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Background/Objectives: Obesity is closely linked to chronic low-grade inflammation and the development of cardio-metabolic comorbidities. Monocyte subsets, which are crucial in immune responses, have been reported to be altered in individuals with obesity, potentially exacerbating inflammation. Although very-low-calorie ketogenic diets (VLCKDs) are recognized for their efficacy in promoting weight loss and improving metabolic health, their impact on circulating monocyte subsets remains poorly understood. The objective of our study is to investigate the impact of VLCKDs on monocyte subset distribution in people with obesity. Methods: Thirty-six participants were divided into four groups—healthy controls, individuals with obesity and no dietary intervention, and individuals with obesity following either a low-calorie diet (LCD) or VLCKD for 28 days. Blood samples were analyzed to assess the distribution of classical monocytes (CMs), intermediate monocytes (IMs), and non-classical monocytes (NCMs) using flow cytometry. Results: Individuals with obesity exhibited significant increases in IMs and NCMs, alongside a decrease in CMs compared to healthy controls. The VLCKD led to a notable shift in monocyte distribution, with increased CMs and reduced IMs and NCMs, restoring levels closer to those observed in healthy individuals. In contrast, the LCD group showed no significant changes in monocyte subsets. Conclusions: VLCKDs may exert anti-inflammatory effects by modulating monocyte subset distribution, offering potential therapeutic benefits in mitigating obesity-related inflammation. These preliminary findings suggest that VLCKDs could be an effective strategy for improving immune function in individuals with obesity. [ABSTRACT FROM AUTHOR]

Background. Very low-calorie ketogenic diets (VLCKD) are an effective weight-loss strategy for obese individuals, reducing risks of liver conditions such as non-alcoholic steatohepatitis and fibrosis. Small extracellular vesicles (sEVs) are implicated in liver fibrosis by influencing hepatic cell phenotypes and contributing to liver damage. This study investigates sEVs derived from serum of 60 obese adults categorized into low fibrosis risk (LR) and intermediate/high fibrosis risk (IHR) groups based on FibroScan elastography (FIB E scores, limit value 8 kPa) and all participants underwent an 8-week VLCKD intervention. Methods. The study examines the impact of these sEVs on fibrosis markers, inflammation, and autophagy in a hepatocyte cell line (HEPA-RG) using bioinformatics, RNA sequencing, lipidomics, RT-PCR, and Western blotting before (T0) and after (T1) VLCKD. Results. sEVs from LR patients post-VLCKD reduced fibrosis related gene expression (e.g., ACTA2) and enhanced proteins associated with regeneration and inflammation (e.g., HDAC6). Conversely, sEVs from IHR patients increased fibrosis and inflammation related gene expression (PIK3CB, AKT1, ACTA2) in hepatocytes, raising concerns about VLCKD suitability for IHR patients. IHR sEVs also decreased expression of HDAC10, HDAC6, HDAC3, MMP19, and MMP2, while increasing modulation of p-AKT, α-SMA, and VIM. Conclusion. These findings underscore the critical role of sEVs in regulating inflammation, remodeling, and hepatic stress responses, particularly in IHR patients, and suggest sEVs could complement instrumental evaluations like FibroScan in fibrosis assessment. [ABSTRACT FROM AUTHOR]

Abstract Background 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). Methods 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. Results 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

Background: 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). Methods: 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. Results: 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). Conclusion: These findings underscore the importance of considering sex-specific responses in personalized obesity treatment strategies, particularly dietary interventions like VLEKTs. [ABSTRACT FROM AUTHOR]

The VLCKD is a diet recognized to promote rapid fat mobilization and reduce inflammation, hepatic steatosis, and liver fibrosis. Extracellular vesicles (EVs) mediate cell-to-cell communication. The aim of the study is to investigate the role of circulating EVs in cell proliferation, ketone bodies, and ROS production in patients on an 8-week VLCKD regimen. Participants were classified as responders (R) or non-responders (NR) to VLCKD treatment based on their fibroscan results. In vitro experiments with the hepatic cell lines HEPA-RG (normal hepatocytes) and LX-2 (stellate cells) were conducted to investigate the effects of circulating EVs on cell viability, ROS production, and ketone body presence. The findings reveal a notable reduction in cell viability in both cell lines when treated with exosomes (EXOs). In contrast, treatment with microvesicles (MVs) did not appear to affect cell viability, which remained unchanged. Additionally, the levels of ketone bodies measured in urine were not consistently correlated with the reduction of fibrosis in responders (R). Similarly, an increase in ketone bodies was observed in non-responders (NR), which was also not aligned with the expected reduction in fibrosis. This inconsistency stands in stark contrast to the levels of Reactive Oxygen Species (ROS), which exhibited a clear and consistent pattern in accordance with the dietary intervention. Finally, in this preliminary study, ROS has been identified as a potential diet adherence marker for VLCKD patients; the ROS levels reliably follow the progression of the fibrosis response, providing a more accurate reflection of the therapeutic effects. [ABSTRACT FROM AUTHOR]

Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinization, inflammation, and bacterial colonization of the hair follicles of the face, neck, chest and back by Propionibacterium acnes. Overall, inflammation and immune responses are strongly implicated in the pathogenesis of acne. Although early colonization with Propionibacterium acnes and family history may play an important role in the disease, it remains unclear exactly what triggers acne and how treatment affects disease progression. The influence of diet on acne disease is a growing research topic, yet few studies have examined the effects of diet on the development and clinical severity of acne disease, and the results have often been contradictory. Interestingly, very low-calorie ketogenic diet (VLCKD) has been associated with both significant reductions in body weight and inflammatory status through the production of ketone bodies and thus it has been expected to reduce the exacerbation of clinical manifestations or even block the trigger of acne disease. Given the paucity of studies regarding the implementation of VLCKD in the management of acne, this review aims to provide evidence from the available scientific literature to support the speculative use of VLCKD in the treatment of acne. [ABSTRACT FROM AUTHOR]

Abstract Background Acne, a chronic inflammatory disease impacting the pilosebaceous unit, is influenced significantly by inflammation and oxidative stress, and is commonly associated with obesity. Similarly, obesity is also associated with increased inflammation and oxidation. The role of diet in acne remains inconclusive, but the very low-calorie ketogenic diet (VLCKD), known for weight loss and generating anti-inflammatory ketone bodies, presents promising potential. Despite this, the effects of VLCKD on acne remain underexplored. This study aimed to investigate the efficacy of a 45-day active phase of VLCKD in reducing the clinical severity of acne in young women with treatment-naïve moderate acne and grade I obesity. Methods Thirty-one women with treatment-naïve moderate acne, grade I obesity (BMI 30.03–34.65 kg/m2), aged 18–30 years, meeting inclusion/exclusion criteria, and consenting to adhere to VLCKD were recruited. Baseline and post-intervention assessments included anthropometric measurements, body composition, phase angle (PhA), trimethylamine N-oxide (TMAO) levels, and reactive oxygen metabolite derivatives (dROMs) as markers of inflammation, dysbiosis, and oxidative stress, respectively. A comprehensive dermatological examination, incorporating the Global Acne Grading System (GAGS) and the Dermatology Life Quality Index (DLQI), was conducted for all women. Results VLCKD resulted in general improvements in anthropometric and body composition parameters. Significantly, there were significant reductions in both the GAGS score (Δ%: − 31.46 ± 9.53, p

