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Effects of Monomeric and Oligomeric Flavanols on Kidney Function, Inflammation and Oxidative Stress in Runners: A Randomized Double-Blind Pilot Study.

ABSTRACT: Nonsteroidal anti-inflammatory drugs are frequently used by athletes in order to prevent musculoskeletal pain and improve performance. In combination with strenuous exercise, they can contribute to a reduction of renal blood flow and promote development of kidney damage. We aimed to investigate whether monomeric and oligomeric flavanols (MOF) could reduce the severity of kidney injuries associated with the intake of 400-mg ibuprofen followed by the completion of a half-marathon in recreational athletes. In this double-blind, randomized study, the original MOF blend of extracts from grape seeds (Vitis vinifera L.) and pine bark (Pinus pinaster L.) or placebo were taken for 14 days preceding the ibuprofen/half-marathon. Urine samples were collected before and after the ibuprofen/half-marathon, and biomarkers of kidney injury, inflammation and oxidative stress were assessed. Intake of MOF significantly reduced the incidence of post-race hematuria (p = 0.0004) and lowered concentrations of interleukin (IL)-6 in the urine (p = 0.032). Urinary neutrophil-associated lipocalin, creatine, albumin, IL-8 and malondialdehyde tended to decrease. The supplementation with MOF in recreational runners appears to safely preserve kidney function, reduce inflammation and promote antioxidant defense during strenuous exercise and intake of a single dose of ibuprofen.

SUBMITTER: Semen KO

PROVIDER: S-EPMC7353060 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Effects of Monomeric and Oligomeric Flavanols on Kidney Function, Inflammation and Oxidative Stress in Runners: A Randomized Double-Blind Pilot Study.

Semen Khrystyna O KO Weseler Antje R AR Janssen Marcel J W MJW Drittij-Reijnders Marie-José MJ le Noble Jos L M L JLML Bast Aalt A

Nutrients 20200601 6

Nonsteroidal anti-inflammatory drugs are frequently used by athletes in order to prevent musculoskeletal pain and improve performance. In combination with strenuous exercise, they can contribute to a reduction of renal blood flow and promote development of kidney damage. We aimed to investigate whether monomeric and oligomeric flavanols (MOF) could reduce the severity of kidney injuries associated with the intake of 400-mg ibuprofen followed by the completion of a half-marathon in recreational a ...[more]

PMID: 32492913

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Project description:BackgroundCardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man's deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded.MethodsIn a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets.ResultsIn the MOF group serum total cholesterol and LDL decreased significantly (P ≤ 0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05) in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P ≤ 0.05).ConclusionOur integrative multi-biomarker approach unveiled the pleiotropic vascular health benefit of an 8 weeks supplementation with 200 mg/d MOF in humans.Trial registrationClinicalTrials.gov NCT00742287.

Project description:Background: In a recent intervention study, the daily supplementation with 200mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. Methodology/Principal Findings: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 869 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNFα-stimulated endothelial cells. Nuclear factor-kappa B reporter gene assays confirmed that MOF decrease the activity of NF-κB. Strong inter-individual variability in the leukocytes DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. However, in individuals, significant changes in DNA methylation of genes involved in leukocyte rolling, adhesion and cytoskeleton remodelling were seen. At the group level, the variation in DNA methylation related to life style and clinical parameters appeared to overrule the magnitude of effects of supplementation with MOF. Conclusion: Our study revealed that regular consumption of MOF modulates the expression of genes in immune cells which, however, cannot be correlated to alterations in the DNA methylome. Remarkably, at the individual level, genes related to leukocyte adhesion pathways present complex variation in DNA methylation. As such, the individual transcriptional and epigenetic modulation of genes involved in early manifestation of cardiovascular diseases constitutes important subcellular mechanisms by which MOF promote vascular health in humans.

