Once upon a time, liver disease mostly afflicted severe alcoholics.
But the American Liver Foundation estimates that about one in four Americans – and three out of four obese Americans – now have “nonalcoholic fatty liver disease” or NAFLD.
Although fat buildup in the liver is not normal, small amounts generally cause little harm or permanent damage.
But if NAFLD progresses, it can lead to nonalcoholic steatohepatitis (NASH) … a more dangerous and insidiously “silent” condition.
The major feature of NASH is fat and protein buildup in the liver, along with inflammation and oxidative (free radical) damage.
Left untreated, NASH can lead to cirrhosis, in which the liver is permanently damaged and scarred and unable to work properly.
What causes
and curbs fatty liver?
Both NASH and NAFLD are becoming more common, probably because of the growing number obese Americans.
During the past decade, the rate of obesity – which promotes diabetes and unhealthful blood cholesterol profiles – has doubled in adults and tripled in children.
Diet plays a central role in promoting or deterring liver disease, diabetes, and related metabolic disorders.
Eating too much sugar, starch, omega-6 fat (from cheap vegetable oils), and saturated fat promotes liver disease. In contrast, foods rich in antioxidants and omega-3s appear to offer protection: see “Coffee and Tea Aid Livers and Prostate”, “Berries May Deter Liver and Metabolic Disorders”, “Omega-3s Deter Fatty Liver; Sweet Drinks Raise the Risk”, and articles in the Omega-3s & Metabolic Health section of our news archive.
OSU study probed the metabolic effects of omega-3s
A new lab study suggests that seafood-source omega-3 fatty acids may bring more metabolic benefits than previously thought.
And its results suggest that fishy omega-3s may hold significant value for prevention of fatty liver disease and its dangerous outcomes.
The research – from scientists at Oregon State University and other institutions – was one of the first to use a method called “metabolomics.”
Metabolomics involves analysis of a food's or a nutrient's metabolic breakdown products … known as “metabolites”.
By examining the metabolites of omega-3 fatty acids, the OSU-led team hoped to reveal their effects on the liver.
We should note that omega-3s come in two basic forms, with distinctly different health impacts:
  • Short-chain omega-3s (ALA) from plant foods
  • Long-chain omega-3s (EPA and DHA) from seafood and fish oil.
The body only needs EPA and DHA, which serve essential roles in the structure and function of every cell in the body.
We can make omega-3 EPA and DHA from ALA, but only one to 10 percent of dietary ALA becomes EPA, and only 10 percent of that becomes DHA.
Critically, only omega-3 EPA and DHA are shown to yield substantial cardiovascular, metabolic, mood, and brain benefits.
And a 2008 animal study from Albany Medical College found that the short chain omega-3 in plant foods (ALA) produced no liver benefits (Sealls W et al. 2008).
Animal study sees potent liver protection from omega-3 DHA
The OSU-led team studied the effects of seafood-source omega-3s in mice fed a regimen resembling the “Western Diet”.
This eating pattern – also known as the “Standard American Diet” (SAD) – is linked to liver inflammation, fibrosis (accumulation of proteins), cirrhosis, and liver failure.
The animals were divided into three groups:
  • Western Diet + refined olive oil
  • Western Diet + omega-3 DHA
  • Western Diet + omega-3 EPA
The omega-3 groups received amounts of EPA or DHA equivalent (on a dose per unit of body weight basis) to the amounts prescribed to reduce elevated blood triglycerides in people.
The animals fed the Western Diet + olive oil developed severe NASH symptoms, including liver hepatosteatosis, inflammation, oxidized (damaged) fats, and fibrosis.
In contrast, both of the omega-3-supplemented groups showed significant, positive changes in vitamin metabolism, carbohydrate (sugar/starch) metabolism, protein function, triglyceride levels, and lipid (fat/cholesterol) metabolism.
Importantly, omega-3 DHA produced substantially more and greater metabolic benefits, compared with omega-3 EPA.
Omega-3 DHA was more effective than EPA at curbing genetic changes known to promote nonalcoholic steatohepatitis (NASH), reducing levels of oxidized fats and cholesterol, and maintaining healthy liver levels of glutathione … one of the body's key internal antioxidants.
