Dextrose 10% Drink is Superior than Sodium Dextrose in Increasing Blood Glucose and Sprint Speed in Soccer Players: a Double-Blinded Randomized Crossover Trial Study


 Background: Sports drink should be formulated to be effective in improving sports performance, but there is no standard of agreement about the most effective formulation. The diversity of situations in which these drinks are used for and the various factors might contribute to its specific efficacy. The main elements of a sports drink are water, sugar and salt. The major constituents which can be manipulated to alter the functional effects of sports drinks are the carbohydrate (CHO) concentration, type and the electrolyte content. The solution of either dextrose (D) 4-8 % or sodium dextrose (Na-D) are able to increase the blood glucose (BG). However, there are still no comparison about the differences in effects between solely D versus Na-D on soccer players. The aim of this study was to examine the effect of D supplementation on BG, VO2max, and sprint speed compared with Na-D. Method: We conducted a double-blinded crossover study of a 22 young male (19±1.1 years) soccer players, consumed either D or Na-D fluid. We compared pre and post data of BG, VO2max and sprint speed between D and Na-D group. The primary outcome was differences in ΔBG between D and Na-D group. Secondary outcomes were differences in ΔVO2max and Δsprint speed between D and Na-D group. Results: The mean BG level was higher in D compared with Na-D group [136±22.9 mg/dl vs 118±21.5 mg/dl] (p = 0.009). Mean differences of ΔBG of D (mean before and mean after) compared with ΔBG Na-D (mean before and mean after) is 16.8mg/dl (p = 0.001). The mean of sprint speed is faster in the D group [15.2±1.25 sec vs 15.9±1.61 sec] (p = 0.019), but we found no significant differences in VO2max between both groups [42.1±3.44 ml/min/kg vs 42.3±3.98 ml/min /kg] (p = 0.834). Conclusion: The present study demonstrated that D drink without added sodium has a large influence effect in increasing the BG level and sprint speed.Trial registration: ClinicalTrials, NCT04206579. Registered 20/12/2019 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04206579?term=NCT04206579&draw=2&rank=1

(GLUTs) (6). SGLT-1, serve as a main pathway of CHO absorption in the gut, in which absorption of glucose is bringing together with sodium-potassium ATPase (7) (8). SGLT-1 shows high a nity-low capacity with a saturation response (9). GLUT-2 will be expressed to the gut apical membrane in high glucose concentration (10). GLUT-2 shows low a nity-high capacity with no saturation response (9), which has greater absorption capacity than the SGLT-1 at high glucose concentration (9) Delivery of the glucose is restricted by the transport capability of SGLT-1 (11).The gut has the capability to assimilate glucose through basal levels via SGLT1, but this capability gets to be constraining once dietary carbohydrate surpasses a certain level (12). The glucose oxidation rates peaks around 50-60g/h for each 60-70g glucose consumed, and can not be increased anymore despite given 180 g/h glucose (11). Since this con nement was not caused by gastric emptying, liver glycogen, and muscle glucose take-up, it was concluded that assimilation had to be limiting (13). When fructose was ingested in expansion of glucose, CHO oxidation rates were lifted over 60 g/h (14), suggested that glucose assimilation across the gut apical membrane was the limiting factor and that the peak transport capability of SGLT-1 was reached (15).
The absorption of glucose can be ampli ed by apical GLUT-2 when the submucosal and enterocyte glucose concentration are lower than in the intestinal lumen (19). During in vitro analysis, following exposure of glucose, the time to reach a steady state of glucose aggregation inside the enterocytes is ≤ 2 min (20) (21). When the gut luminal glucose is lower than the enterocyte concentration, it will ruin apical GLUT-2 for passive glucose assimilation, instead of accommodate net absorption (19) (22).
The distance coverage of soccer players during a match is 9-12 km, of this, 8-12 % are sprinting (23).
Soccer players require energy turnover from aerobic and anaerobic metabolism (24). A considerable oxidation of endogenous glucose stores is obvious in soccer competition (25). The advantageous results of CHO ingestion were related with the preservation of glycogen levels, which serve as an ergogenic effect, such as improved fuel substrate to the brain and muscle (26). As a result, the availability of glucose was appeared to impact soccer performance by improving the capacity to perform the intermittent bouts and may worsens the performance when the concentration is decreased (27).
