Published Clinical Trials

Characterization of Flavonoids in Citrus bergamia (Bergamot) Polyphenolic Fraction by Liquid Chromatography-High Resolution Mass Spectrometry (LC/HRMS)

 

Raffaele SalernoaFrancesca CasaleaCarla CalandruccioaAntonio Procopiob, , 

a Institute of Research for Food Safety & Health (IRC-FSH), University “Magna Graecia” of Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy, b Department of Health Sciences, University “Magna Graecia” of Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy. “The role of Bergamot derived Polyphenolic Fraction (BPF) in Disease States,” PharmaNutrition, Volume 4, Supplement, October 2016, Pages S1–S7.

Source: http://dx.doi.org/10.1016/j.phanu.2015.10.001

Clinical Trial Objective:


Bergamot (Citrus Bergamia Risso et Poiteau) belongs to the family of Rutaceae, genus Citrus, and native to the Calabrian region in Italy. Bergamot juice is a natural antioxidant rich in polyphenols and flavonoids. Flavonoids work at the intestine and liver levels to stimulate fat excretion and reduce fat absorption, and regulates several metabolic enzymes in the liver, blood, and endothelial cells involved in the regulation of carbohydrate and lipid metabolism. The purpose of this study was to identify the flavonoids present in bergamot polyphenolic fraction (BPF) and to develop a UHPLC-HRMS/MS method for identification of flavonoids present in BPF.

Results of Clinical Trial:


The main polyphenol components of BPF are flavonoids and their composition is nearly identical to bergamot juice. BPF contains over 40% flavonoids and the remaining 60% are carbohydrates, fatty acids, and pectins. Individual flavonoids present in BPF were found to regulate several metabolic enzymes, expressed in the liver, blood and endothelial cells. The mass spectrometry data revealed the presence of principal flavonoids neoeriocitrin, naringin, neohesperidin. In addition, other flavonoids in the HMG family include bruteridin, melitidin with other HMG species and flavonoids 6,8-di-C-glicosides.


 

Molecular mechanisms of lipid-and glucose-lowering activities of bergamot flavonoids

 

Elzbieta Jandaab, , Antonella LascalaabConcetta MartinoabSalvatore RagusabSaverio Nuceraa,bRoss WalkeracSanto GratteriaVincenzo Mollaceab

a Institute of Research for Food Safety & Health (IRC-FSH), Campus Germaneto, Catanzaro, Italy, b Health Sciences Department, University “Magna Graecia”, Campus Germaneto, Catanzaro, Italy, c Sydney Adventist Hospital, Sydney, Australia, May 2016.

Source:  http://dx.doi.org/10.1016/j.phanu.2016.05.001

Clinical Trial Objective:


To review the scientific evidence that demonstrates how flavonoids and specifically citrus flavonoids found in bergamot, influence lipid and sugar metabolism at a molecular level, and to study the additional nutraceutical benefits of bergamot polyphenol flavonoids.

Results of Clinical Trial:


Bergamot juice has a high concentration of unique flavonoids (neoeriocitrin, neohesperidin, naringin, melitidin and brutieridin represent more than 95% of Bergamot Polyphenol Fraction). Bergamot polyphenols activate AMP kinase (AMPK), a central regulator of glucose, fatty acids, lipid metabolism, and energy production in several organs. Citrus bergamot polyphenols exert numerous benefits including the regulation of fat, cholesterol, and carbohydrate metabolism. It is comparable to low-dose synthetic drugs (i.e. statins), with no side effects, representing a viable alternative to conventional drugs. Findings from the report state, “Bergamot BPF has a potential to become a “one pill” natural therapy against metabolic syndrome and dyslipidemias.” [1]


 

Studies on the Protective Role of Bergamot Polyphenols in Doxorubicin-induced Cardiotoxicity

 

Cristina Carresia, , Micaela GliozziaCaterina GiancottaaAntonino ScarcellaaFederica Scaranoa, Francesca BoscoaRocco MollaceaAnnamaria TaverneseaCristiana VitaleaVincenzo Musolinoa

a Interregional Research Centre for Food Safety & Health (IRC-FSH), University “Magna Graecia” of Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy, November 2015.  

