Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial

Most, Jasper; Timmers, Silvie; Warnke, Ines; Jocken, Johan W. E.; Boekschoten, Mark V.; Groot, Philip de; Bendik, Igor; Schrauwen, Patrick; Goossens, Gijs H.; Blaak, Ellen E.

doi:10.3945/ajcn.115.122937

Cited by 90 publications

(82 citation statements)

References 52 publications

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“…Participant characteristics Ninety-four overweight and obese white men and women were included in the present study (age 19-69 years; BMI >25 kg/m 2 ). These individuals participated in two larger clinical trials designed to primarily investigate the effects of antibiotics [7] and polyphenol supplementation [19] on insulin sensitivity in humans (Clinicaltrials.gov registration nos. NCT02241421 and NCT02381145, respectively).…”

Section: Methodsmentioning

confidence: 99%

“…Being commonly used as inflammatory markers in the context of obesity [20], insulin resistance [21] and hepatic inflammation [16], plasma TNF-α, IL-6 and IL-8 were measured. In addition to the measurements performed in the previous studies [7,19], for this study, we measured plasma CTSD levels and activity. Plasma samples were diluted and CTSD levels were determined by the CTSD ELISA, according to the manufacturer's protocol (USCN Life Science, Wuhan, China).…”

Section: Methodsmentioning

confidence: 99%

“…For the present study, we calculated that 52 individuals would be needed to demonstrate a significant association between CTSD activity and hepatic insulin sensitivity with a power of 80% (α = 0.05, β = 0.8, effect size f 2 = 0.20). Since we included 94 overweight and obese white men and women that had previously participated in two larger clinical trials [7,19], this study was well powered.…”

Section: Statistical Analysis Statistical Analysis Was Performed By Umentioning

confidence: 99%

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Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

et al. 2019

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Aims/hypothesis Insulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic-euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions. Recently, evidence emerged that plasma cathepsin D (CTSD) is associated with insulin sensitivity and hepatic inflammation. Here, we aimed to investigate whether plasma CTSD is associated with hepatic and/or peripheral insulin sensitivity in humans. Methods As part of two large clinical trials (one designed to investigate the effects of antibiotics, and the other to investigate polyphenol supplementation, on insulin sensitivity), 94 overweight and obese adults (BMI 25-35 kg/m 2 ) previously underwent a two-step hyperinsulinaemic-euglycaemic clamp (using [6,6-2 H 2 ]glucose) to assess hepatic and peripheral insulin sensitivity (per cent suppression of endogenous glucose output during the low-insulin-infusion step, and the rate of glucose disappearance during highinsulin infusion [40 mU/(m 2 × min)], respectively). In this secondary analysis, plasma CTSD levels, CTSD activity and plasma inflammatory cytokines were measured. Results Plasma CTSD levels were positively associated with the proinflammatory cytokines IL-8 and TNF-α (IL-8: standardised β = 0.495, p < 0.001; TNF-α: standardised β = 0.264, p = 0.012). Plasma CTSD activity was negatively associated with hepatic insulin sensitivity (standardised β = −0.206, p = 0.043), independent of age, sex, BMI and waist circumference, but it was not associated with peripheral insulin sensitivity. However, plasma IL-8 and TNF-α were not significantly correlated with hepatic insulin sensitivity. Conclusions/interpretationWe demonstrate that plasma CTSD activity, but not systemic inflammation, is inversely related to hepatic insulin sensitivity, suggesting that plasma CTSD activity may be used as a non-invasive marker for hepatic insulin sensitivity in humans.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Statistical Analysis Statistical Analysis Was Performed By Umentioning

confidence: 99%

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Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

et al. 2019

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“…Indeed, although most data remains in vitro or from animal models, resveratrol (150 mg/ day) has been found to improve mitochondrial function in the skeletal muscle after 30 days administration in obese, but otherwise healthy men (Timmers et al 2011). While a 3-day supplementation of a combination of both resveratrol (150 mg) and epigallocatechin-3-gallate (EGCG) (300 mg) can increase both fasting and postprandial energy expenditure at rest in obese humans (Most et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Acute Resveratrol Administration Increases Neural Effort but Not Whole Body Metabolism or Cognitive Performance in Healthy, Young Participants

