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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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2.
Serum Folate deficiency in HCV related Hepatocellular Carcinoma.
Malaguarnera, G, Catania, VE, Bertino, G, Drago, F, Madeddu, R, Bonfiglio, C, Malaguarnera, M
Scientific reports. 2022;(1):5025
Abstract
Nutritional and environmental factors had been reporting in the progression of hepatocellular carcinoma (HCC). In this study, we focused our intervention in the correlation between the folate status and the progression of HCC in patients with chronic virus C (HCV) infection. Nine-eight patients, HCV positive with HCC and one hundred of patients with HCV positive liver cirrhosis (LC) and one hundred patients with HCV positive chronic hepatitis (CHC) and one hundred control subjects were enrolled. The viremia for hepatitis C patients (HCV) was determined by HCV RNA with polymerase chain reaction. HCV was confirmed by HCV RNA or a positive anti-HCV test with chronic liver disease. The comparison of folate serum levels in HCC patients vs Liver Cirrhosis (LC) patients showed a significant decrease of 1.16 ng/ml P = 0.0006 (95% CI-1.925 to - 0.395), in HCC patients versus CHC a decrease of 1.40 ng/ml P < 0.0001 (95% CI-2.16 to - 0.63), in HCC vs controls a decrease of 3.80 ng/ml P < 0.0001 (95% CI-4.56 to - 3.03). The comparison of homocysteine Hcy serum levels showed a significant increase in HCC vs LC of 4 nmol/L (P < 0.0001, 95% CI 2.77 to 5.22) versus CHC of 9 nmol/L (P < 0.0001, 95% CI 7.78 to 10.22) and vs Controls 9.30 nmol/L (P < 0.0001, 95% CI 8.07 to 10.52). With progression of HCV infection from chronic hepatitis to cirrhosis, then to HCC development, serum folate levels are progressively decreasing together with a progressive increase in serum homocysteine levels reflecting its role in disease progress and carcinogenesis.
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3.
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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4.
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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5.
Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial.
Malaguarnera, G, Catania, VE, Bertino, G, Chisari, LM, Castorina, M, Bonfiglio, C, Cauli, O, Malaguarnera, M
Current pharmaceutical design. 2022;(38):3158-3166
Abstract
BACKGROUND Ageing is characterized by a gradual decline in body function, representing the clinical situation called "frailty". Prefrailty is the intermediate stage between frailty and robust condition. L-carnitine (LC) plays an important role in energy production from long-chain fatty acids in mitochondria, and its serum level is lower in prefrail and frail subjects. OBJECTIVE This study aims to evaluate the effect of Acetyl-L-carnitine (ALCAR) in pre-frail older patients. METHODS We scheduled 3 months of treatment and then 3 months of follow-up. A total of 92 subjects were selected from May, 2009 to July, 2017, in a randomized, observational, double-blind, placebo-controlled study. We scheduled 3 months of treatment and then 3 months of follow-up. ALCAR (oral 1.5 g/bis in die - BID) or placebo groups were used. RESULTS After the treatment, only the treated group displayed a decrease in C reactive protein (CRP) p < 0.001 and an increase in serum-free carnitine and acetylcarnitine (p < 0.05) in Mini-Mental state (MMSE) p < 0.0001 and 6-walking distance (p < 0.0001); ALCAR group vs. placebo group showed a decrease in HDL cholesterol and CRP (p < 0.01), an increase in MMSE score (p < 0.001) and in the 6-walking distance (p < 0.001). CONCLUSIONS ALCAR treatment delays the incidence and severity of onset of degenerative disorders of the elderly in prefrail subjects with improvement in memory and cognitive processes.
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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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7.
Carnitine Serum Levels in Frail Older Subjects.
Malaguarnera, G, Catania, VE, Bonfiglio, C, Bertino, G, Vicari, E, Malaguarnera, M
Nutrients. 2020;(12)
Abstract
Frailty is an expression that reconciles and condenses loss of autonomy, both physical and cognitive decline and a wide spectrum of adverse outcomes due to aging. The decrease in physical and cognitive activity is associated with altered mitochondrial function, and energy loss and consequently morbidity and mortality. In this cross-sectional study, we evaluated the carnitine levels in frailty status. The mean serum concentrations of total carnitine (TC) were lower in frail elderly subjects than in prefrail ones (p = 0.0006), higher in frail vs. robust subjects (p < 0.0001), and higher in prefrail vs. robust subjects (p < 0.0001). The mean serum concentrations of free carnitine (FC) were lower in frail elderly subjects than in prefrail ones (p < 0.0001), lower in frail vs. robust subjects (p < 0.0001) and lower in prefrail vs. robust subjects (p = 0.0009). The mean serum concentrations of acylcarnitine (AC) were higher in frail elderly subjects than in prefrail ones (p = 0.054) and were higher in pre-frail vs. robust subjects (p = 0.0022). The mean urine concentrations of TC were lower in frail elderly subjects than in prefrail ones (p < 0.05) and lower in frail vs. robust subjects (p < 0.0001). The mean urine concentrations of free carnitine were lower in frail elderly vs. robust subjects (p < 0.05). The mean urine concentrations of acyl carnitines were lower in frail elderly subjects than those in both prefrail (p < 0.0001) and robust subjects (p < 0.0001). Conclusion: high levels of carnitine may have a favorable effect on the functional status and may treat the frailty status in older subjects.
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8.
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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9.
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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10.
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.