Scientific evidence demonstrates that a very low-calorie ketogenic diet (VLCKD) is effective and beneficial in the treatment of obesity, capable of reversing the methylome associated with obesity and has immunomodulatory capacity. This effect is in part promoted by nutritional ketosis and could be involved in counteracting obesity-related cancer. The aim of this study was to evaluate the effect of nutritional ketosis on the methylation of genes related to tumor processes in patients with obesity and in breast cancer cells. Based on methylome data (Infinium MethylationEPIC BeadChip, Illumina) from patients with obesity treated with a VLCKD for weight loss (n = 10; n = 5 women, age = 48.8 ± 9.20 years, BMI = 32.9 ± 1.4 kg/m2), genes belonging to cancer-related pathways were specifically evaluated and further validated in vitro in MDA-MB-231 (triple negative) and MCF7 (RE positive) breast tumor cells pretreated for 72 h with βOHB, the main ketone body, secretome from visceral (VATs) or subcutaneous (SATs) adipose tissue of patients with obesity. The cell tumoral phenotype was evaluated by proliferation assay and expression of cancer-related genes. VLCKD-induced nutritional ketosis promoted changes in the methylation of 18 genes (20 CpGs; 17 hypomethylated, 3 hypermethylated) belonged to cancer-related pathways with MAPK10, CCN1, CTNNA2, LAMC3 and GLI2 being the most representative genes. A similar pattern was observed in the MDA-MB-231 cells treated with β-OHB, without changes in MCF7. These epigenetic changes paralleled the tumoral phenotype modulated by the treatments. Taking together these results highlight the potential role of VLCKD as an adjuvant to anticancer treatment in groups more susceptible to the development of cancer such as patients with obesity, exerting epigenetic regulation through nutritional ketosis and weight loss.

This narrative review provides an overview of the various diagnostic tools used to assess cartilage health, with a focus on early detection, nutrition intervention, and management of osteoarthritis. Early detection of cartilage damage is crucial for effective patient management. Traditional diagnostic tools like radiography and conventional magnetic resonance imaging (MRI) sequences are more suited to detecting late-stage structural changes. This paper highlights advanced imaging techniques, including sodium MRI, T2 mapping, T1ρ imaging, and delayed gadolinium-enhanced MRI of cartilage, which provide valuable biochemical information about cartilage composition, particularly the glycosaminoglycan content and its potential links to nutrition-related factors influencing cartilage health. Cartilage degradation is often linked with inflammation and measurable via markers like CRP and IL-6 which, although not specific to cartilage breakdown, offer insights into the inflammation affecting cartilage. In addition to imaging techniques, biochemical markers, such as collagen breakdown products and aggrecan fragments, which reflect metabolic changes in cartilage, are discussed. Emerging tools like optical coherence tomography and hybrid positron emission tomography-magnetic resonance imaging (PET-MRI) are also explored, offering high-resolution imaging and combined metabolic and structural insights, respectively. Finally, wearable technology and biosensors for real-time monitoring of osteoarthritis progression, as well as the role of artificial intelligence in enhancing diagnostic accuracy through pattern recognition in imaging data are addressed. While these advanced diagnostic tools hold great potential for early detection and monitoring of osteoarthritis, challenges remain in clinical translation, including validation in larger populations and integration into existing clinical workflows and personalized treatment strategies for cartilage-related diseases.

Background: Obesity impairs renal function through direct mechanisms, such as proinflammatory adipocytokine production, and indirect mechanisms, including obesity-related comorbidities. Despite the increasing prevalence of obesity and chronic kidney disease (CKD), clinical guidelines for their combined management remain lacking. Very Low Energy Ketogenic Therapy (VLEKT) has demonstrated efficacy in weight loss, but evidence on its safety and efficacy in individuals with obesity and mild renal impairment is limited. This study aimed to assess the efficacy and safety of Phase 1 of VLEKT in individuals with obesity and mild renal impairment. Methods: This cross-sectional study included 73 individuals with overweight or obesity (mean age 53.7 ± 8.8 years; BMI 35.3 ± 4.2 kg/m2) and an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2 (evaluated using the CKD-EPI equation). Anthropometric (weight, BMI, and waist circumference) and biochemical parameters (fasting plasma glucose, insulin, cholesterol profile, triglycerides, AST, ALT, and urea) were collected at baseline and after 45 (±2) days of Phase 1 of VLEKT. Results: At baseline, 54.8% of participants had an eGFR <90 mL/min/1.73 m2, while 45.2% had an eGFR ≥ 90 mL/min/1.73 m2, with no significant differences in sex distribution. After 45 (±2) days of Phase 1 of VLEKT, both groups showed significant reductions in BMI (p < 0.001), waist circumference (p < 0.001), fasting plasma glucose (p ≤ 0.004), insulin (p < 0.001), HOMA-IR (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), LDL/HDL ratio (p ≤ 0.002), triglycerides (p ≤ 0.009), AST (p ≤ 0.034), and ALT (p ≤ 0.009). Notably, the eGFR significantly increased in participants with an eGFR < 90 mL/min/1.73 m2 (p < 0.001), while no changes were observed in those with an eGFR ≥ 90 mL/min/1.73 m2. Conclusions: Phase 1 of VLEKT could effectively promote weight loss and metabolic improvements without compromising renal function, even in individuals with obesity and mild renal impairment. Further research is warranted to confirm the efficacy and safety of VLEKT and to assess outcomes across all protocol phases.

Obesity is constantly growing worldwide, representing a serious concern also for healthcare costs. Current anti-obesity pharmacological strategies, although effective, represent a significant cost for the patient. Similarly, very low energy ketogenic therapy (VLEKT) protocols with replacement meals also have high costs.

The objective of this study was to estimate the average costs of a VLEKT protocol with replacement meals compared with those of isocaloric diets with fresh foods.

VLEKTs with replacement meals and fresh foods were developed considering an ideal young woman and man with grade II obesity (BMI ≥ 35.0 kg/m2). The costs of the individual fresh foods were extrapolated from official Italian databases. The costs of replacement meals were obtained by consulting the catalogs of three companies specialized in VLEKTs operating in Italy.

On a monthly basis, VLEKT with fresh food had an average cost of EUR 253.44 and EUR 295.67, while VLEKT with replacement meals had an average cost of EUR 434.91 and EUR 535.99, for the woman and man, respectively.

