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Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22http://www.jissn.com/content/8/1/22 Effects of carbohydrates-BCAAs-caffeine ingestion on performance and neuromuscular function during a 2-h treadmill run: a randomized, double- blind, cross-over placebo-controlled studySébastien L Peltier1*, Lucile Vincent2, Guillaume Y Millet3, Pascal Sirvent4, Jean-Benoît Morin3, Michel Guerraz5,André Geyssant3, Jean-François Lescuyer1, Léonard Feasson3 and Laurent Messonnier2 Background: Carbohydrates (CHOs), branched-chain amino acids (BCAAs) and caffeine are known to improverunning performance. However, no information is available on the effects of a combination of these ingredients onperformance and neuromuscular function during running.
Methods: The present study was designed as a randomized double-blind cross-over placebo-controlled trial.
Thirteen trained adult males completed two protocols, each including two conditions: placebo (PLA) and SportsDrink (SPD: CHOs 68.6 g.L-1, BCAAs 4 g.L-1, caffeine 75 mg.L-1). Protocol 1 consisted of an all-out 2 h treadmill run.
Total distance run and glycemia were measured. In protocol 2, subjects exercised for 2 h at 95% of their lowestaverage speeds recorded during protocol 1 (whatever the condition). Glycemia, blood lactate concentration andneuromuscular function were determined immediately before and after exercise. Oxygen consumption ( ˙VO2 ), heart rate (HR) and rate of perceived exertion (RPE) were recorded during the exercise. Total fluids ingested were 2L whatever the protocols and conditions.
Results: Compared to PLA, ingestion of SPD increased running performance (p = 0.01), maintained glycemia andattenuated central fatigue (p = 0.04), an index of peripheral fatigue (p = 0.04) and RPE (p = 0.006). Maximalvoluntary contraction, ˙VO2 , and HR did not differ between the two conditions.
Conclusions: This study showed that ingestion of a combination of CHOs, BCAAs and caffeine increasedperformance by about 2% during a 2-h treadmill run. The results of neuromuscular function were contrasted: noclear cut effects of SPD were observed.
Trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT00799630 exercise of longer than 45 min [5-7]. However, the Prolonged running exercises may induce hypoglycemia, observed improvement varies and depends, among other central and/or peripheral fatigue, muscle damage, things, on CHO dosage, exercise intensity and duration, osteoarticular disorders, inflammation and cardiovascu- and the training status of the subjects [8,9]. For exam- lar dysfunction [1-4]. An adapted carbohydrate (CHO) ple, Coyle showed that during a prolonged strenuous supplement during exercise may be useful for limiting cycling exercise (71 ± 1% ˙VO2max) fatigue occurred and/or avoiding hypoglycemia and the associated distur- after 3.02 ± 0.19 h in a placebo trial versus 4.02 ± 0.33 h bance of physical ability. Previous experiments have in a CHO supplement trial (glucose polymer solution, shown that ingested CHOs improve performance during 2.0 g.kg-1 at 20 min and 0.4 g.kg-1 every 20 min there-after) [5]. During a cycling time trial, Jeukendrup et al.
[6] observed that the time needed to complete the set 1Laboratoire Lescuyer, Aytré, France amount of work was significantly shorter with CHOs Full list of author information is available at the end of the article 2011 Peltier et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.
Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 (7.6%) than with the placebo (58.7 ± 0.5 min versus 60.2 [4]. Fatigue is generally defined as the inability to main- ± 0.7 min, respectively), corresponding to a higher per- tain power output [26], and can be central and/or per- centage of the subjects' maximal work rate. It should be ipheral in its origin, these two factors being interrelated.
noted that increased performance is not systematically Several factors have been identified as a cause of periph- observed with CHO ingestion [10]. The mechanisms for eral fatigue (e.g., the action potential transmission along the beneficial effect of CHOs on performance are the sarcolemma, excitation-contraction coupling (E-C), thought to be via the maintenance of plasma glucose actin-myosin interaction), whereas the factors underly- concentrations and the high rates of exogenous CHO ing central fatigue could be located at the spinal and/or oxidation in the latter stages of exercise when muscle supraspinal sites. The tryptophan-5-hydroxytryptamine- and liver glycogen levels are low [5,11,12].
