Search Results (81)

Background: Evidence comparing the effects of novel alternative dietary strategies on resting energy expenditure (REE) with a hypocaloric standard Mediterranean diet (MedDiet) with continuous caloric restriction remains limited. This study aimed to evaluate the effects of diets with varying ketogenic potentials—including a very-low-carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF)—on the REE of individuals with obesity compared to those of a standard MedDiet. Methods: This was a secondary post hoc sub-analysis of a three-month, parallel-arm, randomized clinical trial (RCT) including 160 adults with obesity (body mass index > 30 kg/m²). The participants were randomly assigned to one of five calorie-restricted dietary interventions: control (MedDiet), KD, early time-restricted eating (eTRE), late time-restricted eating (lTRE), or mADF. All interventions featured an individualized energy deficit of 600 kcal/day. In this sub-analysis, a total of 102 participants with valid baseline measures were included. The REE was assessed by indirect calorimetry, and longitudinal trajectories were evaluated using Linear Mixed Models (LMMs) in 98 participants to account for baseline variability and to maximize data retention. Results: The mean age of participants in this sub-analysis was 45.3 years (SD 10.8), and 73.1% were women. The longitudinal modeling confirmed no statistically significant differences in the adjusted REE trajectories among the five dietary groups over the 3-month intervention (Group × Time interaction, p = 0.506). Furthermore, the LMMs showed that total body weight (p < 0.001) and biological sex (p < 0.001) were the variables most strongly associated with REE within the model. No independent associations between circulating beta-hydroxybutyrate levels and REE trajectories were detected. Conclusions: Hypocaloric diets with varying macronutrient distributions and fasting windows did not show statistically significant differences in REE trajectories over the 3-month intervention. In this exploratory sub-analysis, the REE trajectories were more closely associated with individual biological characteristics, particularly body weight and sex, than with the specific dietary strategy employed. Given the modest sample size and exploratory nature of the study, these findings should be interpreted cautiously and require confirmation in larger, adequately powered prospective trials. Full article

Background: Serum uric acid (UA) is increasingly recognized as a cardiovascular (CV) risk factor, with evidence suggesting that CV risk may occur at levels below conventional hyperuricemia thresholds. However, real-world comparative data on the effects of dietary interventions on UA are limited. Objective: The primary objective of this study was to compare the effects of a very low-calorie ketogenic diet (VLCKD), intermittent fasting (IF), and standard dietary advice (free diet, FD) on UA levels and UA-defined CV risk in hypertensive postmenopausal women. Methods: In this prospective, single-center, real-world clinical study, 43 women with essential hypertension and obesity underwent dietary interventions. UA levels were assessed at baseline and after 6 months. Hyperuricemia was defined using both the conventional threshold (≥6.0 mg/dL) and the CV risk-oriented Uric Acid Right for Heart Health (URRAH) cut-off (≥4.7 mg/dL). Analyses included paired tests and ANCOVA adjusted for baseline UA. Results: At baseline, over half of participants exceeded the URRAH threshold. Only VLCKD significantly reduced UA levels (−1.23 mg/dL; p < 0.001), remaining independently associated after adjustment (β = −0.95 mg/dL; p = 0.007). URRAH-defined CV risk decreased significantly only in the VLCKD group (55.6% to 22.2%), with one-third transitioning to lower risk. Conclusions: VLCKD significantly reduced UA levels and UA-defined CV risk, supporting its role as a potentially effective lifestyle intervention in this population. Full article

