Clinical Studies Library

Explore published human, mechanistic, and preclinical research organized by health application, ingredient variation, study design, and measured outcome.

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11 Published Human Clinical Trials

Hypolipemic and hypoglycaemic activity of bergamot polyphenols: From animal models to human studies

This foundational study investigated Bergamot Polyphenolic Fraction (BPF) across key cardiometabolic markers and helped establish the human research platform for bergamot polyphenols. It also explored mechanisms related to cholesterol metabolism and vascular responsiveness.

What It's About: The effects of BPF on cholesterol, triglycerides, blood glucose, and vascular function in people with different cardiometabolic profiles.
What They Did: 237 participants with isolated or mixed hyperlipidemia, with or without elevated glucose, were studied over 30 days. Groups received placebo or 500 mg or 1,000 mg BPF daily; a separate post-statin group received 1,500 mg daily following a washout period.
What They Found: BPF was associated with lower total cholesterol, LDL-C and triglycerides, higher HDL-C, and lower glucose in participants with metabolic syndrome. The study also reported reduced urinary mevalonate and improved flow-mediated vasodilation.
What It Means: The findings established early human evidence that bergamot polyphenols may influence multiple aspects of cardiometabolic function rather than acting on a single lipid marker alone.

Fitoterapia Volume 82, Issue 3, April 2011, Pages 309-316 Vincenzo Mollace, Iolanda Sacco, Elzbieta Janda, Claudio Malara, Domenica Ventrice, Carmen Colica, Valeria Visalli, Saverio Muscoli, Salvatore Ragusa, Carolina Muscoli, Domenicantonio Rotiroti, Franco Romeo

Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL cholesterol, LOX-1 expression and Protein Kinase B phosphorylation in patients with hyperlipidemia

This 30-day human study examined BPF both alone and alongside rosuvastatin in participants with mixed hyperlipidemia. Researchers evaluated not only the lipid profile, but also mevalonate and biomarkers associated with oxidative vascular stress.

What It's About: Whether BPF could influence lipid markers and vascular oxidative-stress biomarkers on its own and enhance the response observed with rosuvastatin.
What They Did: 77 participants were assigned to placebo, rosuvastatin at 10 or 20 mg/day, BPF at 1,000 mg/day, or BPF 1,000 mg/day plus rosuvastatin 10 mg/day for 30 days.
What They Found: BPF and rosuvastatin reduced total cholesterol, LDL-C, the LDL-C/HDL-C ratio, and urinary mevalonate. Adding BPF to rosuvastatin produced a greater effect on the serum lipid profile than rosuvastatin alone and was associated with reductions in malondialdehyde, LOX-1, and phosphoPKB.
What It Means: The findings show that BPF’s research extends beyond conventional lipid measurements and suggest complementary effects on both cholesterol metabolism and markers of oxidative vascular stress when studied with rosuvastatin.

International Journal of Cardiology November 14, 2013 Micaela Gliozzi, Ross Walker, Saverio Muscoli, Cristiana Vitale, Santo Gratteri, Cristina Carresi, Vincenzo Musolino, Vanessa Russo, Elzbjeta Janda, Salvatore Ragusa, Antonio Aloe, Ernesto Palma, Carolina Muscoli, Franco Romeo and, Vincenzo Mollace

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

This 120-day clinical study examined how BPF influenced both advanced lipoprotein profiles and liver-related markers in people with metabolic syndrome and non-alcoholic fatty liver disease. It provides one of the clearest examples of Bergamonte® research looking beyond standard cholesterol values to the broader cardiometabolic picture.

What It's About: The relationship between BPF supplementation, small dense LDL particles, broader lipid and glucose markers, and liver-related measurements in patients with metabolic syndrome and NAFLD.
What They Did: 107 participants with metabolic syndrome and ultrasound-confirmed NAFLD were enrolled. The active group received 650 mg BPF twice daily for 120 days, with lipids, glucose, liver enzymes, inflammatory markers, ultrasound measures, and lipoprotein subclasses evaluated before and after treatment. The methods note that the BPF capsules also contained oleuropein and ascorbic acid.
What They Found: The study reported lower total cholesterol, LDL-C, triglycerides, fasting glucose, liver enzymes, TNF-α, CRP, and hepatorenal index, along with higher HDL-C. Advanced NMR analysis showed a 35% reduction in small LDL, a 38% increase in large LDL, and a 20% increase in total HDL particles.
What It Means: The findings suggest that the studied BPF-containing regimen influenced both conventional cardiometabolic markers and the quality and distribution of lipoprotein particles, while also improving several liver-related measures. This supports a broader metabolic and liver-health research story beyond standard LDL-C alone.