Although more expensive than a common diet, VLEKT should be seen not only as a dietary method for losing weight, but as a non-pharmacological, medicalized nutritional therapy, useful for managing various conditions, even those not directly related to obesity. Like a drug therapy, VLEKT requires the use of specific products that entail a higher cost, to be borne by the patient, but whose benefits should be emphasized, which go beyond weight loss and concern general health, thus considering them as a targeted nutritional strategy.

Although little is yet known about the long-term maintenance of very low-energy ketogenic therapy (VLEKT) effects on body composition, muscle strength and inflammation, it is plausible to assume that changes may occur, particularly during the steps following the ketogenic step, due to the loss of the protective effects of ketones and the concomitant reintroduction of carbohydrates. For this reason, the present study aimed to evaluate the effects of supplementation with 8 g per day of essential amino acids (EAAs) on these parameters.

A total of 68 women of reproductive age and with grade I obesity who had completed 45 days of the ketogenic phase with VLEKT (KeNuT protocol) and 40 days of non-ketogenic phase of KeNuT protocol with VLEKT (phase 3, fruit reintroduction) were included in the study. Half of them (n = 34) followed this first step of the re-educational phase of KeNuT protocol with VLEKT with supplementation with EAAs (Aminotrofic®: 4 g twice daily). Anthropometric parameters, body composition via bioelectrical impedance analysis and high-sensitivity C-reactive protein (hs-CRP) levels were assessed at baseline, pre- and post both dietary interventions.

At the end of 45 days of ketogenic phase with VLEKT (before fruit reintroduction and EAA supplementation), the two groups did not differ in any of the parameters assessed. At the end of the fruit reintroduction phase, the supplemented group showed greater magnitudes of reduction in weight, waist circumference, fat mass (FM) and hs-CRP (p < 0.001 for all) and of increase in muscle strength (p < 0.001), phase angle (p < 0.001), body cell mass (BCM) (p = 0.001), and muscle mass (%) (p < 0.001).

These results underline the usefulness of supplementation with EAAs during the first transitional phase post VLEKT to improve body composition (specifically reduction in FM and increase in BCM), muscle strength, and inflammatory status.

This narrative review explores the role of Medical Nutritional Therapy (MNT) in managing Metabolic-Associated Steatotic Liver Disease (MASLD), previously known as nonalcoholic fatty liver disease. It aims to examine the effectiveness of specific nutritional strategies in preventing and treating this obesity-linked liver disease.

Emerging evidence underscores the benefits of the Mediterranean diet, low-carbohydrate diets, and intermittent fasting in reducing liver fat, improving insulin sensitivity, and mitigating inflammation. Supplementing with vitamin E, omega-3 fatty acids, and silymarin can potentially reduce liver fibrosis and promote liver health. MNT is a key intervention for MASLD management, emphasizing dietary patterns, caloric restriction, and nutraceutical supplementation. Integrating these strategies with lifestyle modifications, including regular physical activity, offers a comprehensive approach to improving metabolic and liver outcomes in patients with MASLD. Further research is needed to refine and personalize these therapeutic interventions.

Background/Objectives: Managing type 2 diabetes mellitus (T2DM) and obesity requires a multidimensional, patient-centered approach including nutritional interventions (NIs) and physical activity. Changes in the gut microbiota (GM) have been linked to obesity and the metabolic alterations typical of T2DM and obesity, and they are strongly influenced by diet. However, few studies have evaluated the effects on the GM of a very-low-calorie ketogenic diet (VLCKD) in patients with T2DM, especially in the mid-term and long-term. This longitudinal study is aimed at evaluating the mid-term and long-term impact of the VLCKD and Mediterranean diet (MD) on the GM and on the anthropometric, metabolic, and lifestyle parameters of 11 patients with T2DM and obesity (diabesity). This study extends previously published results evaluating the short-term (three months) impact of these NIs on the same patients. Methods: At baseline, patients were randomly assigned to either a VLCKD (KETO group) or a Mediterranean diet (MEDI group). After two months, the KETO group gradually shifted to a Mediterranean diet (VLCKD-MD), according to current VLCKD guidelines. From the fourth month until the end of the study both groups followed a similar MD. Previous published results showed that VLCKD had a more beneficial impact than MD on several variables for 3 months of NI. In this study, the analyses were extended until six (T6) and twelve months (T12) of NI by comparing data prospectively and against baseline (T0). The GM analysis was performed through next-generation sequencing. Results: Improvements in anthropometric and metabolic parameters were more pronounced in the KETO group at T6, particularly for body mass index (-5.8 vs. -1.7 kg/m2; p = 0.006) and waist circumference (-15.9 vs. -5.2 cm; p = 0.011). At T6, a significant improvement in HbA1c (6.7% vs. 5.5% p = 0.02) and triglyceride (158 vs. 95 mg/dL p = 0.04) values compared to T0 was observed only in the KETO group, which maintained the results achieved at T3. The VLCKD-MD had a more beneficial impact than the MD on the GM phenotype. A substantial positive modulatory effect was observed especially up to the sixth month of the NI in KETO due to the progressive increase in bacterial markers of human health. After the sixth month, most markers of human health decreased, though they were still increased compared with baseline. Among them, the Verrucomicrobiota phylum was identified as the main biomarker in the KETO group, together with its members Verrucomicrobiae, Akkermansiaceae, Verrucomicrobiales, and Akkermansia at T6 compared with baseline. Conclusions: Both dietary approaches ameliorated health status, but VLCKD, in support of the MD, has shown greater improvements on anthropometric and metabolic parameters, as well as on GM profile, especially up to T6 of NI.

Metaproteomics is a valuable approach to characterize the biological functions involved in the gut microbiota (GM) response to dietary interventions. Ketogenic diets (KDs) are very effective in controlling seizure severity and frequency in drug-resistant epilepsy (DRE) and in the weight loss management in obese/overweight individuals. This case study provides proof of concept for the suitability of metaproteomics to monitor changes in taxonomic and functional GM features in an individual on a short-term very low-calorie ketogenic diet (VLCKD, 4 weeks), followed by a low-calorie diet (LCD). A marked increase in Akkermansia and Pseudomonadota was observed during VLCKD and reversed after the partial reintroduction of carbohydrates (LCD), in agreement with the results of previous metagenomic studies. In functional terms, the relative increase in Akkermansia was associated with an increased production of proteins involved in response to stress and biosynthesis of gamma-aminobutyric acid. In addition, VLCKD caused a relative increase in enzymes involved in the synthesis of the beta-ketoacid acetoacetate and of the ketogenic amino acid leucine. Our data support the potential of fecal metaproteomics to investigate the GM-dependent effect of KD as a therapeutic option in obese/overweight individuals and DRE patients.

