The Role of Physical Exercise as a Therapeutic Tool to Improve Lipedema: A Consensus Statement from the Italian Society of Motor and Sports Sciences (Società Italiana di Scienze Motorie e Sportive, SISMeS) and the Italian Society of Phlebology (Società Italiana di Flebologia, SIF).

PURPOSE OF REVIEW: This consensus statement from the Italian Society of Motor and Sports Sciences (Società Italiana di Scienze Motorie e Sportive, SISMeS) and the Italian Society of Phlebology (Società Italiana di Flebologia, SIF) provides the official view on the role of exercise as a non-pharmacological approach in lipedema. In detail, this consensus statement SISMeS - SIF aims to provide a comprehensive overview of lipedema, focusing, in particular, on the role played by physical exercise (PE) in the management of its clinical features. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal fat accumulation. It is often misdiagnosed as obesity, despite presenting distinct pathological mechanisms. Indeed, recent evidence has reported differences in adipose tissue histology, metabolomic profiles, and gene polymorphisms associated with this condition, adding new pieces to the complex puzzle of lipedema pathophysiology. Although by definition lipedema is a condition resistant to diet and PE, the latter emerges for its key role in the management of lipedema, contributing to multiple benefits, including improvements in mitochondrial function, lymphatic drainage, and reduction of inflammation. Various types of exercise, such as aquatic exercises and strength training, have been shown to alleviate symptoms and improve the quality of life of patients with lipedema. However, standardized guidelines for PE prescription and long-term management of patients with lipedema are lacking, highlighting the need for recommendations and further research in this area in order to optimise therapeutic strategies.

Low-FODMAP diet and hidradenitis suppurativa: the role of nutritionists in the management of dermato-endocrine disorders.

Hidradenitis suppurativa (HS) is a chronic inflammatory, immune-mediated, debilitating skin disease, characterized by subcutaneous nodules, with a still not clear pathophysiology. Although the prevalence is rather low (about 1% in Europe), its clinical complications, as well as the disabling symptomatology, make it necessary multidisciplinary therapeutic approaches. Not recently several authors described the involvement of the well-known gut-skin axis in both pathogenesis and progression of dermatological diseases. In particular, a high frequency of intestinal disorders (such as irritable bowel syndrome and inflammatory bowel disease) has been reported in HS patients, leading to speculate the existence of a relationship between such gut and skin diseases. The keystone in this relationship seems to be an impairment of the physiological gut mucosal barrier structure, resulting in the so-called leaky gut. The leaky gut, thus, might be responsible for a dietary compound-caused activation of the local immune system, with consequent trigging of both local and systemic inflammation, resulting in exacerbation of skin symptoms in HS patients. The current literature suggests the use of a low fermentable, oligo-, di, mono-saccharides and polyols (FODMAP) diet as a valid nutritional strategy in leaky gut. In light of this, we want to evaluate and consider the potential use of low-FODMAP diet in HS patient.

Ketogenic Diet: A Nutritional Therapeutic Tool for Lipedema?

PURPOSE OF REVIEW: This review aims to provide an overview of the current evidence on the efficacy, also considering the anti-inflammatory properties and safety of very low-calorie ketogenic diet (VLCKD) as a potential treatment for lipedema, particularly in the context of obesity. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal and painful fat buildup on the legs and/or arms. It is often misdiagnosed as obesity or lymphedema. However, although lipedema and obesity can coexist, unlike obesity, lipedema usually affects the legs and thighs without affecting the feet or hands, and the abnormal deposition of adipose tissue in lipedema is painful. The current lifestyle interventions are often unsuccessful in the management of lipedema. There is no consensus on the most effective nutritional approach for managing lipedema. Recent studies have suggested that VLCKD may be an effective treatment for lipedema, demonstrating that it is also superior to other nutritional approaches such as Mediterranean diet or intermittent fasting. Lipedema is a chronic and debilitating disease characterized by abnormal and painful accumulation of adipose tissue in the legs. VLCKD has been shown to be an effective treatment for lipedema, especially in the context of obesity, due to its anti-inflammatory properties. However, further research is needed to determine the long-term safety and efficacy of VLCKD as a treatment for lipedema.

