Non-alcoholic fatty liver disease (
NAFLD) has been recognized as a major health burden. It is the most important cause of chronic
liver disease and a major independent cardiovascular risk factor. Lacking a definite treatment for
NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3
polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of
NAFLD have been described. n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors (
hypertension,
hyperlipidemia, endothelial dysfunction and
atherosclerosis) by regulating gene
transcription factors [i.e.,
peroxisome proliferator-activated receptor (
PPAR) α, PPARγ,
sterol regulatory
element-binding protein-1,
carbohydrate responsive
element-
binding protein], impacts both lipid metabolism and on
insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous
lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (
tumor necrosis factor-α and
interleukin-6) and of
oxygen reactive species. Further strengthening the results of the in vitro studies, both animal models and human intervention trials, showed a beneficial effect of n-3 PUFAs on the severity of
NAFLD as expressed by laboratory parameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of
NAFLD in humans, well-designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other
therapies, for the treatment of
NAFLD and non-
alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (
fish oil, flaxseeds,
olive oil) which are typical foods of the
Mediterranean diet, known for its beneficial effects in preventing
obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.