The objective was to evaluate the effects of 6 months of supplementation with Altilix^®, containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix^® (26 men and 24 women, mean age 63 ± 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 ± 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endothelial function were assessed by doppler ultrasound and by flow-mediated dilation of the brachial artery, respectively. The presence and degree of non-alcoholic fatty liver disease (NAFLD) was assessed by the fatty liver index (FLI), and subjects were divided into three subgroups: (1) without NAFLD; (2) with borderline NAFLD; and (3) with NAFLD. After 6 months of Altilix^® supplementation, we found a significant improvement vs. placebo in most of the evaluated parameters, including body weight (−2.40% (95% CI −3.79, −1.01); p < 0.001), waist circumference (−2.76% (95% CI −4.55, −0.96); p = 0.003), HbA1c (−0.95% (95% CI −1.22, −0.67); p < 0.001), plasma lipids, FLI (−21.83% (95% CI −27.39, −16.27); p < 0.001), hepatic transaminases, flow-mediated dilation (10.56% (95% CI 5.00, 16.12); p < 0.001), and carotid intima-media thickness (−39.48% (95% CI −47.98, −30.97); p < 0.001). Further, the improvement in cardiometabolic variables was independent of the degree of hepatic steatosis. Altilix^® supplementation improved hepatic and cardio-metabolic parameters in MetS subjects. Altilix^® supplementation was a beneficial approach in the management of hepatic and cardiometabolic alterations in MetS subjects.

Pre-obesity is a condition that predisposes to the risk of developing obesity, cardiovascular diseases (CVD), and diabetes. Our previous study demonstrated that a Cynara cardunculus (L.) based nutraceutical named Altilix^® (Bionap, Italy), containing chlorogenic acid and luteolin extracts, was able to improve several hepatic and cardio-metabolic parameters. Given this background, we conducted a post-hoc analysis of the Altilix^® study in order to analyze the supplement’s effects in the subgroup of pre-obesity subjects on anthropometry (weight and waist circumference), glucose metabolism (HbA1C, HOMA-IR, and HOMA-β), lipid profile (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol), hepatic functionality (FLI, AST, ALT and AST/ALT), carotid-media thickness (CIMT) and endothelial function (FMD). Fifty subjects from the original study cohort (which consisted of 100 subjects) were chosen with BMI ≥ 25 and < 30 kg/m². All subjects received the Altilix^® supplement (150 mg/day) or placebo using a computer-based random allocation system. After six months of treatment Altilix^® significantly reduced body weight, glycemic, and lipid parameters (total cholesterol, triglycerides, LDL-cholesterol) and improved hepatic functionality, CIMT, and FMD. In conclusion, these results confirm that Altilix^® supplementation has a significant effect on cardiometabolic parameters not only in obese subjects but also in pre-obesity subjects.

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes™, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p < 0.005) and 12 (85.0 [80.0, 90.0] cm, p < 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm; 4 weeks: 102.0 [95.7, 108.3] cm; 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.

Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), naïve to incretin-based therapy, were treated with liraglutide (1.2 mg/day as an add-on to metformin) for 4 months. miRNAs were quantified using real-time polymerase chain reaction. After liraglutide treatment, we found significant reductions in fasting glucose (from 9.8 ± 5.3 to 6.7 ± 1.6 mmol/L, p = 0.0042), glycosylated haemoglobin (HbA1c) (from 8.1 ± 0.8 to 6.6 ± 1.0%, p = 0.0008), total cholesterol (from 5.0 ± 1.0 to 4.0 ± 0.7 mmol/L, p = 0.0011), triglycerides (from 1.9 ± 1.0 to 1.5 ± 0.8 mmol/L, p = 0.0104) and low-density lipoprotein cholesterol (from 2.9 ± 1.2 to 2.2 ± 0.6 mmol/L, p = 0.0125), while the serum levels of miRNA-27b, miRNA-130a and miRNA-210a were significantly increased (median (interquartile range, IQR) changes: 1.73 (7.12) (p = 0.0401), 1.91 (3.64) (p = 0.0401) and 2.09 (11.0) (p = 0.0486), respectively). Since the changes in miRNAs were independent of changes in all the metabolic parameters investigated, liraglutide seems to exert a direct epigenetic effect in T2DM patients, regulating microRNAs involved in the maintenance of endothelial cell homeostasis. These changes might be implicated in liraglutide’s benefits and may represent useful targets for cardiometabolic management.

During the COVID-19 pandemic, several observational studies proved a certain efficacy of nutraceuticals, herbal products, and other dietary supplements as adjuvant therapies used alongside antiviral drugs. Although their use has not been widespread in Italy, according to preliminary evidence, many supplements with demonstrated immunomodulatory effects, such as vitamins C and D, herbal medicines and essential oils, might relieve the respiratory symptoms of COVID-19, since SARS-CoV-2 can activate inflammasome-mediated inflammatory signaling pathways. Other observational studies have shown that herbal treatments, such as Echinacea purpurea and ginseng, help alleviate respiratory symptoms and reduce serum levels of inflammatory cytokines, which are typically overexpressed in both adult and pediatric SARS-CoV-2 patients. Further, vitamins C and D can attenuate the immune response thanks to their cytokine suppression ability and to their known antimicrobial activity and potential to modulate T helper cell response. The strong immune response triggered by SARS-CoV-2 infection is responsible for the severity of the disease. Preliminary data have also shown that L-arginine, an endothelial-derived relaxing factor, is able to modulate endothelial damage, which appears to be one of the main targets of this systemic disease. Finally, some essential oils and their isolated compounds, such as eucalyptol, may be helpful in reducing many of the respiratory symptoms of COVID-19, although others, such as menthol, are not recommended, since it can lead to an undervaluation of the clinical status of a patient. In this narrative review, despite the lack of strong evidence in this field, we aimed to give an overview of the current available literature (mainly observational and cross-sectional studies) regarding herbal products and dietary supplements and their use in the treatment of mild disease from SARS-CoV-2 infection. Obviously, dietary supplements and herbal products do not constitute a standardized treatment for COVID-19 disease, but they could represent an adjunctive and useful treatment when used together with antivirals.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now recognized as the principal hepatic manifestation of obesity and metabolic dysfunction. Its pathogenesis is complex and multifactorial, driven by insulin resistance, low-grade chronic inflammation, oxidative stress, gut microbiota alterations, and abnormalities in lipid metabolism; together, these promote steatosis, lipotoxicity, and progression to fibrosis which can lead to compensated advanced chronic liver disease (cACLD). MASLD is also a multisystem condition closely associated with an increased risk of major adverse cardiovascular events such as myocardial infarction, ischemic stroke, atrial fibrillation, and other extrahepatic complications. In this context, emerging metabolic therapies show significant potential for modifying the natural history of the disease. Glucagon-like peptide (GLP)-1 receptor agonists induce substantial weight loss and improve steatosis and necro-inflammatory activity. Sodium–glucose cotransporter 2 inhibitors (SGLT-2I) reduce glucotoxicity, promote modest weight loss, and lower hepatic fat content by improving insulin sensitivity and inflammatory signaling. Even more promising are dual GLP-1/GIP receptor agonists, which have demonstrated superior efficacy in metabolic control, reducing hepatic steatosis, and potentially modulating fibrotic processes, although definitive histological confirmation is still lacking. Overall, in this review, we discuss the physiopathological mechanisms of MASLD leading to cACLD along with the emerging therapies, such GLP1 receptor agonists, SGLT-2I, and GLP1/GIP which, when combined with structured lifestyle interventions, may attenuate progression toward steatohepatitis (MASH), fibrosis, and, thus, cirrhosis.