"Time" for obesity-related cancer: The role of the circadian rhythm in cancer pathogenesis and treatment.

The circadian rhythm is regulated by an intrinsic time-tracking system, composed both of a central and a peripheral clock, which influences the cycles of activities and sleep of an individual over 24 h. At the molecular level, the circadian rhythm begins when two basic helix-loop-helix/Per-ARNT-SIM (bHLH-PAS) proteins, BMAL-1 and CLOCK, interact with each other to produce BMAL-1/CLOCK heterodimers in the cytoplasm. The BMAL-1/CLOCK target genes encode for the repressor components of the clock, cryptochrome (Cry1 and Cry2) and the Period proteins (Per1, Per2 and Per3). It has been recently demonstrated that the disruption of circadian rhythm is associated with an increased risk of developing obesity and obesity-related diseases. In addition, it has been demonstrated that the disruption of the circadian rhythm plays a key role in tumorigenesis. Further, an association between the circadian rhythm disruptions and an increased incidence and progression of several types of cancer (e.g., breast, prostate, colorectal and thyroid cancer) has been found. As the perturbation of circadian rhythm has adverse metabolic consequences (e.g., obesity) and at the same time tumor promoter functions, this manuscript has the aim to report how the aberrant circadian rhythms affect the development and prognosis of different types of obesity-related cancers (breast, prostate, colon rectal and thyroid cancer) focusing on both human studies and on molecular aspects.

Sex-differences in Mediterranean diet: a key piece to explain sex-related cardiovascular risk in obesity? A cross-sectional study.

BACKGROUND: Mediterranean Diet (MD) has many health benefits, particularly in reducing cardiovascular risk (CVR). However, it is still little known if there are any sex differences in following this nutritional pattern and, thus, the potential sex-related repercussions on CVR in obesity. The study aimed to characterize sex-related adherence to MD and its association with CVR factors in subjects with obesity. METHODS: A total of 968 females (33.81 ± 11.06 years; BMI 34.14 ± 7.43 kg/m2) and 680 males (aged 34.77 ± 11.31years; BMI 33.77 ± 8.13 kg/m2) were included in a cross-sectional observational study. Lifestyle habits, anthropometric parameters, high sensitivity C-reactive protein (hs-CRP), and adherence to MD were evaluated. RESULTS: Females had significantly higher adherence to MD and lower hs-CRP levels than males (p < 0.001). Additionally, females consumed significantly more vegetables, fruits, legumes, fish/seafood, nuts, and sofrito sauce and less quantity of olive oil, butter, cream, margarine, red/processed meats, soda drinks (p = 0.001), red wine, and commercial sweets and confectionery than their counterparts. A PREDIMED score of ≤ 6 was associated with a significantly increased CVR in both sexes. CONCLUSIONS: Females had higher adherence to MD, lower CVR, and different food preferences than males. Although the same PREDIMED threshold has been identified as a spy of CVR, the sex-related preference of individual foods included in the MD could explain the different impact of this nutritional pattern on CVR in both sexes.

Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study.

BACKGROUND: Hidradenitis suppurativa (HS), an inflammatory-based dermatological condition often associated with obesity, poses significant challenges in management. The very low-calorie ketogenic diet (VLCKD) has shown efficacy in addressing obesity, related metabolic disorders, and reducing chronic inflammation. However, its effects on HS remain underexplored. In this prospective pilot study, we aimed to investigate the impact of a 28-day active phase of VLCKD on HS in a sample of treatment-naive women with HS and excess weight. METHODS: Twelve women with HS and overweight or obesity (BMI 27.03 to 50.14 kg/m2), aged 21 to 54 years, meeting inclusion/exclusion criteria and agreeing to adhere to VLCKD, were included. Baseline lifestyle habits were assessed. The Sartorius score was used to evaluate the clinical severity of HS. Anthropometric parameters (waist circumference, weight, height, and body mass index), body composition via bioelectrical impedance analysis, levels of trimethylamine N-oxide (TMAO), oxidized low-density lipoprotein (oxLDL), and derivatives of reactive oxygen metabolites (dROMs) were assessed at baseline and after 28 days of the active phase of VLCKD. RESULTS: VLCKD led to general improvements in anthropometric parameters and body composition. Notably, a significant reduction in the Sartorius score was observed after the intervention (Δ%: - 24.37 ± 16.64, p < 0.001). This reduction coincided with significant decreases in TMAO (p < 0.001), dROMs (p = 0.001), and oxLDL (p < 0.001) levels. Changes in the Sartorius score exhibited positive correlations with changes in TMAO (p < 0.001), dROMs (p < 0.001), and oxLDL (p = 0.002). CONCLUSION: The 28-day active phase of VLCKD demonstrated notable improvements in HS severity and associated metabolic markers, highlighting the potential utility of VLCKD in managing HS and its association with metabolic derangements in women with overweight or obesity.

