Quercetin and muscle recovery -
Pain, joint angle, arm circumference, plasma creatine kinase CK and lactate-dehydrogenase LDH were also assessed. The results showed that Q supplementation significantly attenuated the strength loss compared to PLA.
A greater increase in biomarkers of damage was also evident in PLA with respect to Q. Q supplementation for 14 days seems able to ameliorate the recovery of eccentric exercise-induced weakness, neuromuscular function impairment and biochemical parameters increase probably due to its strong anti-inflammatory and antioxidant action.
Even if the levels of circulating IGF-II are little investigated, a number of studies show that in adult life and in response to exercise its increase seems to be associated with endurance exercise 34 , From what has been observed in our study, quercetin not only has antioxidant effects as already observed in the literature 36 — 45 , but it would seem to have a conditioning effect also on the regulation of the secretion of similar insulin growth factors, which at local level play a fundamental role in hypertrophy, post-workout remodeling and post-workout muscle damage repair.
Since these functions are directly related to the gain of muscular strength and the administration of quercetin not only has ergogenic effects but also reduces the loss of muscle strength associated with damage, this could be used to prevent damage and promote recovery.
It seems obvious that our final observations cannot be generalized since the subjects analyzed were moderately trained, and therefore we cannot know if this flavonoid induces the same effects in very trained or elite athletes.
As a limitation of the present study is the laboratory assay of total IGF-I instead of the analysis of the different IGF-I isoforms.
In fact it is known that there are three different isoforms of IGF-I: two are produced by the muscle IGF-IEa, IGF-IEc [MGF] 46 and one by the liver IGF-IEb under direct control of the growth hormone GH IGF-IEa, is similar in molecular structure to the circulating IGF-I secreted by the liver.
The second isoform, called mechanical growth factor MGF or IGF-1Ec, is secreted in response to muscle contractions and muscle stretch. It performs its functions locally, stimulating proliferation, maturation and growth of muscle cells and of quiescent satellite cells stem cells , after muscle damage Moreover, it was not possible to obtain other biological samples such as muscle biopsies from the subjects.
For this reason, it was not possible to evaluate the presence of fibrotic events or fibroblasts proliferation. In conclusion, dietary supplementation with quercetin, possibly through its anti-inflammatory and antioxidant properties could be a way to prevent, mitigate and promote a faster recovery of EIMD by eccentric training.
Our findings are specific to a sample of young, healthy, trained men. Considering that IGFs production are controlled by ROS, further studies are warranted to determine if similar or more pronounced results can be observed in different experimental conditions e. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
PS: participated in the design of the study, contributed to data collection, data analysis and interpretation of results. RC: participated in the design of the study, contributed to data collection, data analysis and interpretation of results.
ML: contributed to data collection and data analysis. FP: contributed to data collection and data analysis. SS: participated in the design of the study and contributed to interpretation of results. FF: participated in the design of the study and contributed to interpretation of results.
MS: participated in the design of the study and contributed to interpretation of results. IB: participated in the design of the study, contributed to data collection and data analysis.
GD: participated in the design of the study, contributed to data collection and data analysis and contributed to interpretation of results.
LL: participated in the design of the study and contributed to interpretation of results. All authors contributed to the manuscript writing. All authors read and approved the final version of the manuscript.
All authors were involved in the study design and revised the final version of the manuscript, with intervention in the analysis of data, statistical evaluation, and final interpretation of the results of this study. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Hody S, Croisier JL, Bury T, Rogister B, Leprince P.
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Eur J Appl Physiol —9. In particular, an excessive accumulation of ECM components, referred to as muscle fibrosis, causes muscles to become stiff, leading to impaired muscle regeneration and functional recovery, thus decreasing the quality of life of elderly people 5 , 6.
The ECM accumulation is responsible for an increase in muscle stiffness, especially when the muscle is stretched 3. Recently, we have found age-related increases in muscle stiffness in the thigh in a stretched position 7.
Therefore, it is crucial to simultaneously prevent not only the loss of muscle quantity but also the increase in muscle stiffness with aging. It is well recognized that resistance training enhances muscle mass and strength to prevent the progression of sarcopenia 8.