Advances in Biological Chemistry Jan 2014 Micaela Gliozzi, Cristina Carresi, Vincenzo Musolino, Ernesto Palma, Carolina Muscoli, Cristiana Vitale, Santo Gratteri, Giuseppe Muscianisi, Elzbieta Janda, Saverio Muscoli, Francesco Romeo, Salvatore Ragusa, Rocco Mollace, Ross Walker, James Ehrlich, Vincenzo Mollace

Bergamot polyphenolic fraction counteracts erectile dysfunction occurring in patients suffering from type 2 diabetes

This publication examines the relationship between diabetes, endothelial dysfunction, and erectile function, while reporting clinical findings from a BPF® 47% intervention. The research is particularly relevant to Bergamonte® because it connects vascular responsiveness and endothelial function with a measurable functional outcome.

What It's About: Whether a BPF® 47%-based regimen could influence erectile function, penile blood flow, and endothelial responsiveness in men with type 2 diabetes and mild to severe erectile dysfunction.
What They Did: Forty diabetic patients were studied, with BPF® 47% administered at 650 mg twice daily for 120 days. Researchers evaluated International Index of Erectile Function (IIEF), penile artery peak systolic velocity by Doppler, and endothelial function using EndoPAT measurements. The reported BPF capsules also contained oleuropein and ascorbic acid.
What They Found: IIEF scores improved from 12 ± 4 to 18 ± 3, while penile artery peak systolic velocity increased from 22 ± 6 to 29 ± 5 cm/s. EndoPAT measures of endothelial function also improved after the 120-day intervention.
What It Means: The findings suggest that improvements in endothelial responsiveness and arterial blood flow may help explain the functional changes observed in the studied population. Because the clinical regimen included BPF® with additional ingredients, the outcomes should be presented as results of the studied formulation rather than attributed exclusively to BPF® alone.

PharmaNutrition 4S (2016) S41–S46 Vincenzo Mollacea,b,*, Natalia Malaraa, Santo Gratteria, Ernesto Palmaa, Luca Zappiaa, Nicola Costaa, Giuseppe Rosanoa,b, Sara Paonea

Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation including Citrus bergamia, in subjects with moderate cardiometabolic risk factors

This 12-week observational study evaluated F105, a multi-ingredient phytochemical formulation built around bergamot fruit extract, in adults with moderate cardiometabolic risk factors. It paired human clinical measurements with in vitro antioxidant testing to examine both lipid-related outcomes and oxidative-stress activity.

What It's About: Whether a bergamot-centered botanical formulation could influence dyslipidemia, oxidized LDL, and other cardiometabolic risk markers while demonstrating complementary antioxidant activity.
What They Did: Eleven adults completed a 12-week, open-label, one-arm study taking F105 daily. The formula provided 500 mg bergamot fruit extract standardized to 30% flavonoids plus 220 mg of nine additional phytoextracts; researchers measured lipids, oxLDL, ApoB, PAI-1, HbA1c, insulin-related markers, and safety parameters.
What They Found: Across all participants, significant changes were reported in total cholesterol, LDL-C, non-HDL cholesterol, cholesterol/HDL ratio, and ApoB. In a higher-risk subgroup of eight participants, triglycerides decreased 27%, oxLDL 19%, TG/HDL 27%, oxLDL/HDL 25%, and PAI-1 37%. No treatment-related adverse events were reported.
What It Means: The study shows how bergamot fruit extract can function as the central component of a broader phytochemical formulation targeting multiple cardiometabolic markers. Because F105 contained nine additional botanical extracts, the clinical outcomes should be attributed to the F105 formulation as a whole, not to Bergamonte® alone.