Sports drinks are designed to supply CHO, electrolytes and uids to the body, which are absorbed swiftly from the gut. In other words, the period from ingestion until the CHO, electrolytes and uids reach the muscles and brain should be very short (28). Either 3%-10% glucose solution (29) (30) or 12% glucose with sodium added have the ergogenic effects (31). Commercial sports drinks generally contain both combination of CHO and sodium; To the best of our knowledge, there is no trial in which compares the differential effect of solely dextrose supplementation versus sodium dextrose in soccer players in terms of BG concentration, VO 2 max and sprint speed, which may give a new paradigm for the available ergogenic sports drink. Therefore, we designed a randomized, double-blind trial in male soccer players to evaluate the effect of dextrose solution with zero sodium versus the solution of dextrose with 20mM sodium in terms of blood glucose, VO 2 max, and sprint speed. The primary outcome was a mean difference in BG level between D and Na-D intervention. Secondary outcomes were mean differences in VO 2 max and sprint speed. We hypothesized that D supplementation, gives a superior effect than Na-D supplementation in terms of blood glucose, VO 2 max and sprint speed.

Study design and procedure
This study was a randomized crossover (double-blind) design. Participants and researchers were blinded from the administered uid type. Participants were randomly assigned to receive either dextrose (D) solution or sodium dextrose (Na-D) solution. Randomization took place immediately after the participants had been con rmed to be eligible for entering the study. The randomization code of the drink, was not made available to anyone involved in conducting or evaluating the study, and was released after the blind review and the freezing of the nal database. After randomizing, the study was divided into three phases, as shown in Fig. 1. Assessment of health status, dietary intake, measurement of body composition, baseline blood glucose, baseline VO 2 max, and baseline sprint speed were evaluated in phase I. In phase II, we measured the blood glucose before the participants drink the dextrose or sodium dextrose supplementation. We asked the participants to sprint before received the solution, then we record the time and calculating the VO 2 max. After that, we give one type of solution (dextrose or sodium dextrose). In order to have a comparison of the post supplementation effect, the participants repeated the previously mentioned procedures in this phase II. Phase III was similar to phase II except for the nutritional supplementation. The participants could receive either dextrose or sodium dextrose in phase II, and the opposite alternative in phase III. This trial was conducted at UNM Banta-Bantaeng, Makassar, Indonesia, from April 2019 to May 2019.

Supplement preparation
The supplements consisted of dextrose (D) or sodium dextrose (Na-D). Glucose is a monosaccharide, which acts as an essential energy source through aerobic or anaerobic metabolism. Dextrose or Dglucose is an aldohexose stereoisomer of glucose. It is the most commonly occurring isomer of glucose in nature. Our pharmacist used 15 g of dextrose anhydrous to make a 150 ml dextrose 10%, with pH 5.27. Another 150ml Sodium dextrose solution consisted of 10% dextrose, added with 20mM of sodium. The material is taken from Japan (Otsuka Holdings Co., Ltd.) and all of the entire mixing process was supervised by Akademis hospital licensed pharmacist.