Background: Acne, a chronic inflammatory disease impacting the pilosebaceous unit, is influenced significantly by inflammation and oxidative stress, and is commonly associated with obesity. Similarly, obesity is also associated with increased inflammation and oxidation. The role of diet in acne remains inconclusive, but the very low-calorie ketogenic diet (VLCKD), known for weight loss and generating anti-inflammatory ketone bodies, presents promising potential. Despite this, the effects of VLCKD on acne remain underexplored. This study aimed to investigate the efficacy of a 45-day active phase of VLCKD in reducing the clinical severity of acne in young women with treatment-naïve moderate acne and grade I obesity. Methods: Thirty-one women with treatment-naïve moderate acne, grade I obesity (BMI 30.03–34.65 kg/m2), aged 18–30 years, meeting inclusion/exclusion criteria, and consenting to adhere to VLCKD were recruited. Baseline and post-intervention assessments included anthropometric measurements, body composition, phase angle (PhA), trimethylamine N-oxide (TMAO) levels, and reactive oxygen metabolite derivatives (dROMs) as markers of inflammation, dysbiosis, and oxidative stress, respectively. A comprehensive dermatological examination, incorporating the Global Acne Grading System (GAGS) and the Dermatology Life Quality Index (DLQI), was conducted for all women. Results: VLCKD resulted in general improvements in anthropometric and body composition parameters. Significantly, there were significant reductions in both the GAGS score (Δ%: − 31.46 ± 9.53, p < 0.001) and the DLQI score (Δ%: − 45.44 ± 24.02, p < 0.001) after the intervention. These improvements coincided with significant decreases in TMAO (p < 0.001) and dROMs (p < 0.001) levels and a significant increase in PhA (Δ%: + 8.60 ± 7.40, p < 0.001). Changes in the GAGS score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjusting for Δ% FM. Changes in the DLQI score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjustment for Δ% FM. Conclusion: Given the side effects of drugs used for acne, there is an increasing need for safe, tolerable, and low-cost treatments that can be used for acne disease. The 45-day active phase of VLCKD demonstrated notable improvements in acne severity, and these improvements seemed to be attributable to the known antioxidant and anti-inflammatory effects of VLCKD. [ABSTRACT FROM AUTHOR]

Abstract Background Migraine is the second world’s cause of disability. Among non-pharmacological treatments, nutritional intervention, particularly ketogenic diet, represents one of the most promising approaches. Methods This a prospective, single center, randomized, controlled study aimed at evaluating the efficacy of a very low-calorie ketogenic diet (VLCKD) compared to a hypocaloric balanced diet (HBD) in migraine prophylaxis in patients affected by high-frequency episodic migraine (HFEM) with a Body Mass Index (BMI) > 27 kg/m2. Fifty-seven patients were randomly assigned to a VLCKD (group 1) or HBD (group 2). Group 1 patients followed a VLCKD for 8 weeks, followed by a low calorie diet (LCD, weeks 9–12), and a HBD (weeks 13–24), whereas group 2 patients followed a HBD from week 0 to 24. Anthropometric indexes, urine and blood chemistry were assessed at enrollment, baseline, weeks 4, 8, 12, and 24. Migraine characteristics were evaluated at baseline, weeks 8, 12 and 24. Change in monthly migraine days (MMDs) at weeks 5–8 compared to baseline was the primary endpoint. Secondary endpoints encompassed changes in visual analogue scale (VAS), Headache Impact Test-6 (HIT-6) and Short Form Health Survey-36 (SF-36) scores. We also studied effects on circulating lymphocytes and markers of inflammation, changes in plasma aldosterone and renin levels before and after VLCKD or HBD treatment. Results Reduction from baseline in MMDs was greater in VLCKD compared to HBD group at week 8 (p = 0.008), at week 12 (p = 0.007), when ketosis had been interrupted by carbohydrates reintroduction, and at week 24 (p = 0.042), when all patients were following the same dietary regimen. Quality of life scores (SF-36) were improved in VLCKD group at week 8 and 12, and were also improved in HBD group, but only at week 12. Weight-loss was significantly higher in VLCKD group at week 8 (p = 0.002) and week 12 (p = 0.020). At the end of the study weight loss was maintained in VLCKD group whereas a slight weight regain was observed in HBD group. Inflammatory indexes, namely C reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and total white blood cell count (WBC) were significantly reduced (p

Psoriasis is an immune-mediated inflammatory skin disease associated with multiple comorbidities. Considered one of the most common inflammatory skin diseases among the general population, it not only affects the skin, but also negatively impacts other organs and joints. In addition, psoriasis has been associated with several chronic cardio-metabolic diseases such as obesity, which would seem to be (i) a risk factor for the onset of psoriasis and (ii) a worsening factor of the severity of the disease. Weight loss appears to improve severity in overweight patients. Recently proposed as an obesity management nutritional strategy, the very-low-calorie ketogenic diet (VLCKD) has demonstrated significant effects in reducing inflammatory processes. In the current review, we describe the evidence available on psoriasis and VLCKD, and provide a practical guide to the prescription of VLCKD in the different phases, evaluation and management of possible adverse events, and the importance of physical activity as a lifestyle modification to reduce psoriasis and associated comorbidities. Randomized control trials are, however, necessary to determine the most effective VLCKD protocol for patients with obesity and psoriasis, optimal protocol duration, composition of micronutrients and macronutrients, choice of special supplements, and management of carbohydrate reintroduction. [ABSTRACT FROM AUTHOR]