Project description:Background: In a recent intervention study, the daily supplementation with 200mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. Methodology/Principal Findings: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 869 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNFM-NM-1-stimulated endothelial cells. Nuclear factor-kappa B reporter gene assays confirmed that MOF decrease the activity of NF-M-NM-:B. Strong inter-individual variability in the leukocytes DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. However, in individuals, significant changes in DNA methylation of genes involved in leukocyte rolling, adhesion and cytoskeleton remodelling were seen. At the group level, the variation in DNA methylation related to life style and clinical parameters appeared to overrule the magnitude of effects of supplementation with MOF. Conclusion: Our study revealed that regular consumption of MOF modulates the expression of genes in immune cells which, however, cannot be correlated to alterations in the DNA methylome. Remarkably, at the individual level, genes related to leukocyte adhesion pathways present complex variation in DNA methylation. As such, the individual transcriptional and epigenetic modulation of genes involved in early manifestation of cardiovascular diseases constitutes important subcellular mechanisms by which MOF promote vascular health in humans. Two-colors experiment, 7 volunteers : blood samples of 7 men, before and after an intervention of 8 weeks with daily intake of MOF (14 samples).

Project description:BackgroundSolar ultraviolet (UV) radiation has deleterious effects on the skin, including sunburn, photoaging and cancer. Chocolate flavanols are naturally-occurring antioxidant and anti-inflammatory molecules that could play a role in preventing cutaneous UV damage. We investigated the influence of 12-week high-flavanol chocolate (HFC) consumption on skin sensitivity to UV radiation, measured by minimal erythema dose (MED). We also evaluated skin elasticity and hydration.MethodsIn this 2-group, parallel, double-blind, randomized controlled trial, 74 women aged 20-65 years and Fitzpatrick skin phototypes I or II were recruited from the general community in Quebec City, for randomization to either HFC (n = 33) or low-flavanol chocolate (LFC) (n = 41). A blocked randomisation (4), considering date of entry, skin type and age as factors, generated a sequentially-numbered allocation list. Study participants and research assistants were blinded. Totally, 30 g of chocolate were consumed daily for 12 weeks, followed by a 3-week washout period. MED was assessed at baseline and at 6, 9, 12 and 15 weeks. Main outcome was changes in MED at week 12.Results33 participants in the HFC group and 41 in the LFC group were analyzed with 15 weeks of follow-up. Both groups showed similarly-increased MED at 12 weeks (HFC: 0.0252 ± 0.1099 J/cm2 [mean ± standard deviation (SD)]; LFC: 0.0151 ± 0.1118; mean difference (MD): 0.0100 J/cm2; 95% confidence interval (CI): -0.0417 to 0.0618). However, after 3-week washout, the HFC group presented decreased MED (-0.0248 ± 0.1145) whereas no effect was seen in the LFC group (0.0168 ± 0.1698) (MD: -0.0417; 95% CI: -0.1106 to 0.0272). Net temple elasticity increased slightly but significantly by 0.09 ± 0.12 mm in the HFC group at 12 weeks compared to 0.02 ± 0.12 mm in the LFC group (MD: 0.06; 95% CI: 0.01 to 0.12 ). No significant adverse events were reported.ConclusionOur study failed to demonstrate a statistically-significant protective effect of HFC vs. LFC consumption on skin sensitivity to UV radiation as measured by MED.Trial registrationClinicalTrials.gov identifier: NCT01444625.

Project description:Background and objectivesHemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD.Design, setting, participants, & measurementsWe conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics.ResultsCF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4±0.9% to 3.9±0.8% versus placebo, 3.5±0.7% to 3.5±0.7%; P<0.001), with reduced diastolic BP (73±12 to 69±11 mmHg versus placebo, 70±11 to 73±13 mmHg; P=0.03) and increased heart rate (70±12 to 74±13 bpm versus placebo, 75±15 to 74±13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4±0.9% to 2.7±0.6% versus placebo, 3.5±0.7% to 2.0±0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9±0.9% to 3.0±0.7% versus placebo, 3.5±0.7% to 2.2±0.6; P=0.01).ConclusionsDietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD.

Dataset Information

Effects of Monomeric and Oligomeric Flavanols on Kidney Function, Inflammation and Oxidative Stress in Runners: A Randomized Double-Blind Pilot Study.

Publications

Effects of Monomeric and Oligomeric Flavanols on Kidney Function, Inflammation and Oxidative Stress in Runners: A Randomized Double-Blind Pilot Study.

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