In patients with Non-Alcoholic Fatty Liver Disease (NAFLD), supplementation with 4 grams of omega-3 can improve hepatic lipid metabolism. In particular, an increase of at least 2% in DHA concentration in red blood cells, as an effect of omega-3 supplement intake, is associated with a significant reduction of fat deposited in the liver and improved insulin sensitivity of the organ.

This was discovered by researchers from Oxford, Southampton, and Surrey Universities (UK), and published in the European Journal of Clinical Nutrition.

Fatty liver, a widespread problem in Western countries

Fatty liver disease is a cellular condition characterized by the accumulation of triglycerides in liver cells, exceeding 5-10% of the organ's weight. The disease can be caused by increased fat intake, reduced fat disposal, or increased fat synthesis.

• Fatty liver due to excessive fat intake can be caused by a diet too rich in lipids or increased mobilization of fatty acids. The latter may be triggered by factors such as stress, hormones, prolonged fasting, and diabetes.
• Fatty liver due to reduced fat disposal can be caused by a low-protein diet, decreased apolipoprotein synthesis, and vitamin B12 deficiency.
• Fatty liver due to increased lipid synthesis results from accumulation of endogenously synthesized fats and can be caused by some medications or alcohol abuse.

Non-Alcoholic Fatty Liver Disease (NAFLD) includes a group of liver diseases ranging from what is commonly called fatty liver, to NASH (Non-Alcoholic Steatohepatitis), characterized by inflammation, scarring, and tissue death in the liver, up to cirrhosis, the most advanced stage of the disease. Experts consider NAFLD the hepatic manifestation of metabolic syndrome. The prevalence of NAFLD in Western countries is likely due to the rise of overweight and obesity, insulin resistance, diabetes, and high cholesterol. Fatty liver can even be present in children (10% of cases), especially those who are obese. In cases of NAFLD, it is important to follow some recommendations:

• lose weight if obese or overweight
• follow a healthy and balanced diet
• engage in physical activity
• avoid alcoholic beverages
• avoid medications unless strictly necessary

As is known, high doses of omega-3 fatty acids can reduce plasma triglyceride concentrations. Several studies have reported that omega-3s can reduce liver fat and that short-term treatment with these fatty acids improves insulin sensitivity throughout the body. However, the effects of EPA and DHA supplementation on insulin sensitivity in the context of NAFLD remain unclear.

Omega-3 supplementation increases DHA in red blood cells and reduces liver fat

The aim of this new study was to verify if an increase of DHA in red blood cells was associated with changes in signaling molecules of NAFLD. To this end, researchers monitored the effect of supplementation with high doses of omega-3 (about 4 grams per day). Results showed, following supplementation, an improvement in fatty acid oxidation and liver insulin sensitivity. As known, insulin sensitivity facilitates glucose uptake in sensitive tissues such as muscles, liver, and adipose tissue. According to the study, supplements also appeared to reduce the amount of newly deposited fat in the liver—a process called de novo lipogenesis—as well as a 26% reduction in liver fat content.

"Our study results indicate that subjects whose DHA percentage in red blood cells increased by at least 2% experienced favorable effects with changes in hepatic metabolism and insulin sensitivity, factors that may contribute to reducing liver fat content," said Leanne Hodson, co-author of the study.

Study details

The study involved 24 patients with Non-Alcoholic Fatty Liver Disease, 12 of whom received daily supplementation with 1.84 grams of DHA and 1.56 grams of EPA, while the other participants received a placebo based on olive oil. Both groups followed the treatment for 15-18 months.

The concentration of DHA in the membranes of red blood cells was measured in each participant before and after treatment, revealing that in nine patients DHA increased by 2% or more, while in others the increase was less than 2%. In the group with an increase equal or greater than 2% DHA, eight had followed supplementation, while only one belonged to the placebo group, suggesting that the latter may have increased intake of oilseeds in their diet during the study period. Researchers then evaluated possible changes in typical NAFLD parameters, including hepatic and whole-body insulin sensitivity, liver fat content, de novo lipogenesis rate, and oxidation of fatty acids and triglycerides in the blood.

What is the effect of EPA?

This study primarily examined the effect of increased DHA in red blood cells on NAFLD markers. It did not assess whether EPA influenced these parameters, as the effects of EPA and DHA on steatosis cannot be isolated. However, a previous study concluded that DHA is more effective than EPA on changes in liver enzymes. Researchers suggested the need for further studies to measure the effect of a supplement containing only DHA on hepatic metabolism and insulin sensitivity.

To stay updated on the latest scientific research about Omega-3, subscribe to our newsletter.

Source: Hodson et al., Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study. European Journal of Clinical Nutrition 71, 973–979 (2017).