A systematic review suggested a dose-response relationship between resistance training intensity and the increase in muscle mass in elderly people 9.
Our previous study also showed that a higher intensity of resistance exercise was more effective for improving both muscle quantity and quality Recently, the guideline of the Asian Working Group for Sarcopenia suggested that nutritional supplementation has a supportive role in the effects of exercise on muscle mass and function Therefore, even low-intensity resistance training would exert additive effects on muscle quantity and quality when combined with nutrition, whereas there have been few randomized, controlled trials that examined such combination effects Quercetin exists especially as glycoside forms in plants, so-called quercetin glycosides QGs , which are enzymatically converted into the aglycone form during absorption, then exert biological actions QGs are more water-soluble and bioavailable than quercetin aglycone 14 , and thus they are often used as a dietary supplement for human health.
There have been several studies reporting the therapeutic efficacies of quercetin, including for muscular health, such as improving muscle atrophy, through its anti-oxidative and anti-inflammatory activities Quercetin administration suppressed the signaling of muscle degradation to ameliorate muscle atrophy in disuse or glucocorticoid-treated mice 16 , In addition, quercetin also inhibited fibrogenesis in skeletal muscle by regulating the differentiation of muscle progenitor cells Thus, quercetin has the potential to improve muscle atrophy and fibrosis in vivo , but no clinical trials have been conducted.
The aim of the present study was to investigate the combined effect of QG supplementation and resistance training on muscle quantity and stiffness in middle-aged and elderly people.
The hypothesis was that low-intensity resistance exercise combined with QG supplementation provides greater improvement in muscle quantity and stiffness than exercise alone. A further aim was to examine whether the training effects on muscle quantity and stiffness would differ depending on the dose of QGs.
A randomized, double-blind, placebo-controlled, parallel-group, comparative study was designed to evaluate the effects of two different doses of QG supplementation with resistance training on muscle quantity and stiffness.
Community-dwelling Japanese people living in Osaka were recruited, and participants were screened. Fifty-four participants were randomly allocated to the placebo with exercise placebo , mg of QGs with exercise low-QG , and mg of QGs with exercise high-QG groups.
Randomization was performed based on dynamic allocation to maintain balance among the groups in age, sex, and leg muscle mass using a spreadsheet program with the RAND function Microsoft Excel , Microsoft Corporation, Redmond, WA, United States.
The randomization codes for both participants and groups were held in sealed opaque envelopes by two different individuals who were not engaged in the present study. A research nurse kept the envelopes closed until all data were collected and analyzed. The interventions for the 24 weeks of the present study were performed between August and March Magnetic resonance imaging MRI , dual-energy X-ray absorptiometry DXA , and ultrasound shear wave elastography SWE measurements were performed at baseline, at 12 weeks, and at 24 weeks during the intervention.
Blood and urine were sampled following overnight fasting for safety assessment in the screening period, at baseline, at 12 weeks, and at 24 weeks. All participants recorded changes in physical condition and habituation during the intervention period because they were instructed not to change their lifestyles, especially exercise habits, and their compliance with the exercise intervention and capsule intake were checked regularly.
The Ethics Committee of The Fukuda Clinic and Ritsumeikan University approved the study protocol in compliance with the Declaration of Helsinki. All participants provided their written, informed consent prior to their inclusion in the present study.
The present study was registered in the University Hospital Medical Information Network UMIN Clinical Trial Registry UMIN The participants were community-dwelling Japanese men and women, aged 50—74 years, not engaging in exercise regularly, that is not more than twice a week and more than 30 min per times, in the past year before starting the screening.
Exclusion criteria were: the presence of disease affecting the locomotor organs; the presence of cardiovascular disease limiting exercise intervention; a history of serious disorders and clinically significant systemic diseases; having problems doing the exercise intervention; planning weight loss; having previous experience with high-intensity exercise, such as bodybuilder; an irregular lifestyle; a heavy drinker or smoker; consumption of drugs or supplements that affect efficacy evaluation; consumption of drugs consecutively during interventions; not capable of undergoing MRI measurements, such as having magnetic material, a tattoo on the body, or claustrophobia; not capable of swallowing capsules; pregnant women; nursing mothers or women of child-bearing potential; and the presence of any medical condition judged by the medical investigator to be incompatible with participation in the present study.
