Effects of Natural Supplement Containing Chlorogenic Acid and Luteolin on Cardio-metabolic Risk Factors

This is one randomized, double-blind, placebo-controlled study. The purpose of the present study is to evaluate and/or elucidate the role of the natural supplement, containing chlorogenic acid (10-12%) and luteinyl-7-glucoside (2-4%), on cardio-metabolic risk factors.

The research hypothesis is to evaluate whether natural supplement containing chlorogenic acid and luteolin (Puraltilix, BIONAP SRL, Catania, Italy) may improve several cardio-metabolic parameters in subjects with the metabolic syndrome.

All subjects will be evaluated at baseline and after 6 months of treatment (with natural supplement or placebo).

• Natural supplement containing chlorogenic acid and luteolin (Dietary supplement): 50 eligible subjects will receive natural supplement as the oral pills at a fixed dose of 1 pill/day (450 mg/day) for 6 months, as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study.
• Placebo (without any active ingredients) (Other): 50 eligible subjects will receive placebo (without any active ingredients) at a fixed dose of 1 pill/day for 6 months, as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study.

Primary outcomes

• Effect of natural supplement on metabolic parameters including body weight and Body Mass Index (BMI) [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on metabolic parameters, including body weight (kg) and height (m) that will be combined to report BMI in kg/m\^2.
• Effect of natural supplement on metabolic parameters including waist circumference [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on metabolic parameters, including waist circumference (cm).
• Effect of natural supplement on metabolic parameters including plasma lipids [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on metabolic parameters, including plasma lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol HDL-C) (mmol/l), while low-density lipoprotein cholesterol (LDL-C) will be calculated using the Friedewald formula.
• Effect of natural supplement on metabolic parameters including glucose metabolism parameters [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on metabolic parameters, including plasma glycemia (mmol/l).
• Effect of natural supplement on metabolic parameters including plasma insulinemia and HOMA (homeostatic model assessment) index [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on metabolic parameters, including plasma insulinemia (pmol/L) that with glycemia will be combined to report HOMA index.

Secondary outcomes

• Effect of natural supplement on cardio-metabolic parameters including plasma cytokines [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on cardio-metabolic parameters, including plasma cytokines (inflammatory markers and adipokines) (pg/ml), that will be assessed using available enzyme-linked immunosorbent assay (ELISA) kits.
• Effect of natural supplement on cardio-metabolic parameters including plasma lipoproteins [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on cardio-metabolic parameters, including atherogenic lipoproteins as well as the analysis of the full spectrum of lipoprotein subclasses by gel electrophoresis.
• Effect of natural supplement on cardio-metabolic parameters including subclinical atherosclerosis [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on cardio-metabolic parameters, including subclinical atherosclerosis assessed by carotid intima-media thickness (CIMT) (mm).
• Effect of natural supplement on cardio-metabolic parameters including fatty liver index [Change from baseline to 6 months of the supplementation]: Effect of natural supplement containing chlorogenic acid and luteolin on cardio-metabolic parameters, including fatty liver index, a noninvasive method used for steatosis detection and quantification.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Men and women aged >18 years with the metabolic syndrome (as defined by the international criteria: Alberti KG, et al. Circulation. 2009; 120: 1640-5);
* BMI> 25 kg/m\^2;
* Subjects able to swallow whole tablets;
* Informed consent obtained prior to any study-related activities.

Exclusion Criteria:

* Pregnancy or willingness to become pregnant;
* Severe liver dysfunction (ALT >2.5 times upper limit of normal);
* Severe renal failure (eGFR<60 mL/min/1.73 m2 using the MDRD formula);
* Severe infections at the discretion of the investigator (such as HIV, HBV and HCV);
* History or presence of malignant neoplasms within the last 5 years.

• Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct 20;120(16):1640-5. doi: 10.1161/CIRCULATIONAHA.109.192644. Epub 2009 Oct 5. PMID 19805654

• Manfredi Rizzo, MD, PhD, Principal investigator, University Hospital of Palermo, Italy