Results of preliminary trial suggest that omega-3s can match the analgesic power of aspirin, Advil and Celebrex

by Craig Weatherby

Don't throw out your aspirin just yet, but the results of a small clinical study suggest that fish oil may alleviate pain more effectively than anyone could have hoped.

Every year, more than 70 million people use aspirin, Advil, Aleve, Celebrex, and other non-steroidal anti-inflammatory drugs (NSAIDs). While these drugs alleviate inflammation and pain very effectively, they can cause gastric bleeding or heart problems, and are the leading cause of drug-related illness and death reported to the FDA and other regulatory agencies around the world.

Key Points

  • Small uncontrolled trial tested the analgesic effects of fish oil rich in omega-3s.
  • Fish oil capsules permitted 59 percent of study volunteers to discontinue their pain pills.
  • 60 percent said that their pain was improved and 80 percent were satisfied with their improvement.
  • Results are preliminary and require more rigorous testing.

Complications from taking NSAIDs hospitalize more than 100,000 users and kill more than 16,500 annually, while costing the medical system more than $1.5 billion. The magnitude of this problem is declining, thanks to increased use of proton-pump-inhibiting drugs (which have their own costs and side effects), but remains huge.

One expert commenter (Roth SH, 2005) compared the chronic, systemic use of NSAIDs to pharmaceutical “carpet- bombing” whose indiscriminate effects on the body's metabolic pathways yield collateral damage to users' internal organs.

Last August, the findings of a Spanish study of NSAID risks prompted Bryon Cryer, M.D., of the Dallas VA Medical Center to pen an editorial in which he said that although "clinically significant gastrointestinal events with NSAIDs” represent a low risk for any one patient, the widespread use of NSAIDs and aspirin make these complications a significant public health concern that affects hundreds of thousands of NSAID users.

The Spanish study uncovered the fact that one-third of NSAID-associated gastrointestinal deaths occurred in patients taking only low-dose aspirin to stave off heart disease and colon cancer

COX conundrum prompts search for analgesic alternatives

NSAIDs work by blocking one of more of two enzymes called cyclooxygenases (COX), which trigger inflammatory metabolic cascades that produce pain and inflammation.

Both of the two COX enzymes—COX-1 and COX-2—produce inflammation and pain. But each also produces various other effects in the body, especially with regard to their influence on the gut and blood vessels.

Older NSAIDs such as aspirin, Advil, and Aleve block both the COX-1 and COX-2 enzymes, so they are known as “non-selective” NSAIDs. And when COX-1 is blocked, it can result in gastric bleeding and ulcers. Accordingly, because they block the COX-1 enzyme as well as the COX-2 enzyme, older NSAIDs such as aspirin, Advil, and Aleve can produce silent, potentially fatal gastric bleeding.

This downside to the “non-selective” NSAIDs led researchers to look for NSAIDs that would only block the COX-2 enzyme, and this search led to the introduction of the first “selective” COX-2 inhibitors—Celebrex and Vioxx—in the late 1990's.

While COX-2 inhibitors are no more effective at reducing inflammation and pain, they were expected to cause less injury and death related to gastric bleeding.

However, COX-2 inhibitors have not proven to be completely safe with regard to gastric side effects, and appear to present their own risks related to heart health.

COX-2 inhibitors seem to suppress production of prostacyclin (PGI2)—a hormone-like substance that dilates blood vessels and reduces blood clotting—and they may also impair the function of the endothelial cells that constitute the inside of the wall of our blood vessels. This is significant because endothelial cells produce PGI2 and other anti-coagulants that keep the blood vessels open and free of blood clots.

In September of 2004, Merck withdrew its COX-2 inhibitor NSAID, called Vioxx, from the market after discovering that it was associated with an increased number of heart attacks.  In the spring of 2005, the FDA determined that the risks of one of Pfizer's two COX-2 drugs—Bextra—outweighed its benefits, and Pfizer also agreed to add a strong "Black Box" warning to the label of its other COX-2 NSAID, called Celebrex.

The highly public failures of the COX-2 NSAIDs to deliver on their early promise have prompted researchers to look elsewhere for safer, comparably effective analgesics.

The results of clinical trials dating back to the 1980's suggest that long-chain “marine” omega-3s in fish oil can alleviate the pain of rheumatoid arthritis, and that record led researchers at the University of Pittsburgh Medical Center to test the power of omega-3s on neck and back pain.