Antiherpetic Activity of Taurisolo®, a Grape Pomace Polyphenolic Extract.

Herpes simplex virus (HSV) is widespread in the population, causing oral or genital ulcers and, rarely, severe complications such as encephalitis, keratitis, and neonatal herpes. Current available anti-HSV drugs are acyclovir and its derivatives, although long-term therapy with these agents can lead to drug resistance. Thus, the discovery of novel antiherpetic compounds merits additional studies. In recent decades, much scientific effort has been invested in the discovery of new synthetic or natural compounds with promising antiviral properties. In our study, we tested the antiviral potential of a novel polyphenol-based nutraceutical formulation (named Taurisolo®) consisting of a water polyphenol extract of grape pomace. The evaluation of the antiviral activity was carried out by using HSV-1 and HSV-2 in plaque assay experiments to understand the mechanism of action of the extract. Results were confirmed by real-time PCR, transmission electron microscope (TEM), and fluorescence microscope. Taurisolo® was able to block the viral infection by acting on cells when added together with the virus and also when the virus was pretreated with the extract, demonstrating an inhibitory activity directed to the early phases of HSV-1 and HSV-2 infection. Altogether, these data evidence for the first time the potential use of Taurisolo® as a topical formulation for both preventing and healing herpes lesions.

Sharing country experiences: The WHO Global School on Refugee and Migrant Health in Jordan.

In 2021, Jordan was the first country to host the Global School for Refugee and Migrant Health, to improve the knowledge of the public health implications of migration. These perspective articles aim to retrieve salient reflections during the School as a baseline for further enhancement of migrant and health programs. During the School, a compilation of achievements, challenges, and opportunities was discussed around specific interrelated subjects, such as health system management and mental health. Successful examples were provided in the integration of refugees and migrants into health policies. On the other hand, the national health information systems are often not migrant-sensitive and evidence is still poor around mental health problems of refugees and migrants. Health financing remains a critical subject to address in a tailored way. The School highlighted the need to continue the exchange of experiences to promote a common approach to tackle similar needs.

Beneficial Contribution to Glucose Homeostasis by an Agro-Food Waste Product Rich in Abscisic Acid: Results from a Randomized Controlled Trial.

The control of glucose homeostasis represents the primary goal for the prevention and management of diabetes and prediabetes. In recent decades, the hypoglycemic hormone abscisic acid (ABA) has attracted considerable interest in the scientific literature. In this regard, the high ABA concentration in immature fruits led us to consider these food matrices as candidates for diabetes control. Therefore, the beneficial efficacy of a nutraceutical formulation based on thinned nectarines (TNs) rich in ABA was tested through a three-month, three-arm, parallel-group, randomized controlled trial (RCT) conducted on sixty-one patients with type 2 diabetes (T2D). After 3 months, both the treatments with low doses of TN (500 mg 3 times/day) and high doses of TN (750 mg 3 times/day) showed a significant reduction in glycemic parameters compared to baseline. Treatment with low doses of TN showed a greater insulin-sparing effect (fasting plasma insulin, FPI: −29.2%, p < 0.05 vs. baseline) compared to the high-dose group (FPI: −16.5%, p < 0.05 vs. baseline). Moreover, a significant correlation between glycemia and ABA plasmatic levels was observed for both intervention groups at baseline and after 3 months. Overall, our data reasonably support TN as a promising and innovative nutraceutical product able to contribute to the management of glucose homeostasis.

Genotoxic Assessment of Nutraceuticals Obtained from Agricultural Biowaste: Where Do We "AMES"?