Participants
Sample sizes for this research are twenty one, and it was calculated by equation n= [ {(Zὰ + Z ) X Sd } / d ] 2 , with Zὰ = 1.96; Z = 0.842; Sd= 28.2; d=10. Random allocation was performed using a random electronic generator via https://www.random.org/lists/. Our pharmacists staff were responsible to generate the random allocation sequence, enrolled participants, and assigned participants to interventions. After assignment of interventions, all of the participants and us, were blinded. A total of 50 male out eld academy soccer players were screened for the study. Thirty-two participants entered into the inclusion criteria. All were healthy and free of injury in the three months preceding the study. Three participants refused to join, and 6 were dropped out. Twenty-two participants participated (age, 19.6 ± 1.1 years; height, 165.7 ± 5.25 cm; weight, 52.5 ± 8.47 kg; body fat, 12.5 ± 4.68 %; muscle mass, 82 ± 4.7 %; BMR, 1346 ± 147.0 kcal) in the study and were successfully analysed until the end. Prior to enrolling in the study, each participants's physical examination and health history were taken. Eligibility criteria were healthy men soccer players between 18 and 23 years of age, who exercised on average between 8 and 12 h per week the last month prior to inclusion. All participants were within the last meal four hours prior to the test. Exclusion criteria were the use of amylase supplement, suffering from fever and diarrhoea, using laxative agents within 24 h, consuming CHO absorption inhibitors, caffeine, creatinine, beta alanine, sodium bicarbonate supplement within 24 h, mean arterial pressure <65mmHg, knee or muscle injuries, history of diabetes mellitus and heart disease, going through the ketogenic diet program, history of gastrointestinal surgery, and total body fat percentages > 30%. Participants who were currently taking any other dietary supplement, sports drink, or functional food intended to enhance performance or muscle mass, or had taken any of these in the previous week, were also excluded.

Intervention and procedures
The participants were instructed to abstain from exercise 24 h prior to the testing in phase I, II and III, and they arrived at the eld track by car, motorcycle or by public transportation. They were recommended to maintain usual eating pattern 48 h before the test and had a last meal 4 hours before the phase I. In addition, they were told to refrain from coffee and kind of sports drink 48 h prior to the test.
Dietary intake was collected using two days food recall. BG were measured from capillary blood glucose from the ngertip and immediately analysed (Aviva; Accucheck, Roche Diagnostics, Indiana, U.S.A), blood pressure was measured using aneroid sphygmomanometer (R1 shock-proof; Riester, Jungingen, Germany), heart rate was measured with wrist band pulse monitor (Bluetooth 4.0 wireless sport heart rate monitor WP290; Egoman, Shenzen, China), body weight, muscle, fat, water, metabolic rate was measured using the body composition analyzer (BC-545N; Tanita, Tokyo, Japan), body height was measured using a stadiometer (HR-200, Tanita, Tokyo, Japan), sprint speed were measured using a digital stopwatch (S23589 S23589P1; Seiko, Tokyo, Japan) Participants were instructed to refrain from strenuous physical activity in the 2 days preceding trial sessions and recorded all food consumed in the 2 days before the trial. Food records subsequently were analysed using professional German nutrition software (EBISpro, Nutrisurvey 2007). On arrival at the eld, pre supplementation capillary blood samples were collected, and then all players run for 2x100 m and calculated the VO 2 max using Uth-Sorenen-Overgaard-Pedersen formula and sprint speed was recorded. After doing the baseline measurement, each player waited for 15 minutes in order to consume either dextrose or sodium dextrose solution, and then waited for 15 minutes to have another subsequent capillary blood samples measurement. After that, the players run for 2x100 m, recorded the VO 2 max and sprint speed. The players remained in a rested state for 120 minutes as a crossover washed-out period, and then did the same protocol with a different solution.

Statistics
Descriptive statistics were used to characterize the participants (mean, standard deviation (SD), with 95% con dence interval, and signi cance was accepted at p < 0.05. Data were checked for normality as indicated by the Shapiro-Wilk test. Paired samples t tests were used for comparison before and after condition in blood sugar, VO 2 max and sprint speed. All reported p-values were based on two-sided tests.
Exact values of p < 0.05 were considered statistically significant. The data was analysed using IBM SPSS Statistics 25 for windows (SPSS Inc., Chicago, Illinois, USA). The sample size was selected based on an a priori power calculation. Accordingly, with a type I error of 0.05, power analysis revealed that for a 2-tailed paired data Student t test a sample size of 21 individuals is adequate to achieve a power of >80%. To interpret the magnitude of effect, Cohen's d effect sizes (±95% con dence limits) were estimated using a purpose built spreadsheet, with effect size thresholds set at <0.20, >0.50, and >0.80 for small, moderate, large, effects respectively.