Source: http://dx.doi.org/10.1016/j.phanu.2015.11.005

Clinical Trial Objective:


To identify the heart-protective properties of polyphenols, and to understand how the protective qualities of natural antioxidants such as Bergamot Polyphenolic Fraction counteract the side effects of Doxorubicin (DOXO), a widely used drug for preventing the growth of cancers and treating malignant tumors. Even though DOXO is one of the most successful antineoplastic drugs, there are serious side effects and risks. The use of DOXO is limited, especially in children with cancer, due to the development of severe and chronic cardiotoxicity leading to cardiomyopathy and congestive heart failure. Evidence suggests polyphenols, and specifically flavonoids such as bergamot with high anti-oxidant and anti-inflammatory qualities, play a protective role in preventing cardiovascular diseases.

[1] “Molecular mechanisms of lipid-and glucose-lowering activities of bergamot flavonoids,” Elzbieta Janda, Antonella Lascala, Concetta Martino, Salvatore Ragusa, Saverio Nucera, Ross Walker, Santo Gratteri, Vincenzo Mollace,  PharmaNutrition, May 2016, http://dx.doi.org/10.1016/j.phanu.2016.05.001.

Results of Clinical Trial:


Scientific and medical studies have shown that a diet rich in plant foods containing flavonoids, the most common and the most studied group of polyphenols, protects against degenerative diseases such as cancer and cardiovascular diseases. Significant experimental evidence suggests natural antioxidants protect the heart from DOXO toxicity. In light of this evidence, it is crucial to continue investigating alternative approaches to prevent degenerative diseases and cardiovascular diseases, and improve the safety and side effects for cancer treatment while maintaining the anticancer properties of the drug.


 

The Effect of Bergamot Polyphenolic Fraction in Patients with Non-alcoholic Liver Steato-hepatitis and Metabolic Syndrome

 

Micaela GliozziJessica MaiuoloFrancesca OppedisanoVincenzo Mollace

Institute of Research for Food Safety & Health (IRC-FSH), University “Magna Graecia” of Catanzaro, Catanzaro, Italy, PharmaNutrition, Volume 4, Supplement, October 2016, Pages S27–S31.

Source: http://dx.doi.org/10.1016/j.phanu.2015.11.003

Clinical Trial Objective:


To identify the heart-protective properties of polyphenols, and to understand how the protective qualities of natural antioxidants such as Bergamot Polyphenolic Fraction counteract the side effects of Doxorubicin (DOXO), a widely used drug for preventing the growth of cancers and treating malignant tumors. Even though DOXO is one of the most successful antineoplastic drugs, there are serious side effects and risks. The use of DOXO is limited, especially in children with cancer, due to the development of severe and chronic cardiotoxicity leading to cardiomyopathy and congestive heart failure. Evidence suggests polyphenols, and specifically flavonoids such as bergamot with high anti-oxidant and anti-inflammatory qualities, play a protective role in preventing cardiovascular diseases.

Results of Clinical Trial:


Bergamot Polyphenolic Fraction improved both the blood sugar and excessive blood fat (hyperlipemia) in patients with metabolic syndrome and non-alcoholic fatty liver disease. In addition, evidence showed that BPF produced an increase in HDL and a significant a reduction in LDL in patients with metabolic syndrome and non-alcoholic fatty liver disease.


 

Bergamot Polyphenolic Fraction Counteracts Photoageing in Human Keratinocytes

 

Steven Paul Nisticòa, , Ugo BottoniaMicaela GliozziabJames EhrlichcMassimo Finid

a Department of Health Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy, b Institute of Research for Food Safety & Health, University “Magna Graecia” of Catanzaro, Catanzaro, Italy, c University of Colorado, Denver, CO, USA, d IRCCS San Raffaele Pisana, Rome, Italy, December 2015.

Source: http://dx.doi.org/10.1016/j.phanu.2015.11.004

Clinical Trial Objective:


Scientific and medical studies have shown a direct relationship between ultraviolet radiation and the development of skin cancers. Overexposure to UV radiation can lead to a significant reduction in antioxidant supply to the skin, which leads to inflammation and accelerated oxidative damage. Over the past several decades there has been increase in exposure to radiation, especially UV-B, resulting in significant occurrences of photoageing and the skin carcinoma. The purpose of this study was to understand the anti-aging and immune modulating responses of Bergamot Polyphenolic Fraction (BPF). Bergamot Polyphenolic Fraction (38% BPF) is a highly concentrated flavonoid extracted from the citrus bergamot fruit.

