Abstract
Background: Some patients experience statin-induced side effects or prefer nutraceutical approaches for the treatment of dyslipidemia. This has led to a search for alternative therapeutic approaches for dyslipidemia management. In recent studies Citrus bergamia (known as Bergamot) juice was able to reduce serum levels of lipids. Such benefit may be attributed to high amounts of flavonoids contained in Bergamot fruit juice (neoeriocitrin, neohesperidin, naringin). The aim of the present study was to fully investigate the effects of a Bergamot extract on cardio-metabolic parameters, including plasma lipids, atherogenic lipoproteins and subclinical atherosclerosis.Methods: Eighty subjects (42 men and 38 women, mean age: 55 ± 13 years) with moderate hypercholesterolemia [e.g., with plasma LDL-cholesterol concentrations between 160 and 190 mg/dl (between 4.1 and 4.9 mmol/l)] were included. A Bergamot-derived extract (Bergavit R®) was given at a fixed dose daily (150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin and 37% of naringin) for 6 months. Lipoprotein subfractions were assessed by gel electrophoresis. With this methodology low density lipoprotein (LDL) subclasses are distributed as seven bands (LDL-1 and -2 as large LDL, and LDL-3 to -7 as atherogenic small, dense LDL). Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT) using B-mode ultrasound.Results: After 6 months, Bergavit R® reduced total cholesterol (from 6.6 ± 0.4 to 5.8 ± 1.1 mmol/l, p < 0.0001), triglycerides (from 1.8 ± 0.6 to 1.5 ± 0.9 mmol/l, p = 0.0020), and LDL-cholesterol (from 4.6 ± 0.2 to 3.7 ± 1.0 mmol/l, p < 0.0001), while HDL- cholesterol increased (from 1.3 ± 0.2 to 1.4 ± 0.4 mmol/l, p < 0.0007). In addition, a significant increase in LDL-1 (from 41.2 ± 0.2 to 49.6 ± 0.2%, p < 0.0001) was accompanied by decreased small, dense LDL-3, -4, and 5 particles (from 14.5 ± 0.1 to 9.0 ± 0.1% p < 0.0001; 3.2 ± 0.1 to 1.5 ± 0.1% p = 0.0053; 0.3 ± 0.0% to 0.1 ± 0.0% p = 0.0133, respectively). cIMT also decreased from 1.2 ± 0.4 to 0.9 ± 0.1 mm (p < 0.0001).Conclusion: This is the first study investigating the effects of Bergamot flavonoids supplementation on cardio-metabolic risk in dyslipidemic subjects. Bergavit R® (Bergamot juice extract) supplementation significantly reduced plasma lipids and improved the lipoprotein profile. cIMT was also reduced significantly over a relatively short time frame of 6 months.
Highlights
Statins are the most commonly used class of drugs [3-hydroxy3-methylglutaryl Co-enzyme A (HMG-CoA) reductase inhibitors] to lower serum cholesterol levels, with favorable effects on both plasma lipids and lipoproteins (Rizzo and Berneis, 2006a,b; Rizzo et al, 2007; Nikolic et al, 2013; Garcia-Rios et al, 2014)
Bergamot is the common name of the fruit Citrus bergamia Risso which differs from other Citrus fruits in the composition and content of several distinct flavonoids, such as neoeriocitrin, neohesperidin, naringin (Dugo et al, 2005; Nogata et al, 2006)
In addition, large, medium, and small IDL significantly increased after 6 months of Bergavit R supplementation, with the greatest increase in larger IDL-C subclasses, while no significant differences were found for very low-density lipoproteins (VLDL) particles
Summary
Statins are the most commonly used class of drugs [3-hydroxy3-methylglutaryl Co-enzyme A (HMG-CoA) reductase inhibitors] to lower serum cholesterol levels, with favorable effects on both plasma lipids and lipoproteins (Rizzo and Berneis, 2006a,b; Rizzo et al, 2007; Nikolic et al, 2013; Garcia-Rios et al, 2014). Despite several advances in the pharmacological strategies for maintaining lipid homeostasis, some treated patients do not reach their LDL-C goal and remain at increased CV risk (Alagona and Ahmad, 2015), while others experience intolerance especially at high doses of statins (i.e., myopathy, rhabdomyolysis, hepatotoxicity, growth retardation in pediatric population; Banach et al, 2015a,b) In such situations certain alternative therapeutic approaches including the use of dietary supplements and nutraceuticals may be prudent (Patti et al, 2015). A number of supplements for dyslipidemia are available in the market with beneficial effects on plasma lipids, their impact on CV risk remains largely unknown (Mannarino et al, 2014) In this context, several studies have demonstrated multiple health-related properties of the Citrus flavonoids on CV protection (Benavente-Garcia and Castillo, 2008). The aim of the present study was to fully investigate the effects of a Bergamot extract on cardio-metabolic parameters, including plasma lipids, atherogenic lipoproteins and subclinical atherosclerosis
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