Non-steroidal anti-inflammatory drugs (NSAIDs)

“6 out of 7 studies that examined the effect of long-chain omega-3 fatty acid supplementation on nonsteroidal anti-inflammatory drug (NSAID) or corticosteroid use in rheumatoid arthritis patients demonstrated a reduced requirement for anti-inflammatory medication.” 
-Oregon State University

--> Long term NSAID use can be dangerous... 

Long-term use of NSAIDs, nonsteroidal anti-inflammatory drugs, such as Motrin, Advil, Aleve, Vioxx, Celebrex, and Bextra may result in substantial morbidity and mortality.

According to a paper published in the New England Journal of Medicine:¹

• It has been estimated conservatively that 16,500 NSAID-related deaths occur among patients with rheumatoid arthritis or osteoarthritis every year in the US.

• If deaths from gastrointestinal toxic effects of NSAIDs were tabulated separately in the National Vital Statistics reports, these effects would constitute the 15th most common cause of death in the US, right behind AIDS (14th).

• Furthermore, the mortality statistics do not include deaths ascribed to the use of over-the-counter NSAIDs.

• These toxic effects remain largely a "silent epidemic" with many physicians and most patients unaware of the problem.

• Nearly 75% of those who used NSAIDs regularly were either unaware of or unconcerned about possible gastrointestinal complications.

The paper, written in 1999, concludes, "the development of cyclooxygenase-2-selective inhibitors (COX-2) and the formulation of other new, safer NSAIDs should broaden the range of options."

However, today we now know that these promising "new, safer NSAIDs" such as Vioxx and Bextra have largely been withdrawn from the market due to serious adverse side effects such as increased heart attack and stroke.  In fact, all nonsteroidal anti-inflammatory drugs are under safety review, with additional strong warnings on Celebrex.²

Despite these serious side effects, nonsteroidal anti-inflammatory drugs still represent about $9 billion in annual sales to the US drug industry.  Naturally occurring anti-inflammatory agents, such as Omega-3, are largely not patentable in the U.S.  Perhaps this can explain why drug companies have not paid more attention to natural alternatives despite the substantial clinical data behind some of them.

--> Clinical trials show that Omega-3 can safely reduce NSAID use... 

Clinical trials have repeatedly shown that Omega-3 is a safe and effective alternative to NSAID use.  Below are some of the results and conclusions from these studies.

--> Double-Blind, Placebo-Controlled Study³:

The authors of this double-blind placebo-controlled study, published in the highly regarded peer-reviewed medical journal, Arthritis & Rheumatism, conclude:

"Daily supplementation with 2.6 grams of Omega-3 results in significant clinical benefit and may reduce the need for concomitant antirheumatic medication."

About half of the patients reported decreased use of NSAIDs and DMARDs (disease modifying anti-rheumatic drugs):

The OMAPURE™ formula contains the same dose of EPA (the main anti-inflammatory agent of Omega-3) as this highly successful clinical trial.

The researchers observed no serious side effects.

--> Double-Blind, Placebo-Controlled Study⁴:

The authors of this double-blind placebo-controlled study, published in the peer-reviewed medical journal, Arthritis & Rheumatism, conclude:

"Our results confirm that fish oil dietary supplementation results in significant improvement in tender joint counts and other clinical parameters of disease activity from baseline activity."

Specifically, in regard to NSAID use:

"We believe that our data supports the previous observations that selected individuals with RA may discontinue NSAID therapy while consuming Omega-3 supplements."

The researchers observed no serious side effects.

--> Double-Blind, Placebo-Controlled Study⁵:

The authors of this double-blind placebo-controlled, published in the peer-reviewed medical journal, British Journal of Rheumatology, conclude:

"Our results showed that Maxepa (Omega-3) significantly reduced NSAID requirement with the effect detectable at month 3 reaching its maximum at month 12. It is important to note that despite this reduction there was no deterioration in any of the clinical and laboratory variables of disease activity."

At month 12, NSAID use was reduced to under 50% of the original dose in the active treatment group compared to only 84% in the placebo group:

More than 50% of the patients in the Omega-3 treatment group reported that their rheumatoid arthritis was better at the end of the trial compared with less than 15% from the placebo treatment group:

The researchers observed no serious side effects.

