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1.
Diet and Exercise Exert a Differential Effect on Glucose Metabolism Markers According to the Degree of NAFLD Severity.
Bianco, A, Franco, I, Curci, R, Bonfiglio, C, Campanella, A, Mirizzi, A, Fucilli, F, Di Giovanni, G, Giampaolo, N, Pesole, PL, et al
Nutrients. 2023;(10)
Abstract
BACKGROUND Non-Alcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes (T2D) are highly prevalent diseases worldwide. Insulin Resistance (IR) is the common denominator of the two conditions even if the precise timing of onset is unknown. Lifestyle change remains the most effective treatment to manage NAFLD. This study aimed to estimate the effect of the Low Glycemic Index Mediterranean Diet (LGIMD) and exercise (aerobic and resistance) over a one-year period on the longitudinal trajectories of glucose metabolism regulatory pathways. MATERIALS AND METHODS In this observational study, 58 subjects (aged 18-65) with different degrees of NAFLD severity were enrolled by the National Institute of Gastroenterology-IRCCS "S. de Bellis", to follow a 12-month program of combined exercise and diet. RESULTS The mean age was 55 ± 7 years old. Gender was equally distributed among NAFLD categories. There was a statistically significant main effect of time for glycosylated hemoglobin (Hb1Ac) over the whole period (-5.41, 95% CI: -7.51; -3.32). There was a steady, statistically significant decrease of HbA1c in participants with moderate and severe NAFLD whereas this effect was observed after the 9th month in those with mild NAFLD. CONCLUSIONS The proposed program significantly improves glucose metabolism parameters, especially HbA1c.
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A Low Glycemic Index Mediterranean Diet Combined with Aerobic Physical Activity Rearranges the Gut Microbiota Signature in NAFLD Patients.
Calabrese, FM, Disciglio, V, Franco, I, Sorino, P, Bonfiglio, C, Bianco, A, Campanella, A, Lippolis, T, Pesole, PL, Polignano, M, et al
Nutrients. 2022;14(9)
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Non-alcoholic fatty liver disease (NAFLD) is the most common metabolic-associated fatty liver disease. The gut microbiota and its metabolites were demonstrated to play a role in the pathophysiology of NAFLD through the gut–liver axis. The aim of this study was to investigate how different lifestyle interventions, including diet and physical activity, can impact the gut microbiota composition in NAFLD patients after 45 and 90 days of treatment. This study was a randomised controlled trial based on lifestyle interventions. Participants were randomly allocated to one of the six groups. Results showed that nutritional therapies based on dietary interventions contributed to reduce the dysbiosis characterising NAFLD patients, increasing the resilience of microbial communities inhabiting the gut. Furthermore, the adoption of an aerobic exercise programme, in combination with the Mediterranean diet, was able to further ameliorate specific ratios of microbes. Authors conclude that the findings of their study highlight the contribution resulting from the synergistic effect of lifestyle interventions (diet and/or physical activity programs) on the composition of the gut microbiota in NAFLD patients.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, and its prevalence worldwide is increasing. Several studies support the pathophysiological role of the gut-liver axis, where specific signal pathways are finely tuned by intestinal microbiota both in the onset and progression of NAFLD. In the present study, we investigate the impact of different lifestyle interventions on the gut microbiota composition in 109 NAFLD patients randomly allocated to six lifestyle intervention groups: Low Glycemic Index Mediterranean Diet (LGIMD), aerobic activity program (ATFIS_1), combined activity program (ATFIS_2), LGIMD plus ATFIS_1 or ATFIS2 and Control Diet based on CREA-AN (INRAN). The relative abundances of microbial taxa at all taxonomic levels were explored in all the intervention groups and used to cluster samples based on a statistical approach, relying both on the discriminant analysis of principal components (DAPCs) and on a linear regression model. Our analyses reveal important differences when physical activity and the Mediterranean diet are merged as treatment and allow us to identify the most statistically significant taxa linked with liver protection. These findings agree with the decreased 'controlled attenuation parameter' (CAP) detected in the LGIMD-ATFIS_1 group, measured using FibroScan®. In conclusion, our study demonstrates the synergistic effect of lifestyle interventions (diet and/or physical activity programs) on the gut microbiota composition in NAFLD patients.