central fatigue theory has been proposed to explain how A great deal of research has been conducted to test oral administration of BCAAs can attenuate central fati- different combinations of CHOs and their exogenous gue [26]. During prolonged aerobic exercise, the concen- oxidation. In particular, studies have demonstrated that tration of free tryptophan, and thus the uptake of blends of simple carbohydrates containing fructose and tryptophan into the brain, increases. When this occurs, sucrose, glucose, maltose, galactose or maltodextrins 5-hydroxytryptamine (5-HT, serotonin) is produced, promote greater exogenous glucose oxidation than do which has been postulated to play a role in the subjec- isocaloric glucose solutions. The difference is thought to tive feelings of fatigue. Because BCAAs are transported be due, at least in part, to the recruitment of multiple into the brain by the same carrier system as tryptophan, intestinal sugar transporters (sodium glucose transpor- increasing BCAAs plasma concentration may decrease ter-1 and GLUT-5) [13-16]. During exercise, the the uptake of tryptophan in the brain, and consequently ingested glucose is rapidly absorbed into the circulation the feeling of fatigue. Nevertheless, Meeusen et al. [27] and oxidized by the skeletal muscle in a highly efficient have mentioned that brain function is not determined manner. In contrast, ingestion of fructose and galactose by a single neurotransmitter system and the interaction results in less efficient oxidization probably related to between brain serotonin and dopamine during pro- slower absorption and delays linked to hepatic metabo- longed exercise has also been explored as having a regu- lism [17-19]. Nevertheless, when ingested at a rate latory role in the development of fatigue. Hence, designed to saturate intestinal CHO transport systems, Meeusen et al. [27] suggest that an increase in the cen- fructose and galactose enhance postexercise human liver tral ratio of serotonin to dopamine is associated with glycogen synthesis [20].
feelings of tiredness and lethargy. Consequently, it can- Caffeine can also be used to extend endurance exer- not be excluded that the given role of serotonin in the cise and improve performance. Kovacs et al. [21] identi- development of central fatigue is overestimated. Never- fied improvements in performance during cycling time theless, taken together these data suggest that BCAAs trials when moderate amounts of caffeine (2.1 and 4.5 supplements taken during prolonged exercise may have mg.kg-1) were ingested in combination with a 7% CHO beneficial effects on some of the metabolic causes of solution during exercise. This effect may be partly fatigue such as glycogen depletion and central fatigue.
explained by the fact that a caffeine-glucose combina- Consequently it is likely that a beverage containing a tion increases exogenous CHO oxidation more than mixture of CHOs, caffeine and BCAAs would improve does glucose alone, possibly as a result of enhanced an athlete's performance during endurance exercise. To intestinal absorption [22]. It is also possible that the caf- our knowledge, no information is available on the effects feine causes a decrease in central fatigue [23]. In fact of this combination on physical performance and neuro- caffeine can block adenosine receptors even at concen- muscular function. The main purpose of the present trations in the micromolar range [23]. Stimulation of study was therefore to investigate whether ingestion of adenosine receptors induces an inhibitory effect on cen- an association of CHOs (68.6 g.L-1), BCAAs (4 g.L-1) tral excitability.
and caffeine (75 mg.L-1) is efficient in improving physi- Another interesting nutritional strategy to improve cal performance and limiting alterations to neuromuscu- performance is the ingestion of branched-chain amino lar function during a prolonged running exercise.
acids (BCAAs, i.e., leucine, isoleucine and valine) duringexercise. Blomstrand et al. [24] suggested that an intake of BCAAs (7.5 - 12 g) during exercise can prevent or decrease the net rate of protein degradation caused by Subject data are documented in Table 1. The subjects heavy exercise. Moreover, BCAAs supply during exercise regularly trained at least 2 - 4 times per week and had might have a sparing effect on muscle glycogen degrada- been involved in endurance training and competition for tion [25]. It has also been postulated that BCAAs supply at least 3 months. All subjects were habitual caffeine during prolonged exercise might reduce central fatigue users (1 - 2 cups of coffee or equivalent per day). Before Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 Table 1 Main characteristics of the subjects ˙VO2max, maximal oxygen uptake; BMI: Body mass index.