Background/Objectives: The ketogenic diet (KD) is a dietary model that can impact metabolic health and microbiota and has been widely discussed in recent years. This study aimed to evaluate the effects of a 6-week KD on biochemical parameters, gut microbiota, and fecal short-chain fatty acids (SCFAs) in women with overweight/obesity. Methods: Overall, 15 women aged 26-46 years were included in this study. Blood samples, fecal samples, and anthropometric measurements were evaluated at the beginning and end of this study. Results: After KD, the mean body mass index decreased from 29.81 ± 4.74 to 27.12 ± 4.23 kg/m2, and all decreases in anthropometric measurements were significant (p < 0.05). Fasting glucose, insulin, homeostasis model assessment of insulin resistance, hemoglobin A1C, urea, and creatinine levels decreased, whereas uric acid levels increased (p < 0.05). Furthermore, increased serum zonulin levels were noted (p = 0.001), whereas fecal butyrate, propionate, acetate, and total SCFA levels decreased (p < 0.05). When the changes in microbiota composition were examined, a decrease in beta diversity (p = 0.001) was observed. After the intervention, a statistically significant increase was noted in the Firmicutes/Bacteroidetes ratio (p = 0.001). Although Oscilibacter, Blautia, and Akkermensia relative abundances increased, Prevotella relative abundance and Bifidobacter abundance, which were the dominant genera before the KD, decreased. Moreover, the abundance of some pathogenic genera, including Escherichia, Klebsilella, and Listeria, increased. Conclusions: In healthy individuals, KD may cause significant changes in microbial composition, leading to dysbiosis and long-term adverse outcomes with changes in serum zonulin and fecal SCFA levels.

Introduction: The ketogenic diet (KD) is widely used for weight management by reducing appetite, enhancing fat oxidation, and facilitating weight loss. However, the high content of total and saturated fats in a conventional KD may elevate low-density lipoprotein (LDL)-cholesterol levels, a known risk factor for cardiovascular diseases, highlighting the need for healthier alternatives. This study aimed to investigate the effect of a newly developed Healthy Ketogenic Diet (HKD) versus an Energy-Restricted Diet (ERD) on weight loss and metabolic outcomes among adults with obesity. Methods: Multi-ethnic Asian adults (n = 80) with body mass index ≥ 27.5 kg/m2 were randomized either to HKD (n = 41) or ERD (n = 39) for 6 months. Both groups followed an energy-restricted healthy diet, emphasizing on reducing saturated and trans fats. The HKD group additionally limited net carbohydrate intake to no more than 50 g per day. Dietary adherence was supported via the Nutritionist Buddy app with dietitian coaching. The primary outcome was weight change from baseline at 6 months. Secondary outcomes included weight change at 3 months and 1 year, along with changes in metabolic profiles. Data were analyzed using linear regression with an intention-to-treat approach. Results: The HKD group achieved significantly greater mean weight loss at 6 months than the ERD group (-7.8 ± 5.2 kg vs. -4.2 ± 5.6 kg, p = 0.01). The mean weight loss percentage at 6 months was 9.3 ± 5.9% and 4.9 ± 5.8% for the HKD and ERD groups, respectively (p = 0.004). Improvements in metabolic profiles were also significantly better in the HKD group [glycated hemoglobin (-0.3 ± 0.3% vs. -0.1 ± 0.2%, p = 0.008), systolic blood pressure (-7.7 ± 8.9 mmHg vs. -2.6 ± 12.2 mmHg, p = 0.005), and aspartate transaminase (-7.6 ± 15.5 IU/L vs. 0.6 ± 11.5 IU/L, p = 0.01)], with no increase in LDL-cholesterol (-0.12 ± 0.60 mmol/L vs. -0.04 ± 0.56 mmol/L, p = 0.97) observed in either group. Conclusions: The HKD was more effective than the ERD in promoting weight loss and improving cardiometabolic outcomes without elevation in LDL-cholesterol. It can be recommended for therapeutic intervention in patients with obesity.

Obesity has emerged as a significant public health crisis, closely linked to the pathogenesis and progression of chronic kidney disease (CKD). This review explores the intricate relationship between obesity-induced lipid metabolism disorders and renal health. We discuss how excessive free fatty acids (FFAs) lead to lipid accumulation in renal tissues, resulting in cellular lipotoxicity, oxidative stress, and inflammation, ultimately contributing to renal injury. Key molecular mechanisms, including the roles of transcriptional regulators like PPARs and SREBP-1, are examined for their implications in lipid metabolism dysregulation. The review also highlights the impact of glomerular and tubular lipid overload on kidney pathology, emphasizing the roles of podocytes and tubular cells in maintaining kidney function. Various therapeutic strategies targeting lipid metabolism, including pharmacological agents such as statins and SGLT2 inhibitors, as well as lifestyle modifications, are discussed for their potential to mitigate CKD progression in obese individuals. Future research directions are suggested to better understand the mechanisms linking lipid metabolism to kidney disease and to develop personalized therapeutic approaches. Ultimately, addressing obesity-related lipid metabolism disorders may enhance kidney health and improve outcomes for individuals suffering from CKD.

Obesity is a growing public health issue, especially among young adults, with long-term management strategies still under debate. This prospective study compares the effects of caloric restriction and isocaloric diets with different macronutrient distributions on body composition and anthropometric parameters in obese women during a 12-week weight loss program, aiming to identify the most effective dietary strategies for managing obesity-related health outcomes.

