Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study

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.

Efficacy of bergamot: From anti‐inflammatory and anti‐oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations

“…Treatment should involve at least an oral dose of 150 mg/day of flavonoids (Bergamot-derived extract) for 6 months (Toth et al, 2015) or an oral dose of bergamot polyphenolic fraction (BPF) from 500 to 1000 mg/day for 30/60 days (Bruno, Pandolfo, Crucitti, Cacciola, et al, 2017;Gliozzi et al, 2013;Mollace et al, 2011;Toth et al, 2015) for a reduction of body weight or decrease in total cholesterol, triglycerides, LDL and an increase of HDL. Studies in animals confirm these encouraging results, but only in animals kept on a high fat diet.…”

“…Studies suggest a cardio-protective effect of a single daily dose for 6 months of BE (150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin, and 37% of naringin) (Toth et al, 2015) in subjects with hypercholesterolemia with a reduction of total cholesterol (p < 0.0001), triglycerides (p = 0.002), and LDL cholesterol (<0.0001), while HDL cholesterol increased (p = 0.0007).…”

“…Although native to South-East Asia, 80% of bergamot is produced in Calabria, southern Italy, where it grows extensively. The main preparations used are bergamot extracts (BE), with high content of flavonoids, such as neoeriocitrin, neohesperidin, naringin (Toth et al, 2015), bergamot polyphenolic fraction (BPF) (Bruno, Pandolfo, Crucitti, Maisano, Zoccali, et al, 2017), bergamot essential oil (BEO) (Watanabe et al, 2015), and aromasticks with bergamot/sandalwood or frankincense/mandarin/lavender (Dyer, Cleary, McNeill, Ragsdale-Lowe, & Osland, 2016) bergamot/vetivert/geranium (Wiebe, 1998), bergamot/lavender/cedarwood (Graham, Browne, Cox, & Graham, 2003) and bergamot juice (BJ) (Impellizzeri et al, 2015), bergamot/boxthorn extract (Shao, 2003) or bergamot essential oil plus other citrus essential oils plus grapefruit juice (Li, Zhu, Han, & Zhang, 2016) or bergamot flavonoids and other phytoextracts (Babish et al, 2016;Saiyudthong & Marsden, 2011). Bergamot essential oil (BEO) and bergamot juice (BJ) contain up to 93-96% of volatile compounds, such as monoterpenes (25-53% of limonene), as well as discrete quantities of linalool (2-20%) and linalyl acetate (15-40%).…”

Anti-infective potential ofCitrus bergamiaRisso et Poiteau (bergamot) derivatives: a systematic review

“…Over the last decade, some researchers have started to investigate the biological properties of bergamot derivatives, obtaining important scientific achievements. For example, recently, BEO has been evaluated for its potential neuroprotective (Corasaniti et al, 2007) and antiproliferative effects (Celia et al, 2013;Navarra et al, 2015b), while BJ has been suggested as antioxidant (Ferlazzo et al, 2015;Ferlazzo et al, 2016a), antiinflammatory (Risitano et al, 2014;Impellizzeri et al, 2015;Currò et al, 2016), anticancer (Delle Monache et al, 2013;Navarra et al, 2014;Visalli et al, 2014;Ferlazzo et al, 2016b) and hypolipidemic drug (Mollace et al, 2011;Toth et al, 2016).…”

Effectiveness of Citrus Fruits on Helicobacter pylori

“…Over the years, bergamot juice (BJ) has been considered a byproduct of BEO industry; however, within the last decade, it has gained attention by the scientific community due to its potential health effects. Indeed, very recently, its antioxidant [42, 43], anti-inflammatory [18, 44–47], anticancer [29–31, 48], and antihyperlipidemic effects [49, 50] have been reported. What is left of bergamot fruit after the extraction of BEO and its squeezing is called bergamot pastazzo to which we previously characterized the flavonoids and pectins content [7].…”