Clinical Study to Assess the Efficacy and Safety of a Citrus Polyphenolic Extract of Red Orange, Grapefruit, and Orange (Sinetrol-XPur) on Weight Management and Metabolic Parameters in Healthy Overweight Individuals Constantin Dallas, 1 * Alain Gerbi, 2 Yves Elbez, 3 Philippe Caillard, 4 Nicolas Zamaria 5 and Maurice Cloarec 6 1 Fytexia, 3 rue d’Athènes-VIA EUROPA 34350 Vendres, France 2 RDVC Produits Santé, 102 Avenue René Coty, 76600 Le Havre, France 3 Centre Médical, 5 place de la Bastille, 750043 Paris, France 4 Centre d’Exploration Vasculaire, 1 rue saint Antoine, 75004 Paris, France 5 Centre d’Exploration Biologique, 49 avenue de Versailles 75016 Paris, France 6 Association National de Prévention des Maladies, 8 rue duguay Trouin, 75006 Paris, France The present study investigated the efficacy and safety effects of Sinetrol-XPur (polyphenolic citrus dry extract) in weight management; metabolic parameters; and inflammatory, glycemic and oxidative status. In a 12-week, randomized, double-blind, placebo-controlled trial, Sinetrol-XPur was given to overweight subjects twice daily with meals in the tested group (N = 47) versus a placebo group (N = 48). Waist and hip circumference and abdominal fat were decreased in the Sinetrol-XPur group as compared with the placebo group (p < 0.0001) (5.71% vs 1.56% for waist, 4.71% vs 1.35% for hip and 9.73% vs 3.18% for fat). Inflammatory markers were reduced (C-reactive protein: 22.87% vs +61%; fibrinogen: 19.93% vs 1.61%, p < 0.01). Oxidative stress was lowered as seen by the reduction of malondialdehyde (14.03% vs 2.76%) and the increase in superoxide dismutase and glutathione (17.38% vs 2.19% and 4.63% vs 2.36%, respectively, p < 0.01). No adverse effects were observed. Kidney, liver, and lipid panels remained unchanged. These results indicated that Sinetrol-XPur supplementation is a viable option for reducing abdominal fat, waist and hip circumference, and body weight and for improving inflammatory, glycemic, and oxidative status in healthy overweight individuals. Copyright © 2013 John Wiley & Sons, Ltd. Keywords: weight management; citrus extract; polyphenols; overweight; inflammation; oxidative stress. Abbreviations: Apo, apolipoproteins; BMI, body mass index; CRP,C-reactive protein; CV, cardiovascular; FFA, free fatty acid; GSH, glutathione; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MDA, malondialdehyde; SOD, superoxide dismutase; TG, triglyceride INTRODUCTION People are becoming fatter worldwide. Recent data show that excess body fat weight is pandemic, with one-half to two-thirds of the population being overweight or obese in 2006. A greater amount of fat, especially found in the abdominal region, increases the risk of CV diseases and type 2 diabetes (Balkau et al., 2007). Indeed, obesity is associated with decreased HDL and increased LDL and TGs, all risk factors for CV diseases (Kaysen et al., 2009). Furthermore, obesity is associated with low-grade inflammation and chronic inflammatory response characterized by activation of some pro-inflammatory signaling pathways and abnormal production of markers such as fibrinogen and CRP (Fain, 2010). These molecules are implicated in many clinical manifestations of pathologies such as diabetes, arterial hypertension, or CV diseases (Festa et al., 2001; Rodríguez-Rodríguez et al., 2009; Zhang and Zhang, 2010). Fat accumulation is correlated with elevated markers of oxidative stress, which plays critical roles in the development of impaired insulin secretion, diabetes, and atherosclerosis (Furukawa et al., 2004; De Ferranti and Mozaffarian, 2008). Reducing abdominal fat mass and concomitant oxidative stress could be important targets for the prevention of obesity-related diseases (Shen et al., 2009). Excess body fat is the primary characteristic of obe- sity. Therefore, a precise measurement of the percent- age body fat is considered the reference method for defining obesity. Anthropometric indices such as BMI, waist circumference, and waist-to-hip ratio are the most commonly used indicators for assessing abdominal obesity (Singh et al., 1998; Mushtaq et al., 2011). Flavonoids constitute the most important class of poly- phenolic compounds, such as anthocyanins (malvidin, * Correspondence to: Constantin Dallas, Fytexia, 3 rue d’Athènes-VIA EUROPA, 34350 Vendres, France. E-mail: cdallas@fytexia.com PHYTOTHERAPY RESEARCH Phytother. Res. 28: 212–218 (2014) Published online 3 April 2013 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ptr.4981 Copyright © 2013 John Wiley & Sons, Ltd. Received 25 October 2012 Revised 30 January 2013 Accepted 01 February 2013