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Fish Oil: RA Prevention…or Just a Load of Carp?

By: Jay Mehta, MD | March 24, 2016 | What Caught Our Eye

“What about dietary changes?” I’m sure I’m not alone in getting this question more and more frequently with each passing year. It’s interesting that as our drugs get more effective at treating patients, families seem to be more interested in trying to treat with non-pharmacologic means. You may remember the NY Times column “The Boy With a Thorn in His Joints “ from 3 years ago, which set off a bit of a firestorm within our community, about a boy with JIA whose parents tried various alternative and complementary therapies. A rebuttal in Slate discussed the “chemophobia” that is prevalent among our families. TheSlate piece was notable for its comparison of the molecular structure of the “chemical” methotrexate with that of the “natural” four-marvels powder (at the risk of ruining the surprise for you: both are pretty complex).

Much of the interest in dietary interventions relates to omega-3 fatty acids, which are thought to have anti-inflammatory effects. In fact, some work has shown a modest benefit of omega-3 fatty acids on disease activity in rheumatoid arthritis. Unfortunately, no pediatric rheumatologists have been willing to stake their careers on studying this, as a PubMed search for “omega-3 fatty acids and juvenile arthritis” results in exactly 4 publications (one each from Italy, Slovakia, and Egypt. Not sure where the mice from the 4th publication were from). For what it’s worth, the Egyptian study did show some improvement in disease activity, along with lowered cytokine levels, in JIA patients supplemented with 2 grams daily of omega-3 fatty acids.

So, despite the paucity of evidence, let’s presume that there may be some benefit to giving omega-3 fatty acids to our JIA patients and that it’s worth the fish burps that may ensue. A more interesting line of questions starts with what about giving omega-3 fatty acid to people at risk for developing arthritis? Can we prevent them from actually developing the disease? Is there any association between omega-3 fatty acid blood levels and arthritis development? A group led by Jill Norris tried to begin to answer that last question in patients at risk for developing RA in a paper hot off the presses from the Annals of Rheumatic Diseases.

In this paper, they performed two comparisons using subjects at high risk for developing but with no exam evidence of RA in the Studies of the Etiology of RA (SERA) cohort. The first used a nested case-control design to identify associations between red blood cell (RBC) omega-3 fatty acid % and rheumatoid factor and anti-CCP antibodies. The second comparison used the entire SERA cohort to determine whether reported omega-3 fatty acid supplement use was associated with RF and anti-CCP antibodies. They defined subjects as being high risk for developing RA if they had a first-degree relative (FDR) with RA or an FDR with HLA-DR4 (which is an RA risk allele). In looking for these associations, they paid special attention to theshared epitope (SE), which is the strongest genetic predictor of seropositive RA.

What they found was that if a subject was SE-positive, being RF positive was strongly associated with low RBC omega-3 fatty acid % compared with controls. However, this association was not seen for SE-negative subjects. The same was true for anti-CCP; that is, in SE-positive patients, anti-CCP antibody positivity was associated with lower RBC omega-3 fatty acid %.

In the second part of their study, they found that SE-positive subjects who reported using omega-3 supplements were about 1/3 as likely to have positive RF. This effect, again, wasn’t seen in SE-negative subjects. For anti-CCP, the same effect was seen, but the results were not significant.

But what does this all mean for us? After all, very few of our JIA patients have a rheumatoid factor and/or are anti-CCP positive. However, for this subset of patients, there is a strong association with the shared epitope. Because of the known genetic associations, I do counsel families with RF+ polyarticular JIA (probably better described as “childhood-onset RA”) that there is an increased risk of family members to develop arthritis. Should I recommend these families began supplementing their unaffected siblings’ diets with fish oil in the hope of preventing autoantibody development?

Let minnow what you think in the comments…