Background: The very-low-calorie ketogenic diet (VLCKD) is increasingly used before bariatric surgery (BS), but its effects on surgical and long-term outcomes remain unclear. Objective: The aim of this study was to compare the impact of a 4-week VLCKD with a 4-week low-calorie diet (LCD) on preoperative, perioperative and postoperative outcomes for up 12 months in patients undergoing BS. Methods: In this prospective study, 72 (n = 36: VLCKD; n = 36: LCD) patients (mean age 43.2 ± 10.6 years; BMI 45.6 ± 6.4 kg/m²; 87.5% female) submitted to sleeve gastrectomy were enrolled at a tertiary care center from 2022 to 2024. Results: No adverse events were detected with both diets. The VLCKD was associated with a greater preoperative median weight loss percentage (−5.5 vs. −2.6 kg, p < 0.001), BMI reduction (−2.6 vs. −1.2 kg/m², p < 0.001), shorter hospital stay (3.0 ± 0.2 vs. 3.4 ± 0.9 days, p = 0.017), higher day-1 postoperative hemoglobin (12.7 ± 1.3 vs. 12.0 ± 1.2 g/dL, p = 0.024), and lower day-1 postoperative median C-reactive protein levels (9.7 vs. 13.4 mg/L, p = 0.042). These associations were confirmed in a multiple regression model, after adjustments for BMI at enrolment, age and sex. After 6 months, the VLCKD was associated with greater reductions in mean weight loss percentage (−24.9 ± 7.8 vs. −19.6 ± 9.4 kg, p = 0.012), BMI reduction (−11.7 ± 4.4 vs. −8.7 ± 3.9 kg/m², p = 0.003), neck circumference (−4.9 vs. −3.6 cm, p = 0.027) and lower aminotransferase levels. At 12 months, VLCKD patients maintained significant advantages over the same variables, except for neck circumference. Conclusions: A short preoperative VLCKD was safe and was associated with greater short-term weight reduction compared with the LCD, with potential benefits extending to early postoperative recovery and 1-year outcomes. Full article

Background/Objectives: Obesity is a chronic, relapsing disease in which lifestyle modification represents the cornerstone of treatment. Among dietary strategies, ketogenic diets can induce rapid weight loss, whereas the Mediterranean diet is associated with established cardiometabolic benefits but typically produces slower weight reduction. Very-low-calorie ketogenic diets (VLCKDs) are effective for weight loss but are often limited by cost, reliance on meal replacements, and reduced long-term feasibility. This study aimed to evaluate whether a whole-food Mediterranean ketogenic diet with moderate caloric restriction (MedKD) could represent a feasible and effective alternative to VLCKD for weight loss and metabolic improvement in adults with obesity. Methods: This 3-month prospective, real-world study compared VLCKD and MedKD in adults with obesity attending a clinical nutrition program. The primary outcome was percentage weight loss. Secondary outcomes included changes in waist circumference, waist-to-height ratio, insulin resistance (HOMA-IR), lipid profile, kidney function, and treatment tolerability. Clinical and biochemical parameters were assessed at baseline and after the intervention. Group differences and time-by-group interactions were analyzed to evaluate changes over the study period. Results: Sixty-two participants were enrolled, and 55 completed the study (27 VLCKD, 28 MedKD). Baseline characteristics were generally comparable, although the MedKD group had a higher prevalence of diabetes and higher baseline insulin resistance and triglyceride levels. Both dietary interventions resulted in substantial and comparable weight loss (approximately 15% of initial body weight), accompanied by significant reductions in waist circumference and waist-to-height ratio. Insulin resistance improved in both groups, with a greater reduction in HOMA-IR observed in the MedKD group (time × group p = 0.031). Serum creatinine decreased in the VLCKD group and slightly increased in the MedKD group (p = 0.025). Changes in lipid profile were not significantly different between groups. No severe adverse events were reported. Conclusions: A whole-food Mediterranean ketogenic diet with moderate caloric restriction achieved weight loss and metabolic improvements comparable to those observed with VLCKD over three months. These findings suggest that MedKD may represent a feasible alternative to formula-based ketogenic programs, supporting more flexible and personalized dietary strategies in the clinical management of obesity. Full article

Background/Objectives: Obesity is a chronic relapsing disorder associated with many comorbidities. Some evidence suggests that oxytocin (OT) has an anorexigenic effect, but its levels are often increased in obesity. This study investigates the effects of weight loss induced by a very-low-calorie ketogenic diet (VLCKD) on oxytocin levels. Methods: A total of 47 subjects with overweight or obesity, 28 females (60%) and 19 males, with a mean age of 55.5 ± 7.3 years and mean BMI 35.9 ± 4.4 kg/m², underwent VLCKD for 45 days. We assessed anthropometric parameters, metabolic profile, body composition and OT levels at baseline (t0) and at the end of the diet (t1). Results: After weight loss, plasma OT levels significantly dropped. Baseline OT correlated with BMI, fat mass and trunk fat. A linear relationship was observed between Delta OT levels and Delta BMI. Baseline OT was an independent predictor of weight loss and directly correlated with blood ketone levels at the end of the study. An optimal serum OT cut-off that predicts ketosis occurrence was identified. Conclusions: Weight loss obtained with a VLCKD reduces OT levels in patients with excess weight. Baseline OT predicts weight loss and correlates with ketone body levels during a VLCKD. Full article