A certified clinical nutritionist assigned specific diets over a 12-week period to 150 participants, distributed as follows: hypocaloric diets-low-energy diet (LED, 31 subjects) and very low-energy diet (VLED, 13 subjects); isocaloric diets with macronutrient distribution-low-carbohydrate diet (LCD, 48 subjects), ketogenic diet (KD, 23 subjects), and high-protein diet (HPD, 24 subjects); and isocaloric diet without macronutrient distribution-time-restricted eating (TRE, 11 subjects). Participants were dynamically monitored using anthropometric parameters: body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and bioelectrical impedance analysis (BIA) using the TANITA Body Composition Analyzer BC-418 MA III (T5896, Tokyo, Japan) at three key intervals-baseline, 6 weeks, and 12 weeks. The following parameters were evaluated: body weight, basal metabolic rate (BMR), percentage of total body fat, trunk fat, muscle mass, fat-free mass, and hydration status.

All diets led to weight loss, but differences emerged over time. The TRE model resulted in significantly less weight loss compared to LED at the final follow-up (6.30 kg, p < 0.001), similar to the VLED (4.69 kg, p < 0.001). Isocaloric diets with varied macronutrient distributions showed significant weight loss compared to LED (p < 0.001). The KD reduced waist circumference at both 6 and 12 weeks (-4.08 cm, p < 0.001), while significant differences in waist-to-hip ratio reduction were observed across diet groups at 12 weeks (p = 0.01). Post-hoc analysis revealed significant fat mass differences at 12 weeks, with HPD outperforming IF (p = 0.01) and VLED (p = 0.003). LCD reduced trunk fat at 6 weeks (-2.36%, p = 0.001) and 12 weeks (-3.79%, p < 0.001). HPD increased muscle mass at 12 weeks (2.95%, p = 0.001), while VLED decreased it (-2.02%, p = 0.031). TRE showed a smaller BMR reduction at 12 weeks compared to LED.

This study highlights the superior long-term benefits of isocaloric diets with macronutrients distribution over calorie-restrictive diets in optimizing weight, BMI, body composition, and central adiposity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a refined categorization of non-alcoholic fatty liver disease (NAFLD), highlighting the intricate relationship between hepatic steatosis and metabolic dysfunction. Abdominal obesity (AO), a key diagnostic criterion for metabolic dysfunction, predominantly results from inappropriate diet and unhealthy dietary habits. To comprehensively investigate which dietary factors contribute to MASLD through AO and to understand the underlying biological mechanisms, we initially conducted a systematic review of meta-analysis articles in the PubMed database from the past decade, summarizing dietary factors that affect AO. Subsequently, we conducted targeted searches in the PubMed database for these dietary factors and provided a narrative review of the mechanisms of how these dietary factors lead to AO and how AO exacerbates MASLD. A diet characterized by excessive intake of energy, carbohydrates, fructose, or ultra-processed foods (UPFs) is considered inappropriate. Inappropriate diet leads to the formation of MASLD and AO by enhancing pathways such as de novo lipid synthesis (DNL) in the liver, insulin resistance (IR), gut-liver dysfunction, and inflammation. Dietary interventions for inappropriate diets can effectively intervene in and improve MASLD and AO. The mechanism of inappropriate diet on abdominal fat deposition is through excessive energy or the activation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) to increase endocortisol secretion. Then, the excessive accumulation of visceral fat facilitates a rapid and augmented flux of free fatty acids (FFAs) to the liver and initiates a series of deleterious effects, including oxidative stress (OS), endoplasmic reticulum stress (ERS), activation of protein kinase C (PKC) pathways, and inflammation. Additionally, FFAs may mediate excessive lipid deposition and hepatocellular damage through the action of hormones. These pathways to liver damage exacerbate MASLD and progression to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Furthermore, investigating other potential mechanisms by which AO may influence MASLD could offer new recommendations for the treatment guidelines of MASLD.

Polycystic Ovary Syndrome (PCOS) is one of the most common hormonal disorders in reproductive-age women caused by hyperinsulinemia. The portfolio Moderate-carbohydrate diet (PMCD) is a plant-based diet with a carbohydrate content of 40% and incorporates five cholesterol-lowering foods. While, the ketogenic diet is a high-fat diet with 70% fat, promoting a ketosis state. To the best of our knowledge, no study compared the therapeutic effects of these two diets in PCOS patients. Thus, this study aimed to compare the impact of PLCD and KD on anthropometric indices, metabolic status, and hormonal levels in overweight or obese women with PCOS.

This open-label, randomized clinical trial was conducted on forty-six PCOS women. 21 women in PMCD and 19 in the KD group completed the study. The anthropometric indices including body mass index (BMI) and fat body mass (FBM), metabolic markers (fasting blood glucose (FBG)) and plasma lipid profiles including low-density lipoprotein (LDL), triglycerides, and high-density lipoproteins (HDL) were measured. Reproductive hormones such as luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-s) and free testosterone were assessed at the baseline and after the intervention.

However, after 8 weeks both diets demonstrated enhancement in anthropometric indices (BMI, FBM, lean body mass), metabolic status (FBG, insulin serum levels), and reproductive hormones such as LH, free testosterone, and DHEA-s. The mean difference in the KD improved more than the PMCD in the field of BMI reduction (MD (SD) 2.73 (0.351) vs. MD (SD) 1.71 (0.775)) and LH (MD 4.13 (1.375) vs.MD 2.46 (1.105)). Nevertheless, the lipid profile including LDL-C and triglycerides improved more in the PMCD compared to the KD (MD 33.95 (7.345) vs. MD 23.34 (14.136)) and (MD 38.20 (10.757) vs. MD 57.62 (21.688)) respectively. There were no significant changes in the Ferriman-Gallwey score within or between the two groups.

The findings revealed that both diets were effective in improving PCOS manifestations. However, the KD exhibited greater effectiveness in enhancing body measurements, metabolic factors, and reproductive hormone levels compared to the PMCD in obese PCOS women. Furthermore, PMCD could be more beneficial for PCOS women with lipide disorders.

IRCT20200912048693N3, Trial registered 2022-12-14. https://www.irct.ir/trial/67548.

As obesity and chronic kidney disease (CKD) remain a public health issue, we aim to elaborate on their complex relationship regarding pathogenetic mechanisms and therapeutic potential as well. The purpose of this review is to enhance our understanding of the interplay between obesity and CKD in order to timely diagnose and treat obesity-related CKD.