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Exosomal FZD-7 Expression Is Modulated by Different Lifestyle Interventions in Patients with NAFLD.
Scavo, MP, Depalo, N, Rizzi, F, Carrieri, L, Serino, G, Franco, I, Bonfiglio, C, Pesole, PL, Cozzolongo, R, Gianuzzi, V, et al
Nutrients. 2022;(6)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.
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The Effect of Three Mediterranean Diets on Remnant Cholesterol and Non-Alcoholic Fatty Liver Disease: A Secondary Analysis.
Campanella, A, Iacovazzi, PA, Misciagna, G, Bonfiglio, C, Mirizzi, A, Franco, I, Bianco, A, Sorino, P, Caruso, MG, Cisternino, AM, et al
Nutrients. 2020;(6)
Abstract
BACKGROUND Elevated fasting remnant cholesterol (REM-C) levels have been associated with an increased cardiovascular risk in patients with metabolic syndrome (Mets) and Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to estimate the effect of different diets on REM-C levels in patients with MetS, as well as the association between NAFLD and REM-C. METHODS This is a secondary analysis of the MEDIDIET study, a parallel-arm Randomized Clinical Trial (RCT). We examined 237 people with MetS who underwent Liver Ultrasound (LUS) to assess the NAFLD score at baseline, 3-, and 6-months follow-up. Subjects were randomly assigned to the Mediterranean diet (MD), Low Glycemic Index diet (LGID), or Low Glycemic Index Mediterranean diet (LGIMD). REM-C was calculated as [total cholesterol-low density lipoprotein cholesterol (LDL-C)-high density lipoprotein cholesterol (HDL-C)]. RESULTS REM-C levels were higher in subjects with moderate or severe NAFLD than in mild or absent ones. All diets had a direct effect in lowering the levels of REM-C after 3 and 6 months of intervention. In adherents subjects, this effect was stronger among LGIMD as compared to the control group. There was also a significant increase in REM-C levels among Severe NAFLD subjects at 3 months and a decrease at 6 months. CONCLUSIONS fasting REM-C level is independently associated with the grade of severity of NAFLD. LGIMD adherence directly reduced the fasting REM-C in patients with MetS.
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Association between adherence to the Mediterranean Diet and circulating Vitamin D levels.
Zupo, R, Lampignano, L, Lattanzio, A, Mariano, F, Osella, AR, Bonfiglio, C, Giannelli, G, Pergola, G
International journal of food sciences and nutrition. 2020;(7):884-890
Abstract
Vitamin D improves bone density and latest studies show adherence to Med-Diet as protective on osteoporosis. This observational study aimed at investigating the relationship between 25(OH)D levels and adherence to Med-Diet. Body weight, BMI, WC, glucose, insulin, 25(OH)D, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, uric acid, and creatinine serum levels and insulin resistance were determined in 284 overweight/obese subjects not taking medications or supplements. Adherence to Med-Diet was evaluated by using PREDIMED score. High-level of adherence stood out. 25(OH)D was inversely related to BMI, WC, HOMA-IR, serum insulin and triglycerides, while directly to PREDIMED score. Two different regression models confirmed this positive correlation independently of gender and other parameters showing univariate relationship with 25(OH)D. This study argues that a closer adherence to Med-Diet is independently associated with an increase of 25(OH)D suggesting that higher vitamin D levels may contribute to the protective effect of the Med-Diet on osteoporosis.
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Remnant cholesterol as a risk factor for cardiovascular, cancer or other causes mortality: A competing risks analysis.
Bonfiglio, C, Leone, CM, Silveira, LVA, Guerra, R, Misciagna, G, Caruso, MG, Bruno, I, Buongiorno, C, Campanella, A, Guerra, VMB, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2020;(11):2093-2102
Abstract
BACKGROUND AND AIMS Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs). METHODS AND RESULTS Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L). CONCLUSIONS RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor.
