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.

Assessing gender differences in food preferences and physical activity: a population-based survey.

Introduction: Food preferences are influenced by various factors, such as culture, age, and gender. The relationship between food tastes, meal preferences, and eating habits has been studied extensively in recent years; however, research on gender differences in these fields still needs to be addressed. The aim of this study was to investigate gender differences in food preferences and eating habits through self-administered questionnaires in a large Italian population sample. Methods: The online survey included questions on food tastes, meal preferences, eating habits, and sport involvement. Results: The results of the study underline significant gender-specific dietary tendencies among the 2198 participants (1314 females and 884 males, average age 41.1 ± 12.7 yrs). The majority of subjects were in the annual income range between €20,000 and €40,000. Our analysis reveals significant gender differences in dietary preferences and eating habits. Men prefer red and processed meat, with significantly higher consumption rates than women. Women, on the other hand, show a greater inclination towards vegetables, whole grains, tofu, and high-cocoa-content dark chocolate, aligning with healthier food choices. The study also found differences in eating behaviors, including the frequency of meals, snacking habits, and hunger patterns: women tend to eat more frequently and report higher levels of hunger in the morning, while men tend to skip snacks. Furthermore, differences extend to eating contexts, such as the speed of eating, eating out, and eating alone, with men more likely to eat quickly and dine out. Episodes of uncontrolled eating without hunger also differ, with women reporting these behaviors more frequently than men. In addition, the analysis of sports preferences showed distinct patterns, with a lower percentage of women playing sports and those who do play sports preferring endurance and strength training, while men prefer strength training and endurance sports. Discussion: These findings elucidate the complex interplay of biological, cultural, and gender-based factors in shaping dietary preferences and eating behaviors. In particular, our study reveals that gender dynamics significantly influence food choice and eating habits: women tend to choose healthier foods and eat regular meals, while men show preferences for specific tastes and meal-related behaviors. This analysis underscores the nuanced differences between male and female dietary patterns, influenced not only by inherent biological factors such as genetics and hormonal responses but also by societal norms and cultural contexts. Taken together, our results highlight the importance of integrating different perspectives, thus providing valuable insights into the development of public health strategies and tailored nutrition interventions aimed at chronic disease prevention.

Effects of Different Nutritional Patterns and Physical Activity on Body Composition: A Gender and Age Group Comparative Study.

This cross-sectional study analyses differences in dietary habits, taste preferences, variety of protein sources and body composition (BC) profiles among individuals following omnivorous, flexitarian, lacto-ovo-vegetarian and pescatarian diets. Furthermore, it assesses the correlations between these dietary patterns and various sports, classified by exercise intensity, in relation to BC parameters. The study analysed the eating habits and BC data of 1342 participants aged 18-65 years, classified into four diet groups based on their 7-day food diaries and questionnaire responses. Our analysis revealed gender- and age-related differences in weekly food consumption and protein source variety, with men generally consuming more meat, processed meat and fish than women, especially in younger age groups. Differences in dairy and soy consumption were also noted between age groups, while legume and soy preferences showed no gender disparity across all ages. Among non-sporting individuals, vegetarians exhibited lower fat mass (FM%) compared to other diets, while among athletes, vegetarians and pescatarians in in endurance and strength sports, respectively, displayed lower FM%, with flexitarians and omnivores in endurance sports showing higher FM%. Non-athletic omnivores and vegetarians demonstrated a greater proportion of body protein, while among athletes, those engaged in strength training exhibited a higher body protein content across all dietary groups compared to those in endurance training. Among non-athletic groups, vegetarians exhibited the lowest FM/FFM (fat mass/fat-free mass) ratio, while among athletes, vegetarians in endurance sports and participants in strength training across other diets showed lower FM/FFM ratios. The results emphasise the complex interaction between diet, BC and lifestyle choices, revealing how different combinations of diet and sport are associated with optimised BC.