Omega-3s exceed analgesic expectations

While it is a small, preliminary trial, the results of a new study hold out hope that omega-3s might provide some patients with a viable alternative to NSAIDs.

Surgeons at the University of Pittsburgh Medical Center recruited 250 people who had been seen by a neurosurgeon, were experiencing non-surgical neck or back pain, and were taking an NSAID.

One in four were taking one of the older, “non-selective” class of NSAIDs—such as aspirin, ibuprofen (Advil), or naproxen (Aleve)—which block both the COX-1 and COX-2 enzymes related to inflammation and pain.  The remainder were taking the newer COX-2 inhibitors, such as Celebrex or Vioxx.

They were asked to take fish oil supplements everyday for a month, starting at a dose of 2,400 mg of omega-3s (EPA and DHA) for the first two weeks, then dropping to a dose of 1,200 mg for the subsequent two week period, during which they were told to reduce their NSAID use gradually.

One month after the start of the study, the participants were sent a questionnaire designed to gauge their perception of change in joint and spine pain, any side effects, and to what degree they were able to discontinue using their current NSAIDs.

Half of the participants returned their questionnaires, and the results showed that the fish oil worked very well:

  • 59 percent had discontinued their prescription NSAIDs

  • 60 percent said that their pain was improved

  • 60 percent reported that their joint pain had improved

  • 80 percent were satisfied with their improvement

  • 88 percent said they would continue to take the fish oil

None of the respondents reported significant side effects. The researchers noted that the study is far from conclusive, since it was not placebo controlled and lasted only one month.

However, the results are plausible, since the mechanism of anti-inflammatory (hence, analgesic) action of omega-3 fatty acids is well established. It involves the conversion of the fatty acids into anti-inflammatory members of a family of hormone-like messenger chemicals called prostaglandins.

The positive preliminary results led the study authors to propose that as many as two-thirds of people currently taking NSAIDs could discontinue this use and benefit from omega-3 fatty acids to alleviate pain from inflammation:

“Our results mirror other controlled studies that compared ibuprofen and omega-3 EFAs [essential fatty acids] demonstrating equivalent effect in reducing arthritic pain. Omega-3 EFA fish oil supplements appear to be a safer alternative to NSAIDs for treatment of non-surgical neck or back pain in this selective group.

“That close to two thirds of patients could discontinue NSAIDs is certainly provocative, especially given the recent FDA warnings regarding their complications.”

This study is only a start, but we hope it inspires further research in a larger, well-controlled trial.


  • Maroon JC, Bost JW. Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol. 2006 Apr;65(4):326-31.
  • Belch JJ, Ansell D, Madhok R, O'Dowd A, Sturrock RD. Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann Rheum Dis. 1988 Feb;47(2):96-104.
  • Cryer B. A COX-2-specific inhibitor plus a proton-pump inhibitor: is this a reasonable approach to reduction in NSAIDs' GI toxicity? Am J Gastroenterol. 2006 Apr;101(4):711-3.
  • Cryer B. Gastrointestinal safety of low-dose aspirin. Am J Manag Care. 2002 Dec;8(22 Suppl):S701-8. Review.
  • Cryer B. NSAID-associated deaths: the rise and fall of NSAID-associated GI mortality. Am J Gastroenterol. 2005 Aug;100(8):1694-5.  Morgan RW. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med. 1999 Oct 28;341(18):1397; author reply 1398-9.
  • Harel Z, Gascon G, Riggs S, Vaz R, Brown W, Exil G. Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents. J Adolesc Health. 2002 Aug;31(2):154-61.
  • Kremer JM, Lawrence DA, Petrillo GF, Litts LL, Mullaly PM, Rynes RI, Stocker RP, Parhami N, Greenstein NS, Fuchs BR, et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Arthritis Rheum. 1995 Aug;38(8):1107-14.
  • Lanas A. Prevention and treatment of NSAID-induced gastroduodenal injury. Curr Treat Options Gastroenterol. 2006 Apr;9(2):147-56.
  • Roth SH. Nonsteroidal antiinflammatory drug gastropathy: we started it, why don't we stop it? J Rheumatol. 2005 Jul;32(7):1189-91. Review.
  • Sibilia J, Ravaud P, Marck G. [Risk factors for gastrointestinal bleeding associated with low-dose aspirin] Presse Med. 2003 Nov 22;32(37 Pt 2):S9-16. Review. French.