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Effects of 8 Weeks of 2S-Hesperidin Supplementation on Performance

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Effects of 8 Weeks of 2S-Hesperidin Supplementation on Performance nutrients Article Effects of 8 Weeks of 2S-Hesperidin Supplementation on Performance in Amateur Cyclists Francisco Javier Martínez-Noguera 1,* , Cristian Marín-Pagán 1, Jorge Carlos-Vivas 2 and Pedro E. Alcaraz 1 1 Research Center for High Performance Sport, Campus de los Jerónimos Nº 135, Catholic University of Murcia, UCAM, 30107 Murcia, Spain; [email protected] (C.M.-P.); [email protected] (P.E.A.) 2 Health, Economy, Motricity and Education Research Group (HEME), Faculty of Sport Sciences, University of Extremadura. Avda. de la Universidad, s/n., 10003 Cáceres, Spain; [email protected] * Correspondence: [email protected]; Tel.: +34-968-278-566 Received: 9 November 2020; Accepted: 18 December 2020; Published: 21 December 2020 Abstract: 2S-Hesperidin is a flavanone (flavonoid) found in high concentrations in citrus fruits. It has an antioxidant and anti-inflammatory effects, improving performance in animals. This study investigated the effects of chronic intake of an orange extract (2S-hesperidin) or placebo on non-oxidative/glycolytic and oxidative metabolism markers and performance markers in amateur cyclists. A double-blind, randomized, placebo-controlled trial was carried out between late September and December 2018. Forty amateur cyclists were randomized into two groups: one taking 500 mg/day 2S-hesperidin and the other taking 500 mg/day placebo (microcellulose) for eight weeks. All participants completed the study. An incremental test was used to evaluate performance, and a step test was used to measure oxygen consumption, carbon dioxide, efficiency and oxidation of carbohydrates and fat by indirect calorimetry. The anaerobic power (non-oxidative) was determined using Wingate tests (30 s). After eight weeks supplementation, there was an increase in the incremental test in estimated functional threshold power (FTP) (3.2%; p 0.05) and maximum power (2.7%; ≤ p 0.05) with 2S-hesperdin compared to placebo. In the step test, there was a decrease in VO (L/min) ≤ 2 ( 8.3%; p 0.01) and VO R (mL/kg/min) ( 8.9%; p 0.01) at VT2 in placebo. However, there were − ≤ 2 − ≤ no differences between groups. In the Wingate test, there was a significant increase (p 0.05) in ≤ peak and relative power in both groups, but without differences between groups. Supplementation with an orange extract (2S-hesperdin) 500 mg/day improves estimated FTP and maximum power performance in amateur cyclists. Keywords: flavonoid; polyphenols; orange extract; performance; endurance; aerobic; anaerobic; nutrigenomic and sport nutrition 1. Introduction Hesperidin is a flavonoid found mainly in citrus fruits [1], reaching high concentration in sweet orange (Citrus sinensis)[2]. Due to its chemical structure, including a chiral carbon (C-2), hesperidin can be present as S or R isomer (Figure1). 2S-Hesperidin is the predominant natural form in citrus fruits [3], but industrial processing leads to the transformation of the natural S isomer into the R isomer (Figure1)[ 4]. The bioavailability of the two isomers is different, for instance a 5.2-fold higher efficiency in the glucuronidation has been observed for S-hesperetin compared to R-hesperetin in vitro, without any significant change in the sulfonation kinetics [5]. Clinical trials have demonstrated the therapeutic effects of hesperidin and its metabolites in various diseases Nutrients 2020, 12, 3911; doi:10.3390/nu12123911 www.mdpi.com/journal/nutrients Nutrients 2020, 12, 3911 2 of 19 Nutrients 2020, 12, x FOR PEER REVIEW 2 of 19 (e.g., neurological and psychiatric disorders, cardiovascular diseases, etc.) due to its anti-inflammatory antioxidants, inhibition of fat accumulation, improvement in glucose homeostasis and insulin properties, antioxidants, inhibition of fat accumulation, improvement in glucose homeostasis and sensitivity [6–9]. In view of its effects, the pharmaceutical and nutritional industries have extensively insulin sensitivity [6–9]. In view of its effects, the pharmaceutical and nutritional industries have marketed hesperidin. However, little attention has been paid to the effects of hesperidin on exercise extensively marketed hesperidin. However, little attention has been paid to the effects of hesperidin on performance. exercise performance. Figure 1. Structure of hesperidin enantiomers S and R and their metabolites hesperetin, produced by Figurethe intestinal 1. Structure microbiota. of hesperidin Modified enantiomers from Li et S al. and [10 ].R and their metabolites hesperetin, produced by the intestinal microbiota. Modified from Li et al. [10]. Regarding performance, only one acute effects study in humans has investigated 2S-hesperidin [11]. ThisRegarding study showed performance, that