Abstract Background Obesity is a condition that is often associated with sleep disorders, including reduced sleep quality (SQ). Very low calorie ketogenic diet (VLCKD) has proven to be effective in the management of obesity and associated metabolic disorders. However, little is still known about the effects of this promising nutritional protocol on SQ. Thus, the purpose of this study was to investigate the short-term effect of VLCKD on SQ in women with overweight/obesity and if any changes, to identify the predictive factor that through VLCKD modified SQ. Methods Were consecutively enrolled a total of 324 subjects, who met the inclusion criteria and accepted to adhere to VLCKD. Assessment of nutritional status, including anthropometric measurements (height, weight, and waist circumference), bioelectrical impedance analysis (phase-sensitive system, 50 kHz BIA 101 RJL, Akern Bioresearch, Florence, Italy Akern), high sensitivity C reactive protein levels (hs-CRP), and SQ were carried out at baseline and after 31 days of active stage of VLCKD. SQ was evaluated using the validated questionnaire Pittsburgh Sleep Quality Index (PSQI). Results In addition to the expected general improvement of anthropometric parameters and body composition, VLCKD improved significantly SQ, as demonstrated by the improvement of all parameters included in the PSQI questionnaire (p − 8.4% predicted improvement in SQ (p

Objective: The aim of this study is to assess the efficacy of a very low-calorie ketogenic diet (VLCKD) method vs a Mediterranean low-calorie diet (LCD) in obese polycystic ovary syndrome (PCOS) women of a reproductive age. Design: Randomized controlled open-label trial was performed in this study. The treatment period was 16 weeks; VLCKD for 8 weeks then LCD for 8 weeks, according to the Pronokal® method (experimental group; n = 15) vs Mediterranean LCD for 16 weeks (control group; n = 15). Ovulation monitoring was carried out at baseline and afte r 16 weeks, while a clinical exam, bioelectrical impedance analysis (BIA), anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16. Results: BMI decreased significantly in both groups and to a major extent in the experimental group (−13.7% vs −5.1%, P = 0.0003). Significant differences between the experimental and the control groups were also observed in the reduction of waist circumference (−11.4% vs −2.9%), BIA-measured body fat (−24.0% vs −8.1%), and free testosterone (−30.4% vs −12.6%) after 16 weeks (P = 0.0008, P = 0.0176, and P = 0.0009, respectively). Homeostatic model assessment for insulin resistance significantly decreased only in the experimental group (P = 0.0238) but without significant differences with respect to the control group (−23% vs −13.2%, P > 0.05). At baseline, 38.5% of participants in the experimental group and 14.3% of participants in the control group had ovulation, which increased to 84.6% (P = 0.031) and 35.7% (P > 0.05) at the end of the study, respectively. Conclusion: In obese PCOS patients, 16 weeks of VLCKD protocol with the Pronokal® method was more effective than Mediterranean LCD in reducing tot al and visceral fat, and in ameliorating hyperandrogenism and ovulatory dysfunction. Significance statements: To the best of our knowledge, this is the first randomized contr olled trial on the use of the VLCKD method in obese PCOS. It demonstrates the superiority of VLCKD with respect to Mediterranean LCD in reducing BMI with an almost selective reduction of fat mass and a unique effect of VLCKD in reducing v isceral adiposity, insulin resistance, and in increasing SHBG with a consequent reduction of free testosterone. Interestingly, this study also demonstrates the superiority of the VLCKD protocol in improving ovulation, whose occurrence increased by 46.1% in the group treated by the VLCKD method against a rise of 21.4% in the group treated by Mediterranean LCD. This study extends the therapeutic approach possibilities in obese PCOS women.

Background: Protein-sparing modified fast (PSMF) diet is a very-low-carbohydrate ketogenic diet administered to patients with obesity, which preserves lean mass and suppresses appetite as well as continuous enteral feeding. Thus, we aim to evaluate the effect of the PSMF diet administered continuously by nasogastric tube (NGT) or orally. Methods: Patients with a body mass index (BMI) > 34.9 kg/m2 were randomly assigned to receive a whey protein PSMF formula through NGT (ProMoFasT) or orally. Data were collected at baseline and after 150 days. The endpoints were assessed in the intention-to-treat population. Results: We enrolled 20 patients in the ProMoFasT group and 24 in the oral group. No differences in body weight, BMI or waist circumference between the two groups were found after 150 days. At follow-up, FFM (%) and MM (%) results were higher in the ProMoFasT group than the oral group (63.1% vs. 52.9%, p = 0.012 and 45.0% vs. 36.1%, p = 0.009, respectively) and FM (kg) and FM (%) were significantly lower in the ProMoFasT group (36.9 kg vs. 44.0 kg, p = 0.033 and 37.4% vs. 44.9%, p = 0.012, respectively). Insulin levels were lower in the ProMoFasT group than the oral group at follow-up (11.8 mU/L vs. 28.0 mU/L, p = 0.001, respectively). Conclusion: The ProMoFasT is more effective in improving body composition and glucometabolic markers than the same diet administered orally. [ABSTRACT FROM AUTHOR]

Preoperative weight loss before a bariatric surgery reduces long-term complications, but there is no solid evidence for short-term or perioperative complications. This review highlights recent evidence on dietary protocols and the possible correlation between weight loss and surgical complications. Updated evidence was searched in PubMedDirect with the terms "preoperative very low-calorie diet or very-low-calorie ketogenic diet or low-fat diet or intermittent fasting or Mediterranean diet and bariatric surgery or bariatric surgery complications." The main characteristics of each diet, achievements related to weight loss, liver reduction, peri and postoperative outcomes, surgical complications, tolerance, and adherence to the diet are presented from the selected studies. There are few reports about the Mediterranean diet as a strategy to reach these goals. The VLCKD has been associated with better body weight reduction and lesser postoperative complications risk. However, the results in animal models are still controversial. When comparing VLCD with an LCD, there is no apparent superiority between one against the other one. However, LCD has shown better tolerance and adherence than VLCD. There is still a need for more controlled studies to define the best preoperative dietary treatment for weight loss before bariatric surgery since there are controversial positions regarding this issue. [ABSTRACT FROM AUTHOR]

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

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity is a risk factor in terms of adverse effects during hormone stimulation, a reduced response to ovulation induction regimens, reduced success of IVF, and an increased risk of obstetric complications. To resolve this vicious cycle of pathological events, weight loss and lifestyle modifications are promising strategies. Among these possible approaches, the consumption of a very-low-calorie ketogenic diet (VLCKD) or Mediterranean diet (MD) represents a valid option. In our study, 84 obese/overweight PCOS patients were recruited to evaluate the effects induced by the VLCKD and MD on weight, hormonal, and metabolic parameters. BMI decreased significantly among the VLKCD patients compared to the MD patients (both presenting p values < 0.0001 at 90 and 120 days), and a significant reduction in body circumference was observed. At the same time, HOMA index values statistically decreased for the VLCKD patients compared to those on the MD (p value < 0.001 at 90 days and p value < 0.05 at 120 days), and this phenomenon was also observed for AFC at 90 and 120 days (both p values < 0.001) and AMH at 90 days (p value < 0.05). Interestingly, the ovarian hyperstimulation syndrome (OHSS) incidence was statistically lower in the VLKCD patients compared to the MD patients (p < 0.001). We state that these dietary regimes may improve anthropometric parameters (such as BMI) and women's reproductive health, restore menstrual regularity, and reduce the risk of OHSS. Regarding the different nutritional therapies, the results suggest that the VLCKD is an optimal choice for entry into IVF, especially in terms of the time range in which these results are achieved. [ABSTRACT FROM AUTHOR]