Values are means ± SD.
participation, each subject was fully informed of the The experiment comprised two exercise protocols, purpose and risks associated with the procedures, and each of them including two exercise tests performed in their written informed consent was obtained. All sub- different conditions: i.e., with ingestion of the sports jects were healthy, as assessed by a medical examination.
drink (SPD) or with a placebo (PLA) (see Protocols and The study was approved by the Southeast Ethics Com- Figure 1 for details). The two exercise tests in protocol mittee for Human Research (France, ClinicalTrials.gov, 1 were completed in randomized order at least one week apart. At least one week following protocol 1, pro-tocol 2 began. As for protocol 1, the exercise tests in Preliminary testing protocol 2 were performed in randomized order at least At least 1 week before the start of the experimental one week apart. Subjects were instructed to maintain trials, an incremental exercise test to volitional exhaus- their usual daily exercise activity and dietary intake (in tion was performed on a treadmill. This graded exercise particular, their caffeine intake) during the study but not aimed i) to check the tolerance of the subjects to maxi- to consume any solid or liquid nutrients with the excep- mal exercise, ii) to characterize their physical fitness, tion of water for 2 h before each exercise session. All and iii) to familiarize the subjects to the use of the the exercises performed by any one subject were done treadmill and the experimental procedures. After a gen- at the same time of the day. The subjects were tle warm-up, the test started at 10 km.h-1, and velocity instructed to replicate the same meal before each exer- was then increased by 1.5 km.h-1 every 3 min. Oxygen cise session.
uptake ( ˙VO2 ) was measured during the last minute of each 3-min period of the maximal incremental test as Protocol 1: Performance test presented elsewhere [28]. Briefly, subjects breathed Before the exercise, a 20 μL blood sample was collected through a two-way non-rebreathing valve (series 2700, from an earlobe for the assessment of resting blood glu- Hans Rudolph, Kansas City, Missouri, USA) connected cose concentration. Then, in the 15 min preceding the to a three-way stopcock for the collection of gases (100 test, the subjects drank 250 mL of one of the two drinks L bag). The volume of the expired gas was measured in (PLA or SPD). Thereafter, the running test started by a a Tissot spirometer (Gymrol, Roche-la-Molière, France).
gentle warm-up followed by a 2 hour all-out exercise Fractions of expired gases were determined with a para- trial. A beverage volume of 250 mL was provided every 15 min and drunk by the subjects within the next 15 2 analyzer (Servomex, cell 1155B, Crowbor- ough, England) and infrared CO min so that the total fluids ingested before and during 2 analyzer (Normocap Datex). The analyzers were calibrated with mixed gases, the 2-hour exercise was 2 liters. The volume and the composition of which was determined using Scho- kinetics of beverage ingestion was chosen to minimize lander's method [29]. Heart rate (HR) was recorded con- dehydration [16] and gastrointestinal discomfort. The tinuously by a radio telemetry HR monitor (S810, subjects ran without knowing their actual speed. An Polar®, Tampere, Finland). Individual maximal oxygen experimenter changed the velocity of the treadmill fol- lowing each subject's recommendations so that they was determined as previously described [30].
could give their best performance during the 2-hourexercise. At the end of the exercise a second blood sam- Experimental design ple was collected for glucose determination. Total dis- The study was designed as a randomized double-blind tance (km) was recorded and average speed (km.h-1) cross-over placebo-controlled trial. The random alloca- was calculated. Total distance (unknown by the subject) tion sequences were generated by an automated system was considered as physical performance.
under the supervision of the committee of protection ofhuman subjects. The codes were kept confidential until Protocol 2: Standardized exercise the end of the study when the randomisation code was A 20 μL blood sample was collected from the earlobe broken. All the subjects and investigators were blind to for the assessment of resting glucose and lactate con- the randomisation codes throughout the study.
