Resolvin may be the secret of fish oil’s healthy effects
Researchers at Harvard University have found a nanomolecule, resolvin E1, which is formed in the body of EPA, a fatty acid present in fish oil. Resolvin E1 seems to be a potent antiinflammatory agent which explains many of the fish oil´s health effects.Epidemiological and dietary studies strongly indicate that omega-3´s provide tremendous health benefits for a number of diseases, including diabetes, cancer and heart disease. All chronic diseases seem to have one thing in common, a low-grade chronic inflammation, in which immune cells and molecular mediators flood tissues and can create damage. This can lead, for example, to the hardening of the arteries that spurs heart attacks and strokes.
We know that fish oil suppresses inflammation,” says Stephen Prescott, director of the Huntsman Cancer Institute at the University of Utah in Salt Lake City, and an expert on lipids and inflammation. “The question is how does it do it? People have looked for more than 20 years.”
Dr Charles Serhan at Harvard Medical School in Boston and colleagues became intrigued by the problem in 1999, after seeing a study showing that fish oil protects against cardiovascular disease. Subjects in that study had consumed a gram of fish oil each day. “They smelled like mackerel,” said Serhan. But he noticed that almost all of the subjects were also taking aspirin to prevent strokes and heart attacks. Might the two substances be working together? Subsequent research by Serhan and his colleagues has suggested that they do 1,2,3).
Their work in human cells and in mice showed that omega-3 fatty acids in the fish oil are converted into lipids that seem to suppress inflammation. Aspirin speeds up that conversion. The researchers have now pinned down the effect even further by focusing on one of the lipids, called resolvin E1 (RvE1). First they found that healthy human volunteers fed both aspirin and fish oil had resolvin E1 in their bloodstream. Then they created a synthetic form of the lipid and tested its properties. The lipid inhibited the migration of particular human immune cells and dramatically reduced inflammation on the skin of rabbits.
Resolvin E1 molecule
Serhan and his team believe that resolvin E1 works in the body to tone down inflammation, and report their results in The Journal of Experimental Medicine1. “This is a really attractive and interesting hypothesis at this stage,” says Prescott. Raymond DuBois, a lipid researcher at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, echoes that sentiment, calling the work “a great move forward”.
Scaled up Serhan is now working to prove that resolvin E1 does actually help to treat disease. His unpublished data so far show that the synthetic version works in a mouse model of periodontal gum disease. Such disease is driven by inflammation, which weakens the gums and causes teeth to fall out. Resolvin E1 counteracts the process, he says. Serhan now aims to scale up and modify the manufacture of synthetic resolvin E1 so that it can be made cheaply in bulk, and he hopes to start human trials soon.
It’s a powerful substance, comments Prescott. “All you need to do is make a little bit, and bang, you have an effect.” But resolvin E1 is “just the tip of the iceberg”, Serhan adds. His group is also looking at the other lipids that derive from fish oil. He suspects that each one has a part to play in orchestrating the inflammatory response. Understanding how they work could lead to the development of a range of new drugs to counteract inflammation, he predicts.
A new report by Dr Serhan´s team shows that resolvin E1 suppresses intestinal inflammation (3). This explains the findings of a Japanese team, who treated successfully children with colitis ulcerosa (4). Professor Ángel Gil, of Granada University (Spain) recommends E-EPA for the treatment of intestinal inflammation, as it is effective and has no side effects like the traditional medicines, such as cortisone and salazopyrine (5).
In these reports Dr Serhan states that resolvin E1 is produced in the presence of aspirin. In a personal communication to me he ascertains that EPA converts into resolvin E1 even without aspirin, but in lesser amount. Ω
SOURCE: Bio-Vita.fi
1. Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med. 2005;201(5):713-22 [PubMed]
2. Serhan CN. Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and neuroprotectins. Current Opinion in Clinical Nutrition & Metabolic Care 2005;8(2):115-121 [Abstract]
3. Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, Blumberg RS, Serhan CN. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci U S A. 2005 May 12; [PubMed] [Free full text]
4. Shimizu T, Fujii T, Suzuki R, et al. Effects of highly purified eicosapentaenoic acid on erythrocyte fatty acid composition and leukocyte and colonic mucosa leukotriene B4 production in children with ulcerative colitis. J Pediatr Gastroenterol Nutr. 2003 Nov;37(5):581-5. [PubMed]
5. Gil Á. Is eicosapentaenoic acid usefull in the treatment of ulcerative colitis in children?J Pediatr Gastroenterol Nutr. 2003 Nov;37(5):581-5.
More in Nature 8.3.2005