Better yet, supplemental DHA partially or totally prevented metabolic damage caused by characteristic aspects of the Western diet: excessive consumption of processed red meats, sugar, saturated fat, and processed grains.
The team's exhaustive analysis – which covered 320 separate metabolites – established that omega-3 DHA exerted broad effects on all major metabolic pathways.
“We were shocked to find so many biological pathways being affected by omega-3 fatty acids,” said Donald Jump, a professor in the OSU College of Public Health and Human Sciences (OSU 2014).
“A lot of work has been done on fatty liver disease, and we are just beginning to explore the potential for DHA in preventing or slowing disease progression,” he added (OSU 2014).
Omega-3 DHA seen as the key metabolic ally
Prior animal studies at OSU found that DHA beats EPA at preventing the formation of harmful metabolites associated with the Western Diet (Depner CM et al. Jan. 2013).
In one study, supplemental DHA reduced the protein buildup characteristic of liver fibrosis by more than 65 percent (two-thirds).
Those studies used DHA doses equivalent to the two to four grams per day recommended to heart patients who need to lower their triglycerides.
And their encouraging results suggest that DHA brings even more health benefits than has previously been presumed.
“Fish oils are not prescribed to regulate blood glucose levels in diabetic patients,” he added. “But our studies suggest that DHA may reduce the formation of harmful glucose metabolites linked to diabetic complications.” (OSU 2014)
Clearly, we've just scratched the surface when it comes to the potential benefits of omega-3s from seafood.
  • Depner CM, Philbrick KA, Jump DB. Docosahexaenoic acid attenuates hepatic inflammation, oxidative stress, and fibrosis without decreasing hepatosteatosis in a Ldlr(-/-) mouse model of western diet-induced nonalcoholic steatohepatitis. J Nutr. 2013 Mar;143(3):315-23. doi: 10.3945/jn.112.171322. Epub 2013 Jan 9
  • Depner CM, Torres-Gonzalez M, Tripathy S, Milne G, Jump DB. Menhaden oil decreases high-fat diet-induced markers of hepatic damage, steatosis, inflammation, and fibrosis in obese Ldlr-/- mice. J Nutr. 2012 Aug;142(8):1495-503. doi: 10.3945/jn.112.158865. Epub 2012 Jun 27.
  • Depner CM, Traber MG, Bobe G, Kensicki E, Bohren KM, Milne G, Jump DB. A metabolomic analysis of omega-3 fatty acid-mediated attenuation of western diet-induced nonalcoholic steatohepatitis in LDLR-/- mice. PLoS One. 2013 Dec 17;8(12):e83756. doi: 10.1371/journal.pone.0083756. eCollection 2013.
  • National Digestive Diseases Information Clearinghouse (NDDIC). Nonalcoholic steatohepatitis http://digestive.niddk.nih.gov/ddiseases/pubs/nash/
  • Oregon State University (OSU). More benefits emerging for one type of omega-3 fatty acid: DHA. January 23, 2014. Accessed at http://oregonstate.edu/ua/ncs/archives/2014/jan/more-benefits-emerging-one-type-omega-3-fatty-acid-dha
  • Rossmeisl M, Medrikova D, van Schothorst EM, Pavlisova J, Kuda O, Hensler M, Bardova K, Flachs P, Stankova B, Vecka M, Tvrzicka E, Zak A, Keijer J, Kopecky J. Omega-3 phospholipids from fish suppress hepatic steatosis by integrated inhibition of biosynthetic pathways in dietary obese mice. Biochim Biophys Acta. 2013 Dec 1;1841(2):267-278. doi: 10.1016/j.bbalip.2013.11.010. [Epub ahead of print]
  • Sealls W, Gonzalez M, Brosnan MJ, Black PN, DiRusso CC. Dietary polyunsaturated fatty acids (C18:2 omega6 and C18:3 omega3) do not suppress hepatic lipogenesis. Biochim Biophys Acta. 2008 Aug;1781(8):406-14. doi: 10.1016/j.bbalip.2008.06.010. Epub 2008 Jul 4.