centrations. As in protocol 1, 15 min before the test andjust before their gentle warm-up subjects drank 250 mL Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 Figure 1 Experimental design and diagram of flow of subjects through the study protocol. ˙VO2: oxygen consumption; RER: Respiratory Exchange Ratio; HR: heart rate; RPE: rate of perceived exertion.
of PLA or SPD. Thereafter, the subjects exercised for 2 Material and procedures hours at 95% of their individual lowest average speed All exercises were performed on the same treadmill (EF sustained in PLA or SPD during protocol 1; 250 mL of 1800, HEF Tecmachine, Andrezieux-Boutheon, France).
beverage was provided every 15 min. During exercise, Blood lactate and glucose concentrations were deter- mined enzymatically using a YSI 2300 (Yellow Spring ˙VCO2, Respiratory Exchange Ratio (RER: Instrument, USA). ˙VO VO2 ), HR and Rate of Perceived Exertion (RPE) VCO2 were measured as were measured and/or recorded every 20 min. Central described above (see paragraph Preliminary testing). RPE and peripheral fatigue was evaluated before and immedi- was determined using the 6 - 20 point Borg scale [31].
ately after exercise.
Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 Central and peripheral fatigue measurements delivered to the relaxed muscle 3 s after the end of the Tests were performed on the knee extensors. The sub- contraction. This provided the opportunity to obtain a jects were seated in the frame of a Cybex II (Ronkon- potentiated mechanical response and so reduce variabil- koma, NY) and Velcro straps were used to limit lateral ity in activation level (%VA) values. The ratio of the and frontal displacements. The subjects were instructed amplitude of the superimposed doublet over the size of to grip the seat during the voluntary contractions to sta- the control doublet was then calculated to obtain volun- bilize the pelvis. The knee extensor muscles' mechanical tary activation (%VA) as follows: response was recorded with a strain gauge (SBB 200 Kg, Tempo Technologies, Taipei, Taiwan). All measure- %VA = 1 − Superimposed Db100torque/Mean control Db100torque × 100 ments were taken from the subject's right leg, with the Three MVCs separated by 30 s, were performed to knee and hip flexed at 90 degrees from full extension.
determine MVC and %VA. The quadriceps muscle's iso- The isometric contractions performed during the experi- metric twitch peak torque and contraction time and VL ment included 3-4-s maximal voluntary contractions M-wave peak-to-peak amplitude and duration were also and electrically evoked contractions. During the 4 analyzed. To do this, three potentiated single twitches MVCs, the subjects were strongly encouraged. Femoral were evoked after a 4th MVC and averaged. %VA nerve electrical stimulation was performed using a cath- changes were considered as indices of central fatigue.
ode electrode (10-mm diameter, Ag-AgCl, Type Changes in electrically evoked contraction of the relaxed 0601000402, Contrôle Graphique Medical, Brie-Comte- muscle (high-frequency doublet mechanical response, Robert, France) pressed over the femoral nerve in the peak twitch) were the outcome measures for peripheral femoral triangle, 3-5 cm below the inguinal ligament with the anode (10.2 cm × 5.2 cm, Compex, SA, Ecu-blens, Switzerland) placed over the gluteal fold. Electri- Composition of drinks cal impulses (single, square-wave, 1-ms duration) were The doses of CHOs, BCAAs and caffeine were chosen delivered with a constant current, high-voltage (maximal to be as close as possible to those used in previous stu- voltage 400 V) stimulator (Digitimer, DS7A, Hertford- dies [12,15,21,33,34] and the palatability of the sports shire, UK). For all stimulus modalities, stimulation drink. For instance, due to the bitter taste of BCAAs, it intensity corresponded to 120% of optimal intensity, i.
is difficult to incorporate more than 4 g.L-1 of these e. the stimulus intensity at which the maximal amplitude amino acids in a drink. Moreover, theses doses respect of both twitch force and the concomitant vastus latera- the current legislation for dietary products. The nutri- lis (VL) M wave (see below) were reached.