Results of Clinical Trial:


BPF was shown to inhibit UVB effects, mediate decreases in cell viability, inflammatory cytokine biomarker interleukin-1beta (IL-1β), and telomere shortening. Telomere/Telomerase activity is closely linked to cellular health, cancer, and aging.  Aging proliferates as the telomere shortens. The study shows that BPF (38%) protects cells against UVB oxidative stress and photoageing, and potentially against skin related carcinomas.


 

The Protective Role of Bergamot Polyphenolic Fraction on Several Animal Models of Pain

 

Filomena LauroaSara IlariaLuigino Antonio GiancottiaChiara MorabitobValentina MalafogliacMicaela GliozzidErnesto PalmadDaniela SalveminieCarolina Muscolid, , 

a IRCCS San Raffaele, Roccelletta di Borgia, 88021, Catanzaro, Italy, b Department of Experimental Medicine, University of Rome, “Sapienza”, Italy, c Institute for Research on Pain, ISAL-Foundation, Torre Pedrera (RN) Italy, d Institute of Research for Food Safety & Health (IRC-FSH), Department of Health Sciences, University, “Magna Graecia” of Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy, e Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, USA. “The role of Bergamot derived Polyphenolic Fraction (BPF) in Disease States,”PharmaNutrition, Volume 4, Supplement, October 2016, Pages S35–S40.

Source: http://dx.doi.org/10.1016/j.phanu.2016.04.001

Clinical Trial Objective:


In the last 20 years considerable evidence demonstrated the role of oxidative stress in the development and maintenance of hyperalgesia, a condition that causes increased sensitivity to pain or enhanced intensity of pain. Millions of people suffer from chronic pain as a result of nervous system diseases. Treatment is often steroidal anti-inflammatory drugs (SAID), nonsteroidal anti-inflammatory drugs (NSAIDs), and pain medications such as opioids to effectively manage the acute states of diseases. When opiates are used to control long term chronic pain, opiate-induced hyperalgesia can result.

A considerable amount of research and studies have demonstrated the role of oxidative stress in the development of hyperalgesia and suggest the protective role of natural compounds in reducing the biochemical and molecular alterations associated with pain. This study evaluated the effect of Bergamot Polyphenolic Fraction (BPF), a rich and highly concentrated polyphenol, can relieve pain.

Results of Clinical Trial:


This study identified a new property of natural antioxidants derived from Citrus bergamia Risso in reducing pain, and evidence of the protective, anti-inflammatory properties of bergamot polyphenolic fraction. Data in this and other studies, has demonstrated that natural antioxidant fractions exert a protective role during several types of pain in animal models. The pain-relieving therapeutic properties of bergamot extracts is an encouraging, new therapeutic intervention for the management of pain, and represents a promising and innovative approach to counteract the side effects of prolonged use of drugs such as opioids, or to inhibit inflammatory pain.


 

Bergamot Polyphenolic Fraction Counteracts Erectile Dysfunction Occurring in Patients Suffering From Type 2 Diabetes

 

Vincenzo Mollacea, b, , Natalia Malaraa, Santo Gratteria, Ernesto Palmaa, Luca Zappiaa, Nicola Costaa, Giuseppe Rosanoa, b, , Sara Paonea

aInstitute of Research for Food Safety & Health (IRC-FSH), University “Magna Graecia” of Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy; bConsortium NutraMed S.C.A.R.L., Catanzaro, Italy, March 2016.

Source: http://dx.doi.org/10.1016/j.phanu.2015.11.006

Clinical Trial Objective:


Erectile Dysfuntion, commonly known as ED, is the impairment of sexual performance that effects 20–40% of men between 60–69 years old. According to a Massachusetts Male Aging Study, men with diabetes have three times the likelihood of having ED[1].

Men with cardiovascular risk factors or those diagnosed with metabolic syndrome also suffer from ED.  This is caused by damaged endothelial cell functionality and changes to metabolism of testosterone in the liver. Erectile dysfunction (ED) is a complex disease and several studies over the past few decades support the use of medicinal plant extracts as an alternative “natural” approach in the treatment of sexual dysfunction both in men and in woman. This study summarizes the recent advances for treating ED in diabetic patients using bergamot polyphenolic fraction (BPF 47%), a natural antioxidant known to lower serum lipids and glucose. The study also examined the effect of BPF alone and in combination with the natural products Tribulus Terrestris and Epimedium extract in treating ED.