Aims: We aimed to evaluate the efficacy of three different ketogenic diets on migraine and fatigue in chronic and high-frequency episodic migraineurs. Methods: 76 patients with migraine were treated with the KD for at least three months. Three different KD protocols were used (2:1 KD, LGID, and VLCKD). We evaluated the fatigue severity scale (FSS), migraine frequency, migraine intensity, MIDAS, and HIT-6 at the baseline and 3-month follow-up, and we compared the results. We also correlated the mean FSS reduction with the mean migraine frequency, migraine intensity, BMI, fat mass, free-fat mass, MIDAS, and HIT-6 reduction. Results: FSS improved from 4.977 ± 1.779 to 3.911 ± 1.779 at the 3-month follow-up (p < 0.001). This improvement was significant in both high-frequency and chronic migraineurs. Moreover, the three KD protocols effectively improved migraine intensity, frequency, MIDAS, and HIT-6. There was a mild correlation between mean FSS reduction (p < 0.001), mean MIDAS (p = 0.001), and HIT-6 (p = 0.002) reduction. Conclusions: The VLCKD, LGID, and 2:1 KD may improve migraine intensity, frequency, and fatigue in chronic and high-frequency episodic migraineurs. [ABSTRACT FROM AUTHOR]

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

Abstract Background Obesity is accompanied by hormonal, inflammatory and endothelial alterations. These alterations induce a stimulation of several other mechanisms that contribute to the hypertensive state and to increase the cardiovascular morbidity. This pilot, open - label, single- center, prospective clinical trial aimed to evaluate the effect of very low- calorie ketogenic diet (VLCKD) on blood pressure (BP) in women with of obesity and hypertension. Methods A total of 137 women, who met the inclusion criteria and accepted to adhere to VLCKD, were consecutively enrolled. Assessment of anthropometric parameters (weight, height, and waist circumference), body composition (through bioelectrical impedance analysis), systolic (SBP) and diastolic blood pressure (DBP) and blood sample collection were carried out at baseline and after 45 days of the active phase of VLCKD. Results After VLCKD all the women experienced a significant reduction in body weight and an overall improvement of body composition parameters. In addition, high sensitivity C reactive protein (hs- CRP) levels were significantly diminished (p

Abstract Background Very low-calorie ketogenic diet (VLCKD) has shown to significantly reduce body weight and fat mass, as well as inflammation. These effects are supported by nutritional ketosis, which triggers the utilization of the ketone body as an energy source. Medium-chain fatty acids (MCTs) might serve as potential enhancers of ketone bodies production with a greater effect on weight loss. Nevertheless, no clinical studies have evaluated the effect of MCTs supplementation in addition to VLCKD. Therefore, the present study aimed to evaluate whether the supplementation with MCTs can induce a greater weight reduction during the ketogenic phase of VLCKD. Methods In this retrospective study, 263 women with overweight/obesity (body mass index, BMI: 35.7 ± 5.3 kg/m2) aged 37.5 ± 14.2 years followed one of these dietary protocols for 45 days: (a) Control group, 83 participants (31.6%) (VLCKD without MCTs), (b) VLCKD + MCTs group, 86 participants (32.7%) (MCTs supplementation − 20 g/day- during VLCKD starting from the first day of the active phase), (c) VLCKD + earlyMCTs, 94 participants (35.7%) (MCTs supplementation − 20 g/day-starting from 5 days before the beginning of the VLCKD active phase. Anthropometric measures, body composition, and c-reactive protein (CRP) concentrations were collected at the beginning and at the end (45 days) of the VLCKD intervention. Results MCTs supplementation significantly decreased body weight, BMI, and waist circumference as compared to the control group, with a greater effect in the VLCKD + earlyMCTs group. A two-fold decrease in fat mass and an increase in muscle mass were observed in the VLCKD + earlyMCTs group as compared to the control group. As for inflammation, hs-CRP concentrations (assessed as absolute percent change) were significantly lower in the VLCKD + MCTs group (p = 0.009) and the VLCKD + earlyMCTs group (p = 0.011) than in the control group. A logistic regression model showed that VLCKD + earlyMCTs increase the likelihood of improvement of BMI classes (OR: 1.85, 95% CI 1.02–3.36) also after adjusting for the potential confounding factors. Conclusion MCTs supplementation (20 g/day) may be a useful tool to enhance the beneficial effect of VLCKD on the reduction of body weight and fat mass. In particular, MCTs supplementation before the beginning of the VLCKD active phase might facilitate ketosis thus contributing to the effectiveness of the nutritional intervention.

Background: Obesity is a condition that is often associated with sleep disorders, including reduced sleep quality (SQ). Very low calorie ketogenic diet (VLCKD) has proven to be effective in the management of obesity and associated metabolic disorders. However, little is still known about the effects of this promising nutritional protocol on SQ. Thus, the purpose of this study was to investigate the short-term effect of VLCKD on SQ in women with overweight/obesity and if any changes, to identify the predictive factor that through VLCKD modified SQ. Methods: Were consecutively enrolled a total of 324 subjects, who met the inclusion criteria and accepted to adhere to VLCKD. Assessment of nutritional status, including anthropometric measurements (height, weight, and waist circumference), bioelectrical impedance analysis (phase-sensitive system, 50 kHz BIA 101 RJL, Akern Bioresearch, Florence, Italy Akern), high sensitivity C reactive protein levels (hs-CRP), and SQ were carried out at baseline and after 31 days of active stage of VLCKD. SQ was evaluated using the validated questionnaire Pittsburgh Sleep Quality Index (PSQI). Results: In addition to the expected general improvement of anthropometric parameters and body composition, VLCKD improved significantly SQ, as demonstrated by the improvement of all parameters included in the PSQI questionnaire (p < 0.001). Both at baseline and after 31 days of active stage of VLCKD, the PSQI score was significantly associated with BMI, waist circumference, fat mass, fat free mass (p < 0.001 for all) and hs-CRP (p = 0.023). PhA was negatively associated with PSQI score only at baseline (p < 0.001). ∆% PSQI positively correlated with ∆% BMI, ∆% fat mass, ∆% hs-CRP (p < 0.001 for all) and negatively correlated with ∆% fat free mass (p < 0.001), and ∆% PhA (p = 0.031). In the multiple regression analysis ∆% fat mass represented the only predictor of changes in SQ after VLCKD. Finally, in the ROC analysis, a threshold value of ∆% fat mass > − 8.4% predicted improvement in SQ (p < 0.001). Conclusion: In conclusion, VLCKD determines an improvement of SQ in women with overweight and obesity, that was mostly mediated by the reduction of fat mass related to this nutritional protocol. [ABSTRACT FROM AUTHOR]