Results
Baseline characteristic for all 22 participants was shown in Table 1. All of the variables are within normal distribution. All of the participants (n = 22) completed the test without any injuries and none of the participants in both groups reported any kind of side effects. Due to the little differences in muscle (82 ± 4.7%) and total body water percentages (60.7 ± 4.91%) of all participants, we used the similar dose of dextrose and sodium dextrose for all of the participants. The effect of dextrose or sodium dextrose supplementation on blood glucose, VO 2 max and sprint are presented in Figs. 2, 3 and 4 respectively. The mean of blood glucose before and after dextrose supplementation are 91 ± 11.6 mg/dl and 136 ± 22.9 mg/dl. The mean of blood glucose before and after sodium dextrose supplementation are 91 ± 9.1 mg/dl and 118 ± 21.5 mg/dl. Dextrose supplementation had a higher blood glucose level than sodium dextrose (136 mg/dl versus 118 mg/dl). This data was also supported by the mean differences of BG before dextrose supplementation compared with before sodium dextrose was 0.4 ± 5.86 mg / dl, p = 0.747 (95% CI -2.19, 3.01), which means their differences was not statisctically signi cant. The data between dextrose and sodium dextrose group was shown in Table  2 and 3. Another corroboration of the data, was found that the mean differences of BG after dextrose supplementation compared with after sodium dextrose was 17 ± 28.2 mg / dl, p = 0.009 (95% CI 4.7-29.8). Cohen's d effect's size = 0.60. However, to sum it all, the primary endpoint is to know the mean differences of ΔBG in the dextrose group (before and after supplementation) compared with a ΔBG sodium dextrose group (before and after supplementation) as shown in Table 3, which has the p-value of 0.011 and effect's sizes 0.6. Data are presented as mean values ± standard deviations (SD). The P -value represents the signi cance level of the difference between the before dextrose or sodium dextrose and after the dextrose or sodium dextrose supplementation. Cohen's d represents the effect sizes of the p-value. BG, blood glucose; VO 2 max, maximal oxygen uptake; HR, heart rate; BPM, beat per minute. 1 Measured at the end of the sprint sessions. (before and after supplementation) compared with a ΔVO 2 max sodium dextrose group (before and after supplementation), as shown in Table 3, which has a p-value of 0.507 and effect's sizes 0.1, as shown in Table 3.
The mean of sprint speed before and after dextrose supplementation is 14.6 ± 1.33 sec and 15.2 ± 1.25 sec. The mean of sprint speed before and after sodium dextrose supplementation is 14.6 ± 1.46 sec and 15.9 ± 1.61 sec. The mean differences of sprint speed before dextrose supplementation compared with before sodium dextrose were 0.07 ± 0.724 sec, p = 0.640 (95% CI -0.24, 0.39). The mean differences of sprint speed after dextrose supplementation compared with after sodium dextrose was − 0.64 ± 1.184 sec, p = 0.019 (95% CI -1.16, -0.11). Cohen's d effect's size = 0.55. The mean of sprint speed is faster in a dextrose supplementation group than the sodium dextrose group (15.2 sec versus 15.9 sec). This value was supported by the secondary endpoint of this study. The mean differences of Δsprint speed in the dextrose group (before and after supplementation) compared with the Δsprint speed in sodium dextrose group (before and after supplementation) as shown in Table 3, which has a p-value of 0.011 and effect's sizes 0.6, as shown in Table 3.

Discussion
We examined the effect of dextrose versus sodium dextrose supplementation on BG, VO 2 max and sprint speed of the young male soccer players. The main nding was that supplementation with dextrose had a better ergogenic effect than sodium dextrose in terms of BG and sprint speed, but still could not improve the VO 2 max.
Soccer is an intermittent, high-intensity team sport in adult players. Muscle glycogen in certain muscle bres and BG used to drop to levels that may damage cognitive function (32). As a result, soccer players are often advised to consume the CHO solution during competitions to supply muscle glycogen reservations and maintain BG concentrations during the match (5). The effect of CHO solution on energy metabolism to actual soccer matches has been widely known (1). BG levels can be maintained optimally until the end of the game if the players consumed exogenous CHO (33). Consumption of CHO is a nutritional strategy that is usually recommended for soccer players, that aim to maintain endogenous energy stores, and prevent excessive physical and cognitive performance decline throughout the match (5).