Very low-calorie ketogenic diet (VLCKD): a therapeutic nutritional tool for acne?

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.

Obesogenic environments as major determinants of a disease: It is time to re-shape our cities.

Obesity rates are increasing in almost all high- and low-income countries, and population-based approaches are necessary to reverse this trend. The current global efforts are focused on identifying the root causes of obesity and developing effective methods for early diagnosis, screening, treatment, and long-term management, both at an individual and health system level. However, there is a relative lack of effective options for early diagnosis, treatment, and long-term management, which means that population-based strategies are also needed. These strategies involve conceptual shifts towards community- and environment-focused approaches. This review aimed to provide evidence on how environmental factors contribute to the risk of obesity and how reshaping cities can help slow down obesity prevalence rates and improve long-term management.

Chrononutrition in type 2 diabetes mellitus and obesity: A narrative review.

Chrononutrition is a nutritional regimen that follows our biological clock, marked by the changes in metabolism that occur during the day. This regimen includes the distribution of energy, the regularity and frequency of meals, and the importance of these factors for metabolic health. A growing body of animal and human evidence indicates that the timing of food intake throughout the day can have a significant and beneficial impact on the metabolic health and well-being of individuals. In particular, both the timing and frequency of meals have been associated with obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and other chronic conditions. Today's busy lifestyle makes many people skip breakfast and eat late at night. Eating late at night has been shown to cause a circadian misalignment, with the latter having a negative impact on weight control and glucose metabolism. Additionally, some studies have found a relatively strong association between skipping breakfast and insulin resistance, and T2DM. Against the backdrop of escalating obesity and T2DM rates, coupled with the recognized influence of food timing on disease evolution and control, this review aimed to synthesize insights from epidemiological and intervention studies of the interplay of timing of food intake and macronutrient consumption, reporting their impact on obesity and T2DM.

Supplementation with medium-chain fatty acids increases body weight loss during very low-calorie ketogenic diet: a retrospective analysis in a real-life setting.

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.

Can the ketogenic diet improve our dreams? Effect of very low-calorie ketogenic diet (VLCKD) on sleep quality.

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.

Very low-calorie ketogenic diet (VLCKD): an antihypertensive nutritional approach.

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.

Adherence to the Mediterranean diet as a possible additional tool to be used for screening the metabolically unhealthy obesity (MUO) phenotype.

BACKGROUND: The terms metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) categorize subjects with obesity based on the presence or absence of cardio-metabolic risk factors. Detecting MUO phenotype is crucial due to the high risk of cardio-metabolic complications, requiring tailored and intensive follow-up. However, diagnosing MUO is time-consuming and costly. Thus, we aimed to investigate the role of Mediterranean diet (MD) in determining MHO/MUO phenotypes and whether adherence to MD could serve as an additional screening tool for MUO phenotype. METHODS: The study population of this cross-sectional observational study consisted of 275 subjects with obesity. We assessed their lifestyle habits (physical activity and smoking habits), anthropometric measurements (weight, height, waist circumference, body mass index), blood pressure, metabolic parameters, inflammatory marker (high sensitivity C reactive protein levels), adherence to MD (by PREvención con DIetaMEDiterránea (PREDIMED) questionnaire), and MHO/MUO phenotypes. RESULTS: The study included 275 individuals with obesity (256F/19M; 34.0 ± 10.5 years; BMI 38.3 ± 5.95 kg/m2). Among them, 114 (41.5%) exhibited MHO phenotype, while 161 (58.5%) had MUO phenotype. MHO phenotype exhibited favorable anthropometric and cardio-metabolic profiles, characterized by lower waist circumference (p < 0.001), BMI (p < 0.001), insulin resistance (p < 0.001), blood pressure (p < 0.001), inflammation (p < 0.001), and lipid levels (p < 0.001) compared to MUO phenotype. Notably, we found that MHO phenotype had higher adherence to MD (p < 0.001) and consumed more extra virgin olive oil (EVOO) (p < 0.001), vegetables (p < 0.001), fruits (p < 0.001), legumes (p = 0.001), fish (p < 0.001), wine (p = 0.008), and nuts (p = 0.001), while reporting lower intake of red/processed meats (p < 0.001), butter, cream, margarine (p = 0.008), soda drinks (p = 0.006), and commercial sweets (p = 0.002) compared to MUO phenotype. Adherence to MD (p < 0.001) and EVOO (p = 0.015) intake were identified as influential factors in determining the presence of MUO/MHO phenotypes. Furthermore, a PREDIMED score < 5 proved to be the most sensitive and specific cut-point value for predicting the presence of MUO phenotype (p < 0.001). CONCLUSION: High adherence to MD was associated with MHO phenotype. Moreover, we suggest that a specific cut-off of the PREDIMED score could be an indicator to discriminate patients with MUO/MHO phenotypes and therefore help in identifying patients at higher cardiovascular risk who will require specific dietary intervention.