Recent studies reported that chronotype play a role in the development of metabolic comorbidities and in determining dietary habits in obesity. However, little is known if chronotype could predict the efficacy of nutritional approaches for obesity. The aim of this study was to investigate whether chronotype categories can have a role in determining the efficacy of very low-calorie ketogenic diet (VLCKD) in terms of weight loss and changes of body composition in women with overweight or obesity. In this retrospective study we analyzed data from 248 women (BMI 36.03 ± 5.20 kg/m2, aged 38.76 ± 14.05 years) clinically referred for weight loss and who completed a VLCKD program. In all women, we assessed anthropometric parameters (weight, height, and waist circumference), body composition and phase angle (through bioimpedance analysis, Akern BIA 101) at the baseline and after 31 days of active phase of VLCKD. Chronotype score was assessed using Morningness-Eveningness questionnaire (MEQ) at baseline. After 31 days of active phase of VLCKD all enrolled women experienced significant weight loss (p < 0.001) and reduction of BMI (p < 0.001), waist circumference (p < 0.001), fat mass (kg and %) (p < 0.001), and free fat mass (kg) (p < 0.001). Women with evening chronotype experienced significantly less weight loss (p < 0.001) and reduced fat mass (kg and %) (p < 0.001), increased fat free mass (kg and %) (p < 0.001) and phase angle (p < 0.001) than women with morning chronotype. In addition, chronotype score correlated negatively with percentage changes in weight (p < 0.001), BMI (p < 0.001), waist circumference (p < 0.001) and fat mass (p < 0.001) and positively with fat free mass (p < 0.001) and phase angle (p < 0.001) from baseline to the 31st day of active phase of VLCKD. Using a linear regression model, chronotype score (p < 0.001) was the main predictors of weight loss achieved with VLCKD. Evening chronotype is associated with a lower efficacy in terms of weight loss and improvements of body composition after VLCKD in obesity. [ABSTRACT FROM AUTHOR]

(1) Background: this work reports the clinical case of a man who underwent a kidney transplant at the age of 19 for idiopathic interstitial nephritis resulting in renal failure. (2) Methods: the patient also had severe obesity and underwent four cycles of a very low-calorie ketogenic diet (VLCKD) for weight loss. (3) Results: the cycles of diet therapy carried out during a six-year period allowed a significant weight loss (from 103.2 kg in 2012 to 87.5 kg in 2018) with lean mass conservation (from 49.9 kg to 52.5 kg) and a reduction of fat mass (from 53.3 kg to 35.0 kg), as assessed with bioimpedance analysis. Throughout the diet cycles, body weight remained stable, except for a weight regain that occurred between the 2nd and 3rd cycle. Renal function was preserved despite the known mild chronic kidney disease (creatininemia ranged from 1.11 mg/dL to 1.27 mg/dL, and GRF from 91 to 71 mL/min/1.73 m2). (4) Conclusions: this report shows that a VLCKD, performed under strict medical supervision, is safe and effective even in a complex clinical picture.

Background: Obesity is accompanied by hormonal, inflammatory and endothelial alterations. These alterations induce a stimulation of several other mechanisms that contribute to the hypertensive state and to increase the cardiovascular morbidity. This pilot, open - label, single- center, prospective clinical trial aimed to evaluate the effect of very low- calorie ketogenic diet (VLCKD) on blood pressure (BP) in women with of obesity and hypertension. Methods: A total of 137 women, who met the inclusion criteria and accepted to adhere to VLCKD, were consecutively enrolled. Assessment of anthropometric parameters (weight, height, and waist circumference), body composition (through bioelectrical impedance analysis), systolic (SBP) and diastolic blood pressure (DBP) and blood sample collection were carried out at baseline and after 45 days of the active phase of VLCKD. Results: After VLCKD all the women experienced a significant reduction in body weight and an overall improvement of body composition parameters. In addition, high sensitivity C reactive protein (hs- CRP) levels were significantly diminished (p < 0.001), while phase angle (PhA) increased by almost 9% (p < 0.001). Interestingly, both SBP and DBP were significantly improved (-12.89% and − 10.77%, respectively; p < 0.001). At baseline, SBP and DBP showed statistically significant correlations with body mass index (BMI), waist circumference, hs-CRP levels, PhA, total body water (TBW), extracellular water (ECW), Na / K ratio, and fat mass. Even after VLCKD, all correlations among SBP and DBP with the study variables were statistically significant, except for the association between DBP and Na / K ratio. Changes (%) in both SBP and DBP were associated with ∆BMI%, ∆PhA% and ∆hs- CRP levels (p < 0.001). In addition, only ∆SBP% was associated with ∆waist circumference (p = 0.017), ∆TBW (p = 0.017), and ∆fat mass (p < 0.001); while only ∆DBP% was associated with ∆ECW (p = 0.018), and ∆Na / K ratio (p = 0.048). After adjusting for ∆BMI, ∆WC, ∆PhA, ∆TBW, and ∆fat mass, the correlation between changes in ∆SBP and ∆hs -CRP levels remained statistically significant (p < 0.001). Similarly, the correlation between ∆DBP and ∆hs- CRP levels also remained statistically significant after adjustment for ∆BMI, ∆PhA, ∆Na / K ratio, and ∆ECW (p < 0.001). From multiple regression analysis ∆hs- CRP levels seemed to be the main predictor of changes of BP (p < 0.001). Conclusion: VLCKD reduces BP in women with of obesity and hypertension in a safely manner. [ABSTRACT FROM AUTHOR]

