RedCon1 – Citrus Bergamot Part I

RedCon1 – Citrus Bergamot Part I

Citrus Bergamot probably isn’t a very well known or discussed compound/supplement that I have to credit the great Dante Trudel for introducing me to. Citrus bergamot falls under the “health supplement category” and for very good reason. This extract  grows along the Ionic coast of Southern  Calabria, Italy and aids in supporting healthy cholesterol levels, lower inflammatory markers, glucose metabolism, and is a very potent anti-oxidant. I feel its main use for a bodybuilder is its effects on cholesterol levels and its ability to increase high-density lipoproteins (HDLs also known as the “good” cholesterol”) while lowering low-density lipoproteins (LDLs also known as the “bad” cholesterol”.)

Our first bit of literature pertains to bergamot’s ability to reduce plasma lipids. This was a 6 month prospective study from Toth et al that had 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. 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). 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 (1.)

Risitano et al comes in with the literature supporting its ability to reduce LPS-induced inflammatory responses through SIRT1-mediated NF-κB Inhibition in THP-1 Monocytes (3.) They stated “Plant polyphenols exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory genes. Recently, Citrus bergamia has been studied as a natural source of bioactive molecules with antioxidant activity, but few studies have focused on molecular mechanisms underlying their potential beneficial effects. Several findings have suggested that polyphenols could influence cellular function by acting as activators of SIRT1, a nuclear histone deacetylase, involved in the inhibition of NF-κB signaling. On the basis of these observations we studied the anti-inflammatory effects produced by the flavonoid fraction of the bergamot juice (BJe) in a model of LPS-stimulated THP-1 cell line, focusing on SIRT1-mediated NF-κB inhibition. We demonstrated that BJe inhibited both gene expression and secretion of LPS-induced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) by a mechanism involving the inhibition of NF-κB activation. In addition, we showed that BJe treatment reversed the LPS-enhanced acetylation of p65 in THP-1 cells. Interestingly, increasing concentrations of Sirtinol were able to suppress the inhibitory effect of BJe via p65 acetylation, underscoring that NF-κB–mediated inflammatory cytokine production may be directly linked to SIRT1 activity. These results suggest that BJe may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process.” Along the same thought process of its ability to reduce inflammation, Mollace and colleagues researched deeper into the protective effect of bergamot oil extract on lecitine-like oxyLDL receptor-1 expression in balloon injury-related neointima formation. This study evaluates the effect of the nonvolatile fraction (NVF), the antioxidant component of bergamot essential oil (BEO), on LOX-1 expression and free radical generation in a model of rat angioplasty. Common carotid arteries injured by balloon angioplasty were removed after 14 days for histopathological, biochemical, and immunohistochemical studies. Balloon injury led to a significant restenosis with SMC proliferation and neointima formation, accompanied by increased expression of LOX-1 receptor, malondialdehyde and superoxide formation, and nitrotyrosine staining. Pretreatment of rats with BEO-NVF reduced the neointima proliferation together with free radical formation and LOX-1 expression in a dose-dependent manner. These results suggest that natural antioxidants may be relevant in the treatment of vascular disorders in which proliferation of SMCs and oxyLDL-related endothelial cell dysfunction are involved (4.)

References

1. Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study. Toth, P. P., Patti, A. M., Nikolic, D., Giglio, R. V., Castellino, G., Biancucci, T., … Rizzo, M. (2015).  Frontiers in Pharmacology. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702027/)
2. Intraplantar injection of bergamot essential oil induces peripheral antinociception mediated by opioid mechanism. Tsukasa Sakurada, Hirokazu Mizoguchi, Hikari Kuwahata, Soh Katsuyama, Takaaki Komatsu, Luigi Antonio Morrone, Maria Tiziana Corasaniti, Giacinto Bagetta, Shinobu Sakurada. Pharmacol Biochem Behav. 2011 (https://www.ncbi.nlm.nih.gov/pubmed/20932858)
3. Flavonoid Fraction of Bergamot Juice Reduces LPS-Induced Inflammatory Response through SIRT1-Mediated NF-κB Inhibition in THP-1 Monocytes. Risitano, R., Currò, M., Cirmi, S., Ferlazzo, N., Campiglia, P., Caccamo, D., … Navarra, M. (2014).  PLoS ONE, 9(9), e107431. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178028/)
4. The protective effect of bergamot oil extract on lecitine-like oxyLDL receptor-1 expression in balloon injury-related neointima formation. Vincenzo Mollace, Salvatore Ragusa, Iolanda Sacco, Carolina Muscoli, Francesca Sculco, Valeria Visalli, Ernesto Palma, Saverio Muscoli, Luigi Mondello, Paola Dugo, Domenicantonio Rotiroti, Francesco Romeo. J Cardiovasc Pharmacol Ther. 2008 (https://www.ncbi.nlm.nih.gov/pubmed/18413898)
5. Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies. Vincenzo Mollace, Iolanda Sacco, Elzbieta Janda, Claudio Malara, Domenica Ventrice, Carmen Colica, Valeria Visalli, Saverio Muscoli, Salvatore Ragusa, Carolina Muscoli, et al. Fitoterapia. 2011 (https://www.ncbi.nlm.nih.gov/pubmed/21056640)
6. Bergamot Polyphenolic Fraction Enhances Rosuvastatin-Induced Effect on LDL-cholesterol, LOX-1 Expression and Protein Kinase B Phosphorylation in Patients With Hyperlipidemia. Micaela Gliozzi 1 , Ross Walker , Saverio Muscoli , Cristiana Vitale , Santo Gratteri , Cristina Carresi , Vincenzo Musolino , Vanessa Russo , Elzbieta Janda , Salvatore Ragusa , Antonio Aloe , Ernesto Palma , Carolina Muscoli , Franco Romeo , Vincenzo Mollace. Research Centre for Food Safety & Health 2013. (https://www.ncbi.nlm.nih.gov/labs/articles/24239156/)