tional composition of SPD was as follows: maltodextrin The surface electromyographic (EMG) signal was 31.6 g.L-1, dextrose 24.2 g.L-1, fructose 12.8 g.L-1, recorded from the right VL muscle with two pairs of branched-chain amino acids 4 g.L-1, curcumin 250 mg.
bipolar oval self-adhesive electrodes with an inter elec- L-1, piperine 2.6 mg.L-1, caffeine 75 mg.L-1, sodium 884 trode distance of 2.5 cm (10 mm diameter, Ag-AgCl, mg.L-1, magnesium 100 mg.L-1, zinc 5 mg.L-1, vitamins Type 0601000402, Contrôle Graphique Medical, Brie- C 15 mg.L-1, E 5 mg.L-1, B1 0.7 mg.L-1, B2 0.4 mg.L-1, Comte-Robert, France). The position and placement of B3 9 mg.L-1. Composition of the PLA drink: malic and the electrodes followed SENIAM recommendations.
citric acids, xanthan gum, acesulfame potassium, sucra- EMG data were recorded with the PowerLab system 16/ lose, silicium dioxide, yellow FCF, tartrazine. The energy 30 - ML880/P (ADInstruments, Sydney, Australia) at a provided by SPD and PLA was 1254 and 50 kJ.L-1 sample frequency of 2000 Hz. The EMG signals were respectively. SPD and PLA were provided by Nutratletic amplified with an octal bio amplifier - ML138 (ADIn- (Aytre, France).
struments) with bandwidth frequency ranging from 3Hz to 1 kH (input impedance = 200 MΩ, common Statistical analysis mode rejection ratio = 85 dB, gain = 1000), transmitted The results are presented as mean values ± SD. Because to a PC and analyzed with LabChart6 software of the lack of normality, data describing running perfor- mance, blood glucose and lactate concentrations and The twitch interpolation technique was used to deter- neuromuscular variables obtained in the two conditions mine potential change in maximal voluntary activation were compared using the non-parametric Wilcoxon test.
[32]. This consisted in superimposing stimulation at supramaximal intensity on the isometric plateau of a 2 , RER, HR, and RPE were subjected to a two-way repeated-measure analysis of variance describing the maximal voluntary contraction of the knee extensors. In effect of drink ingestion (PLA and SPD) (external fac- this study a high-frequency paired stimulation (doublet tor), exercise duration (internal factor) and their interac- at 100 Hz, Db100) was used instead of a single twitch. A tion. A p-value < 0.05 was considered as significant.
second 100 Hz doublet (control stimulation) was Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 ResultsProtocol 1: Performance testRunning distance was significantly higher, i.e. perfor-mance was better, in SPD than in PLA (22.31 ± 1.85 vs.
21.90 ± 1.69 km, n = 13, p = 0.01). Before exercise,there was no difference in mean glucose concentrationsbetween PLA and SPD (5.60 ± 0.82 and 5.53 ± 0.85mmol.L-1, respectively, n = 13, NS). After exercise,blood glucose was significantly lower than before exer-cise in both groups (4.66 ± 0.48 mmol.L-1, p < 0.001, forPLA, and 5.26 ± 0.78 mmol.L-1, p < 0.01 for SPD). Thechanges in glycemia were significantly more pronouncedin PLA than in SPD (n = 13, p = 0.0002; Figure 2).
Expressed as a percentage, the variations in glycemiawere -16.2 ± 5.4 and -4.7 ± 2.9% for PLA and SPD,respectively (n = 13, p = 0.0007).
Protocol 2: Standardized exerciseFor personal reasons, 2 subjects dropped-out of thestudy. The mean velocity during protocol 2 was 10.3 ±0.6 km.h-1 (n = 11). Changes in ˙VO2 , HR and RPE areshown in Figure 3. For ˙VO2 and HR, no significant effect was observed (Figures 3A and 3B). A group andtime effect was found for RPE (n = 11, group effect: p =0.006, time effect: p < 0.001, cross interaction: NS; Fig-ure 3C). For RER, no differences were found betweenthe two conditions (data not shown). There was no dif-ference in the glucose concentrations before exercise forPLA and SPD (5.40 ± 0.66 and 5.44 ± 0.67 mmol.L-1,respectively, n = 11). Glucose concentration decreasedsignificantly after exercise in PLA (5.09 ± 0.60 mmol.L-1,n = 11, p = 0.001) but remained unchanged in SPD(5.48 ± 0.64 mmol.L-1, n = 11; Figure 4A). There was nodifference in lactate concentration between the two Figure 3 Evolution of oxygen consumption (panel A), heartrate (panel B) and Borg's Rating of Perceived Exertion (panelC) during the standardized exercise protocol (protocol 2).
