term exercises (less than 90 min), further trials reflecting realistic conditions are necessary.
Subgroup analysis of five trials with a duration time higher than 90 min in group 2 resulted in a trend towards a decreased time needed to cover a fixed distance or a fixed set amount of work. A similar trend could be observed in group 4, albeit with only two trials included in the subgroup. Taking all results under consideration, a performance benefit through carbohydrates might be possible when exercise duration exceeds 90 min. However, similar to subgroups with ≤ 90 min, additional studies are required for evidence-based recommendations.

Subgroups carbohydrate concentration
Irrespective of specific carbohydrate concentrations, metaanalytical results of both groups 1 and 3 yielded statistically significant benefits for carbohydrate supplementation. In general, this might be due to multiple factors including maintenance of blood glucose [55][56][57] and high levels of carbohydrate oxidation especially towards the end of exercise [58,59], thus sparing liver glycogen [60][61][62][63], as well as a central effect of carbohydrates [48,52].
Regarding range of carbohydrate concentrations, results were statistically significant in favour of the lower range of 6-8 % of carbohydrate supplementation both in groups 1 and 3, while corresponding results for the higher range was only significant in group 3 (12-18 %), but not in group 1 (10-12 %). However, in both groups, the respective higher concentration range resulted in greater statistical variance when compared to the 6-8 % range. Therefore, one might speculate an impact of the administered carbohydrate type becoming more effective at higher concentrations. A high dose of ingested carbohydrates while exercising may cause gastrointestinal discomfort [64] which subsequently may decrease performance [65]. The maximal rate at which a single type of ingested carbohydrate can be oxidized is 60-70 g/h and ingesting more than this amount will not augment the oxidation rate but rather increases the chance for gastrointestinal discomfort [22]. It has been suggested that the ingestion of carbohydrates that use different, not competing, transporters increases the maximal carbohydrate oxidation rate (up to 105 g/h) [66], which has been verified by numerous studies [24,39,[67][68][69]. In the study by Baur and co-workers [39], three different carbohydrate solutions were examined (8 % glucose solution, 12 % glucose solution, 12 % glucose-fructose (2:1) solution). The glucose-fructose solution achieved the greatest performance improvement, while the 12 % glucose solution did not affect performance significantly. Likewise, three different carbohydrate solutions (a 6 % glucose polymer-sucrose-solution (2:1, 37 g/ h), a 12 % glucose polymer-fructose solution (2.4:1, 75 g/ h), and an 18 % (4.1:1, 111 g/h) glucose polymer-fructose solution) were comparatively investigated in the trial by Mitchell et al. [13]. The best performance outcome was found with the 12 % glucose polymer-fructose solution. Despite no direct measurement of gastrointestinal symptoms, the authors concluded that the 18 % solution caused gastrointestinal distress and therefore the performance enhancement was not as high as with the 12 % solution [13].
Thus, the carbohydrate concentration resulting in optimal performance seems to be dependent on many factors, although our data suggests a more consistent benefit with carbohydrate solutions ranging between 6 and 8 %.

Strengths and limitations
The protocol of the present systematic review was designed to summarize the available evidence on the ergogenic effects of carbohydrate supplementation as an expansion of the results by Colombani et al. [11] focusing on randomized controlled trials investigating the outcomes of their interventions under real-life conditions (no overnight fasting, no time-to-exhaustion tests). Moreover, we decided to categorize trials with respect to types of test and performance measurements. This rigid protocol allows for better comparison between the different trials, it is associated with a number of limitations as well. First of all, the number of studies suitable for meta-analyses turned out to be rather low. All of the 16 trials providing extractable data for meta-analyses used cycling as their exercise mode. Although this might be another aspect increasing the homogeneity of the results, it is not possible to draw any conclusions for other types of exercise such as running. Data on the content of the last meal prior to trials suggest heterogeneous pre-exercise carbohydrate intake between studies. Another common limitation of performance studies is the only low to average power with respect to the number of participants ranging between 16 and 32 volunteers in the present meta-analyses. Since only one trial [39] enrolled subjects with a mean VO 2max that would classify them as elite endurance athletes, the results are most likely not affected by heterogeneity between baseline capacities of study participants. In addition, with the exception of References [29] and [34], all trials were performed with male volunteers hampering transfer of results to female athletes. Following conversion of absolute values into percentage data, results were widely spread yielding improvements in assessed outcomes between 0.

Conclusions
In conclusion there may be a benefit for trained male cyclists when ingesting carbohydrates in a concentration range of 6-8 % just before and/or while exercising longer than 90 min. Due to lack of sufficient data, it is difficult to extrapolate this result to elite or generally female athletes. Moreover, further research is needed to gain additional information on exercise durations lower than 90 min and in a wider variety of types of exercise.

Additional files
Additional file 1: Figure S1. Effects of carbohydrate interventions as compared to placebo on time required to finish a time trial. Forest plot shows pooled standardized mean differences with 95 % confidence intervals (CI) for 6 randomized controlled trials. Subgroup analyses show the results for carbohydrate concentrations ranging between 6-8 % and 10-12 %, respectively. The diamond at the bottom of the graph and the subgroups represents the pooled mean difference with the 95 % CI for all trials following fixed effect meta-analyses. GLU = glucose; FRU = fructose; MAL = maltodextrin; SUC = sucrose. Title: File format: tiff (TIF 7950 kb) Additional file 2: Figure S2. Effects of carbohydrate interventions as compared to placebo on time required to finish a time trial. Forest plot shows pooled standardized mean differences with 95 % confidence intervals (CI) for 7 randomized controlled trials. Subgroup analyses show the results for exercise duration shorter than 90 min or longer than 90 min, respectively. The diamond at the bottom of the graph and the subgroups represents the pooled mean difference with the 95 % CI for all trials following random effects meta-analyses. (TIF 6850 kb) Additional file 3: Figure S3. Effects of carbohydrate interventions as compared to placebo on mean power output. Forest plot shows pooled standardized mean differences with 95 % confidence intervals (CI) for 5 randomized controlled trials. Subgroup analyses show the results for carbohydrate concentrations ranging between 6-8 % and 12-18 %, respectively. The diamond at the bottom of the graph and the subgroups represents the pooled mean difference with the 95 % CI for all trials following fixed effect meta-analyses. GLU = glucose; FRU = fructose. (TIF 7339 kb) Additional file 4: Figure S4. Effects of carbohydrate interventions as compared to placebo on mean power output. Forest plot shows pooled standardized mean differences with 95 % confidence intervals (CI) for 4 randomized controlled trials. Subgroup analyses show the results for exercise duration shorter than 90 min or longer than 90 min, respectively. The diamond at the bottom of the graph and the subgroups represents the pooled mean difference with the 95 % CI for all trials following fixed effect meta-analyses. (TIF 5891 kb) Abbreviations CHO, carbohydrates; CI, confidence interval; FRU, fructose; GLU, glucose; GLUP, glucose polymers; MAL, maltodextrin; MD, mean difference; S + TT, submaximal exercise followed by time trial; SUC, sucrose; TT, time trial