1. Introduction
inflammation, chronic non-communicable diseases
CARDIOVASCULAR DISEASES, INFLAMMATION, METABOLIC DISORDERS, METABOLIC SYNDROME, OXIDATIVE STRESS, TYPE 2 DIABETES, DISEASES
These authors contributed equally to this work.The Mediterranean Diet (MedDiet) is associated with beneficial effects against chronic non-communicable diseases (CNCDs). In particular, the content of micronutrients leads to an improvement of the oxidative and inflammatory profiles. A randomized, parallel, controlled study, on 24 subjects, was conducted to evaluate if 2-week supplementation with a mixed apple and bergamot juice (MAB juice), had a positive impact on the body composition, the biochemical profile, and oxidative and inflammatory gene expression (The components of the diet, macro and micronutrients, represent factors related to the start of metabolic disorders, such as cardiovascular diseases, type 2 diabetes, metabolic syndrome, and other chronic non-communicable diseases (CNCDs) [To counteract CNCD risk factors, it is necessary to adopt a lifestyle medicine, which includes all the actions to be taken before the pathologies become manifest through the adoption of healthy eating habits, possibly integrating foods functional into the diet, and verifying their effects on metabolism and gene expression [The possibility of delaying the onset of CNCDs also lies in the modulation of pathophysiological phenomena dependent on specific micronutrients able to regulate gene expression underlying the phenomenon under observation [Some micronutrients, such as Argine, glutamine, omega-3 fatty acids (n-3), nucleotides, vitamins C and D, and antioxidant compounds, favor the reduction in the inflammation status that characterizes the CNCDs and improves the immune system [The variety of micro and macronutrients, which recombine in a unique way in a food plan adapted to the Mediterranean Diet (MedDiet), contributes to the reduction in CNCDs and cardiovascular mortality, and weight management [The high content of antioxidant molecules, fiber, monounsaturated fats (MUFAs), and a suitable ratio of omega-6 (n-6):n-3 fatty acids of typical MedDiet foods contributes to achieving good health [Specific foods and drinks included in the Mediterranean Diet contain natural bioactive compounds with benefits for health and, above all, for the prevention of various chronic pathologies related to inflammation. Olive oil, fish, red wine, fruit, and vegetables contain phenolic compounds and polar lipid bioactives that justify the anti-inflammatory properties of the MedDiet. In particular, vegetables and fruits, foods rich in flavonoids and antioxidants, potentiate the endogenous antioxidant system and show beneficial effects on inflammation and oxidative stress markers [The apple (Pyrus Malus or Malus communis), belonging to the Rosaceae family, contains flavonols in monomeric or oligomeric form, chlorogenic acid, hydroxycinnamic acids, quercetin glycosides, phloretin glycosides and anthocyanins [The most abundant polyphenols in apple flesh are catechin, procyanidin, epicatechin, and phloridzin [Considering the content of essential vitamins (flavonoids, carotenoids, group B vitamins, vitamin C and E, niacin, and folic acid) the apple has antioxidant power, with the possibility of helping to reduce CNCDs [Bergamot (Citrus bergamia Risso) belongs to the genus Citrus, to the Rutaceae family [There is extensive scientific literature reporting the beneficial effects in whole and fresh fruit intake. However, there are few data attesting to the effectiveness of the consumption of fruit juices, and in particular, those composed of little consumed fruits, such as bergamot for its low palatability.Leopoldini et al., described how brutieridin and melitidine, contained in bergamot, are structural analogs of statins and, for the structure compatible with the active site of the HMG-reductase, block, with a statin-like action, the reduction of coenzyme-A (HMG-CoA) conjugated 3-hydroxy-3-methyl glutaric acid to mevalonic acid [To our knowledge, there is no study that has evaluated the effects of mixed apple and bergamot juice (MAB juice) on lipid and glycemic profile biomarkers concerning the expression of genes related to antioxidant and anti-inflammatory activity.Therefore, a randomized controlled dietary intervention study was initiated in healthy human volunteers with the primary aim of verifying the efficacy of 2-week consumption of MAB juice on the modulation of lipid and glycemic profile in blood, and secondarily on the expression of 