A nutraceutical with Citrus bergamia and Cynara cardunculus improves endothelial function in adults with non-alcoholic fatty liver disease.

OBJECTIVE: Polyphenol intake may prevent hepatic steatosis and cardiovascular disease by potentially improving endothelial function. The purposes of this study are to investigate the association between fatty liver disease and endothelial dysfunction and to test the effects of a nutraceutical containing extracts made from Citrus bergamia and Cynara cardunculus on peripheral vascular endothelial function in adults with liver steatosis. METHODS: We analyzed data from 32 individuals with hepatic steatosis and endothelial dysfunction (reactive hyperemia index ≤ 1.67). Sixteen subjects took 1 capsule/d (300 mg/d) containing Cynara cardunculus extract and bergamot polyphenol fraction, while the other 16 subjects matched for age, sex, and body mass index took 1 capsule/d of placebo (maltodextrin) for 12 wk. All anthropometric parameters were assessed at baseline and after 12 wk as were lipids, glucose, and reactive hyperemia index using an EndoPAT 2000. RESULTS: The mean age was 52 ± 9 y. The mean reactive hyperemia index was 1.15 ± 0.4. After 12 wk, we found a greater increase in reactive hyperemia index in the participants taking the nutraceutical rather than placebo (0.58 ± 0.5 versus 0.13 ± 0.5; P = 0.02, respectively). The stepwise multivariable analysis confirmed a positive association between reactive hyperemia index change and the nutraceutical treatment (B = 0.38; P = 0.025) and negative association with reactive hyperemia index values at baseline (B = -0.81; P < 0.001). No association was found between the reduction in the amount of intrahepatic fat and the improvement of endothelial function (B = 0.002; P = 0.56). CONCLUSIONS: A nutraceutical containing bergamot and artichoke extracts improves peripheral vascular endothelial function in adults with hepatic steatosis and early phase of atherosclerosis.

The Effect of an Innovative Combination of Bergamot Polyphenolic Fraction and Cynara cardunculus L. Extract on Weight Gain Reduction and Fat Browning in Obese Mice.

Obesity is one of the world's most serious public health issues, with a high risk of developing a wide range of diseases. As a result, focusing on adipose tissue dysfunction may help to prevent the metabolic disturbances commonly associated with obesity. Nutraceutical supplementation may be a crucial strategy for improving WAT inflammation and obesity and accelerating the browning process. The aim of this study was to perform a preclinical "proof of concept" study on Bergacyn®, an innovative formulation originating from a combination of bergamot polyphenolic fraction (BPF) and Cynara cardunculus (CyC), for the treatment of adipose tissue dysfunction. In particular, Bergacyn® supplementation in WD/SW-fed mice at doses of 50 mg/kg given orally for 12 weeks, was able to reduce body weight and total fat mass in the WD/SW mice, in association with an improvement in plasma biochemical parameters, including glycemia, total cholesterol, and LDL levels. In addition, a significant reduction in serum ALT levels was highlighted. The decreased WAT levels corresponded to an increased weight of BAT tissue, which was associated with a downregulation of PPARγ as compared to the vehicle group. Bergacyn® was able to restore PPARγ levels and prevent NF-kB overexpression in the WAT of mice fed a WD/SW diet, suggesting an improved oxidative metabolism and inflammatory status. These results were associated with a significant potentiation of the total antioxidant status in WD/SW mice. Finally, our data show, for the first time, that Bergacyn® supplementation may be a valuable approach to counteract adipose tissue dysfunction and obesity-associated effects on cardiometabolic risk.

Bergamot Polyphenol Extract Reduces Hepatocyte Neutral Fat by Increasing Beta-Oxidation.

BACKGROUND: Bergamot polyphenolic fraction (PF) extract exerts a beneficial against liver steatosis. However, the fundamental processes underlying this beneficial effect of bergamot PF remain elusive. In this work, we examined the effect of bergamot PF extract on 2D and 3D hepatocyte cultures. MATERIAL AND METHODS: We evaluated the effect of bergamot PF in 2D and 3D cultures from rat, human hepatoma cells, and human primary hepatocytes. RESULTS: In 2D cell culture, we demonstrated that incubation with bergamot PF decreases intracellular lipid content and is associated with an increase in expression levels of ß-oxidation genes (Acox1, Pparα, and Ucp2) and lipophagy (Atg7). Moreover, we confirm this effect on 3D spheroids and organoids. CONCLUSION: Incubation with bergamot PF reduces intracellular lipid neutral fat potentially by increasing intracellular pathways related to beta-oxidation.

A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease.

BACKGROUND: Currently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S-adenosyl-L-methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease. METHODS: A total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention. RESULTS: After adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (- 34 ± 5 dB/m vs. - 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men. CONCLUSION: Our results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis. Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021-retrospectively registered, https://doi.org/10.1186/ISRCTN70887063.

A Rapid and Cheap Method for Extracting and Quantifying Lycopene Content in Tomato Sauces: Effects of Lycopene Micellar Delivery on Human Osteoblast-Like Cells.