Several pharmaceutical companies are nowadays considering the use of agri-food waste as alternative raw material for the extraction of bioactive compounds to include in nutraceuticals and food supplements. This recycling activity is encountering the support of authorities, which are alarmed by air, soil and water pollution generated by agricultural waste disposal. Waste reuse has several economic advantages: (i) its low cost; (ii) its abundance; (iii) the high content of bioactive molecule (antioxidants, minerals, fibers, fatty acids); as well as (iv) the financial support received by governments eager to promote eco-compatible and pollution-reducing practices. While nutraceuticals produced from biowaste are becoming popular, products that have been risk-assessed in terms of safety are quite rare. This despite waste biomass, in virtue of its chemical complexity, could, in many cases, mine the overall safety of the final nutraceutical product. In this review, we summarize the scientific results published on genotoxicity risk-assessment of bioactive compounds extracted from agricultural waste. The review depicts a scenario where the risk-assessment of biowaste derived products is still scarcely diffuse, but when available, it confirms the safety of these products, and lets us envisage their future inclusion in the list of botanicals allowed for formulation intended for human consumption.

Application of a Rapid and Simple Technological Process to Increase Levels and Bioccessibility of Free Phenolic Compounds in Annurca Apple Nutraceutical Product.

Insoluble bound polyphenols (ISBP) are polyphenolic compounds linked to the food matrix with different interactions limiting both their water extractability and consequent bioaccessibility. The health-promoting potential of polyphenols is historically known and well-demonstrated; specifically, Annurca apple polyphenols were studied both in vitro and in vivo for their effect in controlling cholesterol plasma levels. The aim of the study was the preparation of nutraceutical products based on Annurca apple polyphenolic fraction through the application of a technological process (acid treatment) able to release the ISBP from Annurca apple food matrix and increase polyphenol bioaccessibility. Lyophilized annurca apple (LAA) underwent acid treatment (ATLAA), and differences in released polyphenol levels were analysed by DAD-HPLC. Free-polyphenol levels in samples treated under acid conditions were higher than in untreated ones; in particular, for oligomeric flavan-3-ols (+168% procyanidin B2, +42.97% procyanidin B1 and B2, +156.99% procyanidin C1), catechin (+512.20%), and gallic acid (+707.77%). Furthermore, ATLAA underwent an in vitro gastrointestinal digestion to evaluate the bioaccessibility of contained polyphenols, in comparison to the untreated Annurca apple. The bioaccessibility study indicates a valuable preservation of polyphenolic fraction compared to the control.

A Phase II Study on the Effect of Taurisolo® Administered via AEROsol in Hospitalized Patients with Mild to Moderate COVID-19 Pneumonia: The TAEROVID-19 Study.

BACKGROUND: Polyphenols are the largest class of bioactive compounds in plants, which are synthesized as secondary metabolites. In the last few years, interesting studies have demonstrated the efficacy of polyphenols against coronavirus infections. METHODS: we conducted a phase II multicentric clinical trial (TAEROVID-19) during the first wave of the COVID-19 pandemic in order to assess the safety and feasibility of Taurisolo® aerosol formulation in hospitalized patients suffering from SARS-CoV-2 pneumonia. RESULTS: we observed a rapid decline of symptoms and a low rate of intensive care in patients treated with Taurisolo®, with a faster decline of symptoms. CONCLUSIONS: This is the first trial assessing the safety and feasibility of Taurisolo® aerosol formulation. We could argue that this treatment could act as an add-on therapy in the treatment of COVID-19 patients, owing to both its anti-inflammatory and antioxidant effects. Further controlled trials are needed, which may be of interest to evaluate the compound's efficacy.

Post-Bariatric Hypoglycemia Is Associated with Endothelial Dysfunction and Increased Oxidative Stress.