Background: Metabolic syndrome (MetS) is a multifactorial condition characterized by insulin resistance, dyslipidemia, hypertension, and central obesity, and is strongly influenced by lifestyle factors. Growing evidence highlights the gut microbiota as a key mediator linking diet and physical exercise to cardiometabolic health. Objective: This narrative review aims to qualitatively synthesize current evidence on the effects of physical exercise and major dietary patterns including the Mediterranean diet (MedDiet), Dietary Approaches to Stop Hypertension (DASH), and ketogenic/very-low-calorie ketogenic diets (KD/VLCKD) on gut microbiota composition and function, and their implications for metabolic health in MetS. Methods: A qualitative narrative synthesis of experimental, observational, and interventional human and animal studies was performed. The reviewed literature examined associations between structured physical exercise or dietary interventions and changes in gut microbiota diversity, key bacterial taxa, microbial metabolites, and cardiometabolic outcomes. Considerable heterogeneity across studies was noted, including differences in populations, intervention duration and intensity, dietary composition, and microbiota assessment methodologies. Results: Across human interventional studies, moderate-intensity physical exercise was most consistently associated with increased gut microbial diversity and enrichment of short-chain fatty acid (SCFA)-producing taxa, contributing to improved insulin sensitivity and reduced inflammation. MedDiet and DASH were generally linked to favorable microbiota profiles, including increased abundance of Faecalibacterium prausnitzii, Akkermansia muciniphila, and Bifidobacterium, alongside reductions in pro-inflammatory metabolites such as lipopolysaccharides and trimethylamine N-oxide. In contrast, KD and VLCKD were associated with rapid weight loss and glycemic improvements but frequently accompanied by reductions in SCFA-producing bacteria, depletion of Bifidobacterium, and markers of impaired gut barrier integrity, raising concerns regarding long-term microbiota resilience. Conclusions: Lifestyle-based interventions exert diet- and exercise-specific effects on the gut microbiota–metabolism axis. While MedDiet, DASH, and regular moderate physical activity appear to promote sustainable microbiota-mediated cardiometabolic benefits, ketogenic approaches require careful personalization, limited duration, and medical supervision. These findings support the integration of dietary quality, exercise prescription, and individual microbiota responsiveness into translational lifestyle strategies for MetS prevention and management. Full article

Background: Migraine is a common, disabling neurological disorder with substantial genetic and environmental contributions. Dietary exposures are widely discussed by patients and clinicians as potential triggers or modifiers of attack frequency and severity. We synthesized contemporary evidence on dietary patterns, specific nutrients, and elimination strategies relevant to migraine prevention and management. Methods: We performed a narrative review of PubMed and Google Scholar (inception–August 2025) using combinations of “migraine”, “diet”, “nutrition”, “ketogenic”, “Mediterranean”, “omega-3”, and “gluten”. We prioritized randomized/controlled studies, recent systematic reviews/meta-analyses, and representative observational studies; evidence quality and applicability were appraised descriptively. Results: Higher adherence to a Mediterranean-style diet is associated with lower migraine frequency and disability in observational cohorts. Very low-calorie ketogenic diets significantly reduced monthly migraine attack frequency compared with isocaloric non-ketogenic comparators in an adult randomized controlled trial of participants with overweight or obesity (≥50% responder rate: 74% vs. 6%). Additional supportive evidence from uncontrolled studies, including those involving medium-chain triglyceride supplementation, further corroborates these findings. Omega-3 fatty acids (EPA/DHA) show prophylactic benefit in randomized trials and network meta-analyses, with favorable tolerability. Gluten-free diets may improve headaches in celiac disease and may help selected non-celiac patients. Alcohol (especially red wine) and high, irregular caffeine intake are frequently reported triggers, while evidence for specific foods/additives remains inconsistent. Weight loss and regular physical activity may further reduce burden in people with obesity. Conclusions: Current evidence supports recommending Mediterranean-style eating, consideration of omega-3 supplementation, and selective trials of ketogenic or elimination approaches in appropriate patients, alongside weight management and lifestyle optimization. High-quality, longer-duration RCTs using standardized dietary protocols and adherence biomarkers are needed to define dose–response relationships and enable personalized nutrition in migraine. Full article