Results of Clinical Trial:


Damage to endothelial cell functionality and changes to the metabolism of testosterone in the liver are significantly improved by regular administration of highly concentrated bergamot-derived polyphenolic fraction (BPF) at 47%, a natural antioxidant proven to counteract endothelial dysfunction. When BPF 47% is combined with natural plant extracts Tribulus Terrestris and Epimedium, it restores testosterone levels. Bergamot extract used alone, or in combination with natural plant extracts Tribulus Terrestris and Epimedium to restore testosterone levels, is proven to be effective in treating ED by contributing to better blood vessel protection in patients with heart disease and metabolic disorders such as diabetes.

After 30 days of BPF treatment with (500 and 1000 mg/daily for 30 consecutive days), flow-mediated vasodilation increased significantly, and there were no changes in patients who received a placebo. This suggests that BPF improved the damaged endothelium-mediated vasodilation in patients with hyperlipidemia (also referred to as lipidemia) which is an elevated concentration of lipids in the blood. High levels of lipids, or fat, in the blood produce high cholesterol and high triglycerides contributing to heart disease.

Based on these results, the study then examined the effect of 650 mg twice a day of 47% BPF for 120 consecutive days in 40 diabetic patients with mild to severe ED. The treatment with BPF

47% (650 mg twice a day for 120 consecutive days) significantly improved ED based on several assessments including results of IIEF score and by measuring peak systolic velocity (PSV) in penile artery by means of Doppler analysis. The clinical study confirmed that after 120 day treatment the highly concentrated polyphenolic extract of bergamot (BPF 47%) clearly enhanced arterial blood flow in penile arteries and improvement of endothelial function was also found to contribute to restoring a satisfactory sexual function in diabetic patients. No relevant side effects were described throughout or at the end of the study.

The positive effect of BPF 47% in patients with ED is highlighted when combined with natural products claimed to improve sexual performances in diabetics as well as in non-diabetic subjects suffering from ED. Evidence shows that Bulgarian Tribulus extract enhances testosterone levels in patients with ED, and some components of epimedium extract are proven to inhibit 5-PDE enzyme in a way similar to Sildenafil (VIAGRA_like effect). Therefore, these effects in combination with improved endothelial performance produced by BPF 47%, effectively work together to counteract ED in patients with metabolic syndrome and diabetes.

[1] H.A. Feldman, I. Goldstein, D.G. Hatzichristou, R.J. Krane, J.B. McKinlay, “Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study,” Journal of Urology, 151 (1994), pp. 54-61.


 

Citrus Bergamot Improves Atherogenic Lipoprotein Particle Characteristics in Patients with Non-alcoholic Fatty Liver Disease and Metabolic Syndrome J. Clinical Lipidology. May-June 2015.

 

James E. Ehrlich, MD, Michaela Gliozzi, PhD, Elzbieta Janda, PhD, Ross Walker, MD, Vincenzo Mollace, MD, PhD

Journal of Clinical Lipidology, May–June, 2015, Volume 9, Issue 3, Pages 473–474.

Source: http://dx.doi.org/10.1016/j.jacl.2015.03.099

Clinical Trial Objective:


BPF is a highly concentrated extract of the bergamot citrus fruit indigenous to Calabria, Italy, and has been shown to be a powerful anti-oxidant. The purpose of this study was to determine if Bergamot Polyphenolic Fraction (BPF) could significantly improve cholesterol levels and lipoprotein size, density, and number in patients with Metabolic Syndrome and Non-alcoholic Fatty Liver Disease.

Results of Clinical Trial:


In the study of 107 patients confirmed to have non-alcoholic fatty liver disease and metabolic syndrome, Bergamot Polyphenolic Fraction (BPF) significantly improved all standard measures of cholesterol concentration.  A “natural statin” (HMG-CoA reductase activity) and an inhibitor of sterol absorption in the gut, it demonstrates significant lipid lowering in patients with dyslipidemia , a condition caused by a high level of lipids (cholesterol, triglycerides, or both) carried by lipoproteins in the blood. It also addresses all factors associated with metabolic syndrome. 


