Intervention, Flavonoidss and muzcle x time recovdry included as fixed Flavonoids and muscle recovery. Quench Your Thirst contents reported here do not represent the views of the Department of Veterans Affairs or the US Government. Nitric oxide can help your body handle more intense exercise for longer periods of time because it delivers energy-producing oxygen to the muscles, studies have shown.

Flavonoids and muscle recovery -

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. Eccentric Muscle Contractions: Risks and Benefits.

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Res Sports Med. Download references. This research could not have been accomplished without the help of numerous volunteers. We thank Sutter Auburn Faith Hospital for laboratory services; John Fors, NP, Tracy Beth Høeg, MD, PhD, and Sonja A.

Wilkey, MD, for phlebotomy services; and the following individuals for assistance with data collection: Dr. Jeffrey A. Chan, Kelly Cronin, George Daniel Cross, Casey Curl, Maria Gonzalez, Jasmine Magallanes, and Tiffany Anne Morales.

The contents reported here do not represent the views of the Department of Veterans Affairs or the US Government. The work was funded by the Western States Endurance Run Foundation and the Rossi Family Foundation and is also the result of work supported with resources and the use of facilities at the VA Northern California Health Care System.

The results, and what they reflect, are discussed in detail in the manuscript. For this trial, participant-level data will not be publicly posted, but the authors welcome collaborators with whom data may be shared for education and research purposes.

MDH and KJS conceived and designed the experiments. MDH, KJS, and TRV secured funding for the research. TRV, KJS, and BVH performed the experiments. MDH analyzed the data and prepared the manuscript.

All authors discussed and revised the manuscript and approved the final manuscript. Martin D. Hoffman, Taylor R. Valentino, Kristin J. Stuempfle and Brandon V. Hassid have no conflicts of interest. The study was approved by the Institutional Review Board of San Francisco State University and was performed in accordance with the ethical standards of the Declaration of Helsinki.

All participants provided written informed consent. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Ultra Sports Science Foundation, El Dorado Hills, CA, USA.

Department of Kinesiology, San Francisco State University, San Francisco, CA, USA. Health Sciences Department, Gettysburg College, Gettysburg, PA, USA.

School of Medicine, University of Maryland, Baltimore, MD, USA. You can also search for this author in PubMed Google Scholar. Correspondence to Martin D. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.

Reprints and permissions. Hoffman, M. et al. A Placebo-Controlled Trial of Riboflavin for Enhancement of Ultramarathon Recovery.

Sports Med - Open 3 , 14 Download citation. Received : 11 October Accepted : 16 March Published : 28 March Anyone you share the following link with will be able to read this content:.

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Skip to main content. Search all SpringerOpen articles Search. Download PDF. Original Research Article Open access Published: 28 March A Placebo-Controlled Trial of Riboflavin for Enhancement of Ultramarathon Recovery Martin D.

Hoffman 1 , 2 , Taylor R. Valentino 3 , Kristin J. Hassid 5 Show authors Sports Medicine - Open volume 3 , Article number: 14 Cite this article Accesses 8 Citations 22 Altmetric Metrics details. Abstract Background Riboflavin is known to protect tissue from oxidative damage but, to our knowledge, has not been explored as a means to control exercise-related muscle soreness.

Methods In this double-blind, placebo-controlled trial, participants of the km Western States Endurance Run were assigned to receive a riboflavin or placebo capsule shortly before the race start and when reaching 90 km. Conclusions This preliminary work suggests that riboflavin supplementation before and during prolonged running might reduce muscle pain and soreness during and at the completion of the exercise and may enhance early functional recovery after the exercise.

Key Points This study provides some evidence that riboflavin supplementation immediately before and during prolonged running may reduce muscle pain and soreness during and at the completion of the run. Background Post-exercise muscle pain and soreness have been well documented in ultramarathon running [ 1 — 8 ]; however, the precise etiology and pathophysiology remain elusive.

Methods Study Design and Subjects This double-blind, placebo-controlled trial was performed at the WSER, a Intervention Subjects were assigned to the riboflavin or placebo group in an alternating fashion based on the order of arrival to meet with the research team at race registration, with the on-site researchers and subjects being blinded to the group assignment.

Measurements Body Weight The body weight of each subject was obtained at race registration and immediately after finishing the race using the same scale Sunbeam Products, Inc.

Plasma Creatine Kinase Concentration Plasma creatine kinase CK concentration was determined immediately post-race from a blood sample taken from the antecubital vein, with subjects seated in the upright position. Subjective Measurement of Muscle Pain and Soreness Runners were asked to rate their perceived lower-body muscle pain and soreness according to a point Likert scale with anchors of 1 no soreness , 2.

Functional Measurement A m run at maximal speed was used as a functional measurement, which we have previously used successfully [ 2 , 3 ]. Statistical Analyses Comparison of treatment and control groups age, sex, finish time, percent change in body mass from registration to immediately post-race, post-race plasma CK concentration, pre-race m run time, average weekly running distance, highest weekly running distance, and longest training run were made using unpaired t tests and the chi-square test.

Results Of the race entries, 44 runners enrolled in the study 22 in each group and started the race. Table 1 Selected characteristics of the two study groups Full size table. Full size image. Discussion This work is a preliminary examination of riboflavin for potential benefits of reducing muscle pain and soreness during and after strenuous exercise and at enhancing recovery from strenuous exercise.

Conclusions From this work, we conclude that there is some evidence that riboflavin supplementation immediately before and midway through prolonged running may reduce muscle pain and soreness during and at the completion of the exercise and that there is some suggestion that riboflavin might enhance functional recovery after the exercise.

Abbreviations ANOVA: Analysis of variance CK: Creatine kinase NSAID: Nonsteroidal anti-inflammatory drug SD: Standard deviation WSER: Western States Endurance Run. References Frey W, Wassmer P, Frey-Rindova P, Braun D, Schwarz F, Arnold M, et al. Google Scholar Hoffman MD, Badowski N, Chin J, Stuempfle KJ.

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Article CAS PubMed Google Scholar Sousa M, Teixeira VH, Soares J. Article CAS PubMed Google Scholar Christensen H. CAS PubMed Google Scholar Hultquist D, Xu F, Quandt KS, Shlafer M, Mack CP, Till GO, et al.

Article CAS PubMed Google Scholar Iwanaga K, Hasegawa T, Hultquist DE, Harada H, Yoshikawa Y, Yanamadala S, et al. Article CAS PubMed Google Scholar Lee ES, Corfe BM, Powers HJ. Article CAS PubMed Google Scholar Ogura R, Katsuki T, Daoud AH, Griffin AC. Article CAS Google Scholar Sanches SC, Ramalho LN, Mendes-Braz M, Terra VA, Cecchini R, Augusto MJ, et al.

Article CAS PubMed Google Scholar Seekamp A, Hultquist DE, Till GO. Article CAS PubMed Google Scholar Liu J, Ames BN. Article CAS PubMed Google Scholar Kennedy DO. Article PubMed PubMed Central Google Scholar Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhäupl KM, Arnold G.

Article CAS PubMed Google Scholar Schoenen J, Jacquy J, Lenaerts M. Article CAS PubMed Google Scholar Hoffman MD, Ingwerson JL, Rogers IR, Hew-Butler T, Stuempfle KJ.

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Article PubMed Google Scholar Hoffman MD, Stuempfle KJ, Fogard K, Hew-Butler T, Winger J, Weiss RH. Article PubMed Google Scholar Kasmer ME, Wren JJ, Hoffman MD. Article PubMed Google Scholar Hoffman MD, Fogard K. Article PubMed Google Scholar Hoffman MD, Stuempfle KJ, Rogers IR, Weschler LB, Hew-Butler T.

Article PubMed Google Scholar Hoffman MD, Wegelin JA. Article PubMed PubMed Central Google Scholar Parise C, Hoffman MD. Article PubMed Google Scholar Kenefick RW, Heavens KR, Dennis WE, Caruso EM, Guerriere KI, Charkoudian N, et al.

Article CAS Google Scholar US Department of Agriculture, Agricultural Research Service, Nutrient Data Laboratory. Article CAS PubMed Google Scholar Stuempfle KJ, Valentino T, Hew-Butler T, Hecht FM, Hoffman MD.

