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Oxidative stress is considered one of the main determinants in the pathophysiology of non-alcoholic fatty liver disease (NAFLD) and obesity. The alterations of oxidant/antioxidant balance are related to chronic impairment of metabolism leading to mitochondrial dysfunction. Increased oxidative stress also triggers hepatocytes stress pathways, leading to inflammation and contributing to the progression of non-alcoholic steatohepatitis (NASH). Currently, the first-line therapeutic treatment of NAFLD is based on lifestyle interventions, suggesting the Mediterranean Diet (MD) as a preferable nutritional approach due to its antioxidant properties. However, it is still debated if adherence to MD could have a role in determining the risk of developing NAFLD directly or indirectly through its effect on weight. We enrolled 336 subjects (aged 35.87 ± 10.37 years; BMI 31.18 ± 9.66 kg/m2) assessing anthropometric parameters, lifestyle habits, metabolic parameters (fasting plasma glucose, fasting plasma insulin, triglycerides (TG), total cholesterol, low-density (LDL) and high-density lipoprotein (HDL) cholesterol, alanine transaminase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (γGT), cardio-metabolic indices [Homeostatic Model Assessment Insulin Resistance (HoMA-IR), visceral adipose index (VAI) and fatty liver index (FLI)] and adherence to MD [with the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire]. Subjects with NAFLD had significantly higher anthropometric parameters, cardio-metabolic indices and lower adherence to MD than subjects without NAFLD. In a multiple regression analysis, PREDIMED score was the main predictor of FLI (p < 0.001) and came in first, followed by HoMA-IR, while VAI was not a predictor. A PREDIMED score value of p < 0.001). In conclusion, high adherence to MD resulted in a lower risk of having NAFLD. Adherence to MD could have a direct role on the risk of developing NAFLD, regardless of visceral adipose tissue.

In the pathogenesis of type 2 diabetes mellitus (T2DM), diet plays a key role. Individualized medical nutritional therapy, as part of lifestyle optimization, is one of the cornerstones for the management of T2DM and has been shown to improve metabolic outcomes. This paper discusses major aspects of the nutritional intervention (including macro- and micronutrients, nutraceuticals, and supplements), with key practical advice. Various eating patterns, such as the Mediterranean-style, low-carbohydrate, vegetarian or plant-based diets, as well as healthy eating plans with caloric deficits have been proven to have beneficial effects for patients with T2DM. So far, the evidence does not support a specific macronutrient distribution and meal plans should be individualized. Reducing the overall carbohydrate intake and replacing high glycemic index (GI) foods with low GI foods have been shown as valid options for patients with T2DM to improve glycemic control. Additionally, evidence supports the current recommendation to reduce the intake of free sugars to less than 10% of total energy intake, since their excessive intake promotes weight gain. The quality of fats seems to be rather important and the substitution of saturated and trans fatty acids with foods rich in monounsaturated and polyunsaturated fats lowers cardiovascular risk and improves glucose metabolism. There is no benefit of supplementation with antioxidants, such as carotene, vitamins E and C, or other micronutrients, due to the lack of consistent evidence showing efficacy and long-term safety. Some studies suggest possible beneficial metabolic effects of nutraceuticals in patients with T2DM, but more evidence about their efficacy and safety is still needed.

Obesity involves a chronic state of low-grade inflammation, which is linked to the development of several comorbidities. Recently, the very low-calorie ketogenic diet (VLCKD) has gained great interest in the treatment of obesity, almost ousting the ancient and healthy Mediterranean diet (MD). However, because these dietary regimens exploit different pathophysiological mechanisms, we hypothesize that adherence to the MD may play a role in determining the efficacy of the VLCKD. We enrolled 318 women (age 38.84 ± 14.37 years; BMI 35.75 ± 5.18 kg/m²) and assessed their anthropometric parameters, body compositions, and adherence to the MD (with the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire) at baseline. The anthropometric parameters and body composition were repeated at the end of the VLCKD. At the end of the VLCKD, the women with high adherence to the MD achieved the best results in terms of weight loss and improved body composition. Specifically, the women who were above the median of fat mass (FM)% reduction had the best MD pattern, characterized by a higher consumption of extra virgin olive oil (EVOO), fruits, vegetables, and red wine, as well as a higher adherence to the MD than the women who were below the same median. In a multiple regression analysis, the PREDIMED score was the main predictor of the FM% reduction score and came in first, followed by fruit, EVOO, and glasses of wine, in predicting the percentage reduction in FM. A PREDIMED score value of > 5 could serve as a threshold to identify patients who are more likely to lose FM at the end of the VLCKD. In conclusion, high adherence to the MD resulted in higher VLCKD efficacy. This could be due to the antioxidant and anti-inflammatory properties of the MD, which are capable of establishing a metabolic set-up that is favorable to the onset of more effective ketosis.