et al. 2019

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Research into the cognitive enhancing effects of polyphenols is small but growing. Single doses of the stilbene polyphenol resveratrol can increase cerebral blood flow (CBF) but have failed to improve cognitive performance in young, healthy cohorts. As both CBF and overall energy expenditure are closely related to neural activity, this randomised, double-blind, placebocontrolled, crossover investigation, assessed the metabolic consequences of resveratrol during high cognitive demand via indirect calorimetry (ICa). Twenty-seven, self-reported healthy participants (15 male, 12 female; mean age = 22) who reported themselves free of any food intolerances and any herbal supplementation or prescription medications were recruited for the current study. Participants arrived at the testing facility at 8 a.m. on three separate occasions to complete a serial subtraction demand battery 45 min and 2 and 3 h following administration with 500 mg, 250 mg trans-resveratrol or inert placebo, while connected to an online gas analysis system. A series of within-subjects ANOVAs (with planned comparisons) revealed a significant shift towards higher carbohydrate oxidisation during cognitive demand, as indexed by a significant increase in respiratory exchange ratio (RER) at 45-min and 3-h time points, following administration of 500 mg resveratrol. Despite this, no subsequent resveratrol-related benefits to cognitive performance were observed. These results show that acute supplementation with resveratrol in young, healthy adults can modulate fuel utilization during cognitive demand, yet this does not translate into clear improvements in cognitive performance. This study adds further understanding behind the lack of cognitive effects of resveratrol in young and or healthy individuals. Future research should direct efforts towards assessing the cognitive impact of resveratrol, and other vasoactive polyphenols, in populations with age-related or dietary-induced metabolic deficits.

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“…A number of studies have demonstrated several mechanisms associated with the ameliorative effect of epigallocatechin gallate on IR and associated complications in skeletal muscle. In addition to strengthening muscle integrity [92][93][94], accumulative data has been presented that this catechin can improve insulin sensitivity by enhancing glucose uptake, reduce lactate concentrations, enhancing mitochondrial capacity and stimulating beta-oxidation in cultured cells, or rodents as well as obese human subjects [95][96][97][98][99][100]. Inhibition of oxidative stress, activation of AMPK, increased expression of PGC-1α, NAD-dependent protein deacetylase sirtuin-1 (SIRT1), nuclear respiratory factor 1, medium chain acyl coA decarboxylase, uncoupling protein 3 (UCP3), AKT, and peroxisome proliferator-activated receptor alpha (PPARα) are some of the mechanisms targeted by epigallocatechin to enhance skeletal muscle function in a diseased state [101-104].…”

Section: Epigallocatechin Gallatementioning

confidence: 99%

Skeletal Muscle as a Therapeutic Target for Natural Products to Reverse Metabolic Syndrome

Mazibuko-Mbeje¹,

Dludla²,

Nkambule³

et al. 2018

Muscle Cell and Tissue - Current Status of Research Field

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Natural compounds, especially polyphenols have become a popular area of research mainly due to their apparent health benefits. Increasing the phenolic content of a diet, apart from its antioxidant benefit, has a beneficial effect on signaling molecules involved in carbohydrate and lipid metabolism. These effects could potentially protect against metabolic syndrome, a cluster of metabolic complications such as obesity, insulin resistance and type 2 diabetes that is characterized by a dysregulated carbohydrate, and lipid metabolism. Research continues to investigate various natural compounds for their amelioration of impaired signaling mechanisms that may lead to dysregulated metabolism to find means to improve the life expectancy of patients with metabolic syndrome. In this chapter, a systematic search through major databases such as MEDLINE/PubMed, EMBASE, and Google Scholar of literature reporting on the ameliorative potential of commonly investigated natural products that target skeletal muscle to ameliorate metabolic syndrome associated complications was conducted. The selected natural products that are discussed include apigenin, aspalathin, berberine, curcumin, epigallocatechin gallate, hesperidin, luteolin, naringenin, quercetin, resveratrol, rutin, and sulforaphane.compounds of plant origin have long been shown to possess strong ameliorative properties against various communicable and noncommunicable diseases [1,2]. For example, since its traditional use during the 1950s, artemisinin, an antimalarial qinghao derived lactone, has been the leading therapy for the treatment of Plasmodium falciparum malaria worldwide [3]. Similarly, the traditional use of galegine, an alkaloid isolated from Galega officinalis, led to the discovery of biguanide class of antidiabetic medications such as metformin [4]. Agents such as metformin are effective at lowering blood glucose levels and combating complications associated with insulin resistance (IR), the major characteristic of the metabolic syndrome [5]. However, the continued rise in the mortality of diabetic patients warrants an investigation into alternative therapies to reduce the burden of noncommunicable diseases. Naturally derived compounds such as polyphenols are increasingly explored for their therapeutic potential to reverse IR and thus decrease the risk of developing the metabolic syndrome. This may eventually lead to an increased life expectancy of diabetic individuals [6]. Thus, due to its modulatory effect of glucose and lipid metabolism, skeletal muscle has been a target to a growing number of therapeutic interventions in an effort to reverse IR and improve the management of metabolic syndrome [7,8]. Here, we systematically assessed the available literature on the ameliorative potential of some of the prominent natural products against IR associated complications. A systematic search was conducted on all major databases such as MEDLINE/ PubMed, EMBASE, and Google Scholar, for available literature reporting on the ameliorative properties of some of the promi...

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Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial

Cited by 90 publications

References 52 publications

Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

Acute Resveratrol Administration Increases Neural Effort but Not Whole Body Metabolism or Cognitive Performance in Healthy, Young Participants

Skeletal Muscle as a Therapeutic Target for Natural Products to Reverse Metabolic Syndrome

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