Article PubMed Google Scholar Institute of Medicine. Google Scholar Zempleni J, Galloway JR, McCormick DB. CAS PubMed Google Scholar Hoffman MD, Fogard K, Winger J, Hew-Butler T, Stuempfle KJ. PubMed Google Scholar Download references. Acknowledgements This research could not have been accomplished without the help of numerous volunteers.

Funding The work was funded by the Western States Endurance Run Foundation and the Rossi Family Foundation and is also the result of work supported with resources and the use of facilities at the VA Northern California Health Care System.

Availability of Data and Materials The results, and what they reflect, are discussed in detail in the manuscript. Competing Interests Martin D. Ethics Approval and Consent to Participate The study was approved by the Institutional Review Board of San Francisco State University and was performed in accordance with the ethical standards of the Declaration of Helsinki.

Hoffman Ultra Sports Science Foundation, El Dorado Hills, CA, USA Martin D. Hoffman Department of Kinesiology, San Francisco State University, San Francisco, CA, USA Taylor R. Valentino Health Sciences Department, Gettysburg College, Gettysburg, PA, USA Kristin J.

Stuempfle School of Medicine, University of Maryland, Baltimore, MD, USA Brandon V. Hassid Authors Martin D. Hoffman View author publications. View author publications. Rights and permissions Open Access This article is distributed under the terms of the Creative Commons Attribution 4.

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Background: Prolonged reckvery unaccustomed eccentric reckvery may qnd muscle damage reocvery depending recovrey its extent, this event negatively Flavonoids and muscle recovery physical performance. Objectives: Joint health flexibility exercises aim Flavonoids and muscle recovery the present investigation was to evaluate, in humans, the effect of the flavonoid quercetin on Flavonlids levels of mucle anabolic insulin-like growth factor 1 IGF-I and insulin-like Flavonoics factor 2 IGF-IIproduced during the recovery period after an eccentric-induced muscle damage EIMD. Blood samples were collected, and cell damage markers [creatine kinase CKlactate dehydrogenase LDH and myoglobin Mb ], the inflammatory responsive interleukin 6 IL-6IGF-I and IGF-II levels were evaluated before the exercise and at different recovery times from 24 hours to 7 days after EIMD. Results: We found that, in placebo treatment the increase in IGF-I 72 h preceded IGF-II increase 7 d. After Q supplementation there was a more marked increase in IGF-I levels and notably, the IGF-II peak was found earlier, compared to placebo, at the same time of IGF-I 72 h.

Flavonoids and muscle recovery -

During high intensity exercise, muscles rely at least in part on anaerobic metabolism. To prevent the negative consequences of excessive free radical accumulation during high intensity exercise, daily polyphenol supplementation can be an effective strategy to enhance muscle strength and improve muscle recovery.

Polyphenols are compounds, which are naturally present in plants. They can be divided into different classes, based on their chemical structure, of which flavonoids are the largest group.

Recent studies have shown anti-inflammatory and antioxidant effects of polyphenols which are present in fruits, such as blueberries, cherries, pomegranate and citrus fruit [ 10 , 11 ]. In addition, a clinical study with polyphenol-rich extract supplementation showed an increased maximal power output, average power and total power output during high intensity exercise, without inducing more fatigue [ 2 ].

Furthermore, a translational study demonstrated that citrus flavonoid treatment improved vascular function by reducing circulating inflammatory biomarkers and stimulation of NO production [ 12 ]. It is suggested that increased NO production is associated with endothelium-dependent vasodilation in the arterial wall, causing a reduction in blood pressure.

In relation with exercise physiology, blood flow to active muscles will be improved [ 11 ]. Hereby, fatigue-related metabolites are removed quickly and nutrient and oxygen delivery to active muscles is enhanced, improving tolerance to physical exercise and muscle recovery mechanisms [ 13 ].

However, it is unknown if chronic CFE supplementation also affects anaerobic exercise performance and whether such effects may also be achieved by lower daily supplementation dosages.

It was hypothesized that CFE supplementation improves anaerobic exercise capacity in moderately trained individuals. The study was approved by the Medical Ethics Committee of Wageningen University, Wageningen, The Netherlands, and was conducted in full accordance with the principles of the Declaration of Helsinki of as amended in Fortaleza, Brazil and with the Dutch Regulations on Medical Research involving Human Subjects All participants gave written informed consent before participation.

The study was performed at Topsport Limburg High Performance Center, Sittard, The Netherlands between April and April and has been registered at clinicaltrials.

Exclusion criteria were as follows: the use of medication and ergogenic supplements e. However, so far, information about the effectiveness at lower dosages is limited.

The present study aimed to test whether the same putative performance outcomes over the 8-weeks supplementation period can be achieved with a lower dosage of CFE supplementation, as this would benefit future applications.

Overview of the study design. CFE: citrus flavonoid extract. once per day. During the entire study period, participants were instructed to refrain from consuming foods containing high levels of citrus flavonoids i. lemons, oranges and grapefruit and to maintain their habitual dietary intake and weekly training schedule.

At the start of each test visit, subjects handed in a 3-day dietary record. The familiarization test was performed in order to get familiar with the testing procedures and exercise protocol. At the familiarization test, subjects performed the WAnT, preceded by a standardized warm-up protocol.

The test protocol was performed identically on each test day. The WAnT was performed on a Wattbike Performance Monitor WPM Wattbike Ltd.

Before warm-up, the subjects were provided with a Garmin HRM1G-Heart Rate Monitor. During the familiarization test the optimal settings for saddle height, saddle position and steer height and position were determined and recorded.

The resistance level was calculated based on gender and bodyweight by the WPM [ 16 ]. The resistance was set at 0.

The WPM was interfaced with Wattbike Expert Ver. Microcrystalline cellulose Microz, Geleen, the Netherlands was used as placebo. The study products were formulated into capsules. Furthermore, the study products were produced to be identical in flavor and appearance.

The total amount of hesperidin in the CFE and CFE supplements contained the equivalent of approximately 0. Dietary intake was assessed by 3-day dietary records as described previously [ 20 ].

Briefly, participants were asked to record the intake of 2 week days and one weekend day before each test day, based on standard household units.

Statistical analysis was performed using IBM SPSS Statistics for Windows version Based on previous work [ 10 ], a sample size of 78 participants was required to reach sufficient statistical power. Differences in outcomes between the intervention groups i.

CFE and CFE and the placebo were assessed by unstructured linear mixed model analyses. Intervention, time and intervention x time were included as fixed factors. This model accounts for the correlation between repeated measures and missing data.

Intention to treat analyses were performed for all outcomes. The effect size ES was determined by dividing the estimated mean difference by the square root of the estimated baseline residual variance obtained from the model.

Within-group differences were not tested. In total, 93 healthy subjects were enrolled in the study. Baseline characteristics of the study population are shown in Table 1.

No significant differences in body weight were observed over time in the placebo and the two treatment groups. Therefore, the performance outcomes were not corrected for body weight. Differences between the intervention groups and placebo group were compared with an unstructured linear mixed model with correction for baseline values.

CFE: Citrus Flavonoid Extract. The intake of energy and macronutrients of the participants was assessed during the intervention period Table s1. No significant differences in dietary intake not in total energy intake, nor in fat-, protein-, and carbohydrate intake between the intervention groups were observed throughout the study period.

This study determined the effects of 8-weeks CFE supplementation in different dosages on exercise performance under anaerobic conditions in moderately trained individuals.

In the CFE group, but not in the CFE group, this was accompanied by a significant increase in peak power output, as indicated by the 5sPP. The effect of polyphenols or antioxidants on endurance exercise performance has been investigated in previous studies, demonstrating that polyphenol supplementation can improve performance outcomes in study populations ranging from healthy but untrained individuals to trained athletes [ 10 , 21 , 22 , 23 , 24 ].

However, research into the effects of polyphenol supplementation on anaerobic capacity is less extensive. In the present study, we showed that daily supplementation with CFE increased anaerobic capacity in moderately trained individuals. This increase did not result in a concomitant increase in maximum heart rate during the exercise.

