Researchers at University of California, San Diego have actually peered inside a living cell and mapped the processes that power the celebrated health benefits of omega-3 fatty acids, according to their report published May 14 by Proceedings of the National Academy of Sciences.(1)
This is the first comprehensive study of what omega-3s actually do inside a cell vis-a-vis inflammation, explains UCSD lipid lab director Edward A Dennis, PhD. And it's groundbreaking because it provides important insights into how inflammatory activity might be manipulated.
Benefits were Seen But Not Understood
The therapeutic benefits of omega-3 fatty acids, which are abundant in certain fish oils, have been known at least since the 1950s when cod liver oil was found to be beneficial for people with ailments like eczema and arthritis.
In the 1980s, scientists reported that Eskimos eating a fish-rich diet enjoyed better coronary health than counterparts consuming a “western” diet.
And since then "there have been tons of epidemiological studies linking health benefits to omega-3 oils… but not a lot of deep science," says Dr. Dennis.
Dr. Dennis and co-author Paul C. Norris, a graduate student, fed three different kinds of fatty acid to mouse macrophages - a type of white blood cell: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA).
• EPA and DHA are major polyunsaturated omega-3 fatty acids, essential to a broad range of cellular and bodily functions, and the primary ingredient in commercial fish oil dietary supplements.
• AA is a polyunsaturated omega-6 fatty acid that is prevalent in the human diet, in foods such as meat, seafood and eggs.
Able to Support Inflammatory Response When Needed
In high levels, fatty acids are toxic, so cells typically sequester them as phospholipids in their membranes. When stimulated, however, the fatty acids may be released, provoking a cascading inflammatory response.
• Acute or limited inflammation is, of course, a vital immunological response to physical damage or invasive pathogens.
• But chronic inflammation is harmful and a common element of almost every disease, from diabetes to cancer.
After supplementing the mouse macrophages with fatty acids, the scientists stimulated them to produce an inflammatory response.
• They discovered that omega-3 fatty acids inhibit an enzyme called cyclooxygenase (COX), which produces the prostaglandin hormones that spark inflammation.
• The action is similar to what happens when one takes an aspirin, which disrupts the COX-2 signaling pathway (as a so-called COX-2 inhibitor), thus reducing inflammation and pain.
On the other hand, they discovered that omega-3 oils do not inhibit another group of enzymes called lipoxygenases (LOX), which are also produced by stimulated macrophages.
• One type of generated LOX enzyme in turn produces fat-signaling molecules called leukotrienes, which are pro-inflammatory.
• But, Norris notes, the LOX enzymes may also generate anti-inflammatory compounds called resolvins from EPA and DHA.
These observations, he said, are also helpful in identifying potential adverse effects from taking fish oil.
• Since omega-3 fatty acids possess overlapping functions with COX inhibitor drugs, with well-known side effects, using both in combination can produce unexpected consequences.
• It is this parsing of what's happening inside cells that Dr. Dennis has called "ground-breaking."
"Now,” he says, “we need to learn if we can fine-tune that process so we can use omega-3 oils to:
• Reduce the production of pro-inflammatory prostaglandins
• And boost the production of anti-inflammatory resolvins.”
1. Article: “Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling,” PNAS, May 14, 2012, by Paul C Norris and Edward A Dennis.
Source: Based on University of California - San Diego press release, May 15, 2012