Post-bariatric hypoglycemia (PBH) is a potentially serious complication that may occur after bariatric surgery. Recurrent hypoglycemia may exert detrimental effects on vascular function. The aim of the present study was to evaluate endothelial function and oxygen reactive compounds in patients who experience PBH compared with controls. We performed a cross-sectional study on subjects with PBH (HYPO) and those without (NO-HYPO), detected by seven-day continuous glucose monitoring (CGM) performed at least twelve months after bariatric surgery. We enrolled 28 post-bariatric subjects (17.9% males, mean age 40.6 ± 10.7 years), with 18 in the HYPO group and 10 in the NO-HYPO group. In the two groups, we measured brachial artery flow-mediated dilation (FMD), oxidized low-density lipoproteins (oxLDL) and reactive oxygen metabolites (D-ROMs). The HYPO group had significantly lower FMD values than the NO-HYPO group (3.8% ± 3.0 vs. 10.5% ± 2.0, p < 0.001). A significant correlation was found between FMD and the time spent in hypoglycemia (rho = −0.648, p < 0.001), the number of hypoglycemic events (rho = −0.664, p < 0.001) and the mean glucose nadir (rho = 0.532, p = 0.004). The HYPO group showed significantly higher levels of D-ROMs (416.2 ± 88.7 UCARR vs. 305.5 ± 56.3 UCARR, p < 0.001) and oxLDLs (770.5 ± 49.7 µEq/L vs. 725.1 ± 51.6 µEq/L, p = 0.035) compared to the NO-HYPO group. In the multiple linear regression analysis, hypoglycemia independently predicted FMD values (ß = −0.781, p < 0.001), D-ROMs (ß = 0.548, p = 0.023) and oxLDL levels (ß = 0.409, p = 0.031). PBH is associated with impaired endothelial function accompanied by increased oxidative stress.

The Antioxidant Potential of the Mediterranean Diet as a Predictor of Weight Loss after a Very Low-Calorie Ketogenic Diet (VLCKD) in Women with Overweight and Obesity.

Obesity involves a chronic state of low-grade inflammation, which is linked to the development of several comorbidities. Recently, the very low-calorie ketogenic diet (VLCKD) has gained great interest in the treatment of obesity, almost ousting the ancient and healthy Mediterranean diet (MD). However, because these dietary regimens exploit different pathophysiological mechanisms, we hypothesize that adherence to the MD may play a role in determining the efficacy of the VLCKD. We enrolled 318 women (age 38.84 ± 14.37 years; BMI 35.75 ± 5.18 kg/m²) and assessed their anthropometric parameters, body compositions, and adherence to the MD (with the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire) at baseline. The anthropometric parameters and body composition were repeated at the end of the VLCKD. At the end of the VLCKD, the women with high adherence to the MD achieved the best results in terms of weight loss and improved body composition. Specifically, the women who were above the median of fat mass (FM)% reduction had the best MD pattern, characterized by a higher consumption of extra virgin olive oil (EVOO), fruits, vegetables, and red wine, as well as a higher adherence to the MD than the women who were below the same median. In a multiple regression analysis, the PREDIMED score was the main predictor of the FM% reduction score and came in first, followed by fruit, EVOO, and glasses of wine, in predicting the percentage reduction in FM. A PREDIMED score value of > 5 could serve as a threshold to identify patients who are more likely to lose FM at the end of the VLCKD. In conclusion, high adherence to the MD resulted in higher VLCKD efficacy. This could be due to the antioxidant and anti-inflammatory properties of the MD, which are capable of establishing a metabolic set-up that is favorable to the onset of more effective ketosis.

Polycystic ovary syndrome and cardiovascular risk. Could trimethylamine N-oxide (TMAO) be a major player? A potential upgrade forward in the DOGMA theory.