Investigating the Health Implications of Whey Protein Consumption: A Narrative Review of Risks, Adverse Effects, and Associated Health Issues.

This narrative review critically examines the current research on the health implications of whey protein (WP) supplementation, with a focus on potential risks and adverse effects. WP, commonly consumed for muscle building and weight loss, has been associated with various health concerns. Our comprehensive analysis involved a thorough search of multiple databases, resulting in the inclusion of 21 preclinical and human studies that collectively offer a detailed overview of WP's health impacts. The review reveals significant findings, such as WP's potential link to liver and kidney damage, alterations in gut microbiota, increased acne incidence, impacts on bone mass, and emotional and behavioural changes. These findings underscore the complexity of WP's effects on human health, indicating both beneficial and detrimental outcomes in relation to different posologies in a variety of settings. Our study suggests caution for the protein intake in situations of hepatic and renal compromised functions, as well as in acne susceptibility, while possible beneficial effects can be achieved for the intestinal microbiota, humoral and behavioural level, and finally bone and muscle mass in elderly. We emphasizes the importance of balanced WP consumption and call for more in-depth research to understand its long-term health effects. Health professionals and individuals considering WP supplementation should be aware of these potential risks and approach its use with informed caution.

Mineralocorticoid Receptor Antagonism Prevents Type 2 Familial Partial Lipodystrophy Brown Adipocyte Dysfunction.

Type-2 Familial Partial Lipodystrophy (FPLD2), a rare lipodystrophy caused by LMNA mutations, is characterized by a loss of subcutaneous fat from the trunk and limbs and excess accumulation of adipose tissue in the neck and face. Several studies have reported that the mineralocorticoid receptor (MR) plays an essential role in adipose tissue differentiation and functionality. We previously showed that brown preadipocytes isolated from a FPLD2 patient's neck aberrantly differentiate towards the white lineage. As this condition may be related to MR activation, we suspected altered MR dynamics in FPLD2. Despite cytoplasmic MR localization in control brown adipocytes, retention of MR was observed in FPLD2 brown adipocyte nuclei. Moreover, overexpression of wild-type or mutated prelamin A caused GFP-MR recruitment to the nuclear envelope in HEK293 cells, while drug-induced prelamin A co-localized with endogenous MR in human preadipocytes. Based on in silico analysis and in situ protein ligation assays, we could suggest an interaction between prelamin A and MR, which appears to be inhibited by mineralocorticoid receptor antagonism. Importantly, the MR antagonist spironolactone redirected FPLD2 preadipocyte differentiation towards the brown lineage, avoiding the formation of enlarged and dysmorphic lipid droplets. Finally, beneficial effects on brown adipose tissue activity were observed in an FPLD2 patient undergoing spironolactone treatment. These findings identify MR as a new lamin A interactor and a new player in lamin A-linked lipodystrophies.

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.

Very-low-calorie ketogenic diet vs hypocaloric balanced diet in the prevention of high-frequency episodic migraine: the EMIKETO randomized, controlled trial.