Values are means ± SD.
conditions before exercise (1.65 ± 0.32 and 1.73 ± 0.42mmol.L-1 for PLA and SPD, respectively, n = 11). There Figure 2 Difference in blood glucose concentration before and was a tendency towards a lower blood lactate accumula- after the performance test (protocol 1). Values are means ± SD.
tion (post minus pre exercise values) in SPD (+3.48 ± *** p = 0.0002.
0.60 mmol.L-1) than in PLA (+3.65 ± 0.43 mmol.L-1) (n Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 Figure 4 Difference in blood glucose (panel A) and lactate (panel B) concentrations before and after the standardized exerciseprotocol (protocol 2). Values are means ± SD. *** p < 0.001.
= 11, p = 0.053; Figure 4B) so that lactate concentration neuromuscular functions are summarized in Table 2.
measured after exercise was significantly lower in SPD The statistical analysis showed a deleterious effect of (5.20 ± 0.39 mmol.L-1) than in PLA (5.30 ± 0.35 mmol.
exercise on all the parameters of neuromuscular func- L-1; n = 11, p = 0.01). The parameters of the tion and a higher decline in %VA and Db100 for the Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 Table 2 Neuromuscular variables before and after the standardized 120 min running exercise (Post - Pre)/Pre values * 100 (%) MVC: Maximal voluntary contraction; %AV: maximal voluntary activation; Db100: Mechanical response to a double pulse at 100 Hz; Pt: Mechanical response to asingle pulse; CT: contraction time (single twitch); PPA: M-wave peak-to-peak amplitude; PPD: M-wave peak-to peak duration.
Values are means ± SD. Statistical analysis was conducted on the (post - pre)/pre * 100 i.e., expressed in percentage (%) for PLA and SPD.
PLA condition compared with SPD. Although the altera- found that the positive effect of CHO supplements on tions were lower in SPD than in PLA (-14% vs. -17%, performance was only 2.4% for a 1 hour exercise.
respectively), the decreases in MVC were not significant The results for neuromuscular function in the present between the two conditions.
study are variable. Firstly, both central fatigue and anindex of peripheral fatigue (Db100) were significantly better preserved in the SPD than in the PLA condition.
The main findings of the present study were that inges- Along the same line, RPE was lower in SPD than in tion of the SPD containing CHOs (68.6 g.L-1), BCAAs PLA (Figure 3C). However, although the alterations in (4 g.L-1) and caffeine (75 mg.L-1) immediately prior to MVC were lower in SPD than in PLA (-14% vs. -17%, and during a 2 h all-out or standardized exercise 1) respectively), the global index of neuromuscular fatigue increased running performance significantly, although to (MVC) did not differ significantly between SPD and a moderate extent, 2) favored the maintenance of glyce- PLA. This lack of statistical difference is probably due mia and 3) had variable effects on neuromuscular to high inter-individual changes in MVC. An alternative explanation would be an alteration of excitation-con- Performance, i.e. total distance over a 2 h running traction coupling or muscle fiber excitability. This may exercise, was significantly higher with SPD than in the reduce the difference between SPD and PLA when placebo condition (22.31 ± 1.85 vs. 21.90 ± 1.69 km, MVC (i.e. trains of stimulations) is considered. However, respectively; p = 0.01). However, the increase in physical excitation-contraction coupling and muscle fiber excit- performance was rather small (+1.9%). Several reasons ability do not seem to be affected by SPD as shown by may explain this limited improvement. Firstly, because the lack of difference in the M-wave characteristics and the subjects were not fasted (overnight), it can be peak twitch changes between the two conditions.