Several studies reported an increase in cardiovascular risk (CVR) in women with polycystic ovary syndrome (PCOS), considered primarily as the result of the combination of all the clinical features that characterize the syndrome, including hyperandrogenism, insulin resistance, diabetes, obesity chronic low-grade inflammation. Interestingly, in 2012 it has been proposed the so-called DOGMA theory, suggesting the pivotal role played by microbiota alteration in the development of PCOS. Subsequently, several authors evidenced the existence in PCOS women of a marked dysbiosis, which is related to the development of metabolic diseases and cardiovascular complications, mainly due to the production of bacteria-derived metabolites that interfere with various pathways. Among these, trimethylamine-N-oxide (TMAO) is emerging as one of the most important and studied microbiota-derived metabolites related to the increase in CVR, due to its pro-atherosclerotic effect. The purpose of the present review is to summarize the evidence in order to support the hypothesis that, in women with PCOS, dysbiosis might be further involved in enhancement of the CVR via contributing to the increase of circulating TMAO. Although no observational studies on a large number of patients directly investigated the serum levels of TMAO in PCOS women, this manuscript aimed to drive future studies in this field, concurring in providing a novel approach for both comprehension and treatment of the CVR in PCOS.

Taurisolo®, a Grape Pomace Polyphenol Nutraceutical Reducing the Levels of Serum Biomarkers Associated With Atherosclerosis.

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite recognized as strongly related to cardiovascular diseases (CVD), mainly increasing the risk of atherosclerosis development. Currently, no pharmacological approaches have been licensed for reduction of TMAO serum levels and conventional anti-atherosclerosis treatments only target the traditional risk factors, and the cardiovascular risk (CVR) still persist. This underlines the need to find novel targeted strategies for management of atherosclerosis. In this study we tested the ability of a novel nutraceutical formulation based on grape pomace polyphenols (Taurisolo®) in reducing both the serum levels of TMAO and oxidative stress-related biomarkers in humans (n = 213). After chronic treatment with Taurisolo® we observed significantly reduced levels of TMAO (-49.78 and -75.80%, after 4-week and 8-week treatment, respectively), oxidized LDL (oxLDL; -43.12 and -65.05%, after 4-week and 8-week treatment, respectively), and reactive oxygen species (D-ROMs; -34.37 and -49.68%, after 4-week and 8-week treatment, respectively). On the other hand, no significant changes were observed in control group. Such promising, the results observed allow indicating Taurisolo® as an effective nutraceutical strategy for prevention of atherosclerosis. Clinical Trial Registration: This study is listed on the ISRCTN registry with ID ISRCTN10794277 (doi: 10.1186/ISRCTN10794277).

Potential Functional Snacks: Date Fruit Bars Supplemented by Different Species of Lactobacillus spp.

The influence of the addition of four different potential probiotic strains, Lactiplantibacillus plantarum subsp. plantarum (L. plantarum), Lactobacillus delbruekii subsp. bulgaricus (L. bulgaricus), Lactobacillus acidophilus (L. acidophilus) and Lactinocaseibacillus rhamnosus (L. rhamnosus), in date fruit-based products was investigated in order to evaluate the possibility of producing a functional snack. All bacterial strains tested were able to grow in date fruit palp, reaching probiotic concentrations ranging from 3.1 × 109 to 4.9 × 109 colony-forming units after 48 h of fermentation, and the pH was reduced to 3.5-3.7 or below. The viability of inoculated probiotic bacteria after 4 weeks of storage at 4 °C was slightly reduced. Some biochemical features of the fermented snacks, such as the total phenolic content (TPC), antioxidant activity and detailed polyphenolic profile, were also evaluated. After fermentation, changes in the polyphenol profile in terms of increased free phenolic compounds and related activity were observed. These results may be attributed to the enzymatic activity of Lactobacillus spp. in catalyzing both the release of bioactive components from the food matrix and the remodeling of polyphenolic composition in favor of more bioaccessible molecules. These positive effects were more evident when the snack were fermented with L. rhamnosus. Our results suggest the use of lactic acid fermentation as an approach to enhance the nutritional value of functional foods, resulting in the enhancement of their health-promoting potential.

