For this, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement was considered and the risk of bias (RoB) was assessed by using the Cochrane RoB 2 tool. HPLC chromatogram at 280 nm of procyanidin B 3 before and after in vitro digestion. After completion of the 4 wk EC treatment by Dower et al. A further RCT determined the effects of an intake of cocoa extract providing CF either with DP of 110 (130 mg/d EC, 560 mg/d procyanidins) or with DP of 210 (20 mg/d EC, 540 mg/d procyanidins) on serum lipids compared to a flavanol-free control. Ottaviani J.I., Borges G., Momma T.Y., Spencer J.P.E., Keen C.L., Crozier A., Schroeter H. The metabolome of [2-14C]()-epicatechin in humans: Implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives. Bolus intake of 100 mg EC [24] and 200 mg EC [23,26] increased the sum of glucuronidated, sulfated, and methylated epicatechin metabolites in plasma (AUC08 Cremonini E., Iglesias D.E., Kang J., Lombardo G.E., Mostofinejad Z., Wang Z., Zhu W., Oteiza P.I. Kirch et al. Mood enhance- 0-10 Didn't really get any mood change. Catechin, epicatechin, epigallocatechingallate (EGCG), epicatechingallate (ECG), epigallocatechin (EGC), . Epicatechin metabolites time-profiles were measured in blood to calculate the bioavailability. Both research and empirical usage suggests that epicatechin should be dosed at 1-2mg/kg of bodyweight. Therefore, the RoB in D5 was rated as low for all endpoints [28,29,31]. However, ad libitum food intake remained unchanged [25] and a chronic EC intake neither modulates BW [20,28,29,30,31] nor FM and fat distribution [20]. Finally, all studies which were considered to be eligible were included in this systematic review. Due to an age-related decline in FMD, which is partly ascribed to diminished smooth muscle responsiveness [33], the response on EC intake might be lower in older than in younger adults. Endurance- 12 out of 10 This was the number 1 effect and lasted all 4 weeks. Licensee MDPI, Basel, Switzerland. How does Epicatechin Work? [22] and Alan et al. A dose of 1.0 mg EC/kg BW increased these EC metabolites at each time point of investigation compared to the control (after 1 h, 2 h, 4 h: all p < 0.001; after 6 h: p < 0.01). E, Color change of anthocyanins after the above described reactions (A-D) as indicated by #1 to 4, respectively. Alan M.E., Castle S.M., Serra G., Lvques A., Poquet L., Actis-Goretta L., Spencer J.P.E. Further data extracted: outcomes (parameters of vascular function, glucose and lipid metabolism, inflammation, oxidative stress, appetite sensations, BW, and body composition), EC bioavailability, time points of investigations, conditions to ensure standardization (e.g., nutritional limitations, lifestyle instructions) and parameters/measures for verification (e.g., food records), compliance with intervention, and drop-outs considered. Age and flow-mediated dilation: A comparison of dilatory responsiveness in the brachial and popliteal arteries. (kt-kn) n. 1. As differences at baseline between intervention and placebo group [30] or between EC and control treatments [20,22,23,24,25,26,27,28,29] were not observed in any study, problems with the randomization process are unlikely. Lin X., Zhang I., Li A., Manson J.E., Sesso H.D., Wang L., Liu S. Cocoa flavanol intake and biomarkers for cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials. As TC decreased after daily intake of both DP110 and DP210 as compared with the control, the reduction in TC seems to be linked to ingestion of procyanidins, but not necessarily to that of EC [40]. [27], test drinks were given after breakfast (postprandial). In addition, a selection of the presented results from multiple eligible outcome measurements (e.g., time points) or from multiple eligible analysis of the data is unlikely. [30] did not provide any information on gender. Schulz K.F., Altman D.G., Moher D. CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. Two review authors (L.D., S.D.) Epicatechin-3-gallate is the most biologically active and most abundant catechin in green tea (accounting for 50-80% of the total tea catechins). However, ad libitum food intake after 2.5 h was not modulated by the EC treatment (p 0.05). The difference here is that we will be covering ingredients that are less well known so don't expect a lengthy article on whey protein or BCAAs! Epicatechin is a bioactive compound famously found in dark chocolate. However, neither effects on FMD, pulse wave velocity (PWV), AIx75, SEVR, SBP and DBP (central BP, clinical BP, 24 h ambulatory BP), nor on NOx and ET-1 concentrations in plasma were observed (all p 0.05). Acute study of dose-dependent effects of ()-epicatechin on vascular function in healthy male volunteers: A randomized controlled trial. [28], an additional dose of 100 mg EC was ingested after an overnight fast and the results