 

The Hepatic Effects of Citrus Bergamot Polyphenolic Fraction (BPF) on Patients with Non-alcoholic Fatty Liver Disease and Metabolic Syndrome

 

James Ehrlich, Michaela Gliozzi, Elzbieta Janda, Ross Walker, Vincenzo Mollace

Journal of Clinical Lipidology, Vol. 9, Issue 3, p462–463, May 2015.

Source: DOI: http://dx.doi.org/10.1016/j.jacl.2015.03.084

Clinical Trial Objective:


A highly concentrated extract of Bergamot, a citrus fruit endemic to Calabria, Italy has been shown to be a “natural statin” that is beneficial in patients with dyslipidemia while addressing all the components of metabolic syndrome. There are no approved drugs or adequate treatment for non-alcoholic fatty liver disease (NAFLD), a disorder considered the “hepatic manifestation” of metabolic syndrome.

The purpose of this study was to determine whether bergamot polyphenolic fraction (BPF), a proprietary extract from a unique antioxidant rich citrus fruit (bergamot), could significantly improve hepatic structure and function in patients with both metabolic syndrome and non-alcoholic fatty liver disease (NAFLD).

Results of Clinical Trial:


There were 107 patients who met the NCEP-ATP III criteria for metabolic syndrome and had ultrasonic evidence of severe NAFLD (hepato-renal index 2.5-3.5) after exclusion of alcohol, viral, and immune disorders, and were admitted to the study. Before and after 120 days of BPF 650 mg twice/day, all patients had full lipid analysis including lipoprotein fractionation (NMR), fasting glucose, ALT, AST, steato test, γ-GT, TNF-α (ELISA), CRP and ultrasonographic hepatorenal tests.

Bergamot polyphenolic extract (BPF) is a potent anti-oxidant, AMP kinase activator and HMG-CoA reductase inhibitor that has been proven to address all components of the metabolic syndrome. In the group of 107 patients with confirmed NAFLD and metabolic syndrome, BPF given twice per day before meals significantly improved all measured biochemical and ultrasonographic characteristics of NAFLD in 120 days without reported side effects. There was a striking improvement in hepatic function (biochemical) and structure (echogenic visual loss of hepatic fat) accompanied by lower levels of inflammation. There are no proven therapies for patients with NAFLD and metabolic syndrome, and this study suggests that BPF can be a safe and important treatment.


 

The effect of Bergamot-Derived Polyphenolic Fraction on LDL Small Dense Particles and Non Alcoholic Fatty Liver Disease in Patients with Metabolic Syndrome

 

Micaela GliozziCristina CarresiVincenzo MusolinoErnesto PalmaCarolina MuscoliCristiana VitaleSanto GratteriGiuseppe MuscianisiElzbieta JandaSaverio MuscoliFrancesco RomeoSalvatore RagusaRocco MollaceRoss WalkerJames EhrlichVincenzo Mollace

Advances in Biological Chemistry, April 2014,

Source: DOI: 10.4236/abc.2014.42017   

Clinical Trial Objective:


Metabolic syndrome doubles the risk of developing cardiovascular diseases and increases the risk of developing type 2 diabetes by five times. In addition, recent studies have shown that MS is associated with non-alcoholic fatty liver disease state (NAFLD), one of the most common causes of liver-related deaths worldwide. In this clinical trial of 107 patients at the San Raffaele IRCCS in Rome, the effect of bergamot polyphenolic fraction (BPF) was studied in patients with MS and NAFLD. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days.

Results of Clinical Trial:


In this clinical trial, it was shown that bergamot-deriving polyphenolic fraction (BPF) improved both the elevated levels of blood fat and blood sugar in patients with metabolic syndrome and non-alcoholic fatty liver disease. Patients who received BPF 650 mg twice a day had a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides and an increase of HDL cholesterol (good cholesterol). There was a significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. In addition, results showed a significant reduction of small dense LDL particles (detected by proton NMR Spectroscopy) after being treated with BPF. The data confirms the beneficial effect of bergamot-extract in patients with MS, and suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.