BACKGROUND: Migraine is the second world's cause of disability. Among non-pharmacological treatments, nutritional intervention, particularly ketogenic diet, represents one of the most promising approaches. METHODS: This a prospective, single center, randomized, controlled study aimed at evaluating the efficacy of a very low-calorie ketogenic diet (VLCKD) compared to a hypocaloric balanced diet (HBD) in migraine prophylaxis in patients affected by high-frequency episodic migraine (HFEM) with a Body Mass Index (BMI) > 27 kg/m2. Fifty-seven patients were randomly assigned to a VLCKD (group 1) or HBD (group 2). Group 1 patients followed a VLCKD for 8 weeks, followed by a low calorie diet (LCD, weeks 9-12), and a HBD (weeks 13-24), whereas group 2 patients followed a HBD from week 0 to 24. Anthropometric indexes, urine and blood chemistry were assessed at enrollment, baseline, weeks 4, 8, 12, and 24. Migraine characteristics were evaluated at baseline, weeks 8, 12 and 24. Change in monthly migraine days (MMDs) at weeks 5-8 compared to baseline was the primary endpoint. Secondary endpoints encompassed changes in visual analogue scale (VAS), Headache Impact Test-6 (HIT-6) and Short Form Health Survey-36 (SF-36) scores. We also studied effects on circulating lymphocytes and markers of inflammation, changes in plasma aldosterone and renin levels before and after VLCKD or HBD treatment. RESULTS: Reduction from baseline in MMDs was greater in VLCKD compared to HBD group at week 8 (p = 0.008), at week 12 (p = 0.007), when ketosis had been interrupted by carbohydrates reintroduction, and at week 24 (p = 0.042), when all patients were following the same dietary regimen. Quality of life scores (SF-36) were improved in VLCKD group at week 8 and 12, and were also improved in HBD group, but only at week 12. Weight-loss was significantly higher in VLCKD group at week 8 (p = 0.002) and week 12 (p = 0.020). At the end of the study weight loss was maintained in VLCKD group whereas a slight weight regain was observed in HBD group. Inflammatory indexes, namely C reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and total white blood cell count (WBC) were significantly reduced (p < 0.05) in VLCKD group at week 12. Aldosterone plasma level were significantly increased in both groups at week 8, particularly in VLCKD group. However, electrolytes and renin plasma levels were never altered throughout the study in both groups. CONCLUSIONS: VLCKD is more effective than HBD in reducing MMD in patients with HFEM and represents an effective prophylaxis in patients with overweight/obesity. Trial registration ClinicalTrials.gov identifier: NCT04360148.

Ketogenic Diet as a Possible Non-pharmacological Therapy in Main Endocrine Diseases of the Female Reproductive System: A Practical Guide for Nutritionists.

PURPOSEOF REVIEW: This narrative review explored the role of ketogenic diets (KDs) in improving fertility outcomes, low-grade inflammation, body weight, visceral adipose tissue, and its potential use in certain types of cancer, through its favorable actions on mitochondrial function, reactive oxygen species generation, chronic inflammation, and tumor growth inhibition. RECENT FINDINGS  : Nutrition is crucial to maintain the female reproductive system's health. Evidence on the association between diet and female reproductive system has greatly expanded over the last decade, leading to the identification of specific diet therapy, particularly KDs. KDs has been proved to be an effective weight-loss tool. To date, KDs is being increasingly used in the treatment of many diseases, such as obesity, type 2 diabetes mellitus. KDs is a dietary intervention capable of ameliorating the inflammatory state and oxidative stress through several mechanisms. Due to the increasing use of KDs beyond obesity, this literature review will provide the latest scientific evidence of its possible use in common disorders of the female endocrine-reproductive tract, and a practical guide to its use in these patients.

Prolonged clinical remission of type 1 diabetes sustained by calcifediol and low-dose basal insulin: a case report.

Herein, we describe an unusually prolonged duration (31 months) of the clinical remission phase in a 22-year-old Italian man with new-onset type 1 diabetes. Shortly after the disease diagnosis, the patient was treated with calcifediol (also known as 25-hydroxyvitamin D3 or calcidiol), coupled with low-dose basal insulin, to correct hypovitaminosis D and to exploit the anti-inflammatory and immunomodulatory properties of vitamin D. During the follow-up period, the patient retained a substantial residual ß-cell function and remained within the clinical remission phase, as evidenced by an insulin dose-adjusted glycated hemoglobin value <9. At 24 months, we detected a peculiar immunoregulatory profile of peripheral blood cells, which may explain the prolonged duration of the clinical remission sustained by calcifediol as add-on treatment to insulin.

