BACKGROUND AND AIM: Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH. METHODS: In a cross-sectional study we analysed endothelial function, as assessed by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx), in patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we performed a randomized, cross-over study in 19 subjects with NASH comparing the effect of 14-days administration of 40 g of chocolate at high (dark chocolate, cocoa >85%) versus low content (milk chocolate, cocoa <35%) of polyphenols on FMD and oxidative stress. Compared to controls, NASH and FLD patients had higher Nox2 activity and isoprostanes levels and lower FMD and NOx, with a significant gradient between FLD and NASH. The interventional study showed that, compared to baseline, FMD and NOx increased (from 2.9 ± 2.4 to 7.2 ± 3.0% p < 0.001 and from 15.9 ± 3.6 to 20.6 ± 4.9 μM, p < 0.001, respectively) in subjects given dark but not in those given milk chocolate. A simple linear regression analysis showed that Δ (expressed by difference of values between before and after 14 days of chocolate assumption) of FMD was associated with Δ of Nox2 activity (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs: 0.557; p < 0.001). CONCLUSIONS: Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients.

Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis / Loffredo, L.; Baratta, F.; Ludovica, P.; Battaglia, S.; Carnevale, R.; Nocella, C.; Novo, M.; Pannitteri, G.; Ceci, F.; Angelico, F.; Violi, F.; Del Ben, M.. - In: NMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES. - ISSN 0939-4753. - STAMPA. - 28:2(2018), pp. 143-149. [10.1016/j.numecd.2017.10.027]

Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis

Loffredo, L.
;
Baratta, F.;Battaglia, S.;Carnevale, R.;Nocella, C.;Novo, M.;Pannitteri, G.;Ceci, F.;Angelico, F.;Violi, F.;Del Ben, M.
2018

Abstract

BACKGROUND AND AIM: Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH. METHODS: In a cross-sectional study we analysed endothelial function, as assessed by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx), in patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we performed a randomized, cross-over study in 19 subjects with NASH comparing the effect of 14-days administration of 40 g of chocolate at high (dark chocolate, cocoa >85%) versus low content (milk chocolate, cocoa <35%) of polyphenols on FMD and oxidative stress. Compared to controls, NASH and FLD patients had higher Nox2 activity and isoprostanes levels and lower FMD and NOx, with a significant gradient between FLD and NASH. The interventional study showed that, compared to baseline, FMD and NOx increased (from 2.9 ± 2.4 to 7.2 ± 3.0% p < 0.001 and from 15.9 ± 3.6 to 20.6 ± 4.9 μM, p < 0.001, respectively) in subjects given dark but not in those given milk chocolate. A simple linear regression analysis showed that Δ (expressed by difference of values between before and after 14 days of chocolate assumption) of FMD was associated with Δ of Nox2 activity (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs: 0.557; p < 0.001). CONCLUSIONS: Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients.
2018
cocoa; endothelial function; nicotinamide adenine dinucleotide phosphate oxidase; non-alcoholic steatohepatitis; oxidative stress; polyphenols; medicine (miscellaneous); endocrinology, diabetes and metabolism; nutrition and dietetics; cardiology and cardiovascular medicine
01 Pubblicazione su rivista::01a Articolo in rivista
Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis / Loffredo, L.; Baratta, F.; Ludovica, P.; Battaglia, S.; Carnevale, R.; Nocella, C.; Novo, M.; Pannitteri, G.; Ceci, F.; Angelico, F.; Violi, F.; Del Ben, M.. - In: NMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES. - ISSN 0939-4753. - STAMPA. - 28:2(2018), pp. 143-149. [10.1016/j.numecd.2017.10.027]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1079336
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