A global view of the interplay between non-alcoholic fatty liver disease and diabetes.

Non-alcoholic fatty liver disease (NAFLD) is to date the most common chronic liver disease in clinical practice and, consequently, a major health problem worldwide. It affects approximately 30% of adults in the general population and up to 70% of patients with type 2 diabetes (T2DM). Despite the current knowledge of the epidemiology, pathogenesis, and natural history of NAFLD, no specific pharmacological therapies are until now approved for this disease and, consequently, general strategies have been proposed to manage it. They include: (a) lifestyle change in order to promote weight loss by diet and physical activity, (b) control of the main cardiometabolic risk factors, (c) correction of all modifiable risk factors leading the development and progression of advanced forms of NAFLD, and (d) prevention of hepatic and extra-hepatic complications. In the last decade, several potential agents have been widely investigated for the treatment of NAFLD and its advanced forms-shedding some light but casting a few shadows. They include some glucose-lowering drugs (such as pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors), antioxidants (such as vitamin E), statins or other lipid lowering agents, bile and non-bile acid farnesoid X activated receptor (FXR) agonists, and others. This narrative review discusses in detail the different available approaches with the potential to prevent and treat NAFLD and its advanced forms.

https://www.mdpi.com/1422-0067/22/5/2350/pdf

Treatments for NAFLD: State of Art

Non-alcoholic steatohepatitis is becoming the most important aetiology for advanced liver disease. There has been important progress in the field in recent years and the complexity of the pathophysiology of NASH is better understood. Multiple non-invasive circulating and imaging biomarkers have been tested. The importance of lifestyle has been recognised and several drugs are being tested in clinical trials. This review addresses the challenges that healthcare professionals face in the management of NASH patients.

https://gut.bmj.com/content/gutjnl/71/10/2123.full.pdf

Current therapies and new developments in NASH

It has been established, worldwide, that non-communicable diseases such as obesity, diabetes, metabolic syndrome, and cardiovascular events account for a high percentage of morbidity and mortality in contemporary societies. Several modifiable risk factors, such as sedentary activities, sleep deprivation, smoking, and unhealthy dietary habits have contributed to this increase. Healthy nutrition in terms of adherence to the Mediterranean diet (MD), rich in fruits, legumes, vegetables, olive oil, herbs, spices, and high fiber intake may contribute to the decrease in this pandemic. The beneficial effects of the MD can be mainly attributed to its numerous components rich in anti-inflammatory and antioxidant properties. Moreover, the MD may further contribute to the improvement of reproductive health, modify the risk for neurodegenerative diseases, and protect against depression and psychosocial maladjustment. There is also evidence highlighting the impact of healthy nutrition in female people on the composition of the gut microbiota and future metabolic and overall health of their offspring. It is therefore important to highlight the beneficial effects of the MD on metabolic, reproductive, and mental health, while shaping the overall health of future generations. The beneficial effects of MD can be further enhanced by increased physical activity in the context of a well-balanced healthy lifestyle.

https://www.mdpi.com/2072-6643/13/6/1951/pdf

Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing.

Lifestyle represents the most relevant factor for non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of the metabolic syndrome. Although a tremendous body of clinical and preclinical data on the effectiveness of dietary and lifestyle interventions exist, the complexity of this topic makes firm and evidence-based clinical recommendations for nutrition and exercise in NAFLD difficult. The aim of this review is to guide readers through the labyrinth of recent scientific findings on diet and exercise in NAFLD and non-alcoholic steatohepatitis (NASH), summarizing "obvious" findings in a holistic manner and simultaneously highlighting stimulating aspects of clinical and translational research "beyond the obvious". Specifically, the importance of calorie restriction regardless of dietary composition and evidence from low-carbohydrate diets to target the incidence and severity of NAFLD are discussed. The aspect of ketogenesis-potentially achieved via intermittent calorie restriction-seems to be a central aspect of these diets warranting further investigation. Interactions of diet and exercise with the gut microbiota and the individual genetic background need to be comprehensively understood in order to develop personalized dietary concepts and exercise strategies for patients with NAFLD/NASH.

Diet and exercise in NAFLD/NASH: Beyond the obvious

Objective To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. Design For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). Results Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p Conclusion The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half. Trial registration number NCT03020186.

https://gut.bmj.com/content/gutjnl/70/11/2085.full.pdf

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Abstract Mankai is a cultivated strain of Wolffia globose, an aquatic plant, one of the smallest plants on earth, belonging to the family Lemnaceae, known commonly as Duckweeds. Mankai is being considered as a high-quality substitute for animal protein, and a potential source of vitamin B12(1). In fact, it contains all 9 essential amino acids and its protein profile is extremely close to that of egg. Recently, it has been granted GRAS status, and chosen as a test food in a long-term intervention DIRECT-PLUS (ClinicalTrials.gov identifier (NCT number): NCT03020186) which aims to compare the effect of green-Mediterranean diet (composed with polyphenol enriched food including Mankai) + physical activity (PA) vs. Mediterranen diet + PA vs in 300 volunteers suffering from cardiometabolic disease. Mankai is also rich in iron and has been shown in humans to maintain Iron-Homeostasis and to reverse Anemia in Rats(2). However, molecular characterization of phenolic composition of Mankai plant has not previously been reported. Our initial measurements of total phenolic content determined by Folin-Ciocalteu assay classifies Mankai amongst the foods highest in polyphenols content (8606.7 mg/kg)(3). This poster presents the characterization of Mankai polyphenols according to Vrhovsek et al. 2012 [4] using UHPLC-ESI-MS/MS system, identifying 26 different polyphenols. One of the main advantages of Mankai is its hydroponic cultivation that optimizes yield throughout the year. Light source, water and mineral management can influence the composition of phenolic content. We quantified Mankai polyphenols in 30 different plant batches and 52 different treatments to assess how quality of light may play a major role in the accumulation of secondary plant compounds. Notably, led light seems to enhance the glycated form of luteolin and quercetin compared to sunlight and the aglycone form of luteolin and quercetin are higher in sunlight treatment. The present analysis confirms the high polyphenol status of Mankai, profiles its major polyphenol components and provides new information on how production process in terms of light quality determines polyphenol content.

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Urska Vrhovsek

Papers

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Measuring phenolic compounds in Mankai: a novel polyphenol and amino rich plant protein source