were compared to the placebo treatment (Table 3). The full texts of the remaining 11 records were checked and a further publication was excluded due to a lack of randomized controlled study design (n = 1). This research received no external funding. These effects are ascribed to cocoa flavanols, particularly to ()-epicatechin (EC), a natural ingredient of cocoa. Finally we turn our attention to a 2012 study, which showed that dark chocolate consumption led to a reduction in body fat even in the presence of a higher calorie intake. The RCTs showed no changes in markers of oxidative stress [20,23], suggesting that the antioxidant potential of EC metabolites at the concentrations occurring in plasma after an acute EC ingestion [23] and after 12 h overnight fast following a chronic EC intake [20] is low or does not contribute to protection against lipid peroxidation. EC was administered in water and pure water was given as control. Everything You Need to Know About Epicatechin. Definition of epicatechin in the Definitions.net dictionary. In a study performed on mice, dosing epicatechin at 1mg/kg of bodyweight resulted in increases in nitric oxide and endurance that persisted even in the absence of exercise. D1, bias arising from the randomization process; D2, bias due to deviations from intended interventions; D3, bias due to missing outcome data; D4, bias in measurement of the outcome; D5, bias in selection of reported result [20,22,23,24,25,26,27,28,29,30,31]. None of these studies observed any effects on TGs, TC, LDL-C, and HDL-C after a regular EC intake compared to placebo (all p 0.05) [20,28,30]. [28,29,31] showed a low RoB for each domain. Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. All treatments lasted one month and were matched for theobromine and caffeine. ; risk of bias assessment, L.D., S.D. As it can be implied from the proposed mechanisms of action, an increased NO availability appears to be the underlying mechanism of action of EC on vascular parameters; additionally, a decrease in the vasoconstrictive ET-1 is discussed. Effects came immediately. [26] measured FMD only 1 h and 4 h after EC intake. Due to some concerns in D1 [20,22,23,24,25,26,27,28,30] and/or D5 [22,23,25,26,27,28,30], the overall RoB was judged with some concerns for the outcomes of Schroeter et al. [23] provided no information whether statistical analysis was done in blinded manner; Greenberg et al. [24] investigated healthy men in advanced age (age: 62 9 y, BMI: 25.1 2.1 kg/m2; means SDs). Not all participants of Kirch et al. In addition, peripheral SBP and DBP, laser Doppler imaging (LDI), plasma concentrations of nitrite and nitrate, as well as species derived from nitric oxide (NOx) were assessed. As reviewed recently [15,16,17,18], EC and its metabolites may decrease the production of reactive oxygen species (ROS), e.g., by mitigating the expression and the activity of NADPH oxidase and further ROS-generating enzymes. [30] (both p 0.05). Green tea or epicatechin-3-gallate can quench several different reactive oxygen species, and its health benefits have been partially attributed to its antioxidant properties. Kirch N., Berk L., Liegl Y., Adelsbach M., Zimmermann B.F., Stehle P., Stoffel-Wagner B., Ludwig N., Schieber A., Helfrich H.P., et al. A strength of this systematic review is the application of the revised Cochrane RoB 2 tool and the consideration of additional factors which might have biased the investigated outcomes. Three RCTs investigated regular [20,28,29,30,31] and one RCT the acute-on-chronic [28] EC intake. Second, the duration of EC long-term studies (24 wk) was similar to those of a subgroup of cocoa studies with an intervention period <3 wk, where a treatment effect was observed for FMD, SBP, DBP, FPG, TC, and LDL-C [2]. [28]. ABBREVIATIONS; ANAGRAMS; BIOGRAPHIES; CALCULATORS; CONVERSIONS; DEFINITIONS; GRAMMAR . Furthermore, the amount of EC ingested with cocoa products has shown to predict the decrease in BP in a metaregression analysis of RCTs [14]. A Harvard University study from 2007 shows that epicatechin appears to lower the risk of lethal events linked with four common diseases - diabetes, strokes, cardiovascular disease and cancer - by approximately 10%. Animals lacking myostatin, either due to a defective gene or because theyve been treated with compounds that inhibit production, show huge increases in muscularity. Thus, an acute EC intake seems to increase FMD in young adults, which appears rather unlikely for older ones. As subjects with a BMI between 18 and 35 kg/m2 (>20 and 30 kg/m2 [24], 18 and 35 kg/m2 [26]) were recruited, the dose of 100 mg [24] and 200 mg EC [26] corresponded to an amount of 1.1 to 1.6 mg EC kg/BW [24] and 1.9 to 3.6 g EC kg/BW [26], respectively, if a body height of 1.75 m is assumed. Hence, other ingredients than EC (or in addition