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

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

The effect of the ketogenic diet on Acne: Could it be a therapeutic tool?

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.

Clinical and nutritional management of very-low-calorie ketogenic diet (VLCKD) in patients with psoriasis and obesity: a practical guide for the nutritionist.

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.

Evening chronotype is associated with hormonal and metabolic disorders in polycystic ovary syndrome.

Despite current treatments for polycystic ovary syndrome (PCOS), a considerable number of women with this syndrome do not reach the treatment goal, suggesting the presence of other probable misdiagnosed features of this syndrome that are not taken into account in the assessment and therefore in the therapeutical approach. The aim of this study was to investigate the prevalence of chronotype categories in women with PCOS and their role in determining hormonal and metabolic aspects of PCOS. This observational case-control study was conducted on 112 women with PCOS and 112 healthy women matched for age and body mass index (BMI). At baseline anthropometric parameters such as weight, height, BMI and waist circumference, clinical parameters such as Ferriman-Gallwey (FG) score, biochemical parameters such as fasting plasma glucose, insulin levels and assessment of the homeostasis model of insulin resistance (HoMA-IR), inflammatory parameters such as C-reactive protein (CRP) and hormonal parameters such as testosterone levels were evaluated. Women with PCOS had a lower chronotype score (p < .001) which indicates a higher prevalence of evening chronotype (EC) category (p = .037) compared to controls. After adjustment for BMI, chronotype score was significantly negatively correlated with CRP levels (r = -0.418, p < .001), testosterone levels (r = -0.543, p < .001) and FG score (r = -0.514, p < .001). Linear regression analysis showed that high testosterone levels were among the factors most associated with a lower chronotype score (p < .001), followed by BMI (p < .001) and HoMA-IR (p < .05). In conclusion, there is a higher prevalence of EC in women with PCOS than in women without the condition, which in turn was associated with a worse hormonal and metabolic profile. These findings provide support for the relevance of including chronotype assessment in the treatment of women with PCOS.

Evening chronotype is associated with severe NAFLD in obesity.

BACKGROUND/OBJECTIVES: Chronotype, i.e., the individual attitude to carry out the daily activities at a certain time of the day, has been reported to play a role in metabolic diseases. Thus, the aim of our study was to investigate the association of non-alcoholic fatty liver disease (NAFLD) with chronotype categories in individuals with obesity. SUBJECTS/METHODS: In this cross-sectional study, participants underwent to anthropometric, biochemical, and the Visceral Adiposity Index (VAI) assessment. Chronotype categories were assessed by the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ). The following indirect indices of NAFLD were calculated: Liver Fat Equation (LFE), Hepatic Steatosis Index (HSI) and Index of Non-alcoholic steatohepatitis (ION). RESULTS: The study population consisted of 87 participants (40.3 ± 12.3 years; BMI 45.6 ± 6.3 kg/m2; 64F/23M). According to the chronotype score, 31.0% were morning (MC), 36.8% were intermediate (IC), and 32.2% evening chronotype (EC). Individuals with IC were significantly younger than those with MC and EC (p = 0.002 and p = 0.047, respectively). EC presented significantly higher BMI (p < 0.001), waist circumference (p = 0.007), and hip circumference (p = 0.001) than MC. Moreover, EC had higher BMI (p < 0.001) and waist circumference (p = 0.011) than IC. All participants presented NAFLD (HSI ≥ 36 and LFE ≥ 5). Nevertheless, only individuals with EC were above the threshold of non-alcoholic steatohepatitis evaluated as ION index (ION ≥ 50). Individuals with EC presented significantly higher VAI (p = 0.036), LFE (p = 0.034), HSI (p < 0.001) and ION (p = 0.014) than MC, also after the adjustment for age, gender, and BMI. CONCLUSION: EC is associated with more severe NAFLD independently of age, gender, and BMI than MC and IC in individuals with obesity.