We describe the case of a 22-year-old Italian man who was treated with a form of vitamin D called calcifediol shortly after the diagnosis of type 1 diabetes, which is an autoimmune condition leading to insulin deficiency and to the lifelong need for insulin therapy. Calcifediol was administered, coupled with low-dose insulin, to correct vitamin D insufficiency and to exploit the anti-inflammatory properties of vitamin D. During the follow-up period (31 months), the patient unexpectedly remained on once-daily insulin injection therapy and maintained near-normal blood glucose levels. These findings suggest that calcifediol administration may represent a valid add-on treatment to insulin, with the aim of reducing daily insulin requirements and improving glucose control in patients with recent-onset type 1 diabetes.

Sustainable Strategies for Increasing Legume Consumption: Culinary and Educational Approaches.

Legumes are nutrient-dense crops with health-promoting benefits. However, several barriers are associated with their consumption. Emerging issues including food neophobic tendencies or taboos, unclear dietary guidelines on legume consumption, health concerns, and socio-economic reasons, as well as long cooking procedures, adversely affect legume consumption frequency. Pre-treatment methods, including soaking, sprouting, and pulse electric field technology, are effective in reducing the alpha-oligosaccharides and other anti-nutritional factors, eventually lowering cooking time for legumes. Extrusion technology used for innovative development of legume-enriched products, including snacks, breakfast cereals and puffs, baking and pasta, represents a strategic way to promote legume consumption. Culinary skills such as legume salads, legume sprouts, stews, soups, hummus, and the development of homemade cake recipes using legume flour could represent effective ways to promote legume consumption. This review aims to highlight the nutritional and health effects associated with legume consumption, and strategies to improve their digestibility and nutritional profile. Additionally, proper educational and culinary approaches aimed to improve legumes intake are discussed.

Neutral Effect of Skeletal Muscle Mineralocorticoid Receptor on Glucose Metabolism in Mice.

The mineralocorticoid receptor (MR) is able to regulate the transcription of a number of genes in the myotube, although its roles in skeletal muscle (SM) metabolism still await demonstration. SM represents a major site for glucose uptake, and its metabolic derangements play a pivotal role in the development of insulin resistance (IR). The aim of this study was to investigate the contribution of SM MR in mediating derangements of glucose metabolism in a mouse model of diet-induced obesity. We observed that mice fed a high-fat diet (HFD mice) showed impaired glucose tolerance compared to mice fed a normal diet (ND mice). Mice fed a 60% HFD treated with the MR antagonist Spironolactone (HFD + Spiro) for 12 weeks revealed an improvement in glucose tolerance, as measured with an intraperitoneal glucose tolerance test, compared with HFD mice. To investigate if blockade of SM MR could contribute to the favorable metabolic effects observed with pharmacological MR antagonism, we analyzed MR expression in the gastrocnemius, showing that SM MR protein abundance is downregulated by HFD compared to ND mice and that pharmacological treatment with Spiro was able to partially revert this effect in HFD + Spiro mice. Differently from what we have observed in adipose tissue, where HDF increased adipocyte MR expression, SM MR protein was down-regulated in our experimental model, suggesting a completely different role of SM MR in the regulation of glucose metabolism. To confirm this hypothesis, we investigated the effects of MR blockade on insulin signaling in a cellular model of IRin C2C12 myocytes, which were treated with or without Spiro. We confirmed MR protein downregulation in insulin-resistant myotubes. We also analyzed Akt phosphorylation upon insulin stimulation, and we did not observe any difference between palmitate- and palmitate + Spiro-treated cells. These results were confirmed by in vitro glucose uptake analysis. Taken together, our data indicate that reduced activity of SM MR does not improve insulin signaling in mouse skeletal myocytes and does not contribute to the favorable metabolic effects on glucose tolerance and IR induced by systemic pharmacological MR blockade.

Very Low-Calorie Ketogenic Diet (VLCKD) as Pre-Operative First-Line Dietary Therapy in Patients with Obesity Who Are Candidates for Bariatric Surgery.