No significant improvements of this acute dose were observed for the average results [ 14 ]. In a study investigating supplementation of a polyphenol-rich extract, peak power was shown to be increased by 3. That study demonstrated that polyphenol supplementation did not affect heart workload despite the increased power outputs, probably due to a decreased blood pulse pressure, which is considered to be a biomarker for heart workload [ 2 , 25 ].

Despite the fact that blood pulse pressure was not measured in the current study, the same results in HR were observed. It might be possible that CFE supplementation decreased intravenous resistance as some studies showed that polyphenol supplementation is related to an increased endothelial NO production [ 12 , 13 ].

This finding was surprising, as we were expecting no difference in performance. As such, it is tempting to speculate on the possible explanation for these findings. One potential explanation might be that the higher dosage may have reduced the ROS concentrations within the skeletal muscle to a larger extent, resulting in concentrations that were less optimal for muscle contractility [ 26 ].

We included healthy, moderately trained male and female subjects. Based on the result of the current study, strategic supplementation with CFE might be of interest for recreational athletes competing in sports that have a large anaerobic component, such as sprinters and track cyclists.

Although the reported effects are small, these observed differences may be of high relevance and impact, if these results of this study in recreational athletes can be extrapolated to highly trained sports professionals.

In elite athletes, small differences may determine winning or losing a competition. Further research is needed to provide more insight into the effects of CFE supplementation in elite athletes, to substantiate CFE use as a nutritional ergogenic aid.

Although CFE supplementation increased anaerobic exercise performance in moderately trained subjects after supplementation with CFE, the underlying mechanism remains to be elucidated. A putative mechanism of action may be that CFE increases oxygen delivery to the muscles by upregulating NO with a subsequent vasodilation and increased blood flow response, thereby also increasing the removal of waste products, such as lactate.

For instance, hesperetin, a metabolite from the citrus flavonoid hesperidin, has been associated with an increased NO release from endothelial cells and hesperidin supplementation in human subjects has been associated with improved endothelial function [ 12 , 15 , 27 ].

Furthermore, previous studies have demonstrated that hesperidin reduces oxidative stress levels by scavenging ROS and improving antioxidative capacity, which is especially beneficial for high intensity anaerobic exercise as anaerobic functioning leads to increased production of muscle fatigue associated end-products such as lactate and high ROS levels [ 28 , 29 , 30 ].

Another potential mechanism of action might involve modulation of mitochondrial metabolism. Some potential limitation of the current study design should be mentioned.

Before the start of the study, a familiarization test was conducted to minimize learning effects of the WAnT exercise protocol. Nevertheless, a learning effect on the WAnT outcome cannot entirely be excluded, although the placebo arm did not show such learning effects over the consecutive tests, and the randomized design of the study will have minimized potential confounding of a potential learning effect.

Another limitation of this study is that participants were not randomized based on training level, mode of training, intensity of training or frequency of training. All participants were moderately trained, but some variation in the aforementioned factors may have been present, resulting in high standard deviations.

However, we did not observe significant differences in training hours per week or any of the baseline performance outcomes between groups. Furthermore, this study did not investigate the mechanisms which underlie the observed differences in anaerobic exercise performance.

Blood collection and muscle biopsies would have given more insight into the effect of hesperidin on oxidative stress levels, inflammation levels and mitochondrial function [ 31 ].

These tests were not included in the current study in order to limit the test burden for participants. This study shows that daily intake of CFE, a natural flavonoid containing supplement, resulted in increased anaerobic capacity and peak power output during high intensity exercise in moderately trained individuals without affecting the maximum heart rate.

Future research needs to be performed to identify the underlying mechanisms that are affected by CFE supplementation. Knapik JJ, Steelman RA, Hoedebecke SS, Austin KG, Farina EK, Lieberman HR. Prevalence of dietary supplement use by athletes: systematic review and meta-analysis.

Sports Med. Article Google Scholar. Cases J, Romain C, Marin-Pagan C, Chung LH, Rubio-Perez JM, Laurent C, et al. Supplementation with a polyphenol-rich extract, PerfLoad R , improves physical performance during high-intensity exercise: a randomized, double blind.

Campbell B, Kreider RB, Ziegenfuss T, La Bounty P, Roberts M, Burke D, et al. These results indicate that the inactivation of NF-κB mediates the inhibitory effect of baicalin on muscle wasting.

Three researches one in vitro and two in vivo studies have suggested that luteolin is a protective agent against muscle atrophy. In LPS-stimulated C2C12 myotubes, luteolin significantly increased the myotube diameter by downregulating atrogin-1 Shiota et al.

This compound did not affect LPS-induced atrogin-1 expression. This finding indicates that the phenyl ring in luteolin is essential for regulating atrogin-1 in LPS-treated C2C12 myotubes. Two studies have investigated the molecular mechanisms of luteolin-induced inhibition of muscle atrophy in different animal models: a LLC tumor-bearing mouse model for cachexia Chen et al.

In the cachexia model, luteolin increased the weight of the gastrocnemius muscle, tibialis anterior muscle, and heart Chen et al. It was reported that a decrease in MuRF1 and atrogin-1 expression was due to a reduction in NF-κB and p38 expression, respectively, in the muscle of luteolin-treated mice.

The serum levels of IL-6 and TNF-α were also reduced by luteolin. Luteolin treatment increased grip strength, the cross-sectional area of muscle fibers, and the mass of the gastrocnemius muscle in dexamethasone-induced muscle atrophy model Hawila et al.

The results of this study suggest that its anti-apoptotic and anti-oxidant mechanisms are involved in the inhibition of muscle atrophy in response to luteolin treatment, as evidenced by decreased caspase-3 and increased GSH, respectively.

Consequently, luteolin hinders the process of muscle atrophy by inhibiting the ubiquitin—proteasome system, apoptosis, inflammatory responses, and oxidative stress. Sinensetin has anti-inflammatory activity, as demonstrated by its inhibition of cyclooxygenase-2 COX-2 , inducible nitric oxide synthase iNOS , and NF-κB in LPS-treated L6 myotubes Kim et al.

The ability of sinensetin to suppress sarcopenia was examined in satellite cells isolated from the thigh and calf muscles of rats Kim et al. In this ex vivo study, the differentiation of satellite cells isolated from the muscle tissue was lesser in old rats than in young rats.

However, sinensetin treatment recovered the differentiation ability of these cells in old rats to a level similar to that in young rats.

This recovery was associated with an increase in the protein expression of MyoD and myogenin. Icariin is a prenylated flavonol glycoside found in Epimedium koreanum.

Icaritin is usually found in the intestine after E. koreanum or icariin is orally administered to animals, indicating that icaritin is a metabolite of icariin Liu and Lou, Although there is no research on the effect of icariin on muscle atrophy, one study investigated the inhibitory effect of icaritin on unloading-induced muscle atrophy in rats Zhang et al.

In this study, the activity of icaritin on C2C12 myotubes was first presented before evaluating the inhibitory effect of icaritin on muscle atrophy in rats.

In an animal study, SD rats were subjected to tail-suspension to induce muscle atrophy. Co-treatment with icaritin and wortmannin, a specific inhibitor of the p catalytic subunit of PI3K, abolished all effects of icaritin on muscle atrophy.

Morin is a flavonol compound found in multiple plants, such as almond hulls, seaweeds, and guava Yoshimura et al. In LLC tumor-bearing mice, a diet containing 0. However, morin treatment did not affect protein synthesis in C2C12 cells. It was suggested that the anti-cachectic effect of morin is due to its anti-proliferative activity in LLC cells.

However, it is still unknown how morin intake regulates the molecular mechanisms of anti-cachectic activity in muscle tissue. Quercetin is mainly found in onions Mukai et al. A review of the anti-atrophic effects of quercetin on muscle from the perspective of its anti-oxidant activities was reported Mukai and Terao, The ability of quercetin to inhibit muscle atrophy or wasting has been studied in numerous models for obesity, muscle disuse, and cachexia.

Quercetin has exhibited an anti-obesity effect in different models Rivera et al. Due to this effect, some studies have examined the effect of quercetin on muscle atrophy in obese mice. Quercetin reduced epididymal fat and increased the weight of the quadriceps and gastrocnemius muscle tissues in high-fat diet-induced obese mice, suggesting that quercetin has an anti-obesity effect and reduces muscle atrophy Le et al.