to EC) could be relevant for the effects of cocoa. I loved every minute of this run. (crossover design) [25] were not blinded while analyzing data, and no information was available on the result selection, the outcomes were judged with some concerns. [27] and Schroeter et al. Docking studies confirmed role of () epicatechin in stabilizing iNOS. I was debating going on PH's as I must be close to my genetic limits but having gotten this I think I will try it again, maybe stacking it with something complementary like x factor. The order of assignment was obscured in the RCT of Dower et al. However, epicatechin levels remained stable for the first day of storage but then increased significantly after 5 days of storage . As by Schroeter et al. In addition, caffeine, theanine, theaflavins and phenolic . This might contribute to a negative energy balance. Any of various isomers or derivatives of this compound. Furthermore, all studies used an appropriate statistical analysis (intention-to-treat analyses or modified intention-to-treat analyses excluding participants with missing outcome data) [20,22,23,24,25,26,27,28,29,30,31]. A study conducted on males of an average age of 40 showed that approximately 170mg of epicatechin per day, dosed at 2mg per kg of bodyweight, resulted in almost a 50% increase in follistatin and a 16.6% decrease in myostatin, alongside a strength increase of 7%. Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., et al. The predominant constituents of green tea are polyphenols belonging to the family of catechins, mainly ()-epigalocatechin gallate (EGCG), with lesser amounts of catechin (C), epicatechin (EC), epigalocatechin (EGC) and epicatechin gallate (ECG). [37] revealed that an acute ingestion of pure EC (75 mg) together with methylxanthines (MX; 91.7% theobromine, 8.3% caffeine) increased the bioavailability of EC by 22% (AUC04h) and also the plasma concentrations of EC metabolites after 1 and 2 h compared to the administration of EC without MX. The methods used to measure the outcomes were always appropriate and no methodological differences were reported within a study between the treatments [20,22,23,24,25,26,27,28,29,31] or groups [25,30]. Results of the risk of bias assessment according to the revised Cochrane risk of bias 2 tool for randomized trials [21]. 8600 Rockville Pike We suggest trying it for four weeks at a minimum or taking it on an ongoing basis for best results. (23 6 y, mean SD [27]), which detected an increase in FMD. In other words, epicatechin supplementation offers bodybuilders the potential for better muscle pumps and endurance even when they are not training. the contents by NLM or the National Institutes of Health. In a further RCT of Greenberg et al. h [24]; 2 h value [23,24]; after 1 h and 4 h, analytical details not provided [26]), and in 5 h urine [23]. Mind to muscle focus was in tact. Gutirrez-Salmen et al. Before were judged with low risk (Figure 2). At each time point (wk 0, 6, 12) skin color was measured before and 24 h after irradiation. Kicks in quick and get the pumps as expected from the nitrate but for me the best thing is the other 2 ingredients. Most RCTs were crossover studies [20,22,23,24,26,27,28,29,31], and only two studies had a parallel group design [25,30]. However, 2 h after this acute-on-chronic intake, FMD, EID, as well as NOx concentration in plasma remained unchanged (all p 0.05). EC enrichment did not modulate FMD (after 1 h and 4 h, both p 0.05), SBP and DBP (after 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, and 4 h; all p 0.05), or plasma nitrite concentrations (after 1 h and 4 h, both p 0.05). [31]. 5 (A, C) showed the spatial maps of the substrates underwent conformational changed before and after entering the active hydrophobic pocket of PPO (Fig. -Epicatechin ((+)-Epi) and metabolite profile curves. It has been shown to improve body composition, resulting in a leaner, more toned physique. 3-DG, 3-deoxyglucosone; AGEs, advanced glycation end products; AIx75, augmentation index corrected for a heart rate of 75 bpm; BMI, body mass index; C, control; CEL, N()-(1-carboxyethyl)lysine; CML, N()-(carboxymethyl)lysine; CRP, c-reactive protein; DBP, diastolic blood pressure; EC, ()-epicatechin; ECG, electrocardiogram; EID, endothelium-independent dilatation; ET-1, endothelin-1; f, female; FM, fat mass; FMD, flow-mediated dilatation; FPG, fasting plasma glucose; GFR, glomerular filtration rate; GO, glyoxal; HDL-C, high-density lipoprotein cholesterol; HOMA-, homeostatic model assessment of beta cell function; HOMA-IR, homeostatic model assessment of insulin resistance; hsCRP, high sensitive c-reactive protein; I, intervention; IL-1, interleukin-1beta; IL-6, interleukin-6; IL-8, interleukin-8; LDL-C, low-density lipoprotein cholesterol; m, male; MCP-1, monocyte chemotactic