after ingesting only one one acute single effects 500 study mg dose in humans of either 2S-hesperidinhas investigated 5 h 2S-hesperidin before the test, [11].trained This cyclists study significantlyshowed that improvedafter ingesting average one power single (2.3%),500 mg maximum dose of either speed 2S-hesperidin (3.2%) and total 5 h before energy P the( 4test, sprint trained test; totalcyclists work) significantly (2.6%) with improved 500 mg hesperidinaverage power supplementation (2.3%), maximum in the bestspeed sprint (3.2%) out and the totalfour energy repeated (∑ sprint 4 sprint test test; (4 total30s work) all-out (2.6%) sprints with with 500 5 minmg hesperidin of rest between supplementation sprints). No in significant the best × sprintchanges out were the four observed repeated in any sprint of these test (4 variables × 30 s all- without sprints placebo. with 5 min of rest between sprints). No significantIn humans, changes chronic were observed supplementation in any of ofthese hesperidin variables has with also placebo. been studied. Pittaluga et al. [12] investigatedIn humans, the echronicffect of 250supplementation mL of red-orange of juice,hesperidin which has has also a high been content studied. of hesperidin, Pittaluga onet exerciseal. [12] investigatedperformance the (incremental effect of test)250 mL in healthy, of red-orange trained olderjuice, women.which has Following a high fourcontent weeks of ofhesperidin, consumption on exerciseof ROJ (3 performance per day), these (incremental older women test) significantly in healthy, increasedtrained older their women. work capacity Following by 9.0%four comparedweeks of consumptionto placebo ( of1.5%). ROJ (3 Another per day), chronic these studyolder women evaluated significantly the effect increased of a four-week their work supplementation capacity by − 9.0%of 2S-hesperidin compared to (500 placebo mg/day) (−1.5%). in trained Another cyclists chronic and study observed evaluated significant the effect increases of a infour-week average supplementationpower output (14.9 of 2S-hesperidin W = 5.0%) in (5 a00 10 mg/day) min time-trial in trained test cyclists on a cycle and ergometer,observed significant whereas thoseincreases that inconsumed average power placebo output had a non-significant(14.9 W = 5.0%) increase in a 10 inmin average time-trial power test output on a cycle (3.8 Wergometer,= 1.3%),moreover, whereas thosedifferences that consumed were found placebo when comparinghad a non-significant the groups increase [13]. In addition,in average another power performance-enhancing output (3.8 W = 1.3%), moreover,mechanism differences has been observed were infound other substances,when comparing such as mentholthe groups or capsaicin [13]. In (polyphenols) addition, another through performance-enhancingtaste, but this pathway hasmechanism not been exploredhas been with observ 2S-hesperidined in other [ 14substances,]. such as menthol or capsaicinThe (polyphenols) effect of long-term through intake taste, of but hesperidin this pathway has alsohas not been been investigated explored with in animal 2S-hesperidin studies. [14].Biesemann et al. [15] observed that six weeks of hesperetin supplementation (main metabolite of hesperidin)The effect (50 mgof long-termkg 1 d 1) improvedintake of runninghesperidin performance has also bybeen 28.8% investigated (exercise time in untilanimal exhaustion) studies. · − · − Biesemanncompared toet placeboal. [15] inobserved aged mice. that This six studyweeks also of hesperetin found an improvement supplementation in endogenous (main metabolite antioxidant of hesperidin)enzymes, such (50 mg·kg as reduced−1·d−1) improved glutathione running (GSH), performance oxidized glutathione by 28.8% (exercise (GSSG) time and until GSH:GSSG exhaustion) ratio. compared to placebo in aged mice. This study also found an improvement in endogenous antioxidant enzymes, such as reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH:GSSG ratio. De Oliveira et al. [16] found that four weeks of hesperidin consumption (100 mg/kg body mass) enhanced Nutrients 2020, 12, 3911 3 of 19 De Oliveira et al. [16] found that four weeks of hesperidin consumption (100 mg/kg body mass) enhanced the antioxidant capacity in the continuous swimming group (183%) and decreased the lipid peroxidation (TBARS) in the interval swimming group ( 45%) compared to placebo in rats. − In the same line, a recent study in trained animals reported that intake of hesperidin for four weeks improved performance and prevented immune alterations induced by exhausting exercise compared to placebo [17]. Recently, one parallel-group study has shown improvements in the time until exhaustion (58%) on maximal exercise test at 3 weeks of a 5-week chronic supplementation of 2S-hesperidin (200 mg/kg), but not in placebo group (with differences between groups) [18]. In the same
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