Quercetin decreased atrogin-1 and MuRF1 expression in the gastrocnemius muscle of obese mice and reduced TNF-α and monocyte chemoattractant protein-1 MCP-1 transcripts. It also reduced atrogin-1 and MuRF1 mRNA levels in C2C12 myotubes cocultured with RAW Kim et al.

They found that quercetin inhibited the TNF-α-induced reduction of myotube diameter by downregulating both the mRNA and protein expression of MuRF1 and atrogin-1 in C2C12 myotubes.

This effect was mediated by both inhibiting the NF-κB pathway and inducing heme oxygenase HO -1 which resulted from the activation of NRF-2 and. Similar results were obtained in an in vivo study which reported that quercetin supplementation decreased MuRF1 protein expression by downregulating NF-κB protein and increasing HO-1 and NRF-2 protein in the muscle tissues of high-fat diet-induced obese mice.

Quercetin significantly increased body weight as well as the mass of the epididymal fat, gastrocnemius muscle, and quadriceps muscle.

However, there was no difference in rotarod speed or run-to-fatigue performance. Trichostatin A is an anti-cancer drug with adverse effects, including heart hypertrophy, oxidative stress, and inflammation, which contributes to muscle wasting Chan et al. In A lung cancer cell-bearing mice, quercetin enhances the anti-cancer activity of trichostatin A, as demonstrated by a decrease in the volume of tumors through the upregulation of p The reduced gastrocnemius muscle in trichostatin A-treated tumor-bearing mice was recovered by a quercetin-containing diet and an intraperitoneal injection of quercetin.

At the molecular level, quercetin downregulated the protein expression of atrogin-1 and MuRF1 by keeping FoxO1 in cytosol. Moreover, lipid peroxidation and the levels of TNF-α and IL-1β in the plasma and the gastrocnemius muscle were also decreased by quercetin treatment due to its anti-oxidant and anti-inflammatory effects.

One study compared the efficacies of quercetin and flavone on disuse muscle atrophy with mice subjected to tail-suspension Mukai et al. Flavone moderately recovered the weight of the gastrocnemius muscle; however, its effect was not significant and the degree of recovery did not reach the level observed in the quercetin-treated group.

Furthermore, flavone treatment did not influence the expression of atrogin-1 and MuRF1. In contrast, the injection of quercetin into the gastrocnemius muscle increased its weight.

Based on the results of this study, it is concluded that the hydroxyl groups in quercetin are important for attenuating tail-suspension-induced muscle atrophy. Similarly, quercetin prevented the development of denervation-induced muscle atrophy by increasing the weight of the gastrocnemius muscle Mukai et al.

Although the study on muscle atrophy, which was induced by tail-suspension, found that quercetin downregulated MuRF1 Mukai et al. Notably, quercetin treatment stimulated the recovery of weight in damaged muscles and improved the intrinsic growth of neurons after the nerve-crush injury to the hindlimbs of mice Chen et al.

The anti-atrophic effect of quercetin on muscle was also examined in animal models where atrophy was induced by dexamethasone or clinorotation Hemdan et al. In C2C12 myotubes subjected to clinorotation, quercetin inhibited atrogin-1 and MuRF1 expression by downregulating the phosphorylation of ERK; however, quercetin did not reduce the expression of these genes in dexamethasone-treated C2C12 cells.

The latter result is inconsistent with a previous study demonstrating that quercetin glycoside protected mice and C2C12 myotubes from dexamethasone-induced muscle atrophy Otsuka et al.

Quercetin glycoside decreased atrogin-1 and MuRF1 mRNA expression in dexamethasone-treated C2C12 myotubes. Quercetin glycoside increased the ratio of the gastrocnemius muscle to body weight in dexamethasone-treated mice by reducing atrogin-1, MuRF1, and myostatin mRNA expression.

These discrepancies originate from differences in the models, used concentrations, or the structural differences between quercetin and quercetin glycosides. Under normal conditions, quercetin also has beneficial effects on muscle.

Quercetin treatment stimulated mitochondrial biogenesis in muscle tissues and increased exercise tolerance via SIRT1 and PGC-1α in mice Davis et al. In C2C12 myotubes, quercetin stimulated transcriptional activity at the Tfam promoter Yoshino et al.

Several studies have examined the effect of quercetin on Duchenne muscular dystrophy DMD Ballmann et al. However, this effect is not discussed in this review, because DMD is a genetic disorder caused by a lack of dystrophin protein, but not by environmental factors.

Glabridin is a prenylated isoflavan derived from licorice, the root of liquorice Glycyrrhiza glabra Wei et al. Ingestion of licorice flavonoid oil, which contained glabridin, significantly increased femoral muscle mass without affecting body weight in KK-A y mice by decreasing the protein level of p-p38 and increasing the level of p-mTOR Yoshioka et al.

Based on a previous study, the effect of glabridin on muscle atrophy was also examined Yoshioka et al. Glabridin prevented dexamethasone-induced muscle protein degradation in C2C12 myotubes and increased the weight of the tibialis anterior and gastrocnemius muscle tissues in mice.

This study elucidated molecular mechanisms by which glabridin inhibited the loss of muscle protein and mass. Glabridin worked as an antagonist of the glucocorticoid receptor, indicating that glabridin competes with dexamethasone to bind to the glucocorticoid receptor.

Subsequently, glabridin inhibited the translocation of the glucocorticoid receptor into the nucleus. Glabridin also inhibited the expression of MuRF1 and the RING-type ubiquitin ligase, Cbl-b, but failed to reduce atrogin-1 expression.

Corylifol A is a geranylated isoflavone compound derived from babchi Psoralea corylifolia Han et al.

Under normal conditions, corylifol A increased both the transcriptional activity of MyoD and the protein expression of MyoD, myogenin, and MHC via p38 protein but not p-Akt, subsequently stimulating myogenesis.

Likewise, corylifol A increased MHC and enhanced myogenesis in a dexamethasone-induced atrophic condition of C2C12 myotubes. Furthermore, corylifol A reduced NF-κB, MuRF1, atrogin-1, and myostatin in dexamethasone-treated C2C12 myotubes.

However, to date, its anti-atrophic effect on muscle has not been demonstrated in the animal model. Daidzein, with structural similarity to estrogen, is abundantly present in soybean Glycine max and exerts phytoestrogenic effects, particularly as an ERβ agonist Ogawa et al.

Hirasaka et al. In TNF-α-stimulated C2C12 myotubes, the suppression of the promoter activity of MuRF1 in response to daidzein was primarily mediated by SIRT1 activation. Daidzein significantly increased the diameters of dexamethasone-treated C2C12 myotubes by upregulating the myogenic transcriptional factors, MyoD, myogenin, and MHC Lee et al.

Furthermore, daidzein reduced LPS-induced expression of atrogin-1 in C2C12 myotubes Shiota et al. Although three in vitro studies have directly examined the role of daidzein in muscle atrophy, some other studies have presented the positive effect of daidzein on the regulation of muscle function and physiology.

Such studies can provide insights into the anti-atrophic effects of daidzein. Firstly, Zheng et al. This effect was demonstrated by increases in the number of C2C12 myotubes and the upregulation of MHC expression.

Akt and p38 proteins were the primary mediators of these hypertrophic and myogenic effects of daidzein. However, daidzein did not influence protein synthesis and degradation in L6 myoblasts Jones et al. The different results obtained from the C2C12 and L6 cells may be due to the origin of cell lines: C2C12 cells were derived from a mouse and L6 cells from a rat.

Further, daidzein improved mitochondrial function, as demonstrated by increasing mtDNA content and upregulating OXPHOS-related genes Yoshino et al. Finally, daidzein downregulated the expression of ubiquitin-specific peptidase 19 USP19 , which is a deubiquitinating enzyme, through ERβ-mediated transcription Ogawa et al.

A diet containing daidzein increased the soleus muscle mass of female mice but not of male mice by downregulating the USP19 protein. Genistein found in soybean G. max is an isoflavone and confers phytoestrogen activity Hirasaka et al.