Consumption of CHO has been proven to improve the performance index of expertise in playing soccer, where the reduction in BG levels can negatively in uence the skilled actions involved (34). Considering the performance bene ts of CHO supplementation which is able to reduce glycogen 'depletion' levels throughout the game, it is recommended that soccer players consume 30-60 g / h of exogenous CHO supplementation during competitions to maintain the BG level and glycogen reserves (35). However, the superior effect on the rate of increase in BG of pure ergogenic dextrose supplementation compared with sodium dextrose have not yet been known, therefore started from that point this study was conducted.
We obtained the results of the mean differences of BG after dextrose versus after sodium dextrose group was 136 ± 22.9 mg/dl and 118 ± 21.5 mg/dl. This positive nding may suggest the mechanism that solely dextrose supplementation via a GLUT-2 pathway was able to transport CHO into the plasma faster than SGLT-1 pathway. CHO can be moved through the apical membrane of enterocytes via a GLUT-2 pathway (22), which may occur if the CHO supplementation is given without sodium as a co-transporter, evading the SGLT-1 pathway (36).
In soccer players, an increase in BG levels can be observed from 75 min onwards when a 10% CHOelectrolyte solution is consumed before and during soccer matches, compared to a placebo-uidelectrolyte control (37).
The total CHO concentration in sports drinks is 4-8% and the sodium content is 10-25 mM (38). In this study, we were using a higher CHO concentration of 10% with 20 mM sodium. This condition can explain that at a higher CHO concentration will trigger absorption through the GLUT 2 pathway, possibly without going through the SGLT 1 route. It is also known that the apical GLUT-2 absorption component is greater than the SGLT-1 at high luminal glucose concentrations (39) (40). Apical GLUT-2 is tightly regulated by long and short-term CHO supply and also by local and endocrine hormones, disease (diabetes mellitus), cellular energy level, and the regulation occurs through intracellular signalling pathways (9). Thus, apical GLUT-2 can act as the main pathway for sugar absorption. Apical GLUT-2 acts a guard mechanism by preventing high concentrations of CHO escape into the large intestine (41).
Intestinal CHO absorption consists of SGLT and GLUT types. Activation of GLUT2 in the apical gut membrane increase with glucose concentration (9). and the diffusive component. Evidence shows that the diffusion part is mediated by the translocation of transient GLUT-2 from the intracellular enterocyte vesicles into the apical membrane, especially after high luminal glucose, which allow bulk absorption of glucose (42) (43). The apical GLUT-2 pathway from luminal sugar uptake could be inserted within minutes into the apical of enterocytes in response to high glucose level during food assimilation (16). As in physiologic condition, after a meal, glucose level in the gut lumen rises, which could saturate the SGLT-1. The GLUT-2 pathway in the apical membrane, then facilitate CHO diffusion down the concentration gradient. This study was given supplementation of 150 cc of dextrose 10%, equivalent to 15 grams of dextrose.
The slower mean increment of BG in the administration of sodium dextrose solution can be partly explained by the fact that SGLT-1 is a rate limiting pathway for enterocyte glucose absorption. SGLT-1 uses a transmembrane sodium gradient to carry out the cellular uptake (44). Such a situation may occur slower, considering the condition of soccer players is not in the actual match condition (45), suggesting lesser sodium loss through sweat perspiration that may give a result in a weaker sodium transmembrane gradient (46) (47). Also, one main rule when using sport drinks that contain dextrose and sodium, is that they should not be diluted. This would change the concentrations of CHO and sodium. Both will affect the speed at which the drink empties from the stomach, so the whole mechanism of energy and uid delivery will be delayed. The bene ts of using sports drinks are proven only for adults involved in rigorous exercise, and doing training at hot condition and high humidity (28). VO 2 max differences between groups given dextrose compared with sodium dextrose were not signi cant.
Soccer is predominantly intermittent aerobic sport interspersed with periods of high-intensity anaerobic, which may perform different types of exercise intensities and using the aerobic and anaerobic energy systems. Total duration of active play in soccer is ± 95 min, suggested the main energy source during the match is supplied through aerobic glycolysis. The average VO 2 max during match play was reported to be around 75-80%. The mean and peak heart rate of players was estimated to be around 85 and 98% respectively. Nonetheless, VO 2 max values of soccer players were shown to vary noticeably, with current high level soccer players are suggested to acquire maximal oxygen uptakes between 60-70 ml/kg/min, with an estimated minimum of 65 ml/kg/min in elite soccer players (27).