Ex Vivo Study on the Antioxidant Activity of a Winemaking By-Product Polyphenolic Extract (Taurisolo®) on Human Neutrophils.

Oxidative stress (OxS) has been linked to several chronic diseases and is recognized to have both major causes and consequences. The use of antioxidant-based nutraceuticals has been licensed as an optimal tool for management of OxS-related diseases. Currently, great interest is focused on the valorization of agri-food by-products as a source of bioactive compounds, including polyphenols. In this sense, we evaluated the efficacy of a novel nutraceutical formulation based on polyphenolic extract from Aglianico cultivar grape pomace (registered as Taurisolo®). In particular, we tested both native and in vitro gastrointestinal digested forms. The two extracts have been used to treat ex vivo neutrophils from subjects with metabolic syndrome, reporting a marked antioxidant activity of Taurisolo®, as shown by its ability to significantly reduce both the levels of reactive oxygen species (ROS) and the activities of catalase and myeloperoxidase in the cell medium after stimulation of neutrophils with phorbol 12-myristate 13-acetate (PMA). Interestingly, we observed an increase in intracellular enzymatic activities in PMA-treated cells, suggesting that Taurisolo® polyphenols might be able to activate nuclear factors, up-regulating the expression of this target antioxidant gene. In addition, Taurisolo® reversed the increase in malondialdehyde induced by PMA; reduced the expression of pro-inflammatory genes such as cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNFα) and myeloperoxidase (MPO); and induced the expression of the anti-inflammatory cytokine IL-10. Overall, these results suggest the efficacy of Taurisolo® in contrasting the OxS at blood level, providing evidence for its therapeutic potential in the management of OxS-related pathological conditions in humans.

The neuroprotective effects of polyphenols, their role in innate immunity and the interplay with the microbiota.

Neurodegenerative disorders, particularly in the elderly population, represent one of the most pressing social and health-care problems in the world. Besides the well-established role of both oxidative stress and inflammation, alterations of the immune response have been found to be closely linked to the development of neurodegenerative diseases. Interestingly, various scientific evidence reported that an altered gut microbiota composition may contribute to the development of neuroinflammatory disorders. This leads to the proposal of the concept of the gut-brain-immune axis. In this scenario, polyphenols play a pivotal role due to their ability to exert neuroprotective, immunomodulatory and microbiota-remodeling activities. In the present review, we summarized the available literature to provide a scientific evidence regarding this neuroprotective and immunomodulatory effects and the interaction with gut microbiota of polyphenols and, the main signaling pathways involved that can explain their potential therapeutic application in neurodegenerative diseases.

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function.

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.

Diet-Derived Antioxidants and Their Role in Inflammation, Obesity and Gut Microbiota Modulation.

It is generally accepted that gut microbiota, inflammation and obesity are linked to the development of cardiovascular diseases and other chronic/non-communicable pathological conditions, including cancer, neurodegenerative diseases and ageing-related disorders. In this scenario, oxidative stress plays a pivotal role. Evidence suggests that the global dietary patterns may represent a tool in counteracting oxidative stress, thus preventing the onset of diseases related to oxidative stress. More specifically, dietary patterns based on the regular consumption of fruits and vegetables (i.e., Mediterranean diet) have been licensed by various national nutritional guidelines in many countries for their health-promoting effects. Such patterns, indeed, result in being rich in specific components, such as fiber, minerals, vitamins and antioxidants, whose beneficial effects on human health have been widely reported. This suggests a potential nutraceutical power of specific dietary components. In this manuscript, we summarize the most relevant evidence reporting the impact of dietary antioxidants on gut microbiota composition, inflammation and obesity, and we underline that antioxidants are implicated in a complex interplay between gut microbiota, inflammation and obesity, thus suggesting their possible role in the development and modulation of chronic diseases related to oxidative stress and in the maintenance of wellness. Do all roads lead to Rome?