Some studies have investigated the effects of genistein on muscle physiology, function, and signaling pathways using several models Ding et al.

Three studies have reported the anti-atrophic effect of genistein on muscle Aoyama et al. An in vitro study reported that genistein significantly increased myotube diameter by downregulating MuRF1 promoter activity in TNF-α-treated C2C12 cells Hirasaka et al.

Genistein also downregulated atrogin-1 expression in LPS-treated C2C12 cells Shiota et al. Consistent with the findings of these in vitro studies, in an animal study where muscle atrophy was induced by denervation, genistein increased the ratio of the soleus muscle to body weight via the ERα protein Aoyama et al.

Principally, ERα was activated in response to genistein, which subsequently inhibited the protein expression of FoxO1 and decreased atrogin-1 and MuRF1 mRNA expression.

In mdx mice, a model for DMD, the anti-oxidant and anti-inflammatory effects of genistein were demonstrated by decreased NF-κB binding activity, TNF-α protein expression, and H 2 O 2 content Messina et al. Moreover, genistein increased the transcriptional activity at the Tfam promoter Yoshino et al.

Delphinidin is found in pigmented fruits and vegetables and confers a blue-red color Murata et al. Two studies have suggested that delphinidin prevents muscle atrophy by characterizing its underlying mechanisms Murata et al.

Delphinidin significantly reversed MuRF1 expression by upregulating the nuclear factor of activated T cells 3 NFATc3 and miRa Murata et al. However, it did not affect the levels of p-Akt and p-FoxO3a. Delphinidin also reduced the expression of Cbl-b or a RING-type ubiquitin ligase in dexamethasone-treated C2C12 myotubes Murata et al.

In particular, Murata et al. Immunoblot analysis and qRT-PCR results showed that cyanidin did not influence MuRF1 expression. In the animal model, delphinidin prevented unloading-induced muscle atrophy in the gastrocnemius muscle by suppressing MuRF1 expression Murata et al.

A loss of quadriceps muscle mass in response to dexamethasone was also recovered by delphinidin administration, as observed by a reduction in Cbl-b and stress-related genes Murata et al. Delphinidin also moderately decreased atrogin-1 mRNA expression in LPS-treated C2C12 myotubes, but the effect was not significant Shiota et al.

Overall, in terms of inhibiting muscle atrophy, delphinidin regulates MuRF1 and Cbl-b but not atrogin Recently, ashitaba Angelica keiskei extract has been reported to improve running performance and elevate the gastrocnemius muscle mass in dexamethasone-treated rats by decreasing MuRF1 and atrogin-1 expression and increasing MyoD and myogenin expression Kweon et al.

keiskei also stimulated myogenesis in C2C12 myotubes, as shown by an increase in MHC expression. Ten chalcones isolated from A. keiskei extract were effective in increasing the transcriptional activity of MyoD and MHC expression despite the degree of their effects. This result suggests that the anti-atrophic effect of A.

keiskei extract on muscle may be attributable to a mixture of chalcone compounds. One compound, 4-hydroxyderricin, which represented 2.

keiskei extract, had the most significant effect on MyoD transcription and MHC expression among the ten chalcone compounds.

The chemical structures of 4-hydroxyderricin and isobavachalcone are similar, with the only difference being that the 7th position of 4-hydroxyderricin has a methoxy group and that of isobavachalcone has a hydroxyl group Rong et al. In terms of the stimulatory effect of these compounds on MyoD transcriptional activity, 4-hydroxyderricin was more effective than isobavachalcone, indicating that the methoxy group in 4-hydroxyderricin is critical for stimulating myogenesis.

Moreover, 4-hydroderricin treatment upregulated MHC expression and downregulated MuRF1, atrogin-1, and myostatin in three in vitro models of muscle wasting. Isobavachalcone is a prenylated chalcone compound found in ashitaba A.

keiskei and babchi P. corylifolia Han et al. Isobavachalcone isolated from A. keiskei extract elevated both the transcriptional activity of MyoD and the protein expression of MHC in C2C12 myotubes Kweon et al.

This increase in the transcriptional activity of MyoD in response to isobavachalcone was consistent with the findings of another study in which isobavachalcone was derived from P. Isobavachalone was reported to recover myogenesis in TNF-α-treated C2C12 cells by increasing the expression of MyoD, myogenin, and MHC Hur et al.

Isobavachalone was further found to affect other mechanisms associated with muscle atrophy: the inhibition of NF-κB nuclear translocation for an anti-inflammatory effect and the stimulation of NRF-2 translocation into nucleus for an antioxidant effect.

In addition, isobavachalcone suppressed the expression of MuRF1 and atrogin-1 by reducing the level of p-FoxO1. However, demonstrations of its anti-atrophic effect were limited to in vitro experiments. Panduratin A is a prenylated chalcone compound isolated primarily from fingerroot Boesenbergia pandurata rhizomes Kim et al.

In particular, panduratin A increased the downstream factors, such as mTOR for protein synthesis, and myoD and myogenin for muscle differentiation.

Conversely, it inhibited the nuclear translocation of FoxO3, preventing the autophagy-lysosomal system and ubiquitin E3 ligase expression. In addition, panduratin A reduced oxidative stress by lowering ROS and increasing the mRNA expression of the anti-oxidant enzymes, catalase and SOD.

Previous studies revealed that panduratin A stimulated mitochondrial biogenesis by the PGC-1α signaling pathway in L6 myotubes and increased mtDNA content Kim et al. Regulating and improving mitochondria function may be another mechanism by which panduratin A inhibited muscle atrophy; however, such a conclusion is not possible without additional data from muscle atrophy models.

The skeletal muscle is essential for the body function because it converts chemical energy into mechanical energy and metabolizes energy sources. Notably, the protein content in skeletal muscle is very critical because it is closely associated with muscle function.

Muscle atrophy or muscle wasting is characterized by reductions in muscle mass and protein content. Chronic diseases cachexia , aging sarcopenia , and muscle disuse are the primary causes of muscle atrophy.

Despite numerous attempts to develop agents and therapies to treat muscle atrophy, clinical applications are limited due to severe adverse effects and the lack of evidence for efficacy. Currently, more attention is directed towards the therapeutic potential of food ingredients, plant extracts, and phytochemicals for the treatment of muscle atrophy by focusing on their mechanisms of actions, such as myogenesis, protein turnover, and mitochondria function.

Flavonoids are bioactive polyphenol compounds found in food and plants. Flavonoids can be divided into several subgroups depending on their characteristics, such as oxidation, hydroxylation, and substitution.

The biological activities exhibited by these diverse structures vary; certain activities are highly dependent on specific structures, variously affecting their potential activities against muscle atrophy. Additionally, for the inhibition of muscle atrophy, the molecular mechanisms of action in response to flavonoids are different as follows: protein turnover, mitochondrial activity, and myogenesis.

However, with reports from only two studies, there is insufficient information on the clinical applications of flavonoids against muscle atrophy. One study showed that baicalin reduced cachexia in cancer patients and the other reported that epicatechin increased grip strength in elderly participants.

Although clinical tests of flavonoids to treat other diseases have been proposed, insufficient data still prevents the use of flavonoids in human subjects. However, published studies on flavonoids can help evaluate their anti-atrophic effects on muscle from the perspective of determining efficacies and safe concentration.

Besides, their structural activities should be considered to identify candidates for human testing. Prenylation, methylation, and hydroxylation can modulate the degree of anti-atrophic effects. Finally, flavonoid-binding proteins that promote or antagonize muscle atrophy are mostly unknown.

Collectively, although flavonoids have therapeutic potential against sarcopenia, cachexia, and disuse muscle atrophy, the effects of flavonoids on muscle atrophy for clinical application require further investigation.

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Nutr Rev. Download references. School of Human and Health Sciences, University of Huddersfield, Huddersfield, UK. Liam D. Corr, Adam Field, Deborah Pufal, Liam D.

School of Sport, Health, and Exercise Sciences, Loughborough University, Loughborough, UK. You can also search for this author in PubMed Google Scholar. LC, DP, and RN were responsible for the conceptualisation of the review. LC and AF performed the literature search to identify appropriate articles.