Phase angle as an easy diagnostic tool for the nutritionist in the evaluation of inflammatory changes during the active stage of a very low-calorie ketogenic diet.

BACKGROUND AND AIMS: Very low-calorie ketogenic diets (VLCKDs) have recently gained increasing interest for their anti-inflammatory effects. Phase angle (PhA), a bioelectrical impedance analysis (BIA)-derived measure used as a screening tool to assess inflammatory status in various clinical conditions has recently been suggested as a novel predictor of inflammatory status in correlation with high-sensitivity C-reactive protein (hs-CRP) levels. PhA's usefulness in monitoring inflammatory status changes in patients with obesity during active phase VLCKD has not yet been explored. The aim of this pilot study was to examine the role of PhA as a biomarker detecting early inflammatory status changes in women with overweight and obesity 1 month into the active stage of a VLCKD. METHODS-RESULTS: This uncontrolled, single-center, open-label pilot clinical study investigated 260 consecutively enrolled Caucasian women aged 18-69 years (BMI 25.0-50.9 kg/m2) after 31 days of an active stage VLCKD. Anthropometric measurements and PhA were assessed. hs-CRP levels were determined by nephelometric assay. Dietary compliance, physical activity recommendations, and ketosis status were tested weekly by telephone recall. At Day 31, BMI, WC, and hs-CRP levels were observed to have decreased (∆-7.3 ± 2.9%, ∆-6.3 ± 5.0%, and ∆-38.9 ± 45.6%; respectively), while PhA had increased (∆+8.6 ± 12.5%). Changes in ∆ hs-CRP were significantly correlated with changes in BMI, WC, and PhA (p < 0.001). After adjusting for confounding variables, the correlation between changes in ∆ PhA and ∆ hs-CRP remained statistically significant, albeit attenuated (p = 0.024). CONCLUSION: This is the first study reporting how, along with the expected rapid effect on body weight, PhA changes during active stage VLKCD occurred very early on and independently of weight loss, and were negatively associated with hs-CRP levels. These findings further support the VLCKD as a first-line dietary intervention to obtain a rapid effect on the obesity-related inflammatory status. They also suggest the possible role of PhA as an easy diagnostic tool to detect inflammation, thereby avoiding blood sampling and expensive biochemical assays. It is also posited that changes in PhA could help nutritionists correctly plan the different stages of the VLCKD protocol.

VLCKD: a real time safety study in obesity.

BACKGROUND: Very Low-Calorie Ketogenic Diet (VLCKD) is currently a promising approach for the treatment of obesity. However, little is known about the side effects since most of the studies reporting them were carried out in normal weight subjects following Ketogenic Diet for other purposes than obesity. Thus, the aims of the study were: (1) to investigate the safety of VLCKD in subjects with obesity; (2) if VLCKD-related side effects could have an impact on its efficacy. METHODS: In this prospective study we consecutively enrolled 106 subjects with obesity (12 males and 94 females, BMI 34.98 ± 5.43 kg/m2) that underwent to VLCKD. In all subjects we recorded side effects at the end of ketogenic phase and assessed anthropometric parameters at the baseline and at the end of ketogenic phase. In a subgroup of 25 subjects, we also assessed biochemical parameters. RESULTS: No serious side effects occurred in our population and those that did occur were clinically mild and did not lead to discontinuation of the dietary protocol as they could be easily managed by healthcare professionals or often resolved spontaneously. Nine (8.5%) subjects stopped VLCKD before the end of the protocol for the following reasons: 2 (1.9%) due to palatability and 7 (6.1%) due to excessive costs. Finally, there were no differences in terms of weight loss percentage (13.5 ± 10.9% vs 18.2 ± 8.9%; p = 0.318) in subjects that developed side effects and subjects that did not developed side effects. CONCLUSION: Our study demonstrated that VLCKD is a promising, safe and effective therapeutic tool for people with obesity. Despite common misgivings, side effects are mild, transient and can be prevented and managed by adhering to the appropriate indications and contraindications for VLCKD, following well-organized and standardized protocols and performing adequate clinical and laboratory monitoring.