Background: The very low-calorie ketogenic diet (VLCKD) represents an opportunity to attain clinically relevant weight loss in obese patients. Functional hypogonadism represents a frequent hormonal disorder associated with obesity and visceral fat accumulation characterised by low testosterone levels and subnormal luteinising hormone (LH) levels. Aim: To evaluate the early effects of VLCKD on serum total testosterone (TT) levels in non-diabetic obese patients. Methods: Twenty-two obese male patients (mean age 39.3 ± 11.7 years, mean body mass index (BMI) 38.2±6.4 kg/m2) were enrolled and treated for 28 days with VLCKD. Anthropometric and hormonal variables were assessed before, during and after diet intervention. Results: After 7 and 28 days on a VLCKD, a significant and persistent reduction in body weight, BMI, fat mass, blood glucose, insulin and homeostasis model assessment index was observed compared with baseline. TT significantly increased after 7 days (+35 ± 64 ng/dl) and 28 days (+74 ± 97 ng/dl) on a VLCKD. In addition to TT, a significant increase in serum sex hormone-binding globulin levels was observed after 7 (+2.1 ± 4.1) and 28 days (+7.7 ± 10.0). However, both calculated free testosterone and LH did not change after 7 or 28 days of VLCKD. Following cessation of VLCKD, hypogonadal subjects achieved a higher percentage of total weight loss (8.5% ± 1.5%), a greater reduction in weight (-9.94 ± 1.66 kg), fat mass (-7 ± 2.1 kg) and waist circumference (-6.31 ± 2.65 cm) and a greater improvement in glycaemia (-8.75 ± 10.92 mg/dl) as compared with eugonadal subjects. Furthermore, hypogonadal subjects exhibited a trend of higher TT increase (+98.12 ± 71.51 ng/dl) as compared with eugonadal subjects. Conclusions: VLCKDresults in rapid improvements in TT levels associated with weight loss in male obese non-diabetic subjects, particularly in the presence of obesity-related hypogonadism. [ABSTRACT FROM AUTHOR]

Background: It is widely demonstrated that obesity and hypogonadism are bi-directionally correlated, since the hypogonadism prevalence is higher in obese population, while weight loss increases testosterone serum levels. Several approaches are available to contrast weight excess, from simple dietary regimens to more complex surgical procedures. Ketogenic diets (KD) fit in this context and their application is growing year after year, aiming to improve the metabolic and weight patterns in obese patients. However, KD influence on testosterone levels is still poorly investigated. Objectives: To systematically evaluate the potential effect of KD on testosterone levels. Methods: A systematic literature search was performed until April 2022 including studies investigating testosterone levels before and after KD. Secondary endpoints were body weight, estradiol and sex-hormone binding globulin serum levels. Any kind of KD was considered eligible, and no specific criteria for study populations were provided. Results: Seven studies (including eight trials) were included in the analysis for a total of 230 patients, five using normocaloric KD and three very low calories KD (VLCKD). Only three studies enrolled overweight/obese men. A significant total testosterone increase was recorded after any kind of KD considering 111 patients (2.86 [0.95, 4.77], p = 0.003). This increase was more evident considering VLCKD compared to normocaloric KD (6.75 [3.31, 10.20], p < 0.001, versus 0.98 [0.08, 1.88], p = 0.030). Meta-regression analyses highlighted significant correlations between the post-KD testosterone raise with patients' age (R-squared 36.4, p < 0.001) and weight loss (R-squared 73.6, p < 0.001). Conclusions: Comprehensively, KD improved testosterone levels depending on both patients' age and KD-induced weight loss. However, the lack of information in included studies on hormones of the hypothalamic-pituitary-gonadal axis prevents an exhaustive comprehension about mechanisms connecting ketosis and testosterone homeostasis. [ABSTRACT FROM AUTHOR]

Background: Very low-calorie ketogenic diet (VLCKD) has shown to significantly reduce body weight and fat mass, as well as inflammation. These effects are supported by nutritional ketosis, which triggers the utilization of the ketone body as an energy source. Medium-chain fatty acids (MCTs) might serve as potential enhancers of ketone bodies production with a greater effect on weight loss. Nevertheless, no clinical studies have evaluated the effect of MCTs supplementation in addition to VLCKD. Therefore, the present study aimed to evaluate whether the supplementation with MCTs can induce a greater weight reduction during the ketogenic phase of VLCKD. Methods: In this retrospective study, 263 women with overweight/obesity (body mass index, BMI: 35.7 ± 5.3 kg/m2) aged 37.5 ± 14.2 years followed one of these dietary protocols for 45 days: (a) Control group, 83 participants (31.6%) (VLCKD without MCTs), (b) VLCKD + MCTs group, 86 participants (32.7%) (MCTs supplementation − 20 g/day- during VLCKD starting from the first day of the active phase), (c) VLCKD + earlyMCTs, 94 participants (35.7%) (MCTs supplementation − 20 g/day-starting from 5 days before the beginning of the VLCKD active phase. Anthropometric measures, body composition, and c-reactive protein (CRP) concentrations were collected at the beginning and at the end (45 days) of the VLCKD intervention. Results: MCTs supplementation significantly decreased body weight, BMI, and waist circumference as compared to the control group, with a greater effect in the VLCKD + earlyMCTs group. A two-fold decrease in fat mass and an increase in muscle mass were observed in the VLCKD + earlyMCTs group as compared to the control group. As for inflammation, hs-CRP concentrations (assessed as absolute percent change) were significantly lower in the VLCKD + MCTs group (p = 0.009) and the VLCKD + earlyMCTs group (p = 0.011) than in the control group. A logistic regression model showed that VLCKD + earlyMCTs increase the likelihood of improvement of BMI classes (OR: 1.85, 95% CI 1.02–3.36) also after adjusting for the potential confounding factors. Conclusion: MCTs supplementation (20 g/day) may be a useful tool to enhance the beneficial effect of VLCKD on the reduction of body weight and fat mass. In particular, MCTs supplementation before the beginning of the VLCKD active phase might facilitate ketosis thus contributing to the effectiveness of the nutritional intervention. [ABSTRACT FROM AUTHOR]

(1) Background: this work reports the clinical case of a man who underwent a kidney transplant at the age of 19 for idiopathic interstitial nephritis resulting in renal failure. (2) Methods: the patient also had severe obesity and underwent four cycles of a very low-calorie ketogenic diet (VLCKD) for weight loss. (3) Results: the cycles of diet therapy carried out during a six-year period allowed a significant weight loss (from 103.2 kg in 2012 to 87.5 kg in 2018) with lean mass conservation (from 49.9 kg to 52.5 kg) and a reduction of fat mass (from 53.3 kg to 35.0 kg), as assessed with bioimpedance analysis. Throughout the diet cycles, body weight remained stable, except for a weight regain that occurred between the 2nd and 3rd cycle. Renal function was preserved despite the known mild chronic kidney disease (creatininemia ranged from 1.11 mg/dL to 1.27 mg/dL, and GRF from 91 to 71 mL/min/1.73 m²). (4) Conclusions: this report shows that a VLCKD, performed under strict medical supervision, is safe and effective even in a complex clinical picture. [ABSTRACT FROM AUTHOR]