Identifying and quantifying the beneficial molecules contained in nutraceuticals is essential to predict the effects derived from their consumption. This study explores a cheap and rapid method for quantifying lycopene content from a semi-solid matrix. In addition, it compares the in vitro effects of the extracts obtained from different tomato sauces available on the local market with Osteocol®, a patented tomato sauce from southern Italy. We performed a liquid extraction of lycopene using suitable solvents. The lycopene extracted was encapsulated in surfactant micelles and finally tested in vitro on Saos-2 cells. The effects exerted by lycopene on ALP and Wnt/ß-catenin pathways were investigated by Western blotting. Hexane was found to be the best solvent for lycopene extraction. Spectrophotometrical and HPLC analyses showed similar trends. Osteocol® contained 39 ± 4 mg lycopene per 100 g of sauce, while the best commercial product contained 19 ± 1 mg/100 g. The Osteocol® lycopene extract increased ALP and ß-catenin protein expressions in a dose-dependent manner, also showing statistically significant results (p < 0.05 respectively). In conclusion, despite both techniques showing similar final results, UV/VIS spectrophotometer is preferable to HPLC due to its cheap, rapid, and accurate results, as well as for the opportunity to analyze lycopene-loaded micelles. The extraction and release of lycopene to bone cells positively influences the differentiation of osteoblasts and increases the expression of the ALP and ß-catenin proteins. As a consequence, as a lycopene-rich sauce, Osteocol® represents a useful supplement in the prevention of osteoporosis compared to its commercial competitors.

Hemp Seeds in Post-Arthroplasty Rehabilitation: A Pilot Clinical Study and an In Vitro Investigation.

Osteoarthritis is a type of degenerative joint disease that results from the breakdown of joint cartilage and underlying bone. Due to their antioxidants and anti-inflammatory action, the phytochemical constituents of many vegetable varieties could represent a new frontier for the treatment of patients with Osteoarthritis and are still being explored. The aim of this pilot human study was to investigate the effects of pasta enriched with hemp seed flour on osteoarticular pain and bone formation markers in patients in post-arthroplasty rehabilitation. Another purpose was to evaluate the effect of hemp seed extract on bone metabolism, in vitro. A pilot, controlled, clinical study was conducted to verify the feasibility of pain symptom reduction in patients with Osteoarthritis undergoing arthroplasty surgery. We also investigated the effect of hemp seed extract on the Wnt/ß-catenin and ERK1/2 pathways, alkaline phosphatase, RANKL, RUNX-2, osteocalcin, and COL1A on Saos-2. After 6 weeks, the consumption of hemp seed pasta led to greater pain relief compared to the regular pasta control group (-2.9 ± 1.3 cm vs. -1.3 ± 1.3 cm; p = 0.02). A significant reduction in serum BALP was observed in the participants consuming the hemp seed pasta compared to control group (-2.8 ± 3.2 µg/L vs. 1.1 ± 4.3 µg/L; p = 0.04). In the Saos-2 cell line, hemp seed extract also upregulated Wnt/ß-catenin and Erk1/2 pathways (p = 0.02 and p = 0.03) and osteoblast differentiation markers (e.g., ALP, OC, RUNX2, and COL1A) and downregulated RANKL (p = 0.02), compared to the control. Our study demonstrated that hemp seed can improve pain symptoms in patients with osteoarthritis undergoing arthroplasty surgery and also improves bone metabolism both in humans and in vitro. However, more clinical studies are needed to confirm our preliminary findings.

Roles and competencies in the nutritional domain for the management of the metabolic diseases and in the hospital setting: A position paper of the Italian College of Academic Nutritionists, MED-49 (ICAN-49).

Epidemiological evidence has confirmed the potential causal relationship between specific dietary factors and non-communicable diseases. However, currently nutrition was shown to be insufficiently integrated into medical education, regardless of the country. Without an adequate nutrition education, it is reasonable to assume that future physicians, as well as other health care professionals, will be not able to provide the highest quality care to patients in preventing and treating non-communicable diseases. Furthermore, the insufficient availability of physicians with specializations in nutrition has posed the basis for the development of non-medical careers in the field of nutrition. The present document was drafting by the Italian College of Academic Nutritionists, MED-49 (ICAN-49), with the aim to provide an overview on the nutritional competency standards covered by several health care professionals (Physicians Clinical Nutrition Specialists, Clinical Dietitians, Professional Clinical Nutrition Specialists, etc) for the prevention of diseases and/or support of pharmacological therapies. The aim of the ICAN 49 is to suggest a major shift in practice opportunities and roles for many nutritionists, especially for the management of the metabolic diseases, and promote a paradigm change: a clinical and educational leadership role for Physician Clinical Nutrition Specialists in the hospital setting.

Randomized Clinical Trial: Bergamot Citrus and Wild Cardoon Reduce Liver Steatosis and Body Weight in Non-diabetic Individuals Aged Over 50 Years.

