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Background: Autophagy is a cellular pathway with the ability to maintain cell homeostasis through the elimination of damaged or useless cellular components, and its deregulation may initiate or aggravate different human diseases. Flavonoids, a group of plant metabolites, are able to modulate different molecular and cellular processes including autophagy., Objective: To review the effects of flavonoids on autophagy pathway in both invasive and noninvasive human diseases, focusing on the global outcomes in their progression. Moreover, the efficacy of the combination of flavonoids with drugs or other natural nontoxic compounds was also reviewed., Methods: A literature search was performed to identify and analyze peer-reviewed publications containing in vitro and in vivo studies focused on autophagy deregulation in different proliferative and non-proliferative pathologies and the potential protective effects of flavonoids., Results: Analyzed publications indicated that imbalance between cell death and survival induced by changes in autophagy play an important role in the pathophysiology of a number of human diseases. The use of different flavonoids as autophagy modulators, alone or in combination with other molecules, might be a worthy strategy in the treatment of cancer, neurodegenerative disorders, cardiovascular diseases, hepatic diseases, leishmaniasis, influenza, gastric ulcers produced by Helicobacter pylori infection, diabetes, asthma, age-related macular degeneration or osteoporosis., Conclusion: Flavonoids could potentially constitute important adjuvant agents of conventional therapies in the treatment of autophagy deregulation-related diseases. Moreover, combined therapy may help to diminish the doses of those conventional treatments, leading to reduced drug-derivative side effects and to improved patients' survival., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis. Creatine administration is known to decrease the consumption of Sadenosyl methionine and also reduce the homocysteine production in liver, diminishing fat accumulation and resulting in beneficial effects in fatty liver and non-alcoholic liver disease. Different studies have shown that creatine supplementation could supply brain energy, presenting neuroprotective effects against the encephalopathy induced by hyperammonemia in acute liver failure. Creatine is also taken by many athletes for its ergogenic properties. However, little is known about the adverse effects of creatine supplementation, which are barely described in the literature, with reports of mainly hypothetical effects arising from a small number of scientific publications. Antioxidant effects have been found in several studies, although one of the theories regarding the potential for toxicity from creatine supplementation is that it can increase oxidative stress and potentially form carcinogenic compounds.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in adults and its prevalence is rising around the world. This pathology is characterized by accumulation of liver fat, which exceeds 5% of liver weight in absence of alcohol consumption, viral infection or other hepatic etiology. Since NAFLD has been associated with obesity, insulin resistance, diabetes or alteration of lipid profiles, it is considered as the liver manifestation of metabolic syndrome. Pathogenic mechanisms of NAFLD have not been clearly elucidated, but different events such as lipid accumulation, insulin resistance, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction and inflammation are involved. Modifications in lifestyle constitute the first line for the management of NAFLD. Nutritional interventions include low fat and carbohydrate diet with higher polyunsaturated fatty acids ingestion. Moreover, supplementation with antioxidant and cytoprotective agents could be useful to decrease oxidative stress, inflammation and fibrosis. Physical activity enables to reduce the expression of lipogenic genes, fat accumulation, or insulin resistance and improves cardiorespiratory fitness. Benefits have been found following both aerobic exercise and resistance training, and remain even after exercise cessation. However, more studies are required to analyze the molecular and cellular mechanisms involved in nutritional and physical intervention, and to define the volume of activity required and its association with weight loss. In this paper, we offer an updated overview of the mechanisms implicated in the progression of NAFLD, and analyze the beneficial effects of nutritional interventions and physical exercise in the prevention and treatment of this condition.