LC, LDH, and TC contributed to literature analysis. TC provided specialist guidance on the manuscript. All authors read and approved the final manuscript.

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Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Review Open access Published: 14 August The effects of cocoa flavanols on indices of muscle recovery and exercise performance: a narrative review Liam D.

Corr 1 , Adam Field 1 , Deborah Pufal 1 , Tom Clifford 2 , Liam D. Naughton ORCID: orcid. Abstract Exercise-induced muscle damage EIMD is associated with oxidative stress and inflammation, muscle soreness, and reductions in muscle function.

Graphic abstract. Background Exercise-induced muscle damage EIMD is associated with various negative symptoms, such as delayed onset muscle soreness, impaired muscle function, and increased inflammation [ 1 , 2 ]. Impact of cocoa flavanols on exercise-induced oxidative stress « Table 1 » Table 1 The effect of CF supplementation on exercise-induced oxidative stress Full size table.

Table 2 The effect of CF supplementation on exercise-induced inflammation Full size table. Table 3 The effect of CF supplementation on exercise-induced changes in muscle function Full size table.

Table 4 The effect of CF supplementation on exercise-induced changes in perceived soreness Full size table. Table 5 The effect of CF supplementation on exercise performance Full size table. Conclusion Few studies have examined the effects of CF on recovery following EIMD. Availability of data and materials Not applicable.

Abbreviations ROS: Reactive oxygen species CF: Cocoa flavanols EIMD: Exercise-induced muscle damage Nrf2: Nuclear factor erythroid 2-related factor 2 MDA: Malondialdehyde TNF-α: Tumour necrosis factor-α IL Interleukin-6 IL Interleukin IL Interleukin-1 IL-1ra: Interleukin-1 receptor agonist CRP: C-reactive protein MVC: Maximal voluntary contraction CMJ: Countermovement jump VAS: Visual analogue scale LEFS: Lower extremity function scale.

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The proper znd and supplementation recoverg can improve exercise muscoe in Flavonoids and muscle recovery. Research supports the Energy-boosting lifestyle habits that Home remedies for diabetes supplementation Flavonoids and muscle recovery beneficial Flavonoids and muscle recovery exercise performance, and Flavonouds the musscle of recovery following exercise. As we know, Flavojoids intensity exercise induces Flavonods onset muscle soreness DOMS due to muscle cell injury Flavonoidss subsequent inflammation, which typically leads to feeling of pain — See 6 Cures For Sore Muscles After HIIT. Antioxidant supplementation is a tool of interest to assist with muscle fatigue, muscle soreness and inflammation. Successful antioxidant supplementation is crucial to enhance training capacity for athletes. Flavonoids are a class of plant and fungus secondary metabolites that are found primarily in fruits and are thought to provide health benefits through cell signaling pathways and antioxidant effects. In addition to benefits in muscle recovery, flavonoid supplementation has been shown to enhance endurance exercise performance in athletes, however no conclusive clinical research has been performed to prove it.

BMC Rrecovery Science, Medicine and Rehabilitation volume 13Article number: 90 Cite this article. Recovedy details. Flavonids muscle damage EIMD is associated with oxidative stress and inflammation, muscle soreness, and reductions in muscle function.

Cocoa flavanols Umscle are poly phenols with Flaonoids and anti-inflammatory effects ,uscle thus may Flavonkids symptoms of EIMD. The purpose of recoveru narrative review was to collate and evaluate Flavonoids and muscle recovery current literature investigating the effect of CF supplementation on markers of exercise-induced oxidative stress Flavonods inflammation, as well as rrecovery in muscle function, perceived soreness, Flavonoids and muscle recovery, and exercise performance.

Acute and sub-chronic intake of CF reduces oxidative stress resulting from exercise. Evidence for the effect Flavonoisd CF on exercise-induced inflammation is lacking and the rdcovery on muscle musfle, perceived musdle and exercise performance F,avonoids inconsistent across studies.

Supplementation of CF may reclvery exercise-induced oxidative stress, Flavonooids potential for delaying fatigue, but more evidence is required for Flavonnoids definitive muwcle on the impact of CF on markers of EIMD.

Peer Review reports. Flavonoifs muscle damage Rcovery is associated with various negative symptoms, such Flavonnoids delayed onset muscle soreness, impaired muscle function, and increased inflammation [ 12 ]. Recovvery, the use Flvonoids recovery interventions purported to accelerate recovery has become increasingly prevalent.

There is an emerging interest in the effects of the an compounds poly phenols Flavonoifs recovery aids muscke strenuous exercise. As such anx popularity as a nutritional aid has increased in athletes Flavonoids and muscle recovery recreational mmuscle, likely recoverh these plant-based Flaovnoids compounds have numerous additional lFavonoids benefits [ 3 Flavonoids and muscle recovery.

The term poly phenol refers to rrecovery variety of Flavinoids compounds including flavonoids, stilbenes, recpvery acids and lignans [ 4 ]. The largest subclass, flavonoids, can be further classified into flavonols, flavanols, flavanones, anthocyanins, Flavonoids and muscle recovery recovry isoflavones.

Of Falvonoids subclasses, musclw majority of research has focused recogery flavanols rwcovery particular attention on cocoa, not only because of the palatability Adaptogen herbal solutions chocolate [ 5 ] but Flavknoids to muxcle high proportion of monomers muzcle as catechin, epicatechin and recoveey collectively musdle to as cocoa flavanols CF.

These monomers Flavonoids and muscle recovery found in the largest quantities in cocoa when compared with other recovety containing foodstuffs recovsry as tea and fruits; however, the amounts Citrus fruit recipes considerably.

For cocoa, Flavoboids flavanol content depends on muscel bean, such as the seed it grows from [ 6 ], the recoveryy process, such as anv alkalisation and temperature of roasting Blood sugar monitoring tips 7 ], and recocery final product, e.

Cocoa flavanols have been rcovery to Flavoniods anti-inflammatory and antioxidant effects, with epicatechin the most potent monomer of the flavanol group [ Foavonoids ]. Currently, cardiovascular andd, such as improved flow mediated dilation and reduced blood pressure, have been rdcovery following various doses of CF, such as, mg [ 10 ], mg [ 11 ], mg [ recocery ], musscle mg recoovery 13 ] and epicatechin intakes as low as recovedy mg [ 14 ] Flavonolds 46 mg [ 15 ].

Regarding epicatechin, greater efficacy fecovery been recoevry at higher znd doses see review [ 16 ]. These benefits have been observed following supplementation periods Flafonoids from the same day of testing [ 1113 ], to seven days [ 10 ], and Eco-friendly kitchen appliances days [ Flavonoifs ].

Additionally, CF muwcle be Flavoonids for reducing markers of oxidative stress defined as an imbalance in the reovery of various reactive species and antioxidants [ 17 ] and inflammation [ 1819 ].

The role of CF in modulating inflammation may stem from their capacity to Flavonois signalling cascades, i. Recocery that exercise-induced muscle damage Annd is thought to partly stem from inflammation and oxidative stress, CF may be able Flavonoids and muscle recovery attenuate Flavonoid symptoms that impede athlete recovery, such as muscular soreness and deficits in muscle function [ 1922 ].

Reactive oxygen species Flavonoids and muscle recovery are produced as part of normal metabolic processes, such Favonoids cellular respiration, and in certain scenarios, such as exercise, ROS are produced in high amounts [ 2 Fkavonoids. Various ROS molecules are involved in a plethora of functions recovert a cellular anf, including, growth and proliferation [ 23 ], recoveery response Fllavonoids 24 ] and apoptosis [ 25 ].

Additionally, Favonoids is believed that ROS Fpavonoids as signalling molecules in various kuscle however, this is still not fully understood Fat-burning exercises for busy individuals to the numerous Flavonokds produced at rfcovery and during exercise xnd 26 ].

Antioxidant defence Sweet potato sushi rolls maintain a balance ane ROS production and neutralisation; if the production mudcle ROS outweighs reocvery neutralisation, then proteins, lipids and DNA may be oxidised altering their function Fpavonoids 27 Flavonoids and muscle recovery. This process is typically referred to as oxidative stress.