The preservation of muscle mass, which is positively associated with muscle strength, has been included among the benefits of ketogenic diets due to the synergistic effects exerted by the reduction in visceral adipose tissue and obesity-related pro-inflammatory status. The handgrip strength (HGS) test is widely used as a single indicator to represent overall muscle strength. The possible association of changes in HGS in patients with obesity during the consumption of a very low-calorie ketogenic diet (VLCKD) has not yet been investigated. The aim of this prospective study was to assess the efficacy of VLCKD on promoting changes in HGS and high-sensitivity C-reactive protein (hs-CRP) levels, as a serological marker of obesity-related, low-grade inflammation, in a population of women with obesity after 45 days of active phase of the VLCKD. This pilot, uncontrolled, single-center, open-label clinical trial examined 247 Caucasian women, aged 18–51 years (body mass index, BMI: 30.0–50.9 kg/m2) who were consecutively enrolled following 45 days of active phase the VLCKD. Anthropometric measures and physical activity were evaluated. Muscle strength was measured by HGS using a grip strength dynamometer. Body composition was evaluated using a bioelectrical impedance analysis (BIA) phase-sensitive system. hs-CRP levels were determined by nephelometric assay. Adherence to the VLCKD, ketosis status, and physical activity were checked weekly by phone call. At day 45, BMI, fat mass (FM), and hs-CRP levels were significantly decreased (∆-7.5 ± 3.1%, ∆-15.6 ± 9.0%, and ∆-39.9 ± 44.6%; respectively; p < 0.001 for all three parameters), while HGS had increased (∆+17.4 ± 13.2%; p < 0.001). After adjusting for ∆BMI, ∆waist circumference, ∆hs-CRP levels, and physical activity, the correlation among changes in ∆HGS (kg), ∆FM (kg), and ∆ fat free mass (FFM) (kg) remained statistically significant (r = −0.331, and r = 0.362, respectively; p < 0.001). Interestingly, the correlation between ∆HGS with ∆FM (r = −0.288, p < 0.001) and ∆FFM (r = 0.395, p < 0.001) were also independent of the percentage of weight loss. We are the first to report that, along with a significant reduction in body weight and an overall improvement in body composition and inflammatory status, the muscle strength evaluated by the HGS test increased in a population of women with obesity after 45 days of the active phase of the VLCKD, also following adjustment for common confounding variables. [ABSTRACT FROM AUTHOR]

Bariatric surgery (BS) is the most effective treatment in reducing weight and the burden of comorbidities in patients with severe obesity. Despite the overall low mortality rate, intra- and post-operative complications remains quite common. Weight loss before BS reduces surgical risk, but studies are inconclusive regarding which is the best approach to apply. In this review, we summarize the current evidence on the effect of a ketogenic diet (KD) before BS. All studies agree that KD leads to considerable weight loss and important improvements in terms of surgical risk, but populations, interventions and outcomes are very heterogeneous. KD appears to be a safe and effective approach to induce weight loss before BS. However, randomized controlled trials with better-defined dietary protocols and homogeneous outcomes are necessary in order to draw firm conclusions. [ABSTRACT FROM AUTHOR]

BackgroundThe prevalence of sarcopenic obesity (SO) is increasing worldwide, posing important challenges to public health and national health care system, especially during the COVID pandemic. In subjects with SO, it is essential to reduce body weight, and to preserve lean mass, to avoid worsening of muscle function. Adequate nutrition and correct physical activity is essential to counteract SO progression. Very Low Calorie Ketogenic Diet (VLCKD), a well-established nutritional intervention for obesity, has been also indicated for the treatment of SO. To date, the effects of physical training during VLCKD have not been investigated.AimThis pilot study aims to determine the efficacy of VLCKD combined with interval training, compared to a VLCKD alone, on weight-loss, body composition, and physical performance in participants with SO.Materials and methodsTwenty-four participants with SO, aged between 50 and 70 years, who met the inclusion criteria, accepted to adhere to a VLCKD (

Abstract The novel coronavirus disease (COVID-19) is posing a serious challenge to the health-care systems worldwide, with an enormous impact on health conditions and loss of lives. Notably, obesity and its related comorbidities are strictly related with worse clinical outcomes of COVID-19 disease. Recently, there is a growing interest in the clinical use of ketogenic diets (KDs), particularly in the context of severe obesity with related metabolic complications. KDs have been proven effective for a rapid reduction of fat mass, preserving lean mass and providing an adequate nutritional status. In particular, the physiological increase in plasma levels of ketone bodies exerts important anti-inflammatory and immunomodulating effects, which may reveal as precious tools to prevent infection and potential adverse outcomes of COVID-19 disease. We discuss here the importance of KDs for a rapid reduction of several critical risk factors for COVID-19, such as obesity, type 2 diabetes and hypertension, based on the known effects of ketone bodies on inflammation, immunity, metabolic profile and cardiovascular function. We do believe that a rapid reduction of all modifiable risk factors, especially obesity with its metabolic complications, should be a pillar of public health policies and interventions, in view of future waves of SARS-CoV-2 infection.

Background: Obesity was consistently associated with a poor prognosis in patients with COVID‐19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. Aim: To evaluate the methylation levels of angiotensin‐converting enzyme 2 (ACE2) gene, the main entry receptor of SARS‐CoV‐2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very‐low‐calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). Materials and Methods: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4–6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. Results: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity‐associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. Conclusion: Obesity‐related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID‐19 pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose Obesity is one of the major public health problems worldwide and bariatric surgery is considered the gold standard treatment for severe obesity. Although the literature supports the safety and efficacy of the very low-calorie ketogenic diet (VLCKD) in patients with obesity, there is no study analyzing the use in case of failure or weight regain after bariatric surgery. This work has the purpose of assessing the response to a VLCKD (Pnk® method) in this population. Methods We have conducted an observational, retrospective, and descriptive study with the analysis of medical charts of private offices where patients were examined between 2014 and 2019, totalizing 11 participants who underwent Roux-en-Y gastric bypass (RYGB) without a reduction of 50% in body weight excess or any weight regain after the surgery. The patients followed the first stage of a commercial weight loss program (Pnk® method) which consists of a VLCKD (600–800 kcal/day), low in carbohydrates and lipids. Results A significant reduction was observed (p-value < 0.05) in weight, body mass index (BMI), abdominal circumference (AC), and glycated hemoglobin (A1C) post-ketogenic diet. Uric acid, transaminases, urea, and creatinine values did not show differences between pre- and post-ketosis. During the course of the study, no serious adverse events were reported. Conclusion This study has shown that the ketogenic diet can be recommended as an effective and safe treatment for patients who progressed with insufficient weight loss or regain after bariatric surgery. [ABSTRACT FROM AUTHOR]

Morbid obese people are more likely to contract SARS-CoV-2 infection and its most severe complications, as need for mechanical ventilation. Ketogenic Diet (KD) is able to induce a fast weight loss preserving lean mass and is particularly interesting as a preventive measure in obese patients. Moreover, KD has anti-inflammatory and immune-modulating properties, which may help in preventing the cytokine storm in infected patients. Respiratory failure is actually considered a contraindication for VLCKD, a very-low calorie form of KD, but in the literature there are some data reporting beneficial effects on respiratory parameters from ketogenic and low-carbohydrate high-fat diets. KD may be helpful in reducing ventilatory requirements in respiratory patients, so it should be considered in specifically addressed clinical trials as an adjuvant therapy for obese patients infected with SARS-CoV-2.