Obesity and CKD pose significant intertwined challenges to global health, affecting a substantial portion of the population worldwide. Obesity is recognized as an independent risk factor, intricately contributing to CKD pathogenesis through mechanisms such as lipotoxicity, chronic inflammation, and insulin resistance. Recent evidence highlights additional factors including hemodynamic changes and intestinal dysbiosis that exacerbate kidney dysfunction in obese individuals, leading to histologic alterations known as obesity-related glomerulopathy (ORG). This narrative review synthesizes current knowledge on the prevalence, pathophysiology, clinical manifestations, and diagnostic strategies of obesity-related kidney disease. Furthermore, it explores mechanistic insights to delineate current therapeutic approaches, future directions for managing this condition and controversies. By elucidating the multifaceted interactions between obesity and kidney health, this review aims to inform clinical practice and stimulate further research to address this global health epidemic effectively.

Chronic kidney disease (CKD) is a serious health concern with an estimated prevalence of about 13.4% worldwide. It is cause and consequence of various comorbidities, including cardiovascular diseases. In parallel, common pathological conditions closely related to ageing and unhealthy dietary habits increase the risk of CKD development and progression, including type 2 diabetes and obesity. Among these, obesity is either independent risk factor for new onset kidney disease or accelerates the rate of decline of kidney function by multiple mechanisms. Therefore, the role of diets aimed at attaining weight loss in patients with obesity is clearly essential to prevent CKD as to slow disease progression. Various dietary approaches have been licensed for the medical dietary therapy in CKD, including low-protein diet and Mediterranean diet. Interestingly, emerging evidence also support the use of low-carbohydrate/ketogenic diet (LCD/KD) in these patients. More specifically, LCD/KDs may efficiently promote weight loss, improve metabolic parameters, and reduce inflammation and oxidative stress, resulting in a dietary strategy that act globally in managing collateral conditions that are directly and indirectly related to the kidney function.

This consensus statement from the Italian Society of Endocrinology (SIE), working group of the Club Nutrition - Hormones and Metabolism; the Italian Society of Nutraceuticals (SINut), Club Ketodiets and Nutraceuticals "KetoNut-SINut"; and the Italian Society of Nephrology (SIN) is intended to be a guide for Endocrinologist, Nutritionists and Nephrologist who deal with the management of patients with obesity with non-dialysis CKD providing a practical guidance on assessing nutritional status and prescribing the optimal diet in order to best manage obesity to prevent CKD and its progression to dialysis.

Obesity is recognized as a public health challenge. During the last three decades, the global age-standardized prevalence increased from 8.8% to 18.5% in women and from 4.8% to 14.0% in men, with an absolute current number of 878 million obese subjects. Obesity significantly increases per se the risk of developing disability and chronic diseases, including chronic kidney disease (CKD). Specifically, obesity acts as a major, modifiable cause of CKD onset and progression toward kidney failure; as such, it is considered by the International Society of Nephrology a major health priority. This review analyses the effectiveness, safety and practicability of non-pharmacological anti-obesity interventions in CKD as the different patient phenotypes that may take advantage of personalized approaches.

The use of bioelectrical impedance analysis (BIA) is now well established in healthcare as an essential support tool for patient management in various clinical settings. Its use in sports is rapidly expanding due to the valuable insights it offers, helping to better structure athletes' diets and training programs, thereby optimizing their performance. In the context of sport, however, there is a consensus regarding the importance of proper interpretation of BIA-derived data, which cannot be limited to mere estimation of body composition. In this sense, therefore, the evaluation and interpretation of raw bioelectrical parameters, including resistance, reactance, and phase angle (PhA) is of relevant importance. The assessment of PhA is particularly significant in the context of sports, as it is closely linked to key factors such as muscle mass, strength, and overall muscle quality. However, the existing relationship between PhA and systemic, and loco-regional inflammation, which, in a broader sense, is the rationale behind its use for assessing and monitoring localised muscle damage. Thus, the importance of PhA monitoring during training becomes evident, as it plays a crucial role in assessing and potentially identifying functional impairments, such as overtraining syndrome, as well as muscle injury and related changes in fluid distribution, at an early stage. The aim of this review is to provide the scientific basis necessary to consider the use of whole-body PhA as an indicator of overtraining.

Obesity is a public health crisis, with prevalence rates tripling over the past 60 y. Although lifestyle modifications, such as diet and physical activity, remain the first-line treatments, recent anti-obesity medications (AOMs) have been shown to achieve greater reductions in body weight and fat mass. However, AOMs also reduce fat-free mass, including skeletal muscle, which has been demonstrated to account for 20% to 50% of total weight loss. This can equate to ∼6 kg or 10% of total lean mass after 12-18 mo, a loss comparable to a decade of human aging. Despite questions surrounding the clinical relevance of weight loss-induced muscle loss, the importance of adopting lifestyle behaviors such as eating a protein-rich diet and incorporating regular resistance training to support skeletal muscle health, long-term weight loss maintenance, and overall well-being among AOM users should be encouraged. Herein, we provide a rationale for the clinical significance of minimizing weight-loss-induced lean mass loss and emphasize the integration of diet and physical activity into AOM clinical care. Owing to a lack of published findings on diet and physical activity supporting skeletal muscle health with AOMs, specifically, we lean on findings from large-scale clinical weight loss and diet and exercise trials to draw evidence-based recommendations for strategies to protect skeletal muscle. We conclude by identifying gaps in the literature and emphasizing the need for future experimental research to optimize skeletal muscle and whole-body health through a balance of pharmacotherapy and healthy habits.

Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS).

EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. β-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months.

It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS.

The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

Obesity, a prevalent and multifactorial disease, is linked to a range of metabolic abnormalities, including insulin resistance, dyslipidemia, and chronic inflammation. These imbalances not only contribute to cardiometabolic diseases but also play a significant role in cancer pathogenesis. The rising prevalence of obesity underscores the need to investigate dietary strategies for effective weight management for individuals with overweight or obesity and cancer. This European Society for the Study of Obesity (EASO) position statement aimed to summarize current evidence on the role of obesity in cancer and to provide insights on the major nutritional interventions, including the Mediterranean diet (MedDiet), the ketogenic diet (KD), and the intermittent fasting (IF), that should be adopted to manage individuals with overweight or obesity and cancer. The MedDiet, characterized by high consumption of plant-based foods and moderate intake of olive oil, fish, and nuts, has been associated with a reduced cancer risk. The KD and the IF are emerging dietary interventions with potential benefits for weight loss and metabolic health. KD, by inducing ketosis, and IF, through periodic fasting cycles, may offer anticancer effects by modifying tumor metabolism and improving insulin sensitivity. Despite the promising results, current evidence on these dietary approaches in cancer management in individuals with overweight or obesity is limited and inconsistent, with challenges including variability in adherence and the need for personalized dietary plans.