Background: Non-alcoholic fatty liver disease is the most common cause of liver-related morbidity and mortality in the world. However, no effective pharmacological treatment for this condition has been found. Purpose: This study evaluated the effect of a nutraceutical containing bioactive components from Bergamot citrus and wild cardoon as a treatment for individuals with fatty liver disease. The primary outcome measure was the change in liver fat content. Methods: A total of 102 patients with liver steatosis were enrolled in a double-blind placebo controlled clinical trial. The intervention group received a nutraceutical containing a Bergamot polyphenol fraction and Cynara Cardunculus extract, 300 mg/day for 12 weeks. The control group received a placebo daily. Liver fat content, by transient elastography, serum transaminases, lipids and glucose were measured at the baseline and the end of the study. Results: We found a greater liver fat content reduction in the participants taking the nutraceutical rather than placebo (-48.2 ± 39 vs. -26.9 ± 43 dB/m, p = 0.02); The percentage CAP score reduction was statistically significant in those with android obesity, overweight/obesity as well as in women. However, after adjustment for weight change, the percentage CAP score reduction was statistically significant only in those over 50 years (44 vs. 78% in placebo and nutraceutical, respectively, p = 0.007). Conclusions: This specific nutraceutical containing bioactive components from Bergamot and wild cardoon reduced the liver fat content during 12 weeks in individuals with liver steatosis over 50 years. If confirmed, this nutraceutical could become the cornerstone treatment of patients affected by liver steatosis. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN12833814.

Bergamot Polyphenol Fraction Exerts Effects on Bone Biology by Activating ERK 1/2 and Wnt/ß-Catenin Pathway and Regulating Bone Biomarkers in Bone Cell Cultures.

Epidemiological studies show that fruit consumption may modulate bone mineral density. However, data regarding the effect of the Citrus bergamia Risso (Bergamot orange), a citrus fruit containing a high concentration of flavonoids, on bone health are still lacking. In this study, we investigated the effects of Bergamot polyphenols on the Wnt/ß-catenin pathway in two distinct bone cell types (Saos-2 and MG63). Findings showed that exposure to 0.01 and 0.1 mg/mL doses upregulate ß-catenin expression (p = 0.001), osteoblast differentiation markers (e.g., RUNX2 and COL1A), and downregulate RANKL (p = 0.028), as compared to the control. Our results highlight, for the first time, that Bergamot polyphenols act on bone cells through the ß-catenin pathway. In vivo studies are necessary to fully understand Bergamot's role against bone resorption.

Effect of the replacement of dietary vegetable oils with a low dose of extravirgin olive oil in the Mediterranean Diet on cognitive functions in the elderly.

BACKGROUND: Numerous studies have investigated the role of the monounsaturated fatty acid and other dietary factors in the prevention of cognitive decline but the short-term effect of a low dose of extravirgin olive oil on cognitive performances in the elderly have not still been investigated. Our aim was to investigate whether the replacement of all vegetable oils with a lower amount of extravirgin olive oil, in the contest of a Mediterranean Diet, would improve cognitive performances, among elderly Italian individuals. METHODS: 180 elderly individuals were randomly assigned to these treatment groups for 1 year: (1) MedDiet plus extravirgin OO, 20-30 g/day; (2) control MedDiet. The cognitive sub-test of ADAScale was used to detect cognitive decline progression over 12 months. RESULTS: ADAS-cog score variation after 1 year, adjusted for food groups which were different between groups, was - 1.6 ± 0.4 and - 3.0 ± 0.4 in the MedDiet and MedDiet plus extravirgin OO groups, respectively (p = 0.024). Extravirgin OO intake was 30 g ± 12 and 26 g ± 6 in the MedDiet and MedDiet plus extravirgin OO groups, respectively (p = 0.044). CONCLUSIONS: We demonstrated the higher short-term improvement of cognitive functions scores in individuals of the MedDiet plus low dose of extravirgin olive oil rather than MedDiet alone. Extravirgin olive oil is the best quality oil and may have a neuroprotective effect.

Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: focus on protection against cardiovascular and metabolic diseases.

The overall health beneficial action of olive oil phenolic components is well established. Recent studies have elucidated the biological effects of two isolated compounds, namely oleuropein and hydroxytyrosol, with particular attention on their antioxidant activity. Thus, a protective action has been demonstrated in preclinical studies against several diseases, especially cardiovascular and metabolic disorders. The present review will describe the biological effects of oleuropein and hydroxytyrosol, with particular attention on the molecular mechanism underlying the protective action on cardiovascular and metabolic alterations, as demonstrated by in vitro and in vivo experimental studies performed with the isolated compounds.

Hypokalemia during the early phase of refeeding in patients with cancer.

OBJECTIVE: Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding. METHODS: In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed. RESULTS: Significant weight loss (∼20%) was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p = 0.03 for potassium and 0.02 for protein, respectively). Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day). CONCLUSION: Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding.

Hypokalemia during the early phase of refeeding in patients with cancer

OBJECTIVE: Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding. METHODS: In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed. RESULTS: Significant weight loss (∼20%) was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p = 0.03 for potassium and 0.02 for protein, respectively). Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day). CONCLUSION: Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding. .