protein-1; MG-H1, N()-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine; MGO, methylglyoxal; NOx, species derived from nitric oxide; oxLDL, oxidized low-density lipoprotein; PWV, pulse wave velocity; RCT, randomized controlled trial; SAA, serum amyloid A; SBP, systolic blood pressure; sE-selectin, soluble endothelial selectin; SEVR, subendocardial viability ratio; sICAM-1, soluble intercellular adhesion molecule-1; sVCAM-1, soluble vascular adhesion molecule-1; TC, total cholesterol; TGs, triglycerides; TNF-, tumor necrosis factor alpha; vWf, von Willebrand factor; WHR, waist-to-hip ratio. [27] also examined the effects of pure EC intake on the FMD in healthy young men (n = 20, age: 23 6 y, BMI: 23.2 6.8 kg/m2; means SDs) after an overnight fast. Vascular metabolites (endothelin-1 (ET-1), S-nitrosothiols (SNO), nitrite) were assessed in plasma and urine. Three wheat cultivars (Boolani, Roushan and Fornota) were inoculated with Puccinia triticina strain 140 and placed in greenhouse and concentrations of catechin, epicatechin and their enantiomers were monitored in three steps; healthy leaves before and after exposed and also diseased leaves after exposed. 1 except for plasma ()-epicatechin concentration, 2 sample size estimation for flow-mediated dilatation, 3 sample size estimation for other treatments not relevant for the present review, 4 sample size estimation for triglycerides, 5 sample size estimation for systolic blood pressure, 6 results on nitric oxide only published for baseline and 2 h values, 7 AUCs for appetite sensations not mentioned, 8 systolic and diastolic blood pressure and species derived from nitric oxide not mentioned, 9 results on some biomarkers not mentioned in registration, e.g., advanced glycation end products and endothelin-1; some registered biomarkers not published, e.g., asymmetric dimethyl arginine, 10 data on flow-mediated dilatation not available due to methodological difficulties (personal communication). Healthy non-smokers with impaired endothelial function (peak FMD: Hypertriglyceridemic (age: 1855 y, TGs: 5.213.0 mmol/L) without pharmacologic treatment or with a stable dose of statins 6 wk prior to screening, Overweight or obese (BMI: 25 kg/m) non-smokers at cardiovascular risk (SBP 130 or DBP 85 mmHg, and FPG > 5.55 mmol/L or fasting TGs > 1.69 mmol/L or TC > 5.2 mmol/L), Details on the investigation of outcome markers, Details on statistical analysis described, Outcomes reported according to registration. independently assessed the RoB of the included studies by applying the revised Cochrane Risk of Bias 2 (RoB 2) tool for randomized trials [21]. 1 number of participants completing the study (number of participants included), 2 baseline characteristics are expressed as means SDs or medians [IQRs]. U.S. Department of Agriculture (USDA) USDA Database for the Flavonoid Content of Selected Foods. The STANDS4 Network. [28] and Kirch et al. A number of large-scale epidemiological studies have demonstrated an association between the consumption of these foods and cognitive function, as well as improved blood flow. The .gov means its official. The effect of an EC intake on parameters of cardiometabolic health was estimated by a narrative synthesis based on the results from individual studies with respect to the target population, the type and content of intervention, the type of outcome, and the treatment effect. If information about study registration was missing, bias in selection of the reported result (D5) was always assessed with some concerns [22,23,26,30]. As bodybuilders we sometimes overlook the importance of health, but without good health it is of course impossible to optimise ones fitness levels. [30] investigated high sensitive CRP (hsCRP), but the treatment effect could not be calculated, as data on the correlation coefficient were not available. by using a self-made Excel template: study design, details on intervention (amount, duration, and application of EC) and of the control/placebo treatment, participants (sample size, dropout rate, demographics, criteria of eligibility), sample size estimation, statistical analysis, and country in which the study had been performed. 