Considering differences in body composition and inflammatory status between sexes, as well as recent recommendations advocating for personalized dietary approaches, this study aimed to explore how sex influences weight loss, changes in body composition, and inflammatory status in subjects with grade I and II obesity undergoing a 45-day of the Very Low-Energy Ketogenic Therapy (VLEKT).

Participants (21 premenopausal females and 21 males), included in the study adhered to the 45-day of the VLEKT and underwent assessments of anthropometric parameters (weight, height, body mass index-BMI -, and waist circumference), body composition via bioelectrical impedance analysis, and inflammatory status measured by high sensitivity C-reactive protein (hs-CRP) levels at baseline and post-intervention.

At baseline, premenopausal females and males did not differ in BMI (p = 0.100) and hs-CRP levels (p = 0.948). Males demonstrated overall larger benefits than premenopausal females from the VLEKT in terms of weight loss (Δ% = - 11.63 ± 1.76 vs - 8.95 ± 1.65 kg, p < 0.001), fat mass (Δ% = - 30.84 ± 12.00 vs -21.36 ± 4.65 kg, p = 0.002), and hs-CRP levels (Δ% = - 41.42 ± 21.35 vs - 22.38 ± 17.30 mg/L, p = 0.003). Of interest, in males phase angle values are statistically improved compared to female (Δ% = 17.11 ± 9.00 vs 7.05 ± 3.30°, p < 0.001).

These findings underscore the importance of considering sex-specific responses in personalized obesity treatment strategies, particularly dietary interventions like VLEKTs.

In addition to recent discussions of low-carbohydrate, high-fat diets (LCHF) from a performance perspective, there is a paucity of knowledge regarding influence of the combined effect of an exercise and nutritional intervention, which varies in carbohydrate (CHO) intake and glycemic indices, on blood lipid levels in recreationally active men.

A total of 65 male runners (VO2 peak = 55 ± 8 mL·min-1·kg-1) completed a 10-week ad libitum nutritional regimen (LOW-GI: ≥ 65% low GI CHO per day, n = 24; HIGH-GI: ≥ 65% high GI CHO per day, n = 20; LCHF: ≤ 50 g CHO daily, n = 21) with a concurrent prescribed endurance training intervention. Fasting total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined before and after the intervention. Additionally, 24-h dietary recalls were completed twice weekly.

Following the intervention, TC was significantly higher in LCHF (196 ± 37 mg·dL-1) compared to both LOW-GI (171 ± 41 mg·dL-1) and HIGH-GI (152 ± 28 mg·dL-1, p < 0.001). Additionally, LDL-C levels increased in LCHF (+17 ± 21 mg·dL-1, p = 0.001), while they decreased in both CHO groups (p < 0.05, respectively). Only the HIGH-GI group demonstrated a significant reduction in HDL-C (-3 ± 9 mg·dL-1, p = 0.006), while a decrease in TG was only significant in LOW-GI (-18 ± 36 mg·dL-1, p = 0.008).

Although mean blood lipid levels remained within the normal range, the data indicate that a low-carbohydrate, high-fat (LCHF) diet leads to unfavorable changes in individual blood lipid profiles compared to carbohydrate-rich diets. Therefore, it is recommended that the impact of a low-carbohydrate diet on blood lipids be considered when counseling active and healthy individuals.

The very-low calorie ketogenic diet (VLCKD) is recommended as an effective dietary approach for the management of obesity. This study investigated changes in circulating biomarkers of redox homeostasis induced by a multiphase VLCKD in obese individuals. A total of 40 obese subjects were prescribed a multiphasic VLCKD for eleven weeks. Anthropometric measurements, body composition parameters, calorimetric measures, and standard laboratory markers of glucose and lipid metabolism were evaluated at baseline (T0) and at the end of the dietary intervention (T1). Additionally, circulating markers of oxidative damage and antioxidant status were analyzed in serum and erythrocytes. Compared to T0, at T1 the multiphase VLCKD induced significant weight loss and reduction of waist circumference, with beneficial effects on body composition parameters and the glucose/lipid biochemical profile. Moreover, a decrease in serum markers of oxidative damage was reported at T1, while no changes in serum markers of antioxidant status and in erythrocyte redox markers were observed. In addition, a significant association was found between variations in anthropometric measurements, body composition, glucose metabolism parameters, and changes in circulating markers of oxidative damage. Regression models showed that variation in lipofuscin was significant predictor of changes in body mass index, fat mass, visceral adiposity, and insulin sensitivity. In conclusion, this study demonstrated that the multiphase VLCKD improves serum redox balance by reducing markers of oxidative damage in obese individuals, highlighting the interplay between adiposity, glucose metabolism, and redox homeostasis in the pathogenesis of obesity. Furthermore, these data provide a rationale for future investigations aimed at testing serum lipofuscin as a reliable redox marker in obesity.

Tirzepatide (TZP) is a new anti-obesity drug, and little is currently known about its effect on body composition (BC) in people with overweight or obesity. The aim of this study is to conduct a systematic review on the impact of TZP on BC compartments in this population during weight loss programs. Literature searches, study selection, method development, and quality appraisal were performed. The data were synthesized using a narrative approach, in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Of the 1379 papers retrieved, 6 randomized controlled trials met the inclusion criteria and were reviewed, revealing the following findings. Firstly, TZP was shown to result in a significant reduction in total fat mass (FM), visceral adipose tissue (VAT) and waist circumference (WC) between baseline and short as well as intermediate follow-ups. Compared to other anti-obesity medications (e.g., dulaglutide and semaglutide) taken over the same duration, TZP showed a superior decrease in body fat compartments (i.e., total FM, VAT and WC). Finally, the effect of TZP on fat-free mass (FFM) is still uncertain because the findings remain inconclusive. In conclusion, TZP appears to be an effective strategy for achieving significant improvements in body fat and its distribution, but additional investigations are still needed to determine the impact of TZP on lean mass in this population.

