Abstract
Long-chain omega-3 fatty acids have shown to regulate lipid metabolism and reduce fat accumulation in the liver. This trial investigated the effect of flaxseed oil, as a rich source of alpha-linolenic acid, on fatty liver and cardiometabolic risk factors in patients with non-alcoholic fatty liver disease (NAFLD). The randomized, double-blind, controlled trial was performed on 68 NAFLD patients who divided into flaxseed (n=34) and sunflower (n=34) oil groups. Patients were given a hypocaloric diet (-500 kcal/d) and 20 g/d of the corresponding oil for 12 weeks. Fatty liver grade, liver enzymes, and cardiometabolic parameters were determined. The intention-to-treat approach was used for data analysis. Fatty liver grade significantly decreased in both groups (-0.68 in flaxseed vs. -0.29 in sunflower, P=0.002). ALT and AST decreased in both groups (P<0.01). Also, significant reduction was observed in blood glucose (P=0.005) and fat mass (P=0.01) of flaxseed and muscle mass (P=0.01) of sunflower group. However, none of these alterations was significantly different between the groups. Weight, waist circumference, and blood pressure significantly decreased in both groups but only weight change was significantly different between groups (P=0.01). Interleukin-6 did not significantly change in either group but showed a significant between-group difference (P=0.03). Overall, the results showed that in the context of a low-calorie diet and moderate physical activity, flaxseed oil may benefit NAFLD patients to improve fatty liver grade, weight, and interleukin-6 compared to sunflower oil.
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Key Points
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. It is a mild form of liver disease with accumulation of fat in hepatocytes. But if left untreated, NAFLD can progress to nonalcoholic steatohepatitis (NASH) and more severe diseases such as cirrhosis, hepatic failure, and liver cancer. Limited number of animal studies investigated the effect of flaxseed oil on NAFLD and showed promising results. Here the effect of flaxseed oil on fatty liver and liver enzymes along with cardiometabolic risk factors in NAFLD patients was studied. As the control, sunflower oil which has previously been used as placebo in similar investigations on NAFLD patients was used. The findings indicated that in the context of a weight loss program (hypocaloric diet plus physical activity), 12-week consumption of flaxseed oil decreased fatty liver grade compared to sunflower oil without changing liver enzymes and cardiometabolic risk factors. Both groups indicated significant reduction in weight, waist circumference, and blood pressure, indicating that a part of these improvements has likely occurred due to the weight loss program. In addition to fatty liver grade, flaxseed oil caused significant decrease in weight and IL-6 compared to sunflower oil. Besides the plausible direct effect of flaxseed oil on liver steatosis, the improvement in fatty liver grade may have resulted at least partly from weight reduction because both groups demonstrated significant decrease in weight and waist circumference.
Flaxseed oil caused significant reduction in IL-6 compared to sunflower oil. Circulating IL-6 is an important pro-inflammatory cytokine associated with NASH development, systemic insulin resistance, and diabetes. The plausible anti-inflammatory effect of flaxseed may be rendered through reduction in fat mass. Overall, results of this trial suggest that in the context of a low-calorie diet plus moderate exercise, 12 weeks consumption of 20 g/d flaxseed oil may mitigate fatty liver grade and decrease weight and IL-6 of NAFLD patients to a greater extent than sunflower oil. Decreasing aminotransferases, waist circumference, and systolic and diastolic blood pressure were benefits that came along with weight loss program as they changed similarly in both treatments. Since IL-6 is an important inflammatory cytokine in NAFLD, future studies with flaxseed oil are suggested to be conducted on patients with more severe cases of NAFLD and NASH. Benefits of flaxseed oil may be more substantial in patients with more severe cases of NAFLD and with higher levels of aminotransferases.