[1] Michael Crane, “Bergamot Polyphenols Tackle Liver Conditions Linked to Metabolic Syndrome,” June 3, 2016, Nutritional Outlook, http://www.nutritionaloutlook.com/science/bergamot-polyphenols-tackle-liver-conditions-linked-metabolic-syndrome


 

Bergamot Polyphenolic Fraction Enhances Rosuvastatine-Induced Effect on LDL-Cholesterol, LOX-1 Expression and Protein Kinase B Phosphorylation in Patients with Hyperlipidemia

 

Gliozzi M1Walker RMuscoli SVitale CGratteri SCarresi CMusolino VRusso VJanda ERagusa SAloe APalma EMuscoli CRomeo FMollace V.

International Journal of Cardiology, December 2013, Volume 170, Issue 2, pp. 140—145,

Source: DOI:  10.1016/j.ijcard.2013.08.125

Clinical Trial Objective:


For people at risk of cardiovascular disease and metabolic syndrome, statins are the most commonly prescribed drug to reduce cardiometabolic risk. Although statins are the most widely used treatment for prevention and treatment for this disorder, statins have serious side effects in some patients.

In this clinical trial, the use of bergamot-derived polyphenolic fraction (BPF) was studied for its effect on rosuvastatin-induced hypolipidemic (low level of blood sugar) and ability to protect blood vessels in patients with mixed hyperlipidemia (high levels fat in the blood). The study involved 77 patients with elevated serum LDL-C and triglycerides. The control group received placebo. Patients were randomly assigned to a control group receiving placebo (n=15).

Results of Clinical Trial:


Two groups received rosuvastatin (10 and 20mg/daily for 30 days; n=16 for each group), a

One group received BPF alone (1000 mg/daily for 30 days; n=15)

One group received BPF (1000 mg/daily given orally) plus rosuvastatin (10mg/daily for 30 days; n=15)

 

The study showed that the combination of BPF with rosuvastatin significantly improved the rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone (both doses of rosuvastatin and BPF reduced total cholesterol, LDL-C, the LDL-C/HDL-C ratio in hyperlipidemic patients compared to the control group). The lower-lipid result was associated with significant reductions of biomarkers used for detecting oxidative vascular damage, suggesting the multi-benefit improvements of BPF in patients on statin therapy.


 

Telomere and Telomerase Modulation by Bergamot Polyphenolic Fraction in Experimental Photoageing in Human Keratinocytes

S.Nisticò, J. Ehrlich, M. Gliozzi, J. Maiuolo, E. Del Duca,C. Muscoli,V. Mollace

Istituto San Raffaele Pisana - Journal of Biological Regulators and Homeostatic Agents, Volume 29, Issue 3, pp. 723-728, September 2015.

Clinical Trial Objective:


Photoaging is premature aging of the skin caused by repeated exposure to ultraviolet radiation (UV) from the sun, as well as from artificial UV radiation. Ultraviolet radiation is the cause of most age-associated changes in skin appearance. Epidemiological and experimental data show a direct relationship between ultraviolet radiation and the development of human skin cancers.

Extensive research has been conducted involving botanical phytochemicals  and flavonoids with antioxidant and/or anti-inflammatory properties to examine their skin photoprotective properties.  Clinical and animal studies have shown that bergamot polyphenol fraction (38% BPF) has powerful antioxidant and anti-inflammatory activity.

This study examined the effect of 38% BPF, a highly concentrated extract of the bergamot fruit (Citrus bergamia) on UVB-induced photoaging by examining cytokine (protein secreted by lymph cells that affects cellular activity and controls inflammation) inflammation, changes in telomere length/telomerase, and cellular viability in human immortalized HaCaT keratinocytes (the predominant cell type in the epidermis, the outermost layer of the skin, consisting of 90% of the cells).

Results of Clinical Trial:


Results from the study suggest that bergamot polyphenol fraction (38% BPF) protects HaCaT cells against UVB-induced oxidative stress and markers of photoageing when given in a dose-dependent manner. The antioxidant properties of BPF, a highly concentrated extract of the bergamot fruit, appears to change basic cellular signal transduction pathways, leading to anti-aging and immune modulating reactions.

Due to the alarming increase of skin cancer and dermatological conditions related to excessive exposure to solar ultraviolet (UV) radiation, bergamot polyphenol fraction may also be a useful supplement in skin care products.