The improved efficacy and generally favorable safety profile of recently approved and emerging antiobesity medications (AOMs), which result in an average weight reduction of ≥15%, represent significant advancement in the treatment of obesity. This narrative review aims to provide practical evidence-based recommendations for nutritional assessment, management, and monitoring of patients treated with AOMs. Prior to treatment, clinicians can identify preexisting nutritional risk factors and counsel their patients on recommended intakes of protein, dietary fiber, micronutrients, and fluids. During treatment with AOMs, ongoing monitoring can facilitate early recognition and management of gastrointestinal symptoms or inadequate nutrient or fluid intake. Attention should also be paid to other factors that can impact response to treatment and quality of life, such as physical activity and social and emotional health. In the context of treatment with AOMs, clinicians can play an active role in supporting their patients with obesity to improve their health and well-being and promote optimal nutritional and medical outcomes.

In an attempt to clarify the most appropriate nomenclature for the very low-calorie ketogenic diets (VLCKD), we propose to change the nomenclature and acronym of this medical nutrition therapy. The new definition and acronym proposed by the "KetoNut" panel of experts of the Italian Society of Nutraceuticals (SINut) and the Italian Association of Dietetics and Clinical Nutrition (ADI) is Very Low-Energy Ketogenic Therapy (VLEKT).

In the last few years, different authors have focused on the issue of confusion in the nomenclature of ketogenic diets. In detail, have been differentiated the VLCKD that provides < 800 kcal per day, which is intended for the weight loss in the medical treatment of obesity, and a eucaloric ketogenic diet, which contains more calories from fat (predominantly unsaturated) and with specific ketogenic ratios, for allow growth in children while helping, at the same time, to establish epileptic seizure control. In recent years, ketogenic diets have attracted great interest for their efficacy in the treatment of epilepsy and other neurological diseases but also in patients with overweight and obesity-related metabolic disorders. Nevertheless, although ketogenic diets are a dietary intervention designed to induce nutritional ketosis, different diets with different macronutrients' composition have been called with this name. The confusion in the nomenclature of ketogenic diets may result in significant bias and mistakes in the interpretation of the current scientific evidence.

This review aims to critically examine how VLCKD affects plasma lipoprotein, lipid and cholesterol metabolism. Cardiovascular disease is a worldwide health problem affecting millions of people and leading to high rates of mortality and morbidity. There is a well-established association between cardiovascular disease and circulating cholesterol. Various dietary recommendations are currently available for the management of dyslipidemia.

The very low-calorie ketogenic diet (VLCKD) is becoming increasingly popular as a treatment option for several pathological conditions, including dyslipidemia. In addition to being low in calories, the VLCKD's main feature is its unique calorie distribution, emphasizing a reduction in carbohydrate consumption in favor of fat as the primary calorie source. Lowering calorie intake through a VLCKD can reduce the endogenous production of cholesterol. However, if the foods consumed are from animal sources, dietary cholesterol intake may increase due to the higher fat content of animal products. When combined, these dietary practices may have opposing effects on plasma cholesterol levels. Studies investigating the impact of VLCKD on plasma cholesterol and low-density lipoprotein cholesterol levels report contradictory findings. While some studies found an increase in low-density lipoprotein cholesterol levels, others showed a decrease in total cholesterol and low-density lipoprotein cholesterol, along with an increase in high-density lipoprotein cholesterol.

Considering the high prevalence of obesity and related metabolic impairments in the population, the unique role nutrition has in weight loss, reversing metabolic disorders, and maintaining health cannot be overstated. Normal weight and well-being are compatible with varying dietary patterns, but for the last half century there has been a strong emphasis on low-fat, low-saturated fat, high-carbohydrate based approaches. Whereas low-fat dietary patterns can be effective for a subset of individuals, we now have a population where the vast majority of adults have excess adiposity and some degree of metabolic impairment. We are also entering a new era with greater access to bariatric surgery and approval of anti-obesity medications (glucagon-like peptide-1 analogues) that produce substantial weight loss for many people, but there are concerns about disproportionate loss of lean mass and nutritional deficiencies.

No matter the approach used to achieve major weight loss, careful attention to nutritional considerations is necessary. Here, we examine the recent findings regarding the importance of adequate protein to maintain lean mass, the rationale and evidence supporting low-carbohydrate and ketogenic dietary patterns, and the potential benefits of including exercise training in the context of major weight loss. While losing and sustaining weight loss has proven challenging, we are optimistic that application of emerging nutrition science, particularly personalized well-formulated low-carbohydrate dietary patterns that contain adequate protein (1.2 to 2.0 g per kilogram reference weight) and achieve the beneficial metabolic state of euketonemia (circulating ketones 0.5 to 5 mM), is a promising path for many individuals with excess adiposity.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development and enlargement of multiple kidney cysts, leading to progressive kidney function decline. To date, Tolvaptan, the only approved treatment for this condition, is able to slow down the loss of annual kidney function without stopping the progression of the disease. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the drug's impact on quality of life. The recent literature suggests that cystic cells are subject to several metabolic dysregulations, particularly in the glucose pathway, and mitochondrial abnormalities, leading to decreased oxidative phosphorylation and impaired fatty acid oxidation. This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, ketogenic diets, and exogenous ketosis), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions' effect.

Diabetes mellitus is a global health crisis affecting millions. Nutrition plays a vital role in its management and prevention. While carbohydrate reduction is beneficial for glycemic control, various dietary approaches exist. The ketogenic diet, characterized by very low carbohydrate intake, has shown promise in weight management and blood sugar control. However, its potential for preventing type 2 diabetes mellitus (T2DM) remains largely unexplored. To evaluate the ketogenic diet's potential in preventing T2DM, this review searched the PubMed database for studies published between 2013 and 2023. Findings suggest that the diet can effectively aid weight loss and improve blood glucose levels. Some evidence indicates reduced reliance on diabetes medications. However, effects on cholesterol levels are inconsistent, and long-term adherence challenges exist. Additionally, potential micronutrient deficiencies and safety concerns require careful consideration. While the ketogenic diet offers potential benefits, further research is needed to establish its efficacy and safety as a long-term prevention strategy for T2DM. However, the results of the present study indicate the need for further research in this area, utilizing rigorous methodology.