Background: Elevated BMI in women is linked to metabolic and endocrine imbalances that impair fertility and increase pregnancy risks. While >10% weight loss before an Assisted reproductive technology (ART) treatment may improve outcomes, sustained results through conventional diets are challenging. A very-low calorie ketogenic diet (VLCKD) promotes rapid fat loss while preserving lean mass and may offer long-term benefits. This study evaluated the efficacy (≥10% weight loss without lean mass reduction), adherence, metabolic effects, and pregnancy outcomes of a meal replacement VLCKD in women with overweight or obesity scheduled for ART. Methods: This monocentric, prospective case-series was conducted at the Obesity and Work Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan (September 2019–September 2023). Eligible women underwent a three-phase dietary program: a 3-month VLCKD (<800 kcal/day), a 6-month transition with gradual carbohydrate reintroduction, and a Mediterranean-style maintenance diet. Participants were monitored for safety, body composition, adherence, and biochemical changes. Results: Of 52 women enrolled, 40 initiated the VLCKD; 27 (68%) achieved ≥10% weight loss while preserving lean mass. Eleven conceived naturally during or after the diet; 22 underwent ART, with 12 additional pregnancies. This corresponds to a 58% pregnancy rate among those who began the VLCKD. Significant improvements were observed in body mass index (BMI), fat mass, waist circumference, glucose metabolism, lipid profile, and liver function. No adverse events were reported. Conclusions: A meal replacement VLCKD protocol is feasible, well-tolerated, and associated with significant improvements in weight, especially in body composition, metabolic health, and potentially outcomes in women with overweight or obesity awaiting ART. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy experienced by females. Diagnosis of PCOS is established when at least two of the following are present: hyperandrogenism, oligo-anovulation, and/or polycystic ovaries. Conservative treatment for PCOS includes dietary modifications and physical activity. The purpose of this scoping review was to evaluate the efficacy of a ketogenic diet in improving biochemical measures and reducing the severity of PCOS symptoms. Methods: CINAHL, PubMed, and Google Scholar databases were searched to find research published in peer-reviewed journals between 2019 and 2025. An article was included in this scoping review if the study assessed the effectiveness of a ketogenic diet on improving the signs and symptoms in patients with PCOS. Results: Eight studies met the inclusion criteria. Weight loss was achieved by subjects who adopted a very low-calorie ketogenic diet (VLCKD), low-calorie ketogenic diet (LCKD), classic ketogenic diet (CKD), or a Mediterranean eucaloric ketogenic diet (KEMEPHY). Patients with PCOS who consumed a ketogenic diet experienced improved biochemical measures, including androgen levels, lipid levels, HOMA-IR, blood glucose, insulin, LH/FSH ratio, DHEAS, SHBG, AFC, and AMH. A ketogenic diet was also associated with improvements in menstruation, fertility, and OHSS. Conclusions: Adopting a short-term ketogenic diet may have positive health benefits for patients with PCOS. Full article