Canadian Journal of Physiology and Pharmacology Volume 94, Number 12, December 2016 John G. Babish, Clinton J. Dahlberg, Joseph J. Ou, William J. Keller, Wei Gao, Mohan R. Kaadige, Holly Brabazon, Joseph Lamb, Hani C. Soudah, Xiaolan Kou, Zhe Zhang, Linda M. Pacioretty, and Matthew L. Tripp

A 13-week low glycemic load diet and lifestyle modification program combining low glycemic load protein shakes and targeted nutraceuticals improved weight loss and cardio-metabolic risk factors

This 13-week randomized exploratory study examined whether adding targeted nutraceuticals, including a bergamot-containing antioxidant formulation, to a low-glycemic diet and lifestyle program could provide additional cardiometabolic benefits in overweight adults with metabolic risk factors.

What It's About: Whether a comprehensive nutraceutical program could enhance the effects of diet, exercise, and behavioral modification on weight, body composition, lipid markers, inflammation, nitric oxide biomarkers, and overall cardiovascular risk.
What They Did: Forty-four participants were randomized to a low-glycemic diet and lifestyle program alone (DIET) or the same program plus protein shakes and multiple targeted nutraceuticals (PROG). The supplement program included phytosterols, fish oil, berberine, probiotics, vitamins/minerals, and CardioxLDL, a formulation containing bergamot fruit extract and other botanical antioxidants.
What They Found: Compared with DIET alone, the PROG group showed greater reductions in body weight, fat mass, total cholesterol, LDL-C, triglycerides, several lipid ratios, ApoB, and hs-CRP. Median body weight decreased 11.9% versus 7.8%, triglycerides 50.8% versus 30.6%, and the PROG group showed a 40% reduction from baseline in estimated 10-year cardiovascular risk.
What It Means: The findings suggest that adding the complete targeted nutraceutical program to diet and lifestyle modification provided additional benefits across multiple cardiometabolic measures. Because the intervention combined numerous supplements, protein shakes, diet, and exercise, the study cannot attribute these outcomes specifically to bergamot or Bergamonte® alone.

Canadian Journal of Physiology and Pharmacology Volume 95, Number 12, December 2017 Clinton J. Dahlberg, Joseph J. Ou, John G. Babish, Joseph J. Lamb, Sarah Eliason, Holly Brabazon, Wei Gao, Mohan R. Kaadige, and Matthew L. Tripp

Effects of 12-week supplementation of Citrus bergamia extracts-based formulation CitriCholess on cholesterol and body weight in older adults with dyslipidemia: a randomized, double-blind, placebo controlled trial

This 12-week randomized, double-blind, placebo-controlled trial evaluated a Citrus bergamia extract-based formulation in older adults with dyslipidemia. The study looked at both lipid metabolism and body-composition measures, including LDL-C, body weight, BMI, and waist circumference.

What It's About: Whether daily supplementation with CitriCholess could influence cholesterol-related markers and weight-management measures in older adults with elevated blood lipids.
What They Did: Ninety-eight participants completed the trial, with 48 receiving CitriCholess and 50 receiving placebo for 12 weeks. The active formulation supplied 500 mg/day of Citrus bergamia extract standardized to 25% bioflavonoids, together with plant sterol esters, orange oil, and vitamins C, B6, B12, and folic acid.
What They Found: After 12 weeks, LDL-C was significantly lower in the CitriCholess group than placebo. The active group also showed significantly greater changes in body weight, BMI, and waist circumference, while between-group differences in total cholesterol and triglycerides did not reach statistical significance.
What It Means: The results provide controlled clinical evidence that the studied bergamot-based formulation may support both lipid metabolism and healthy weight-management measures in older adults. Because CitriCholess contained several additional active ingredients, the outcomes should be attributed to the complete formulation rather than bergamot extract alone.