--> Double-Blind, Placebo-Controlled Study⁶:

The authors of this double-blind placebo-controlled, published in the peer-reviewed medical journal, Annals of the Rheumatic Diseases, conclude:

"Results at 12 months showed a significant subjective improvement for EPO (evening primrose oil) and EPO/fish oil compared to placebo.   In addition, by 12 months the patients receiving EPO and EPO/fish oil had significantly reduced their NSAIDs."

Over 90% patients on active treatment felt a subjective improvement in their condition at 12 months:

The researchers observed no serious side effects.

--> Double-Blind, Placebo-Controlled Study⁷:

The authors of this double-blind placebo-controlled, published in the peer-reviewed medical journal, Rheumatology International, investigated the effects of fish oil on subjects taking two different diets (vegetarian diet and Western diet).  The authors conclude:

"Administration of fish oil reduced the disease activity in both groups (vegetarian and Western diet)."

The researchers noted that in patients on fish oil during months 6-8, a significant reduction of NSAID medication was advised by the physician.   The corticosteroid doses were also reduced (at statistically significant levels) after 3 months of treatment on fish oil.

The researchers observed no serious side effects.

--> Clinical Survey⁸:

The authors of this clinical survey, University of Pittsburgh Medical Center neurosurgeons, published in the peer-reviewed medical journal, Surgical Neurology, conclude:

"That close to two thirds of patients could discontinue NSAIDs is certainly provocative, especially given the recent FDA warnings regarding their complications.   The effectiveness of Omega-3 EFAs in rheumatoid and some cases of osteoarthritis has been demonstrated."

The authors also conclude that Omega-3 appear to be a safer alternative to NSAIDs:

"Our results mirror other controlled studies that compared ibuprofen and Omega-3 EFAs demonstrating equivalent effect in reducing arthritic pain.   Omega-3 EFA fish oil supplements appear to be a safer alternative to NSAIDs for treatment of nonsurgical neck or back pain in this selective group."

The researchers observed no serious side effects.

--> Double-Blind, Placebo-Controlled Study⁹:

The authors of this double-blind placebo-controlled, published in the peer-reviewed medical journal, Scandanavian Journal of Rheumatology, conclude:

"We observed that the fish oil patients had less need of NSAID medication both at 3 and 6 months, and that they after 3 months showed improved health status as registered with the physician's assessment of global arthritis activity."

The researchers observed no serious side effects.

--> Omega-3 is a natural and safe anti-inflammatory...

The FDA recognizes Omega-3 as GRAS (generally regarded as safe) up to 3 grams daily.   Clinical trials consistently report no or mild side effects from Omega-3 supplementation.  One recent clinical study comments on the safety of Omega-3:

"The positive human clinical effects of Omega-3 EFAs are now the subject of more than 900 scientific articles, with many showing that Omega-3 EFA fish oil acts as a natural anti-inflammatory and, thus, a possible alternative choice to NSAIDs. This research supports its safe and effective use for many inflammation-related conditions and its low incidence of side effects."⁸

References:

1. Wolfe MM, Lichtenstein DR, Singh G:  Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs.   N Engl J Med  1999 Jun 17;340(24):1888-99 
2. Roth SH:  Nonsteroidal antiinflammatory drug gastropathy: we started it, why don't we stop it? J Rheumatol  2005 Jul;32(7):1189-91. 
3. Geusens P, Wouters C, Nijs J, Jiang Y, Dequeker J:  Long-term effect of n-3 fatty acid supplementation in active rheumatoid arthritis: a 12 month double blind controlled study.  Arthritis Rheum 1994; 37:824-9.  Abstract
4. Kremer JM, Lawrence DA, Petrillo GF, Litts LL, Mullaly PM, Rynes RI, et al: Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs.  Arthritis Rheum 1995 Aug;38(8):1107-14.  Abstract
5. Lau CS, Morley KD, Belch JJ:  Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis--a double-blind placebo controlled study.  Br J Rheumatol 1993 Nov;32(11):982-9.   Abstract
6. 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. Abstract
7. Adam O, Beringer C, Kless T, Lemmen C, Adam A, Wiseman M, Adam P, Klimmek R, Forth W:   Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis.  Rheumatol Int 2003 Jan;23(1):27-36. Abstract
8. 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. Abstract
9. Skoldstam L, Borjesson O, Kjallman A, Seiving B, Akesson B:  Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis.   Scand J Rheumatol 1992;21(4):178-85. Abstract