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Effects of Some Food Components on Non-Alcoholic Fatty Liver Disease Severity: Results from a Cross-Sectional Study.
Mirizzi, A, Franco, I, Leone, CM, Bonfiglio, C, Cozzolongo, R, Notarnicola, M, Giannuzzi, V, Tutino, V, De Nunzio, V, Bruno, I, et al
Nutrients. 2019;11(11)
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Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic (liver) fat accumulation. Lifestyle interventions are the only known effective treatment for NAFLD. The aim of this study was to estimate associations between the consumption of some food group components with the grade of severity in NAFLD subjects. The study is a cross-sectional nutritional randomised clinical trial, which enrolled 136 subjects (79 males) with moderate or severe NAFLD. Results showed that some food group components were associated with a lower or a higher risk of developing severe NAFLD, and that, within the same food group, some components with a protective or promoter action are present. Authors conclude that their findings could help to elaborate personalised dietary counselling to treat NAFLD.
Abstract
Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and more recently with NAFLD. Methods: This is a baseline cross-sectional analysis of 136 subjects (79 males) enrolled consecutively in the NUTRIATT (NUTRItion and Ac-TiviTy) study. Study subjects had moderate or severe NAFLD diagnosed by using Fibroscan-CAP. Food Frequency Questionnaire was used to obtain information about food intake. Statistical analysis included descriptive statistics and a multivariable logistic regression model. Results: The mean age was 49.58 (±10.18) with a mean BMI of 33.41 (±4.74). A significant inverse relationship was revealed between winter ice-cream intake and NAFLD severity (O.R. 0.65, 95% C.I. 0.95-0.99); chickpeas intake and NAFLD severity (O.R. 0.57, 95% C.I. 0.34-0.97), and not industrial aged-cheeses type (O.R. 0.85, 95% C.I. 0.74-0.98). A statistically significant positive association also emerged between rabbit meat (O.R. 1.23, 95% C.I. 1.01-1.49), industrial type aged cheeses (O.R. 1.17, 95% C.I. 1.01-1.35), milk-based desserts (no winter ice cream) (O.R. 1.11, 95% C.I. 1.01-1.21), fats (O.R. 1.12, 95% C.I. 1.01-1.25), and NAFLD severity. Conclusion: The fresh foods from non-intensive farming and high legume intake that characterize the Mediterranean diet would seem to be beneficial for patients with NAFLD.
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Dietary fiber and health outcomes: an umbrella review of systematic reviews and meta-analyses.
Veronese, N, Solmi, M, Caruso, MG, Giannelli, G, Osella, AR, Evangelou, E, Maggi, S, Fontana, L, Stubbs, B, Tzoulaki, I
The American journal of clinical nutrition. 2018;(3):436-444
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Abstract
BACKGROUND Several studies have suggested that higher consumption of dietary fiber is beneficial for a variety of health outcomes. However, many results have been inconclusive and, to our knowledge, there has been no attempt to systematically capture the breadth of outcomes associated with dietary fiber intake or to systematically assess the quality and the strength of the evidence on the associations of dietary fiber intake and different health outcomes or medical conditions. OBJECTIVE The aim of this study was to describe the diverse health outcomes convincingly associated with dietary fiber consumption. DESIGN This was an umbrella review of systematic reviews with meta-analysis of observational studies. For each association, random-effects summary effect size, 95% CIs, and 95% prediction intervals were estimated. We also assessed heterogeneity, evidence for small-study effect, and evidence for excess significance bias. We used these metrics to evaluate the credibility of the identified evidence. RESULTS Our literature search identified 1351 abstracts. Of these, 18 meta-analyses including a total of 298 prospective observational studies and 21 outcomes were included. Outcomes studied included cancer and precancer lesions (n = 12), cardiovascular diseases (CVDs; n = 3), all-cause and specific-cause mortality (n = 4), type 2 diabetes (n = 1), and Crohn disease (n = 1). Overall, 6 (29%) of the 21 eligible outcomes reported highly significant summary results (P < 1 × 10-6); these included CVD and CVD mortality, coronary artery disease, pancreatic cancer, and gastric cancer. Overall, 3 of 21 (14%) outcomes presented convincing evidence (pancreatic cancer, CVD mortality, and all-cause mortality), but only CVD and all-cause mortality were based on prospective studies. Two other outcomes (10%), CVD and coronary artery disease, presented highly suggestive evidence based on prospective studies. CONCLUSION Our results support dietary recommendations that promote higher fiber intake as part of a healthy diet.