While a broad consensus exists that integrated nutrition and regular exercise are foundational for health maintenance and serve as a robust non-pharmacological strategy against cardiometabolic diseases, the nuanced interplay between these elements remains incompletely understood. Through multifaceted interactions, these factors profoundly influence primary metabolic organs, notably the skeletal muscle and adipose tissue. Despite the critical nature of this interactivity, a holistic understanding of the combined effects of physical activity and dietary practices is still emerging. This narrative review aims to elucidate the intertwined roles of nutrition and exercise. It provides a comprehensive overview of their synergistic dynamics and emphasizes the importance of a dual-focus approach in mitigating and managing cardiometabolic disorders, predominantly obesity and type 2 diabetes.

The ketogenic diet, characterized by high fat and low carbohydrates, has gained popularity not only as a strategy for managing body weight but also for its efficacy in delaying cognitive decline associated with neurodegenerative diseases and the aging process. Since this dietary approach stimulates the liver's production of ketone bodies, primarily β-hydroxybutyrate (BHB), which serves as an alternative energy source for neurons, we investigated whether BHB could mitigate impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges such as saturated fatty acids. Here, we observe that, in cultured primary cortical neurons, exposure to palmitic acid (200μM) decreased surface levels of glutamate GluA1-containing AMPA receptors, whereas unsaturated fatty acids, such as oleic acid and ω-3 docosahexaenoic acid (200μM), and BHB (5mM) increased them. Furthermore, BHB countered the adverse effects of palmitic acid on synaptic GluA1 levels in hippocampal neurons, as well as excitability and plasticity in hippocampal slices. Additionally, daily intragastric administration of BHB (100 mg/kg/day) for two months reversed cognitive impairment induced by a saturated high-fat diet (49% of calories from fat) in a mouse experimental model of obesity. In summary, our findings underscore the significant impact of fatty acids and ketone bodies on AMPA receptors abundance, synaptic function and neuroplasticity, shedding light on the potential use of BHB to delay cognitive impairments associated with metabolic diseases.

African American (AA) women have the highest prevalence of obesity in addition to health disparities in preventable diet-related diseases (i.e., diabetes, hypertension), which places them at increased risk for cardiovascular disease. The purpose of this pilot study was to assess the feasibility, acceptability, and preliminary effectiveness of the Keto Prescribed+ (KetoRx+) program on associated physical and psychosocial outcomes among this population. The KetoRx+ program is a healthy eating and thinking educational intervention. The program combined online and in-person community group sessions over 8 weeks. The Keto Prescribed+ was found to be feasible and acceptable with comments on ways to increase acceptability from participants completing program (n = 10). Physical outcomes changed showed an average decrease in weight of 10lbs (SD = 5), baseline average 226lbs. Waist-to-hip ratio and systolic blood pressure also trended down. Psychosocial outcomes showed improvement trends. The KetoRx+ program is feasible and acceptable for overweight or obese AA women. Preliminary efficacy was established for most physical and psychosocial outcomes. However, more research is needed to identify specific program components contributing to healthy lifestyle behavior change and to establish program efficacy and effectiveness. Culturally adapted community-based biopsychosocial interventions using ketogenic nutrition therapy may help improve cardiovascular health of adult AA women.

Metabolic endotoxemia is a severe health problem for residents in developed countries who follow a Western diet, disrupting intestinal microbiota and the whole organism's homeostasis. Although the effect of endotoxin on the human immune system is well known, its long-term impact on the human body, lasting many months or even years, is unknown. This is due to the difficulty of conducting in vitro and in vivo studies on the prolonged effect of endotoxin on the central nervous system. In this article, based on the available literature, we traced the path of endotoxin from the intestines to the blood through the intestinal epithelium and factors promoting the development of metabolic endotoxemia. The presence of endotoxin in the bloodstream and the inflammation it induces may contribute to lowering the blood-brain barrier, potentially allowing its penetration into the central nervous system; although, the theory is still controversial. Microglia, guarding the central nervous system, are the first line of defense and respond to endotoxin with activation, which may contribute to the development of neurodegenerative diseases. We traced the pro-inflammatory role of endotoxin in neurodegenerative diseases and its impact on the epigenetic regulation of microglial phenotypes.

The challenge of addressing obesity persists in healthcare, necessitating nuanced approaches and personalized strategies. This study aims to evaluate the effects of diverse therapeutic interventions on anthropometric and biochemical parameters in individuals with overweight and obesity within a real-world clinical context.

A retrospective analysis was conducted on 192 patients (141 females, 51 males) aged 18 to 75, with a BMI ranging from 25 to 30 (14.1%) and BMI ≥ 30 (85.9%), observed over a 12-month period at our Endocrinology Unit. Treatment cohorts comprised individuals following different regimens: Mediterranean Diet (MD), with an approximate daily intake of 1500 kcal for women and 1800 kcal for men (71% patients); Ketogenic Diet (KD), utilizing the VLCKD protocol characterized by a highly hypocaloric dietary regimen < 800 kcal/day (14% patients); metformin, administered using the oral formulation (5% patients); pharmacological intervention with GLP1-RA administered via subcutaneous injection with incremental dosage (10% patients). Supply constraints limited the efficacy of Liraglutide, whereas Semaglutide was excluded from comparisons due to its unavailability for obesity without diabetes. Blood tests were conducted to assess lipid profile, glycemic profile, and anthropometric parameters, including BMI, waist circumference, and waist-to-height ratio.

Significant BMI changes were observed from baseline to 6 months across MD, KD, and Liraglutide groups (p < 0.05). KD exhibited notable reductions in waist circumference and waist-to-height ratio within the initial quarter (p < 0.05), with a significant triglyceride decrease after 6 months (p < 0.05), indicating its efficacy over MD. Liraglutide demonstrated a substantial reduction in HbA1c levels in the first quarter (p < 0.05). During the first three months, the ANOVA test on fasting blood glucose showed a statistically significant impact of the time variable (p < 0.05) rather than the specific treatments themselves (Liraglutide and KD), suggesting that adherence during the early stages of therapy may be more critical than treatment choice.

Positive outcomes from targeted interventions, whether pharmacological or dietary should encourage the exploration of innovative, long-term strategies that include personalized treatment alternation. The absence of standardized protocols underscores the importance of careful and tailored planning in managing obesity as a chronic condition.

This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification.

Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote.

The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative.

The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.