The primary outcome in the present study was the change in thigh muscle CSA on MRI over 24 weeks. Secondary outcomes were changes in vastus lateralis VL muscle CSA, whole-body lean mass by DXA, and shear wave velocity SWV, an index of tissue stiffness in three different positions by SWE.
Safety was assessed based on the incidence of side effects and adverse events, such as feeling cold, lassitude, or muscular pain, among the groups during the week intervention.
To evaluate muscle CSAs, a 3. The images of the right midthigh at the center of the end-to-end images from the mm-thick slices were analyzed to measure thigh and VL muscle CSAs by SliceOmatic Ver 4.
Dual-energy X-ray absorptiometry Lunar iDXA; GE Healthcare United Kingdom Limited, Buckinghamshire, United Kingdom was used for whole-body composition assessment. Lean mass was obtained from leg, arm, and whole-body regions. All measurements were performed by a medical technologist of Ritsumeikan University.
Shear wave velocity of the right VL was measured by an ultrasound SWE apparatus Aixplorer version 12, Supersonic Imagine, Aix-en-Provence, France with a linear array probe SL , as previously reported 7.
The SWE measurements were performed in this order. The participants were instructed to relax completely throughout the measurements. In each position, three measurements were performed i. The SWE data were analyzed using the software included with the ultrasound apparatus to calculate SWV over the region of interest, which was as large as possible, in VL without aponeurosis or subcutaneous adipose tissue.
It was confirmed that no pixel in the region of interest reached the saturation limit of SWV For each position, the average of three measurements was used for further analyses.
All measurements and analyses of the SWE data were performed by an examiner with more than 5 years of experience. Participants performed resistance exercise programs 3 days per week every Monday, Wednesday, and Friday for 24 weeks, as previously reported Briefly, a well-trained instructor conducted the training program, which constituted a 5-min warm-up, min resistance training using machines including leg extension, leg curl, leg press, and chest press, and 5-min cool-down.
For evaluating 1-RM, the indirect method of the 1-RM test was used, as previously reported Attendance and numbers of sets completed were checked by instructors to calculate the attendance rates. Experimental supplements contained mg or mg of QGs.
QGs were enzymatically manufactured at San-Ei Gen F. Osaka, Japan from isoquercitrin prepared from quercetin O -rutinoside. Participants took six capsules including 0 mg of QGs placebo group , mg of QGs low-QG group , or mg of QGs high-QG group with the same color. The weights and volumes of all capsules were adjusted to be equal using dextrin, silicon oxide, and calcium stearate.
Compliance with capsule intake in each participant was checked by the study diary. Per-protocol set PPS analysis was used for efficacy assessment according to the statistical analysis plan. Baseline characteristics were compared among the groups by one-way ANOVA for quantitative variables and the chi-squared test for categorical variables.
Differences between groups over time were analyzed by two-way repeated-ANOVA. The full analysis set was used for safety assessment. Statistical analyses were carried out using IBM SPSS Statistics for Windows, Version Of the 54 participants allocated to the three groups, 3 withdrew consent prior to the intervention or dropped out because of the exclusion criteria.
Another 3 participants were excluded from the analysis because they fulfilled the exclusion criteria. Mean attendance rates during the week resistance exercise program were Mean compliance rates for capsule intake during the week intervention were There were no significant differences in baseline characteristics including age, sex, height, weight, and SMI among the groups Table 1.
Figure 1. Flowchart of this study. Of the participants recruited, 54 were randomly allocated to the placebo, low-QG, and high-QG groups. QG, quercetin glycoside. The combined effects of QG supplementation and resistance training during the week intervention on muscle quantity and stiffness were evaluated using MRI, DXA, and SWE measurements Table 2.
There were no significant differences among the groups in the parameters at baseline. During the week intervention period, a significant group × time interaction was not observed in thigh muscle CSA set as the primary outcome, as well as the VL muscle CSA and lean body mass measured by MRI and DXA.