"Forever young at the table": metabolic effects of eating speed in obesity.

BACKGROUND: Cardiometabolic diseases (CMD) are recognized as the main causes of morbidity and mortality in developed countries. In recent years eating speed (ES) has been of particular interest since some studies have associated it with the development of obesity and CMD. However, the different impact of the ES at which main meals are eaten on the risk of developing these diseases has not yet been identified. Thus, we aimed to investigate the effect of ES at the main meals (breakfast, lunch, and dinner) on the risk of developing cardiometabolic diseases (type 2 diabetes mellitus, dyslipidaemia and hypertension) in middle-aged Caucasian subjects with obesity. METHODS: For this purpose we carried out a cross-sectional, observational study. One hundred and eighty-seven middle-aged subjects aged 43.6 ± 16 years were enrolled of which anthropometric parameters and lifestyle habits were studied. A dietary interview was performed to collect information about meal duration and eating habits at the main meals. According to median value of meal duration, meals were classified in two groups: fast eating group (FEG) and slow eating group (SEG). RESULTS: The prevalence of dyslipidaemia was more than twice in FEG compared to SEG at lunch and dinner. For all main meals, FEG had a significantly higher risk of dyslipidaemia than SEG (p < 0.05) in unadjusted model. However, when the model was adjusted for age, BMI, physical activity, smoking and alcohol use and medication, the result remained significant for lunch and dinner (p < 0.05). CONCLUSION: The results of our study suggest that fast eating increases at lunch and dinner increase the risk of developing dyslipidaemia in obesity.

Harnessing the Synergy of SGLT2 Inhibitors and Continuous Ketone Monitoring (CKM) in Managing Heart Failure among Patients with Type 1 Diabetes.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-is) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-is in T1D HF management alongside emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests that SGLT2-is significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-is into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-is and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim to employ clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

Nutritional interventions in prison settings: a scoping review.

BACKGROUND: Mounting evidence has shown that incarceration can affect the health and well-being of individuals and increase the risk of noncommunicable diseases (NCDs). Diet quality is known to be one of the main determinants of risk of NCDs, and dietary changes are the first approach used in primary care to reduce the incidence of NCDs. OBJECTIVE: This scoping review aimed to summarize the evidence for (1) the diet quality of inmates, and (2) the effect of nutritional intervention in prison systems. In addition, we aimed to describe limitations in the current literature and to suggest potential future research areas. METHOD: A systematic search was performed in 2 databases (PubMed and Web of Science) using predefined search terms and covering the period May 2023 to June 2023. Additionally, reference lists from the retrieved studies were hand-searched to identify any additional relevant publications. The identified literature was screened based on defined search strategies, criteria, and research questions defined using the PICo (population or problem, interest, and context) framework. The review was conducted referring to the PRISMA-ScR and the PICo framework. RESULTS: A total of 19 studies out of 63 initially identified records were included in this review (11 cross-sectional evaluations and 9 intervention-based studies). In almost all studies, assessment of the diet quality of menus showed the menus to be nutritionally adequate, except for having a higher-than-recommended intake of total energy, saturated fatty acids, sodium, cholesterol, and sugar. In addition, some studies reported a lower-than-recommended intake of fiber, magnesium, potassium, vitamins D, E, and A, and omega-3 fatty acids. Nutritional interventions were mainly planned in the form of workshops, seminars, and written material to deliver information on healthy dietary choices. Although no significant changes in inmates' dietary choices were observed in any of the studies, a high participation rate was detected. CONCLUSION: Inmates might require additional prevention intervention to reduce their susceptibility to cardiometabolic diseases by virtue of their isolation from community facilities. Interventions should be tailored to the characteristics of prison settings and inmates to increase adherence to nutritional recommendations.