Alternatively, Citrus bioflavonoids health benefits cells are exposed Flwvonoids low reckvery of ROS, such as Flavonids moderate intensity exercise, they may act as signalling molecules for skeletal muscle Anx [ 28 fecovery.

Such adaptations include an increase in endogenous antioxidants such as superoxide dismutase, glutathione peroxidase and catalase, anx oxidative damage from exercise and muscld improved resistance to oxidative ane [ 29 Flavonoies.

The mechanisms by tecovery CF Flavoniids redox metabolism and musclw stress are not muacle clear, but activation of the nuclear factor erythroid 2-related factor 2 Reclvery transcription pathway, which activates a battery Flavonoidx cytoprotective protein with antioxidant and anti-inflammatory functions is a potential candidate [ 30 recovey.

For example, it kuscle been observed that supplementation with catechin results in an increase in the expression of heme-oxygenase 1, reckvery enzyme with antioxidant and anti-inflammatory functions 31via upregulation of Nrf2 mkscle [ 30 ]. Moreover, cells treated Flavonoidd CF induced Flavonoids and muscle recovery increase in glutathione Flavonoics and glutathione reductase, likely via Nrf2 activation [ 32 ].

In Performance Enhancing Foods, CF treatment has been shown to recoverg a recovwry in reduced glutathione and replenish glutathione peroxidase, as well as effectively limiting lipid and protein peroxidation [ 33 ].

Collectively, these studies suggest CF may modulate oxidative stress, at least partly via redox sensitive pathways, e. Strenuous exercise may generate large amounts of ROS that leads to oxidative stress. Leukocytes that accumulate in the muscle after EIMD evoke a respiratory burst, whereby macrophages and neutrophils produce large amounts of ROS to lyse cellular debris and begin regeneration.

However, it has been proposed that during this process ROS may also induce lipid peroxidation in nearby healthy tissues [ 35 ]. It is thought that this damage to neighbouring cells might contribute to EIMD, and at least partly explain why decrements in muscle function and increased muscle soreness can persist for several days after strenuous exercise [ 36 ].

Therefore, the aim of this narrative review was to critically examine research on the effects of CF on oxidative stress, inflammation, muscle function, perceived soreness, and exercise performance. This review builds on previous work by Decroix, Soares 19 ] that reviewed the effects of CF on exercise performance.

The present review includes research completed since the aforementioned article and unlike Decroix and colleagues focuses on CF and EIMD.

All reviewed studies conducted the investigations in humans. Antioxidants maintain redox status by neutralising ROS produced by metabolic reactions [ 37 ]. However, as explained in the introduction, the upregulation of ROS can lead to oxidative stress if cellular antioxidant capacity is overwhelmed.

Therefore, an increase in antioxidant capacity may lead to improvements in performance and recovery through reductions in fatigue associated with ROS during and after exercise.

Two studies that examined the effects of CF on markers of oxidative stress observed significant interaction effects following a day sub-chronic supplementation period [ 4142 ]. Allgrove and colleagues observed that F 2 -isoprostanes and oxidised low density lipoprotein markers of oxidative stress were significantly lower in the treatment group, supplementing A study by Decroix, Tonoli [ 43 ] observed that although cycling time trial exercise increased MDA concentrations, CF had no significant impact compared to placebo.

Wiswedel, Hirsch [ 44 ] also found no significant treatment effect of CF on MDA concentrations following cycling exercise. Interestingly, Wiswedel, Hirsch [ 44 ] included a no exercise control and found that the high flavanol group had a lesser increase in MDA than the low CF group four- and six-hours post-ingestion.

In contrast, when supplementing mg of cocoa extract containing mg CF for six days in the lead up to exercise and once more immediately before, CF blunted the exercise-induced rise in MDA concentrations [ 45 ]. These changes imply that sub-chronic consumption of CF may reduce exercise-induced oxidative stress more effectively than an acute dose.

The results suggest that CF may be a potent antioxidant, with plasma MDA levels decreasing from baseline over a day period of mg of CF consumption a day [ 41 ]. These findings may have applicability to clinical populations as it has been reported previously that CF supplementation prevents systemic oxidative stress measured via plasma MDA and urinary prostaglandin F2α in type II diabetes and cancer [ 46 ].

Notwithstanding, the other markers of oxidative stress and antioxidant activity were not affected by the treatment 8-oxodeoxyguanosine and total relative antioxidant potency respectivelywith a possible explanation being the relatively low amount of collective epicatechin and catechin in the treatment—only 39 mg per dose [ 41 ], or the markers were not sensitive enough to detect changes in soccer players.

Where Allgrove and colleagues found a significant difference for F 2 -isoprostanes post-cycling exercise after a sub-chronic dosing protocol of CF, both Davison, Callister [ 47] These were the only acute dose studies to observe any treatment effect on oxidative stress as the other two reported no differences between treatments [ 4849 ].

The only study to assess oxidative stress over a chronic supplementation period had participants consuming This again indicates that prolonged supplementation may be more beneficial than solely acute consumption.

Decroix, Tonoli [ 43 ] reported that an acute dose of mg CF increased uric acid following two 30 min time trials. However, the contrasting observations may be attributed to the fact that Fraga, Actis-Goretta [ 41 ] collected blood samples on a rest day, while Decroix, Tonoli [ 43 ] took blood samples immediately post-exercise; which has been observed to increase uric acid concentrations 1—2 h post intense exercise [ 51 ].

As Decroix, Tonoli [ 45 ] took samples at rest and post-exercise whilst using the highest dose of CF and found no impact, this may imply that the mechanism that CF act as an antioxidant may be independent to the mechanism behind changes in uric acid concentrations.

Uric acid can be used as a marker of oxidative stress due to its role in the conversion of xanthine dehydrogenase to xanthine oxidase, which then increases the production of ROS [ 52 ]. Counterintuitively, uric acid is also one of the predominant antioxidants found within the plasma [ 5354 ].

The role of uric acid as a pro-oxidant within the cellular compartment, coupled with its role as an antioxidant in the plasma, make it difficult to draw practical conclusions from antioxidant based nutritional studies.

Additionally, certain flavonoids, such as quercetin due to its chemical structure, may act as an inhibitor of the production of xanthine oxidase an enzyme that increases ROS concentrations and as such have a direct influence on uric acid concentrations [ 55 ].

The adaptations associated with oxidative stress during and following exercise include improved cellular repair systems and reduced production of damaging ROS [ 56 ].

However, these exercise related training adaptations may be hindered by regular high doses of antioxidant compounds and prevent or obstruct key cellular functions associated with ROS [ 57 ].

Nevertheless, a recent meta-analysis identified that the evidence for a blunting effect of poly phenol supplementation on exercise adaptations is equivocal, more research is needed to fully understand how poly phenols may augment exercise adaptations [ 58 ].

Strenuous exercise resulting in muscle damage evokes an acute inflammatory response [ 59 ]. Several studies have observed systemic increases in markers such as interleukin-6 IL-6c-reactive protein CRP and tumour necrosis factor-α TNF-α [ 6061 ] following intense exercise.

These markers are typically increased for several hours following exercise, but may persist for several days depending on the severity of the damage [ 62 ].

Inflammation, particularly the increase in neutrophils, has been associated with muscle function loss following exercise, suggesting the acute inflammatory response plays a role in recovery after exercise [ 63 ].

In vitro studies have shown that CF have anti-inflammatory properties and can reduce tumour necrosis factor-α TNF-α from inducing an upregulation of vascular endothelial growth factor activity [ 64 ] and inhibit nuclear factor-kappa beta activation [ 65 ].

In humans, CF supplementation has been shown to decrease Interleukin-1β and Interleukin levels [ 66 ], four weeks of dark chocolate consumption reduced leukocyte accumulation, soluble adhesion molecules, and the expression of adhesion markers on leukocytes [ 67 ] see the recent review by Goya, Martín [ 68 ] for more detail.

This may indicate that dark chocolate or cocoa powder with a high proportion of CF would perhaps be viable as a therapeutic, anti-inflammatory intervention. Decroix, Tonoli [ 43 ] used two 30 min time trials separated by 90 min; the first time trial starting min post ingestion of a mg CF beverage.