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Aerobic Physical Activity and a Low Glycemic Diet Reduce the AA/EPA Ratio in Red Blood Cell Membranes of Patients with NAFLD.
Tutino, V, De Nunzio, V, Caruso, MG, Bonfiglio, C, Franco, I, Mirizzi, A, De Leonardis, G, Cozzolongo, R, Giannuzzi, V, Giannelli, G, et al
Nutrients. 2018;(9)
Abstract
Omega-6 Polyunsaturated Fatty Acids (PUFAs), through the eicosanoids derived from arachidonic acid (AA), are able to modulate the inflammatory processes, whereas omega-3 PUFAs, such as eicosapentaenoic acid (EPA), exert anti-oxidant and anti-inflammatory effects. An unbalanced AA/EPA ratio in favor of AA leads to the development of different metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the effects of different diets, alone and in combination with two physical activity programs, on the AA/EPA ratio value in erythrocyte membranes of patients with NAFLD. One hundred forty-two subjects with NAFLD were enrolled in the study and randomized into six treatment groups. AA/EPA ratio was significantly reduced after 90 days of treatment with only a program of aerobic activity. However, it appears that the combination of physical activity and a Low Glycemic Index Mediterranean Diet (LGIMD) was more efficacious in reducing AA/EPA levels, at 45 days of treatment, even if this effect was not maintained over time. The combined effect of diet and physical activity reduced the AA/EPA ratio value improving the score of steatosis. Dietary intake of omega-3 PUFAs, in association with a healthy lifestyle, may be used in the prevention protocols for many chronic diseases, including NAFLD.
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Irisin Serum Levels in Metabolic Syndrome Patients Treated with Three Different Diets: A Post-Hoc Analysis from a Randomized Controlled Clinical Trial.
Osella, AR, Colaianni, G, Correale, M, Pesole, PL, Bruno, I, Buongiorno, C, Deflorio, V, Leone, CM, Colucci, SC, Grano, M, et al
Nutrients. 2018;(7)
Abstract
BACKGROUND Irisin, a hormone-like myokine, regulates energy homeostasis and mediates the benefits of physical activity on health. METHODS To estimate the effect of different diets on irisin concentrations in subjects with the Metabolic Syndrome (MetS). METHODS Subjects with MetS were derived from a population survey; 163 subjects were enrolled and randomized to a: Low Glycaemic Index (LGID), Mediterranean (MD) or Low Glycaemic Index Mediterranean (LGIMD) Diet, and the groups were compared, also with 80 controls without MetS. Sociodemographic, medical and nutritional data were collected and fasting blood samples drawn. Subjects underwent LUS and bioimpedentiometry. Generalized Estimating Equations were performed. RESULTS At baseline, lower irisin concentrations were observed in MetS subjects. Mean irisin levels increased in all diet groups but only the LGID group reached statistical significance, as well as showing an interaction between LGID and time at the sixth month examination (4.57, 95% CI −1.27, 7.87). There was a positive effect of Vegetable Proteins (0.03, 95% CI −0.01,0.06) and Saturated Fatty Acids (0.04, 95% CI 0.01, 0.07) on irisin concentrations. In the LGIMD, a positive effect on Fat-Free Mass (0.38, 95% CI 0.19, 0.57) and a negative effect on the Body Mass Index (−0.75, 95% CI −1.30, −0.19) were observed. CONCLUSIONS There seems to be a link between diet and muscle physiology. We showed that patients following a LGID had higher levels of irisin, a promising biomarker of muscle activity.