A psoriasis vulgaris flare is characterized by a rapid intensification of symptoms, which is often triggered by various factors that can worsen the condition. The risk factors for these exacerbations are numerous and include obesity, antihypertensive drugs, and psychological stress. Moreover, links have been documented between type II diabetes, hypertension, and psoriasis vulgaris. The present case report describes a 52-year-old female patient who presented at the clinic with disseminated erythematous-squamous plaques and patches covered by thick, white-pearly, easily detachable scales, along with stress, fatigue, anxiety, severe pruritus, irritability, insomnia, and decreased self-esteem. Her past medical regimen included various conventional topical options, including calcipotriol combined with betamethasone, clobetasol, betamethasone combined with salicylic acid, and betamethasone combined with gentamicin, yet the condition remained refractory, with periodic flare-ups. The integrated and personalized therapeutic approach aimed to target both the dermatological issues and the associated systemic and psychological factors contributing to the condition. The therapeutic strategy implemented in this case combined psychological counseling sessions, a very low-calorie ketogenic diet, oral supplementation with anti-inflammatory and antioxidant vitamins and minerals, topical treatments utilizing urea and Dead Sea-mineral-based formulations, and rosemary extract-based scalp care, without requiring additional conventional treatment. This comprehensive approach led to significant improvement, ultimately achieving complete remission of the patient’s psoriasis. The associated comorbidities were well controlled with the specified medication, without any further complications. Thus, the importance of alternative options was emphasized, particularly in the context of an incurable disease, along with the need for continued research to improve the ongoing therapeutic management of psoriasis vulgaris. Such approaches are essential to reducing the risk of flare-ups and to achieving better management of associated risk factors. Full article

Background: Lipedema is a chronic disease of subcutaneous adipose tissue that predominantly affects women and is frequently associated with endocrinopathies such as insulin resistance and obesity. Its pathogenesis is still unclear, and treatment, which requires a multi-disciplinary approach, is prolonged over time and is not always effective. There is currently no drug treatment available for this disease. Methods: Five different cases of women with lipedema and insulin resistance, treated with Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) and once-weekly exenatide, in association or not with lifestyle changes (diet or physical activity) for 3 to 6 months are described. Changes in anthropometric parameters, symptoms, clinical findings and the thickness of superficial adipose tissue measured by ultrasound were evaluated. Results: Treatment with exenatide, whether combined with a change in diet or physical activity, resulted in a reduction in the characteristic symptoms of lipedema, in pain evoked by pinching the adipose tissue fold and in the thickness of subcutaneous adipose tissue at the levels of the lower limbs, abdomen and upper limbs. In four out of five cases, a reduction in body weight was observed, particularly during the first three months of treatment and in cases with greater metabolic impairment. Clinical, instrumental and subjective improvements were also observed in cases where there was no reduction in body weight and in patients who had previously undergone lower limb liposuction. Conclusions: The improvement in symptoms and clinical signs of lipedema, in addition to the reduction in adipose tissue in patients with lipedema and insulin resistance with exenatide, suggests a novel pharmacological approach to the disease, which can be combined with other conservative and surgical treatments to promote weight reduction. These results also highlight the association of this disease with metabolic alterations and the fundamental role of an accurate diagnosis followed by the treatment of comorbidities and excess weight in these patients. Full article

Background: Obesity is a major global public health issue with no fully satisfactory solutions. Most nutritional interventions rely on caloric restriction, with varying degrees of success. Very low-calorie ketogenic diets (VLCKD) have demonstrated rapid and sustained weight loss by inducing ketone bodies through lipolysis, reducing appetite, and preserving lean mass while maintaining metabolic health. Methods: A prospective clinical study analyzed sociodemographic, anthropometric, and adherence data from 7775 patients undergoing a multidisciplinary nutritional single-arm intervention based on a commercial weight-loss program. This method, using protein preparations with a specific balanced nutritional profile, aimed to identify key predictors of weight-loss success and classify population phenotypes with shared baseline characteristics and weight-loss patterns to optimize treatment personalization. Results: Statistical and machine learning analyses revealed that male gender (−9.2 kg vs. −5.9 kg) and higher initial body weight (−8.9 kg vs. −4.0 kg) strongly predict greater weight loss on a VLCKD, while age has a lesser impact. Two distinct population clusters emerged, differing in age, sex, follow-up duration, and medical visits, demonstrating unique weight-loss success patterns. These clusters help define individualized strategies for optimizing outcomes. Conclusions: These findings translationally support associations with the efficacy of a multidisciplinary VLCK weight-loss program and highlight predictors of success. Recognizing variables such as sex, age, and initial weight enhances the potential for a precision-based approach in obesity management, enabling more tailored and effective treatments for diverse patient profiles and prescribe weight loss personalized recommendations. Full article