hypothesized that initial muscle and liver glycogen In the present study, glycemia decreased during the stores were high, limiting the effects of SPD ingestion as all-out exercise (protocol 1) in both conditions, but the has been previously shown [15]. Secondly, the impor- decrease was lower in SPD than in PLA. Furthermore, tance of nutritional strategy during exercise of less than glycemia remained stable during the standardized event 2 hours seems to be limited [5,6,12]. The study by Coyle in SPD while it decreased in PLA (protocol 2). If SPD is et al. [5] is of interest here. If the effect of CHO supple- helpful in maintaining glycemia, it should nevertheless ments improved performance by 33% (182 min PLA vs.
be noted that the subjects were not hypoglycemic at the 242 min in subjects using CHO supplements) during an end of the exercise whatever the protocol or PLA condi- exercise at 71% of ˙VO tion. It has been postulated that the improved mainte- 2 max, it should be noted that glu- cose concentrations and CHO oxidation differed nance of blood glucose levels with the ingestion of between the two conditions only after 80 min and 160 glucose may not be a potential mechanism for improved min of exercise, respectively. Moreover, in a recent performance during prolonged exercise [12]. However meta-analysis of 72 studies, Karelis et al. [12] showed Nybo [35] showed that when blood glucose homeostasis that the mean performance effect in studies with exer- was maintained by glucose supplementation, central fati- cise durations higher than 2 h was significantly greater gue seemed to be effectively counteracted and perfor- than in studies with exercise durations below 2 h. Our mance (average force production) increased. Of note is results agree with those of Jeukendrup et al. [6] who the fact that Nybo [35] detected central fatigue during a2 min sustained maximal isometric contraction of the Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 knee extensors but not during short contractions as in prolonged running exercise has been attributed to the the present study. Glucose ingestion can stimulate the inhibitory effect if afferent fibers [40]. In particular, this secretion of insulin and blunt the exercise-induced rise could be due to reduced motoneurone excitability or to in both free fatty acids and free tryptophan and could presynaptic inhibition, probably resulting from thin consequently decrease central fatigue by attenuating the afferent fiber (group III-IV) signaling which may have rise in brain 5-HT (serotonin) [36,37]. Of note, RPE was been sensitized by the production of pro-inflammatory lower in SPD than in PLA (Figure 3C). Therefore, it is mediators produced during prolonged running exercise possible that in the present study, maintenance of blood (e.g. [41]). Group III-IV afferent fibers may also contri- glucose homeostasis indirectly acted via central fatigue bute to the submaximal output from the motor cortex to improve performance.
[42]. It is not known whether SPD had an effect on During sustained exercise, BCAAs are taken up by the inflammation in the present study since no pro-inflam- muscles and their plasma concentration decreases.
matory markers were assessed.
Decreased plasma BCAAs levels may lead to an One limitation of this study is the fact that the volun- increased plasma free tryptophan/BCAAs ratio, thus teers were studied in a post absorptive state. This choice favoring the transport of tryptophan into the brain and was made in an attempt to reproduce habitual race con- consequently the synthesis of 5-HT. The subsequent ditions since the main aim of this study was to investi- production of serotonin could be responsible for the gate if ingestion of an association of CHOs, BCAAs and feeling of fatigue during and after sustained exercise.
caffeine was useful in improving running performance.
Nevertheless, it has been suggested that BCAAs supple- Other limitation concerns the lack of control of food mentation during prolonged exercise may decrease cen- intake before the trials. This may introduce variability tral fatigue via reduced tryptophan uptake and 5-HT between the trials and potentially between the condi- synthesis in the brain [4]. Indeed, because BCAAs and tions. Although the fact i) of performing the different free tryptophan are transported into the brain by the conditions in a randomized order, ii) of starting every same carrier system, BCCAs supplementation during session at the same time of the day and iii) of instruct- exercise would decrease the plasma free tryptophan/ ing the subjects to replicate the same meal before each BCAAs ratio. This would i) dampen the transport of exercise session, allows to some extent limitation of tryptophan into the brain, ii) impede the subsequent variability between trials, it does not remove totally this synthesis and release of 5-HT, and consequently iii) variability. A careful attention should be paid in the reduce or delay the feeling of fatigue during and after future in the control of food intake before but also 2-3 sustained exercise days prior to testing.