Bariatric surgery is currently the most effective method for achieving long-term weight loss and reducing the risk of comorbidities and mortality in individuals with severe obesity. The pre-operative diet is an important factor in determining patients' suitability for surgery, as well as their post-operative outcomes and success in achieving weight loss. Therefore, the nutritional management of bariatric patients requires specialized expertise. Very low-calorie diets and intragastric balloon placement have already been studied and shown to be effective in promoting pre-operative weight loss. In addition, the very low-calorie ketogenic diet has a well-established role in the treatment of obesity and type 2 diabetes mellitus, but its potential role as a pre-operative dietary treatment prior to bariatric surgery has received less attention. Thus, this article will provide a brief overview of the current evidence on the very low-calorie ketogenic diet as a pre-operative dietary treatment in patients with obesity who are candidates for bariatric surgery.

Health Effects of Red Wine Consumption: A Narrative Review of an Issue That Still Deserves Debate.

A strong controversy persists regarding the effect of red wine (RW) consumption and health. Guidelines for the prevention of cardiovascular diseases (CVD) and cancers discourage alcohol consumption in any form, but several studies have demonstrated that low RW intake may have positive effects on CVD risk. This review evaluated randomised controlled trials (RCTs), examining the recent literature on the correlations between acute and chronic RW consumption and health. All RCTs published in English on PubMed from 1 January 2000 to 28 February 2023 were evaluated. Ninety-one RCTs were included in this review, seven of which had a duration of more than six months. We assessed the effect of RW on: (1) antioxidant status, (2) cardiovascular function, (3) coagulation pathway and platelet function, (4) endothelial function and arterial stiffness, (5) hypertension, (6) immune function and inflammation status, (7) lipid profile and homocysteine levels, (8) body composition, type 2 diabetes and glucose metabolism, and (9) gut microbiota and the gastrointestinal tract. RW consumption mostly results in improvements in antioxidant status, thrombosis and inflammation markers, lipid profile, and gut microbiota, with conflicting results on hypertension and cardiac function. Notably, beneficial effects were observed on oxidative stress, inflammation, and nephropathy markers, with a modest decrease in CVD risk in five out of seven studies that evaluated the effect of RW consumption. These studies were conducted mainly in patients with type 2 diabetes mellitus, and had a duration between six months and two years. Additional long-term RCTs are needed to confirm these benefits, and assess the potential risks associated with RW consumption.

A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation.

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5+) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5+, or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5+ administration significantly reduced lipids' accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5+ inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5+ significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5+ may be able to counteract adipogenesis and then obesity by inducing fat browning.

Could very low-calorie ketogenic diets turn off low grade inflammation in obesity? Emerging evidence.

Obesity is an emerging non-communicable disease associated with chronic low-grade inflammation and oxidative stress, compounded by the development of many obesity-related diseases, such as cardiovascular disease, type 2 diabetes mellitus, and a range of cancers. Originally developed for the treatment of epilepsy in drug non-responder children, the ketogenic diet (KD) is being increasingly used in the treatment of many diseases, including obesity and obesity-related conditions. The KD is a dietary pattern characterized by high fat intake, moderate to low protein consumption, and very low carbohydrate intake (<50 g) that has proved to be an effective and weight-loss tool. In addition, it also appears to be a dietary intervention capable of improving the inflammatory state and oxidative stress in individuals with obesity by means of several mechanisms. The main activity of the KD has been linked to improving mitochondrial function and decreasing oxidative stress. ß-hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species, improving mitochondrial respiration. In addition, KDs exert anti-inflammatory activity through several mechanisms, e.g., by inhibiting activation of the nuclear factor kappa-light-chain-enhancer of activated B cells, and the inflammatory nucleotide-binding, leucine-rich-containing family, pyrin domain-containing-3, and inhibiting histone deacetylases. Given the rising interest in the topic, this review looks at the underlying anti-inflammatory and antioxidant mechanisms of KDs and their possible recruitment in the treatment of obesity and obesity-related disorders.