The analgesic, heart, and colon benefits of aspirin are clear.
All of these are likely related to the drug's anti-inflammatory effects.
But despite a medical history dating back to the late 1800's, it's never been clear how aspirin kills pain or eases inflammation.
Several years ago, researchers made the landmark finding that aspirin triggers production of potent inflammation-ending molecules called resolvins.
The body routinely makes resolvins from metabolic byproducts of the two major omega-3s found in fish fat and human cells: EPA and DHA.
Resolvins are used by the body to end, or “resolve” the inflammation resulting from its immune response to injuries and infections.
Chronic, unresolved inflammation drives major disease conditions such as heart disease, cancer, arthritis, and dementia.
Persistent inflammation is caused by sugary, starchy diets, stress, excess intake of omega-6 fats (from vegetable oils), sedentary lifestyles, and unhealthy habits like smoking and drinking.
Now, Boston-based scientists report the discovery of a new resolvin – called D3 – which the body makes from omega-3 DHA (Dalli J et al. 2013).
And they found that aspirin stimulates production of resolvin D3: a finding that suggests omega-3 DHA may provide the basis for anti-inflammatory drugs far safer and more powerful than aspirin.
Potent new anti-inflammatory agent helps explains aspirin's power
The study was led by Charles Serhan, M.D., who we heard speak about resolvins, omega-3s, and aspirin at a 2012 omega-3 conference in Boston.
Dr. Serhan ranks among the most respected, innovative biomedical researchers in the world ... the first Endowed Distinguished Scientist at Boston's Brigham and Women's Hospital and a full Professor at Harvard Medical School.
Several years ago, he and his team discovered four potent inflammation-resolving compounds that the body makes from omega-3 EPA (RvE1 and RvE2) and DHA (RvD1 and RvD2).
His team's new study revealed the existence and actions of a third DHA-derived resolvin called RvD3. Why does this discovery matter?
As Dr. Serhan said, “… resolvin D3 from DHA [RvD3] persists longer at sites of inflammation than either RvD1 or RvD2 in the natural resolution of inflammation in mice.”
And he added a key point: “This finding suggests that this late-resolution-phase resolvin D3 might display unique properties in fighting uncontrolled inflammation.” (Cell 2013)
Serhan's team reported making another important discovery in the new study:
“We also identified the human receptor that is activated by resolvin D3, which is critical in understanding how resolvin D3 works in the body to resolve inflammation.” (Cell 2013)
Aspirin works like DHA, via a different pathway Serhan's team also confirmed that aspirin triggers production of a longer-acting form of resolvin D3 through a different pathway.
“Aspirin is able to modify an inflammatory enzyme to stop forming molecules that propagate inflammation and instead produce molecules [normally made] from omega-3 fatty acids, like resolvin D3, that help inflammation to end,” explained coauthor Nicos Petasis, Ph.D., of the University of Southern California.
“We were able to produce by chemical synthesis both resolvin D3 and aspirin-triggered resolvin D3 in pure form, which allowed us to establish their complete structures and biological activities,” added Dr. Petasis. (Cell 2013)
When given to mice or administered to human cells, resolvin D3 from DHA and aspirin exerted extremely potent inflammation-ending effects.
And when human cells were exposed to both versions of resolvin D3, they exerted even greater anti-inflammatory effects than either one alone.
As he said, “With this new information, investigators will now also be able to study the pro-resolving and anti-inflammatory actions of resolvin D3 in other systems.” (Cell 2013)
No doubt, researchers will want to determine which inflammation-driven diseases might be treated with this newly identified resolvin … and how to turn it into a safe drug.
Can omega-3 DHA be the basis of a better, safer alternative to aspirin?
At the 2012 Boston meeting we attended, Dr. Serhan noted that DHA is hundreds of times more effective at producing resolvins, compared with aspirin.
This does not mean that eating a milligram of DHA has the analgesic or anti-inflammatory power as taking a milligram of aspirin.
Why is this? Rather than making resolvins from DHA itself, the body produces them from certain metabolic byproducts of DHA, which occur in very small amounts.
These metabolic products of omega-3 DHA make very promising candidates for development of powerful drugs.
Such DHA-derived drugs should be far safer than aspirin.
An estimated 107,000 people are hospitalized annually in the United States for serious gastrointestinal complications related to aspirin and other non-steroidal anti-inflammatory drugs NSAIDs (Singh G 1999).
And it is estimated that – among arthritis patients alone – up to 16,500 NSAID-related deaths occur each year in the United States (Singh G 1999; Silagy CA et al. 1993).
Aspirin can also produce adverse side effects in people with high blood pressure, a family history of stroke, stomach ulcers, and liver or kidney problems.
- Cell. Aspirin and omega-3 fatty acids work together to fight inflammation. February 21, 2013. Accessed at http://www.eurekalert.org/pub_releases/2013-02/cp-aao021313.php
- Dalli J, Winkler JW, Colas RA, Arnardottir H, Cheng CY, Chiang N, Petasis NA, Serhan CN. Resolvin d3 and aspirin-triggered resolvin d3 are potent immunoresolvents. Chem Biol. 2013 Feb 21;20(2):188-201. doi: 10.1016/j.chembiol.2012.11.010.
- Serhan CN, Arita M, Hong S, Gotlinger K. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids. 2004 Nov;39(11):1125-32. Review.
- Serhan CN, Gotlinger K, Hong S, Arita M. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat. 2004 Apr;73(3-4):155-72. Review.
- Silagy CA, McNeil JJ, Donnan GA, Tonkin AM, Worsam B, Campion K. Adverse effects of low-dose aspirin in a healthy elderly population. Clin Pharmacol Ther. 1993 Jul;54(1):84-9.
- Singh G, Rosen Ramey D, Morfeld D, et al. Gastrointestinal Tract Complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. Arch Intern Med 1996;156:1530-1536.
- Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol 1999;26(56):18-24.
- Singh G. Gastrointestinal Complications of Prescription and over-the-counter nonsteroidal anti-inflammatory drugs: A view from the ARAMIS database. Am J Ther 2000;7:115-121.
- Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med. 1998 Jul 27;105(1B):31S-38S. Review.
- Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999 Jun 17;340(24):1888-99. Review.