 

Mechanisms Underlying the Anti-Tumoral Effects of Citrus bergamia Juice

 

Simona Delle Monache1, Patrizia Sanità, Elena Trapasso, Maria Rita Ursino, Paola Dugo, Marina Russo, Nadia Ferlazzo, Gioacchino Calapai, Adriano Angelucci, Michele Navarra 

PLoS One. April 16, 2013; 8 (4):e 61484.

Source:  DOI: 10.1371/journal.pone.0061484

Clinical Trial Objective:


Citrus Bergamia Risso & Poiteau, is cultivated almost exclusively along the southern coast of the Calabria region in Italy where the particular environmental conditions are favorable for its cultivation. Bergamot juice is obtained from the endocarp of the fruit, which was previously considered just a secondary and discarded product. The primary flavonoids in bergamot juice are flavanones and flavones.

Several studies have analyzed the chemical composition of bergamot juice for its elevated flavonoids content and health benefits. The goal of this study was to continue building upon the growing evidence of the biological activity and the antitumor potential of natural products rich in flavonoids. Specifically, this study sought to explore in vitro the potential anti-tumoral activity of Citrus Bergamia (bergamot) juice to determine its molecular interaction with cancer cells.

Results of Clinical Trial:


Flavonoids inhibiting cancer cell formation has been demonstrated both in vitro and in vivo. Bergamot juice reduced the growth rate of different cancer cell lines, with the maximal growth restriction was observed in neuroblastoma cells after 72 hours of exposure to 5% Bergamot juice (SH-SY5Y). Neuroblastoma is a cancer that develops from immature nerve cells that occurs most often in infants and young children.  Bergamot (Citrus Bergamia) juice has a particularly high content and a unique composition of flavonoids. Neoeriocitrin, neohesperidin, naringin, melitidin and brutieridin represent more than 95% of Bergamot Polyphenol Fraction (BPF), andrhoifolin, diosmin, poncirin and others can be found in the remaining 5%.

Citrus flavonoids change the cell cycle by stopping or slowing progression. In addition, several flavonoids have demonstrated radical-scavenging and anti-inflammatory activities. The qualitative data confirm those previously reported and confirmed that bergomot juice is rich in flavonoids. Flavanone glycosides brutieridin and melitidin are the primary components considered to be responsible for lipid-lowering activity. This data suggests methods in which bergamot juice can inhibit important molecular pathways related to cancer-associated aggressive phenotype. Long-term use of Bergamot juice created a significant reduction in serum cholesterol, triglycerides and low-density lipoprotein (LDL) levels as well as an increase in high-density lipoprotein (HDL) levels in vivo. It is also important to note that flavonoids do not present any toxicological risk.


 

Hypolipemic and Hypoglycaemic Activity of Bergamot Polyphenols: From Animal Models to Human Studies

 

Mollace V1Sacco IJanda EMalara CVentrice DColica CVisalli VMuscoli SRagusa SMuscoli CRotiroti DRomeo F.

Fitoterapia, April 2011, Volume 82, Issue 3, pp. 309-16.

Source: DOI: 10.1016/j.fitote.2010.10.014

Clinical Trial Objective:


The purpose of this study was to evaluate the potential effect of Bergamot Polyphenol Fraction (BPF) in patients suffering from Hypolipemic and Hypoglycaemic conditions. The clinical trial investigated the effect of bergamot extract (BPF) in diet-induced hyperlipemia in Wistar rats and in 237 patients suffering from hyperlipemia either associated or not with hyperglycaemia.

Results of Clinical Trial:


Bergamot Polyphenol Fraction (BPF) was given orally to both rats and to patients for 30 days, BPF reduces total and LDL cholesterol levels (an effect accompanied by elevation of cHDL), triglyceride levels and by a significant decrease in blood glucose. In addition, BPF inhibited HMG-CoA reductase activity and improving blood vessel and artery flow, creating an efficient phytotherapeutic method of treating hyperlipemic and hyperglycaemic disorders.


 

The Use of Bergamot Derived Polyphenolic Fraction in Cardiometabolic Risk Prevention and its possible Mechanisms of Action

 

Ross Walker*Elzbieta JandaVincenzo Mollace

* Consultant Cardiologist, Sydney Adventist Hospital, Sydney, Australia, Department of Health Sciences, University “Magna Graecia,” Campus Salvatore Venuta, Germaneto, Catanzaro, Italy, Department of Health Sciences, University “Magna Graecia” of Catanzaro, Complesso Nini’ Barbieri, Roccelletta di Borgia, Catanzaro, Italy. Polyphenols in Human Health and Disease, 2014, Pages 1087–1105, Volume 2: “Polyphenols in the Prevention and Treatment of Vascular and Cardiac Disease, and Cancer.”