Lipids in Health & Disease 2017 Dec 22;16(1):251. Yong Cai, Guoqiang Xing, Tian Shen, Shuxian Zhang, Jianyu Rao and Rong

Metabolic outcomes of bergamot polyphenolic fraction administration in patients treated with second-generation antipsychotics: a pilot study

This pilot study explored whether BPF supplementation could influence weight and metabolic parameters in patients receiving second-generation antipsychotics, a medication class commonly associated with weight gain and metabolic complications. The research provides a distinct look at Bergamonte® in a population facing medication-related metabolic challenges.

What It's About: Whether BPF supplementation could help address changes in body weight and cardiometabolic markers associated with long-term second-generation antipsychotic treatment.
What They Did: Fifteen outpatients receiving second-generation antipsychotics took 1,000 mg of BPF daily for 30 days. Researchers evaluated body weight and BMI along with fasting glucose, HbA1c, total cholesterol, HDL-C, LDL-C, and triglycerides.
What They Found: BPF administration was associated with a statistically significant reduction in body weight (P = .004) and a trend toward reduced BMI (P = .005). No significant changes were observed in the measured glucose or lipid parameters during the 30-day study.
What It Means: The findings provide preliminary evidence for a potential role of BPF in weight-management applications, while also showing that the short intervention did not significantly alter the other metabolic markers measured. The small sample size and pilot design make the findings exploratory and support the need for larger, controlled studies.

Journal of Nutritional Biochemistry 40 (2017) 32–35 Antonio Bruno⁎, Gianluca Pandolfo, Manuela Crucitti, Antonino Maisano, Rocco A. Zoccali, Maria Rosaria Anna Muscatello

Bergamot Polyphenolic Fraction Supplementation Improves Cognitive Functioning in Schizophrenia. Data From an 8-Week, Open-Label Pilot Study

This 8-week open-label pilot study explored whether BPF supplementation could influence cognitive and executive functioning in patients with schizophrenia receiving second-generation antipsychotics. The research extends the Bergamonte® evidence base into cognition, with particular attention to executive control and verbal fluency.

What It's About: Whether daily BPF supplementation could support cognitive and executive performance in patients with schizophrenia who were already receiving second-generation antipsychotic treatment.
What They Did: Twenty outpatients received 1,000 mg of BPF daily for 8 weeks. Cognitive performance was evaluated using the Wisconsin Card Sorting Test (WCST), verbal fluency testing, and the Stroop Color-Word Test, alongside psychiatric symptom assessment.
What They Found: At week 8, participants showed significant improvement in WCST perseverative errors and semantic fluency, both with P = 0.004. Improvements were also observed as trends in WCST categories, phonemic fluency, and Stroop performance.
What It Means: The findings provide preliminary evidence that BPF may influence specific aspects of cognitive and executive functioning. Because this was a small, open-label pilot study without a placebo control, the results are exploratory and warrant confirmation in larger, well-controlled clinical trials.

Journal of Clinical Psychopharmacology: August 2017 - Volume 37 - Issue 4 - p 468-471 Antonio Bruno, MD, PhD, Gianluca Pandolfo, MD, PhD, Manuela Crucitti, MD, Clemente Cedro, MD, PhD, Rocco Antonio Zoccali, MD, and Maria Rosaria Anna Muscatello, MD, PhD

Bergamot Polyphenolic Fraction supplementation improves metabolic balance, endothelial function and maximal oxygen uptake in athletes

This controlled crossover study evaluated BPF Gold in trained cyclists, examining whether supplementation could influence nitric oxide availability, endothelial function, cardiometabolic markers, and aerobic performance. The research connects Bergamonte® science directly with vascular function and sports-nutrition applications.

What It's About: Whether BPF Gold supplementation could support nitric oxide production and endothelial responsiveness while influencing oxygen utilization and exercise performance in trained athletes.
What They Did: Thirty healthy, well-trained male cyclists completed BPF Gold and placebo protocols separated by a 2-week washout period. Participants received 650 mg BPF Gold twice daily for 4 weeks, with researchers measuring nitric oxide, ADMA, EndoPAT vascular indices, lipid markers, maximal oxygen uptake, heart rate, and peak power.
What They Found: BPF Gold significantly increased baseline nitric oxide and improved measures of endothelial function compared with placebo. The study also reported higher VO₂max and peak power, lower maximal exercise heart rate, and favorable changes in total cholesterol, LDL-C, and HDL-C. Changes in nitric oxide were positively correlated with changes in VO₂max.
What It Means: The findings suggest that BPF Gold may support exercise performance through a vascular pathway involving greater nitric oxide availability, improved endothelial responsiveness, and enhanced oxygen utilization. This provides clinical support for positioning BPF Gold within cardiovascular-performance and sports-nutrition formulations.