Background: Obesity is a growing global health concern associated with numerous comorbidities and high medication burden. This study aimed to evaluate the impact of low- and very-low-calorie diets (LCD/VLCD), combined with intensive lifestyle changes, on comorbidities and medication use in hospitalized patients with class II and III obesity. Methods: A retrospective cohort study was conducted using medical records of patients hospitalized for 3–6 months at a specialized obesity hospital in Brazil. Prescription data for antihypertensive, hypoglycemic, and lipid-lowering drugs were compared at admission, 3, and 6 months. Descriptive statistics, chi-squared tests, and t-tests were used to compare medication use and weight change over time. Results: Among 246 patients, the proportion of those using antihypertensives decreased from 74.4% at admission to 44.7% at 6 months (p < 0.02), with significant reductions also observed at 3 months (p < 0.001). Hypoglycemic prescriptions also declined at 3 months (p = 0.01), but not significantly at 6 months. Lipid-lowering medication use showed no significant changes. Average weight loss was 11% at 3 months and 21.3% at 6 months. Conclusions: Hospitalization with LCD/VLCD and lifestyle therapy was associated with a short-term reduction in medication burden, especially antihypertensives, supporting the potential of inpatient multidisciplinary strategies for severe obesity management. Full article

Background: Trimethylamine N-oxide (TMAO) is a gut- and food-derived molecule. Elevated TMAO concentrations have been associated with an increased risk of cardiovascular disease (CVD) and all-cause mortality, highlighting its significance as a potential biomarker for adverse health outcomes. Given these associations, it is hypothesized that lifestyle interventions, such as healthy dietary patterns and exercise, could reduce TMAO concentrations. The aim of this systematic–narrative hybrid literature review was to evaluate the relationship between various lifestyle interventions and TMAO. Methods: MEDLINE (via PubMed^®), Scopus^®, and grey literature were searched until July 2024 for eligible clinical trials. Case reports, case series, case studies and observational studies were excluded, as well as studies that investigated food products, nutraceuticals, dietary supplements or have been conducted in the pediatric population. Results: In total, 27 studies were included in this review. While some dietary interventions, such as plant-based, high-dairy, very low-calorie ketogenic diet or the Mediterranean diet, were associated with lower TMAO concentrations, others—including high-protein and high-fat diets—were linked to an increase in TMAO concentrations. Studies that incorporated a combination of nutrition and exercise-based intervention presented neutral results. Conclusions: The relationship between dietary interventions and TMAO concentration remains controversial. While certain interventions show promise in reducing TMAO levels, others yield mixed or contradictory outcomes. Further research, including well-structured RCTs, is needed to investigate the aforementioned associations. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver dysfunction worldwide, characterized by hepatic steatosis that may progress to nonalcoholic steatohepatitis and cirrhosis. Owing to its strong association with metabolic disorders, current management focuses on weight reduction via lifestyle modifications. Recently, the very-low-calorie ketogenic diet (VLCKD) has emerged as a promising intervention due to its potential for rapid weight loss and reduction in liver fat. This review aims to evaluate the clinical evidence regarding the impact of ketogenic diets on hepatic steatosis. We conducted an extensive MEDLINE literature search in databases including PubMed, Scopus, and Web of Science up to December 2024. Studies assessing the effects of ketogenic or low-carbohydrate high-fat diets on liver fat, evaluated by imaging, histology, or biochemical markers, were included. The analysis indicates that ketogenic diets significantly reduce hepatic fat content and improve metabolic parameters, including insulin sensitivity and liver enzyme levels. Evidence further suggests that substituting saturated fats with unsaturated fats or replacing carbohydrates with proteins may enhance these benefits. However, considerable variability exists among studies and long-term data remain limited. Although short-term outcomes are encouraging, potential adverse effects such as dyslipidaemia, gastrointestinal disturbances, and transient ‘keto flu’ symptoms require careful clinical monitoring. Future research should focus on elucidating underlying mechanisms, optimizing dietary composition, and assessing long-term safety to establish ketogenic diets as a robust strategy for managing MASLD. Full article