Caffeine ingestion might also affect central fatigue [38]. Human experiments have revealed that caffeine induces increases in central excitability, maximal volun- This study has shown for the first time that ingestion of tary activation, maximal voluntary force production and a combination of CHOs (68.6 g.L-1), BCAAs (4 g.L-1) spinal excitability (for review, see Kalmar and Cafarelli and caffeine (75 mg.L-1) immediately before and during [23]). The effect of caffeine on the central nervous sys- a 2 h running exercise in standardized laboratory condi- tem could be via its action on the blockage of adenosine tions significantly increased treadmill running perfor- receptors at concentrations in the micromolar range mance by about 2% in trained subjects. Moreover, [23]. Stimulation of adenosine receptors induces an inhi- ingestion of a drink associating these components dur- bitory effect on central excitability.
ing a standardized 2 h running exercise maintained gly- The present results show that concomitantly, CHOs, cemia and significantly decreased RPE, central fatigue BCAAs and caffeine supplementation reduce central and an index of peripheral fatigue as compared to the fatigue and RPE. Nevertheless, it is impossible in the placebo condition.
present case to distinguish the individual contribution ofeach of them (CHOs, BCAAs and caffeine) in the posi-tive effect of the sports drink on central fatigue and AcknowledgementsThis work was financed by Laboratoire Lescuyer (private enterprise).
The decrease in %VA (%VA changes were considered as indexes of central fatigue) is similar to the deficit Laboratoire Lescuyer, Aytré, France. 2Exercise Physiology Laboratory, Department of Sport Sciences, University of Savoie, F-73376 Le Bourget du observed in previous studies involving running exercises Lac Cedex France. 3Université de Lyon, F-42023, Saint-Etienne, France.
of comparable duration [39] and was only slightly, 4Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des although significantly improved by the energy drink.
Adaptations Métaboliques à l'Exercice en conditions Physiologiques etPathologiques (AME2P), BP 80026, F-63171 Aubière Cedex, France.
The moderate influence on %VA could be explained by 5Laboratory of Psychology and Neurocognition (UMR 5105), University of the fact that at least part of the decrease in %VA after Savoie, 73000 Chambéry, France.
Peltier et al. Journal of the International Society of Sports Nutrition 2011, 8:22 Authors' contributions 19. Ahlborg G, Bjorkman O: Splanchnic and muscle fructose metabolism SLP, GYM, PS, AG, MG, JFL and LM developed the study protocol. AG was during and after exercise. J Appl Physiol 1990, 69:1244-1251.
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Annual litigation report 2004

• Counterfeiting of Cartier products restrained Cartier International B.V v Choosy corner Name of firm not determinative of its statusZuko Engineers v Ministry of Commerce & Industries • Deception/confusing similarity not found in use of 'BLACK LABEL' on beer products United Breweries Ltd. v Khodays Brewing and Infringement of Mitsubishi pen design restrained

Effects of jsog-6 on protection against bone loss in ovariectomized mice through regulation of osteoblast differentiation and osteoclast formation

Chung et al. BMC Complementary and Alternative Medicine 2014, 14:184http://www.biomedcentral.com/1472-6882/14/184 Effects of JSOG-6 on protection against bone lossin ovariectomized mice through regulation ofosteoblast differentiation and osteoclast formation Hwa-Jin Chung1, Lan Cho1, Joon-Shik Shin2, Jinho Lee2, In-Hyuk Ha2, Hyen Joo Park1 and Sang Kook Lee1* Background: JSOG-6 is used as a traditional medicine to relieve the symptoms associated with inflammation,rheumatism, and osteoporosis in Korea. In the present study, we investigated the effects of JSOG-6 on bone lossprevention both in in vitro and in vivo as well as its underlying mechanism of action.