Source: http://dx.doi.org/10.1016/B978-0-12-398456-2.00084-0

Clinical Trial Objective:


Bergamot (Citrus bergamia Risso et Poiteau) fruits are characterized by a unique and particularly high concentration of flavonoids including neoeriocitrin, neohesperidin, naringin, melitidin and brutieridin. Bergamot Polyphenol Fraction (BPF) is a concentrate of bergamot juice that is rich in polyphenols. This study analyzed the protective and preventative qualities of BPF to counteract cardiovascular risk.

Results of Clinical Trial:


Experimental and clinical studies done in Italy and Australia showed that patients treated with BPF create a significant reduction in lipid parameters in the blood of patients with hyperlipidemia ranging from 15 up to 40% for total cholesterol and cholesterol-LDL. In addition, there was a significant reduction (mean 41.0±2.6%) in plasma triglyceride levels, as well as blood glucose (22.3±1.0%) in a subgroup of patients with metabolic syndrome.

BPF is an excellent alternative for statin-intolerant patients and for those with low risk. For patients with a high risk of cardiovascular disease, BPF can be taken with statins to offer significant resilience against cardiometabolic risk factors. “The robust performance of BPF in clinical practice against cardiometabolic risk factors can be explained in the light of scientific evidence showing that bergamot flavonoids influence lipid and sugar metabolism acting as 3-hydroxy-3-methlglutaryl coenzyme A (HMG-CoA) reductase inhibitors and AMP kinase (AMPK) activators.[1]


 

Use of a Novel and Natural Antioxidant Compound (Bergamot) in the Management of Statine Intolerance

 

S.Muscoli,D. DellaRocca, M. Macrini, V. Cammalleri, A. Viele, G.A. Volpe, D. Sergi, G.P. Ussia, F. Romeo

European Heart Journal, August 2013.

Source: DOI: http://dx.doi.org/10.1093/eurheartj/eht308.P2539 P2539

Clinical Trial Objective:


Statins are widely prescribed for the positive effects they have on cardiovascular heart disease, stroke and vascular disease due to their ability to lower lipoprotein (LDL), however many patients are statin-intolerant due to serious side effects. For these patients, and those who prefer a natural approach to reduce their risk cardiovascular diseases, polyphenols, specifically flavonoids, represent an alternative due to their anti-oxidative and anti-inflammatory proprieties.

The purpose of this study was to evaluate the therapeutic qualities of bergamot polyphenol fraction (BPF) in a group of 38 patients with statin intolerance. The control group consisted of 35 statin intolerant patients. During the course of a six month follow-up, the effects of BPF were evaluated for their effect on total cholesterol (tchol), cLDL, HDL cholesterol (cHDL), triglycerides

Results of Clinical Trial:


Bergamot fruits have the highest content of flavonoids of any citrus fruit. The primary flavones are Bruteridin and Melitidin which have a 3-hydroxy-3-methylglutaryl moiety and a similar structure  to the natural substance HMG-CoA reductase. This causes it to exhibit statin like proprieties. BPF was administered over 6 months (1500 mg/day) and led to a 14.4 + 1.3% reduction in total cholesterol, a 26.0 + 1.4% reduction in LDL cholesterol, and a 10 + 1.5% increase in HDL cholesterol,  compared to the control group. There was also a significant reduction (mean 30.0+2.6%) in plasma triglyceride levels as well as a significant decrease in glucose levels (22.3+1.0%).

The study concluded BPF is a natural antioxidant compound that exhibits statin-like properties. Therefore it may provide a unique therapeutic approach to reduce cholesterol in patients who are statin intolerant, in addition to being a safe strategy to manage hyperglycemic disorders.

[1] “The Use of Bergamot-Derived Polyphenol Fraction in Cardiometabolic Risk Prevention and its Possible Mechanisms of Action,” ResearchGate, https://www.researchgate.net/publication/285181343_The_Use_of_Bergamot-Derived_Polyphenol_Fraction_in_Cardiometabolic_Risk_Prevention_and_its_Possible_Mechanisms_of_Action