Background: Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear. Aim: To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism. Methods: Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks. Results: Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment. Conclusions: This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism. [ABSTRACT FROM AUTHOR]

Summary: First identified as a feasible treatment for intractable epilepsy, the ketogenic diet (KD) has recently gained popularity thanks to growing evidence on applications such as weight loss, most importantly, but also NAFLD, cancer, neurologic conditions and chronic pain. As with any treatment, whether pharmacologic or not, the KD might not be an appropriate intervention for every individual, and a number of contraindications have been proposed, now deeply rooted into clinical practice, excluding de facto many patients that could benefit from its use. However, many of these concerns were expressed due to the absence of clinical studies conducted on fragile populations, and an assessment of lately emerged evidence relative to KD safety is currently lacking and much needed. We herein provide a critical revision of the literature behind each safety alert, in order to guide through the treatment options in the case of subjects with an indication to the KD and a borderline safe situation. Based on available evidence, the possible use of this diet as a therapeutic intervention should be assessed on a patient‐to‐patient basis by adequately skilled medical doctors, keeping in mind current recommendations, but reading them through the knowledge of the current state of the art. [ABSTRACT FROM AUTHOR]

Context: We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on the microbiota in patients with obesity and insulin resistance to test the hypothesis that protein source may modulate the response to VLCKD interventions.Subjects and Methods: Forty-eight patients with obesity (19 males and 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass index [BMI] 35.9 ± 4.1 kg/m2) were randomly assigned to three 45-day isocaloric VLCKD regimens (≤800 kcal/day) containing whey, plant, or animal protein. Anthropometric indexes; blood and urine chemistry, including parameters of kidney, liver, glucose, and lipid metabolism; body composition; muscle strength; and taxonomic composition of the gut microbiome were assessed. Adverse events were also recorded.Results: Body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, and total and low-density lipoprotein cholesterol decreased in all patients. Patients who consumed whey protein had a more pronounced improvement in muscle strength. The markers of renal function worsened slightly in the animal protein group. A decrease in the relative abundance of Firmicutes and an increase in Bacteroidetes were observed after the consumption of VLCKDs. This pattern was less pronounced in patients consuming animal protein.Conclusions: VLCKDs led to significant weight loss and a striking improvement in metabolic parameters over a 45-day period. VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins. VLCKDs incorporating whey protein are more effective in maintaining muscle performance. [ABSTRACT FROM AUTHOR]

During the last decades, several interventions for the management of overweight and obesity have been proposed. Among diets, the first studies focused on the effect of water only and total fasting diets with or without proteins. Unfortunately, they were found to be associated with adverse events which lead to the abandon of these strategies. Interestingly, despite the radical approach, total fasting was effective and generally well tolerated. A strict connection between protein-calorie malnutrition and increased in morbidity and mortality in hospitalized patients was found at that time. Then, the seminal works of Blackburn and his collaborators lead to the introduction of the protein-sparing modified fast. Encouraged by the early results using this intervention, diets evolved to the current very-low-calorie ketogenic diets (VLCKD). In the present review, results of studies on the VLCKDs are presented and discussed, with a particular reference to the protocolled VLCKD. Also, a recent proposal on the nomenclature on the ketogenic diets is reported. Available evidence suggests VLCKDs to be effective in achieving a rapid and significant weight loss by means of an easily reversible intervention which could be repeated, if needed. Muscle mass and strength are preserved, resting metabolic rate is not impaired, hunger, appetite and mood are not worsened. Symptoms and abnormal laboratory findings can be there, but they have generally been reported as of mild intensity and transient. Preliminary studies suggest VLCKDs to be a potential game-changer in the management of type 2 diabetes too. Therefore, VLCKDs should be considered as an excellent initial step in properly selected and motivated patients with obesity or type 2 diabetes, to be delivered as a part of a multicomponent strategy and under strict medical supervision. [ABSTRACT FROM AUTHOR]

Since excessive sugar consumption has been related to the development of chronic metabolic diseases prevalent in the western world, the use of sweeteners has gradually increased worldwide over the last few years. Although low- and non-calorie sweeteners may represent a valuable tool to reduce calorie intake and prevent weight gain, studies investigating the safety and efficacy of these compounds in the short- and long-term period are scarce and controversial. Therefore, future studies will need to elucidate the potential beneficial and/or detrimental effects of different types of sweeteners on metabolic health (energy balance, appetite, body weight, cardiometabolic risk factors) in healthy subjects and patients with diabetes, obesity and metabolic syndrome. In this regard, the impact of different sweeteners on central nervous system, gut hormones and gut microbiota is important, given the strong implications that changes in such systems may have for human health. The aim of this narrative review is to summarize the current evidence for the neuroendocrine and metabolic effects of sweeteners, as well as their impact on gut microbiota. Finally, we briefly discuss the advantages of the use of sweeteners in the context of very-low calorie ketogenic diets. [ABSTRACT FROM AUTHOR]

Very low calorie ketogenic diet (VLCKD) has been proposed as a promising option to achieve a significant weight loss in a short time period. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety in patients with overweight and obesity. Four databases were searched on May 2019. Studies reporting data on body weight, body mass index (BMI), waist circumference, body composition, blood pressure, HbA1c, lipids, and markers of liver and kidney function were selected. Discontinuation was also assessed. Twelve studies were included. VLCKD was associated with weight losses of −10.0 kg (I2 = 6%) and − 15.6 kg (I2 = 37%) in studies with a ketogenic phase up to and of at least four weeks, respectively. The weight lost during the ketogenic phase was stable in the subsequent follow-up up to two years (p = 0.12). Also, VLCKD was associated with reductions of BMI (−5.3 kg/m2), waist circumference (−12.6 cm), HbA1c (−0.7%), total cholesterol (−28 mg/dl), triglycerides (−30 mg/dl), AST (−7 U/l), ALT (−8 U/l), GGT (−8 U/l), systolic and diastolic blood pressure (−8 and − 7 mmHg, respectively). No changes in LDL cholesterol, HDL cholesterol, serum creatinine, serum uric acid and serum potassium were found. Serum sodium increased during VLCKD (+1.6 mEq/l). The overall prevalence of patients discontinuing VLCKD was 7.5% and this was similar to patients undergoing a low calorie diet (p = 0.83). The present review supports the use of VLCKD as an effective strategy for the management of overweight and obesity. Future guidelines should include a specific recommendation for this intervention. [ABSTRACT FROM AUTHOR]