Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

Abstract

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.

Pharmacologic Management of Non-Alcoholic Fatty Liver Disease

“…PUFA act by regulating gene transcription factors involved in hepatic lipid metabolism [52] which have down-stream effects of increased insulin sensitivity, inhibition of hepatic lipogenesis, increased fatty acid oxidation and reduction of pro-inflammatory cytokines [53]. Various studies using a range of PUFA dosages, composition of the PUFA and duration of treatment have not found consistent results in the context of NAFLD Table 4 [53]. More importantly, most of the studies did not evaluate histological endpoints of treatment.…”

“…Among the first trials, Capanni et al found that PUFA improved liver aminotransaminases, metabolic profiles and hepatic steatosis on imaging [54]. Other studies have provided collaborative observations [53]. A meta-analysis of 9 trials and 355 patients found that there were beneficial changes in hepatic steatosis but less convincing evidence of improvement in aminotransaminases with PUFA therapy [55].…”

“…In addition, PUFA has been shown to improve hypertension, dyslipidemia and cardiovascular disease [50], diseases closely related to NAFLD [51]. PUFA act by regulating gene transcription factors involved in hepatic lipid metabolism [52] which have down-stream effects of increased insulin sensitivity, inhibition of hepatic lipogenesis, increased fatty acid oxidation and reduction of pro-inflammatory cytokines [53]. Various studies using a range of PUFA dosages, composition of the PUFA and duration of treatment have not found consistent results in the context of NAFLD Table 4 [53].…”

Supplementation With 2:1 Ratio of N-6:n-3 Polyunsaturated Fatty Acid Improves Liver Steatosis and Serum Cytokine Levels in Young Obese Balinese Women: A Randomized Clinical Trial

“…It facilitates the influx of free fatty acids from the adipose tissue into the liver, hepatic oxidative stress, cytokine production, reduced VLDL secretion, and the growth of the intestinal microbiome [43]. Unhealthy diet and a sedentary lifestyle can alter the stability of the intestinal microbiome composition.…”

Opportunities to enhance alternative sources of long-chainn-3 fatty acids within the diet

“…Aquaculture (salmon and trout) accounted for over 70 % of the consumption of oil in 2011 primarily in Chile and Peru. However, direct human consumption of fish oil has been increasing over the past 5 years, due to marketer's influence and due to an increase in awareness of health benefits of long-chain (LC) n-3 PUFA, such as prevention of type-2 diabetes (Asian, Eskimos), prevention of insulin-resistance (3,4) , decrease in plasma TAG (5) , anti-inflammatory effect (6) , the defect of brain and retina development (only if deficiency in LC n-3 PUFA), primary cardiovascular prevention (5) , anti-stress and anti-adrenergic effect (7,8) and decrease in liver steatosis (9) . Because of these health benefits and of some deleterious effects of deficiency, many national and international recommendations have been proposed about the optimal intake of LC n-3 PUFA for the general population.…”