VL SWV in the knee fully flexed position at 24 weeks was significantly decreased compared with baseline —0. The changes in SWV in the knee fully flexed position over 24 weeks were significantly larger in both the low and high-QG groups than in the placebo group low-QG vs.
No correlation was also observed between VL SWV and 1-RM muscular strength Supplementary Figure 1. Table 2. Effects of the intervention on muscle quantity and stiffness in the PPS analysis. Figure 2. Relationships between muscle quantity and stiffness during the week intervention in the PPS analysis.
VL, vastus lateralis; CSA, cross-sectional area; and SWV, shear wave velocity. No side effects due to QG supplementation were observed. There were no severe adverse events and no significant difference in the incidence of adverse events among the placebo In the present study, the week intervention effects of QG supplementation combined with low-intensity resistance training on muscle quantity and stiffness as an index of fibrosis were investigated in middle-aged and elderly people.
For muscle quantity, there were no significant differences in thigh CSA on MRI between QG supplementation with exercise and placebo with exercise, as well as each lean body mass on DXA.
For muscle stiffness, both and mg QG supplementation with exercise significantly decreased SWV of VL in a stretched position i. This is the first report to show that the combination of nutrition and exercise could improve age-related changes in passive muscle stiffness.
Extracellular matrix components are responsible for muscle stiffness 3 , Thus, it is reasonable to use muscle stiffness as an index of ECM components. Previously, we identified an increase of VL muscle stiffness in full knee flexion from In animal studies, the excessive ECM accumulation in older muscles was reduced by resistance training with change of the gene expression related to ECM turnover 22 , Moreover, the acute stimulus of resistance exercise also decreased the gene expression associated with skeletal muscle ECM remodeling in elderly men However, no longitudinal studies evaluating the effects of exercise on muscle fibrosis caused by aging have been available.
The present study is the first to demonstrate the effects of long-term resistance training on ECM accumulation in middle-aged and elderly people Table 2 , albeit indirectly through muscle stiffness assessment using ultrasound SWE. Furthermore, QG supplementation with both and mg combined with exercise improved muscle stiffness more than exercise alone Table 2.
To support these data, administration of quercetin, an active form of QGs in target tissues, decreased muscle fibrosis by suppressing inflammatory cytokines in mdx mice In addition, no significant correlation was observed between muscle stiffness in the stretched position and muscle CSA in VL, as well as their changes during the week intervention Figure 2 , indicating that the intervention effects on muscle stiffness were independent of those on muscle quantity.
These findings suggest that QG supplementation exerts additive effects on the improvement of passive muscle stiffness with resistance training.
Antioxidants have been commonly used anx protect against muscpe secondary to exercise; xnd, there Quercetin and muscle recovery been mixed results. In rwcovery, there Quercetin and muscle recovery been some debate that using musc,e doses of antioxidants, such as Increase endurance for rugby C Berry Growing Season E, may counteract the upregulation of endogenous antioxidant defenses that are naturally triggered as a response to exercise. Quercetin, a polyphenol, has been shown to have both strong antioxidant and anti-inflammatory properties. Recently, quercetin has received a lot of attention for its strong immune properties. It is one of the ubiquitous flavonoids found in many Chinese herbs, fruits, and vegetables. Common foods include blueberries, red onions, broccoli, cauliflower, kale, and many nuts. High-intensity Querctin exercise has the potential to cause certain temporary cellular changes Quercetin and muscle recovery increased cellular metabolism, the production rfcovery reactive oxygen species ROSmuscle soreness, and exercise-induced muscle damage EIMD. Recent research -day meal planner that certain micronutrients recpvery as quercetin may play Miscle role in cellular Quercetin and muscle recovery and post-exercise recovery. Quercetin is a molecule classified as a flavonoid that is found in many fruits and vegetables including onions, apples, leafy greens, berries, and green tea. Evidence suggests it plays a supportive role in antioxidative status and inflammatory health. It may promote healthy tissue function through the regulation of senescent cells and may help regulate SIRT1 pathways. Quercetin is thought to act as an adenosine receptor antagonist, which may help support nerve transmission and muscular integrity. It also has the potential to scavenge ROS and help regulate glutathione levels.
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