People with high tness (as measured by VO 2 max) are more physically active in their daily life than those with low tness. VO 2 max is a modi able variable and it can be increased through exercise. High intensity interval resting training was found to improve VO 2 max more effectively than moderate continuous session (48). We found no differences between the two groups because it has been known that VO 2 max is not only in uenced by BG levels, but also by other factors, such as cardiorespiratory tness (49). However, to determine if a dose-response relationship exists between exercise intensity and traininginduced increases in VO 2 max, result from meta-analysis suggests that exercise training intensity has no effect on the elevation of training-induced VO 2 max, but similar adaptations can be achieved in low training doses at higher exercise intensities than higher training doses of lower intensity (50). VO 2 max is a measurement of the maximum capacity to utilize oxygen in multilevel exercise tests, and act as a measure of the cardiorespiratory tness system in soccer players. The cardiovascular and thermoregulatory systems are rst affected by low hydration, especially when exercise is performed in the high temperature or high humidity conditions (28), but in this experiment design, the players were not performed in the heat environment.
During soccer training sessions, 6-7% CHO solutions have succeeded in increasing the sprint speed (33).
Glycogen breakdown declines with a simultaneous elevation in extra-muscular BG levels, to maintain normal BG during the match (27). CHO supplementation improved intermittent running, soccer skill performance, the distance covered during the game and were correlated with the maintenance of glycogen levels when compared to a placebo beverage (27). The faster sprint speed in the dextrose group might be explained by the effect of the faster increment in BG mean in the dextrose group, served as a readily available substrate to fuel the muscle glycogen. CHO concentration in the sports drinks range in between 4-8% and the sodium content are between 10-25 mM (38), but in this study, we used a higher CHO concentration reached the 10% with 20 mM sodium. This fact may explain that at higher CHO concentrations, it will trigger absorption through the GLUT 2 pathway without going through the SGLT 1.
Half-time for apical GLUT 2 membrane insertion was very rapid (∼3.5 min) and correlated with activation of the protein kinase C βII isoform. The transient presence of GLUT 2 in the apical enterocyte has been proved using antibodies to epitopes within N-terminal regions. Its location in the apical membrane has been con rmed by cell immuno uorescence imaging using extracellular loop antibody. GLUT 2 can transport glucose and has a very high Kt (transport constant) for glucose, indicate that apical GLUT 2 has the role for the diffusive component of glucose absorption, which at high glucose levels, the GLUT2 component accounted for ± 75% of the absorption (16). In animal model, when the glucose concentration is higher in the intestinal gut lumen than in plasma, rapid tra cking of GLUT2 to the apical membrane occurs in enterocytes, accounts for the facilitated glucose absorption (51). With BG level rising faster in the dextrose group, it will provide the added bene t of a faster sprint speed. The possible underlying mechanism was because of the increased availability of substrates which can be used as a rapid fuel for muscle contraction (14). However, the limitation of our study is the research was not performed under real soccer match.

Conclusions
Our study indicated that solely dextrose supplementation effectively supports blood sugar and sprint speed in soccer players. A solution of 150 ml dextrose 10% elevated blood glucose faster than sodium dextrose solution. On the basis of our results, we conclude that with regard to the beginning of the soccer match, a 10% of dextrose solution ingested 15 minutes before the match, could elevate BG faster and may have a good impact in sprint velocity, as in the beginning of a match, to kick off and dominate it. These ndings suggest a future suggestion to re-evaluate the energy drink which nearly always has a mixture of CHO and electrolyte.  Blood glucose differences. Blood glucose differences before and after dextrose supplementation (p = 0.001). Blood glucose differences before and after sodium dextrose supplementation (p = 0.001). Shading bar: blood glucose before supplementation; white bar: blood glucose after supplementation VO2max differences. VO2max differences before and after dextrose supplementation (p = 0.282).