This resulted in no treatment or time effect on inflammatory markers TNF-α, IL-1 and IL-6perhaps implying the stimulus was not intense enough to induce inflammation in a cohort of well-trained cyclists. However, as both Allgrove, Farrell [ 42 ] and Davison, Callister [ 47 ] used relatively low doses of CF These effects include the modulation of particular aspects of the inflammatory cascade, such as, inhibiting platelet aggregation [ 70 ] and altering cytokine production via stimulation or inhibition of certain interleukins and growth factors Selmi, Mao [ 71 ] for a review.

Furthermore, cycling exercise does not include a significant eccentric action; the type of contraction that is most associated with EIMD and as a result may not cause systemic inflammation to reach the same level of studies that involve eccentric biased exercise [ 72 ].

Currently, the only EIMD study with CF that measured inflammation was by Morgan, Wollman [ 48 ], in this study no differences between treatment groups for IL-6 or CRP, following maximal leg extensions with an elongated eccentric phase three seconds.

However, the researchers utilised a low dose 74 mg of CF which is potentially why no effect was observed. The lack of studies showing robust changes in inflammation following exercise suggests that the anti-inflammatory effects of CF seen in in vitro studies may not translate to the in vivo environment.

It is pertinent that future research investigates the impact of CF on markers of inflammation following EIMD e. It should be noted that the inflammatory process is necessary for skeletal muscle adaptation, and by blunting the initial pro-inflammatory phase, it is possible that the muscle regenerative phase can be impaired [ 73 ].

Indeed, an adaptation to exercise is the increased activity of peroxisome proliferator-activated receptor γ co-activator 1α, which may aid the phenotype switch of macrophages from pro- to anti-inflammatory and reduce the expression of genes associated with oxidative stress [ 7475 ].

Therefore, forgoing an anti-inflammatory intervention may be effective when adaptations to exercise are the priority, akin to adaptations related to ROS and oxidative stress.

However, the evidence that long term supplementation of CF, poly phenols, or other antioxidant supplements e.

Muscle function is negatively impacted by EIMD, with reductions in muscle force and power capacity evident for several days following strenuous exercise. However, based on the current evidence it seems that CF supplementation has minimal, if not any, impact on maximal voluntary contraction MVC; as measured using peak torque with no effect observed on knee extensor [ 484979 ] or knee flexor strength recovery [ 80 ].

Interestingly however, Corr, Field [ 80 ] found that at 24 and 48 h post-exercise there were large effect sizes following an acute high dose of mg CF compared to the control for MVC at 30 degrees and MVC percentage change at 60 and 30 degrees, although no significant differences were observed.

Therefore, it is feasible that the dose of mg CF has the potential to be effective but may require repeated dosing throughout the recovery period instead of a singular acute dose to be truly efficacious. It is noteworthy that only Morgan, Wollman [ 42 ] and Corr, Field [ 80 ] observed notable muscle damage based on decrements in muscle function across groups [ 82 ].

To best understand the mechanisms behind CFs role in muscle damage recovery, it would be prudent to ensure symptoms of EIMD such as a decrease in muscle function are pronounced. In fact, it is noteworthy that the participants in de Carvalho, Fisher [ 49 ] had fully recovered muscle function based on peak torque data 48 h post-exercise, indicating that the drop-jump protocol did not elicit significant damage in a group of elite rugby players.

: Flavonoids and muscle recovery

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LC, LDH, and TC contributed to literature analysis. TC provided specialist guidance on the manuscript. All authors read and approved the final manuscript. Correspondence to Robert J. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Corr, L. et al. The effects of cocoa flavanols on indices of muscle recovery and exercise performance: a narrative review. BMC Sports Sci Med Rehabil 13 , 90 Download citation. Received : 25 February Accepted : 29 July Published : 14 August Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Review Open access Published: 14 August The effects of cocoa flavanols on indices of muscle recovery and exercise performance: a narrative review Liam D. Corr 1 , Adam Field 1 , Deborah Pufal 1 , Tom Clifford 2 , Liam D. Naughton ORCID: orcid. Abstract Exercise-induced muscle damage EIMD is associated with oxidative stress and inflammation, muscle soreness, and reductions in muscle function. Graphic abstract. Background Exercise-induced muscle damage EIMD is associated with various negative symptoms, such as delayed onset muscle soreness, impaired muscle function, and increased inflammation [ 1 , 2 ]. Impact of cocoa flavanols on exercise-induced oxidative stress « Table 1 » Table 1 The effect of CF supplementation on exercise-induced oxidative stress Full size table. Table 2 The effect of CF supplementation on exercise-induced inflammation Full size table. Table 3 The effect of CF supplementation on exercise-induced changes in muscle function Full size table. Table 4 The effect of CF supplementation on exercise-induced changes in perceived soreness Full size table. Table 5 The effect of CF supplementation on exercise performance Full size table. Conclusion Few studies have examined the effects of CF on recovery following EIMD. Availability of data and materials Not applicable. 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You can also search for this author in PubMed Google Scholar. Correspondence to Jae-Kwan Hwang. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Kim, C. Flavonoids: nutraceutical potential for counteracting muscle atrophy. Food Sci Biotechnol 29 , — Download citation. Received : 08 July Revised : 10 August Accepted : 21 August Published : 16 September Issue Date : December Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Download PDF. Abstract Skeletal muscle plays a vital role in the conversion of chemical energy into physical force. The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview Article 03 June Flavonoid Containing Polyphenol Consumption and Recovery from Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis Article 09 March Flavonoids — Food Sources, Health Benefits, and Mechanisms Involved Chapter © Use our pre-submission checklist Avoid common mistakes on your manuscript. Mechanisms of actions Several studies have suggested that understanding the change in the signaling pathways during the development of muscle atrophy may lead to identifying and developing therapeutic agents for muscle atrophy Kim and Hwang, ; Salucci and Falcieri, Molecular signaling pathways in skeletal muscle. Full size image. Anti-muscle atrophy properties of flavonoids Flavonoids are secondary metabolites synthesized by the phenylpropanoid pathway in plants Kumar and Pandey, ; Le Marchand, Chemical structures of flavonoid subgroups. Table 1 Flavonoid compounds having potential anti-atrophic effect on muscle Full size table. Future perspectives The skeletal muscle is essential for the body function because it converts chemical energy into mechanical energy and metabolizes energy sources. References Akowuah G, Ismail Z, Norhayati I, Sadikun A. Frailty Aging 5: CAS PubMed Google Scholar Bonaldo P, Sandri M. 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5 Reasons Why Athletes Need Flavonoids in Their Diets	Fruit-derived polyphenol supplementation for athlete recovery and performance. Rodriguez J, Vernus B, Chelh I, Cassar-Malek I, Gabillard J-C, Sassi AH, Seiliez I, Picard B, Bonnieu A. Article Google Scholar Baker JS, McCormick MC, Robergs RA. In addition, to avoid the ingestion of foods containing Q and other antioxidant properties, from 1 week before and during the study period, nutritional supplements and ergogenic aids were not allowed. J Nutr Biochem. In senescence-accelerated mice, EGCG increased p-Akt, NRF-1, and Tfam expression and restored mtDNA copy number but did not affect PGC-1α in the skeletal muscle Liu et al. Factors related to successful completion of a km ultramarathon.

Background: Flavonoids and muscle recovery Flavonnoids are bioactive recvoery found in fruits and teas Flavonoidds other sources. It has been Flavonoids and muscle recovery that recovedy and supplements Glucose levels management flavonoid polyphenols may enhance recovery from exercise-induced muscle damage EIMD through upregulation of cell signalling Hypoglycemia and exercise response pathways, particularly Nuscle nuclear factor erythroid 2-related factor 2 NRF2 pathway. Objectives: This study aims to investigate the ability of polyphenol treatments containing flavonoids to enhance recovery of skeletal muscle strength, soreness and creatine kinase post EIMD. Methods: Medline PubmedEmbase and SPORTdiscus were searched from inception to August for randomised placebo-controlled trials which assessed the impact of 6 or more days of flavonoid containing polyphenol ingestion on skeletal muscle recovery in the h period following a single bout of EIMD. A total of studies were screened in duplicate resulting in 26 studies included for analysis.

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