J Sports Med Ther. 2018; 3: 053-061. Rocco Mollace, Micaela Gliozzi, Annamaria Tavernese, Vincenzo Musolino, Cristina Carresi, Miriam Scicchitano, Ernesto Palma, Saverio Nucera, Francesca Bosco, Federica Scarano, Francesca Oppedisano, Alessia Maretta, Jessica Maiuolo2, Saverio Muscoli, Santo Gratteri, Francesco Romeo and Vincenzo Mollace

Atherogenic Index Reduction and Weight Loss in Metabolic Syndrome Patients Treated with A Novel Pectin-Enriched Formulation of Bergamot Polyphenols

This 90-day randomized, double-blind, placebo-controlled trial evaluated a pectin-enriched bergamot polyphenol extract complex (BPE-C) in adults with metabolic syndrome. The study examined weight management alongside lipid, glucose, insulin-resistance, atherogenic-index, and appetite-related hormone measurements.

What It's About: Whether a full-spectrum, pectin-enriched bergamot formulation could influence body weight and BMI while also improving the broader cardiometabolic profile in people with metabolic syndrome.
What They Did: Fifty-two participants were randomized to placebo, 650 mg BPE-C daily, or 1,300 mg BPE-C daily for 90 days; 45 completed the study, with 15 participants in each group. Researchers measured body weight, BMI, cholesterol, triglycerides, glucose, insulin, HOMA-IR, atherogenic index of plasma (AIP), and the energy-balance hormones leptin, ghrelin, and adiponectin.
What They Found: BPE-C produced dose-responsive changes across multiple markers. In the high-dose group, body weight decreased 14.8%, BMI 15.9%, LDL-C 41.4%, triglycerides 31.9%, and fasting glucose 18% from baseline. AIP fell from approximately 0.45 to 0.19, while HOMA-IR and insulin decreased and adiponectin increased.
What It Means: The study provides controlled human evidence that the pectin-enriched bergamot complex can address several interconnected aspects of metabolic health at the same time, including weight, lipid balance, glucose regulation, insulin sensitivity, and appetite-related signaling. The findings also support the value of the full-spectrum formulation, rather than treating its effects as attributable to flavonoids alone.

Nutrients 2019, 11, 1271 Antonio Soccorso Capomolla, Elzbieta Janda, Sara Paone, Maddalena Parafati, Tomasz Sawicki, Rocco Mollace, Salvatore Ragusa and Vincenzo Mollace

A Growing Research Portfolio Across Multiple Health Applications

Bergamonte® is supported by a diverse body of scientific literature that extends beyond conventional lipid research. The clinical library includes human studies examining cholesterol and lipoprotein particles, fasting glucose, liver biomarkers, body weight, appetite-related hormones, cognitive performance, nitric oxide, oxygen utilization, endothelial function, and sexual health.

The broader research portfolio also includes review papers and laboratory, cellular, and preclinical studies exploring antioxidant activity, inflammatory signaling, autophagy, oxidative stress, lipid metabolism, and other mechanisms associated with bergamot polyphenols. Together, these studies help product developers connect ingredient composition and biological pathways with clinically measured outcomes while clearly distinguishing human evidence from supporting mechanistic research.

Bring the Bergamonte® Science Into Your Next Formula

Have a product concept or want to explore where Bergamonte® fits within your formulation? Connect with the HP Ingredients team to discuss the research, ingredient options, technical documentation, samples, and formulation considerations relevant to your specific application and development goals.

Clinical Studies Library

Download the Bergamonte® White Paper

11 Published Human Clinical Trials

A Growing Research Portfolio Across Multiple Health Applications

Bring the Bergamonte® Science Into Your Next Formula

Download the Bergamonte®
White Paper