Impact of a food supplement containing Citrus limon L. Osbeck and Vitis vinifera L. extracts, Hesperidin and Chromium in combination with an isocaloric diet on glucose and lipid metabolism in subjects with impaired fasting blood glucose: a single-center, controlled, randomized, parallel-arm, double-blind clinical trial

Alessandro Di Minno^1,2Maria Vittoria Morone³Daniele Giuseppe Buccato¹Lorenza Francesca De Lellis¹Hammad Ullah⁴Luca Borromeo¹Angela Cerqua⁵Roberto Piccinocchi⁶Agostino Greco⁷Salvatore Santonastaso⁷Danaé Larsen⁸Hesham Rushed El-Seedi⁹Costanza Valentina Riccioni¹⁰Alessandra Baldi¹Gaetano Piccinocchi¹¹Xiang Xiao¹²Roberto Sacchi¹³Maria Daglia^1*

• ¹Universita degli Studi di Napoli Federico II Dipartimento di Farmacia, Naples, Italy
• ²CEINGE Biotecnologie Avanzate sc a rl, Naples, Italy
• ³Universita degli Studi della Campania Luigi Vanvitelli Dipartimento di Medicina Sperimentale, Naples, Italy
• ⁴University of Management and Technology, Lahore, Pakistan
• ⁵Universita degli Studi di Napoli Federico II Dipartimento di Scienze Mediche Traslazionali, Naples, Italy
• ⁶Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy
• ⁷Azienda Sanitaria Locale Caserta, Caserta, Italy
• ⁸The University of Auckland School of Chemical Sciences, Auckland, New Zealand
• ⁹Islamic University of Madinah, Medina, Saudi Arabia
• ¹⁰Esserre Pharma Srl, Rome, Italy
• ¹¹Comegen Società Cooperativa Sociale, Naples, Italy
• ¹²Jiangsu University School of Food and Biological Engineering, Zhenjiang, China
• ¹³Applied Statistic Unit, Department of Earth and Environmental Sciences, University of Pavia, Pavia, Italy

Abstract Impaired fasting glycemia (IFG) puts carriers at a significantly higher risk of developing type 2 diabetes and cardiovascular disease. Lifestyle changes, such as increased physical activity and a healthy diet rich in fiber and low in sugar, can often reverse prediabetes and significantly reduce the risk of progressing to type 2 diabetes metabolic disorders, especially diabetes. [1]. This randomized clinical trial aims to evaluate the efficacy and tolerability of a food supplement (FS) containing Citrus limon L. Osbeck and Vitis vinifera L. extracts, hesperidin from Citrus sinensis L. Osbeck, and chromium, in individuals with impaired fasting blood glucose , with the final goal of investigating whether the use of a combination of ingredients, known to exert their positive effects through different mechanisms of action, is a helpful strategy for improving glucose metabolism. Sixty-two subjects (aged 18–75 years) with IFG levels ranging from 100–to 125 mg/dL were assigned to receive either a FS or a placebo (n = 31 per group) for 6 months, in combination with an isocaloric diet. Participants took two tablets daily. Biochemical parameters related to glucose and lipid metabolism and markers of liver and kidney functionality were evaluated at baseline (T0), and after 3 and 6 months. The treatment group showed a significant improvement in fasting glycemia after 3 months, with normalization of glucose levels (P < 0.001 vs T0), unlike the placebo group. Statistically improvements were also observed in HDL and LDL cholesterol and triglycerides. Daily intake of the tested FS in combination with an isocaloric diet significantly improved glucose and lipid metabolism, suggesting that the combination of ingredients with different mechanisms of action can be considered a valuable strategy for improving impaired fasting blood glucose and lipid profiles. This study is listed on the ISRCTN registry (www.isrctn.com) under the ID number ISRCTN15062713, https://doi.org/10.1186/ISRCTN15062713.