38. Healthy men and women of older age (60 8 y, mean SD) with impaired endothelial function (FMD 5.4 1.2%, mean SD) ingested an EC-enriched drink (200 mg EC + 1 g maltodextrin, 200 mL water) and an EC-free control (1 g maltodextrin, 200 mL water) 2 h after a standardized breakfast. [28] examined the effects of a regular EC intake (100 mg/d for 4 wk) in healthy men and women, aged 66 8 y (mean SD), compared to placebo. Epicatechin is a bioactive compound famously found in dark chocolate. Criteria on studies quality to assess the risk of bias. 5 treatment effect was calculated using r = 0.508 for SBP and r = 0.539 for DBP [20]; 6 treatment effect was calculated considering r = 0.840 for glucose and r = 0.393 for insulin; not possible for fructosamine as r was not available [20], 7 treatment effect was calculated using r = 0.780 for TGs, r = 0.825 for TC, r = 0.852 for LDL-C, r = 0.881 for HDL-C, r = 0.783 for TG/HDL-C, r = 0.875 for non-HDL-C [20]; 8 hsCRP was determined, but the treatment effect could not be calculated as r was not available [20]. It works by increasing follistatin levels, in turn inhibiting the actions of myostatin in the body to remove the brakes on muscle growth. and transmitted securely. Details on the antioxidative status in plasma and/or urine were assessed in several acute studies [23,24,26,27], in the acute-on-chronic trial [28], and in long-term interventions [20,28]. No effects were observed at other time points of the investigation (0.5 mg kg/BW: 1 h, 4 h, 6 h; 1.0 mg kg/BW: 4 h, 6 h; all p 0.05) or after an intake of 0.1 mg EC/kg BW (1 h, 2 h, 4 h, 6 h; all p 0.05). Furthermore, only Dower et al. [20] did not find any changes; on the other hand, this remains open for Gutirrez-Salmen et al. In all long-term studies, EC intake modulated neither BW [20,28,29,31] (BW not measured [30]) nor FM and fat distribution [20]. However, three of them present the results on different outcomes obtained from a single study [28,29,31]. Any discrepancies in the selection process were discussed until a consensus was reached. Second, it should be noted that the subjects of both acute studies without effects on FMD were much older (62 9 y [24], 60 8 y [26]; means SDs) than those of Schroeter et al. A recently published RCT of Sansone et al. HHS Vulnerability Disclosure, Help In this series of articles we want to focus our attention on some of the innovative ingredients out there that have been shown to deliver significant improvements in performance or body composition. 150-152 The mechanism proposed by Mehta and Whalley 153 (Scheme 7) proceeding through ionization of the 4-hydroxy group and B-ring quinone methide intermediates (96) and (97) via a reversible Michael addition is supported by the . The judgements are shown in Figure 2. In a recent study, 44 epicatechin was directly compared with its analog epigallocatechin gallate (EGCG) and a also in their active forms (phosphorylated AMPK and LKB1) as a 0.25% concentration in drinking water administered to 20-month-old male C57BL mice fed standard . Parker B.A., Ridout S.J., Proctor D.N. This is surprising, as growing evidence exists that cocoa-rich foods improve the parameters of cardiovascular health [2,3,4,5,6,7] and EC is discussed as a functional ingredient of cocoa. Changes in further vascular parameters were not observed. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The results of the studies appear to be valid whether or not effects were observed. HPLC analysis of epicatechin in the pericarp extracts of the fruit at 0 d (G) and 8 d (H), with an epicatechin standard (F) as reference. Correspondingly, the RoB in measurement (D4) was judged as low for all outcomes [20,22,23,24,25,26,27,28,29,30,31]. I wouldn't run this any shorter than 6 weeks at least. Most trials were robust RCTs, which are considered as a gold standard for effectiveness research, and which imply blinding, concealment of allocation, intention-to-treat analysis, and a sufficiently large sample size [41]. Treatment with statins was only allowed if using a stable dose for at least 6 wk prior screening. Was there anything in particular that resonated with you (or riled you)? Release 3.2 (November 2015) [(accessed on 4 July 2022)]; Ottaviani J.I., Momma T.Y., Heiss C., Kwik-Uribe C., Schroeter H., Keen C.L. Myostatin inhibition - the secret to amazing muscle gain. Additionally, beneficial effects on serum lipids are possible, as EC can modulate the expression of transcription factors involved in triglyceride and cholesterol synthesis; EC may activate 5-AMP-activated protein kinase, which stimulates the catabolism of lipids and glucose. It can be used for as long as you like and should be taken on an ongoing basis for best results. Records were excluded for the following reasons: (1) no human intervention study (e.g., in vitro or animal study, review); (2) intervention with other flavonoids than EC (e.g., (+)-epicatechin, quercetin) or providing additional flavonoids or compounds beyond EC (e.g., by cocoa, dark chocolate, or green tea) unless these were also part of the control treatment; (3) EC not administered orally; (4) study without randomized controlled design; (5) no parameters of cardiometabolic outcomes (e.g., gene expression profiles); (6) subjects in particular life conditions (e.g., pregnancy) or suffering from severe diseases (e.g., cancer), or using medications which might favor cardiometabolic disorders (e.g., glucocorticoids, antiretroviral therapy).
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