Rheumatoid Arthritis and Omega-3 Fatty Acids: Decades of Studies Yield No Clear Answer

According to a report from the National Center for Health Statistics, fish oil is the most popular supplement taken by US adults.¹ Fish oil contains omega-3, a group of essential polyunsaturated fatty acids (FAs) studied for everything from cardiovascular disease to cancer to diabetes to arthritis.²

In an interview with Rheumatology Advisor, Sara Tedeschi, MD, MPH, a rheumatologist at Harvard Medical School and Brigham and Women’s Hospital in Boston, explained that research interest in omega-3 stems from its anti-inflammatory effects. “It has been recognized for decades that omega-3 [FAs] decrease the production of pro-inflammatory cytokines,” she said.

Omega-3 FAs consist of 2 main types: long-chain and short-chain. Long-chain FAs include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are derived from marine animals such as fish, seals, mussels, and krill. The primary short-chain omega-3 FA is alpha-linolenic acid, a plant-based FA derived from seeds, nuts, and vegetable oil, which Dr Tedeschi said is only “partially converted to EPA and DHA after ingestion.” The body’s inefficiency at converting alpha-linolenic acid is why omega-3 supplements typically use marine oil, a direct source of EPA and DHA.

Studies of Omega-3 Supplementation for Rheumatoid Arthritis Symptoms

Because rheumatoid arthritis (RA) is characterized by chronic inflammation, it is not surprising that researchers have long been interested in whether omega-3 supplements can improve RA symptoms. In a review article, Dr Tedeschi and associate Karen Costenbader, MD, MPH, also from Brigham and Women’s Hospital, called omega-3 FAs “the most thoroughly studied potential dietary therapy for RA.”³ Dr Tedeschi confirmed that “a number of clinical trials have studied omega-3 FA supplementation vs placebo in RA patients and demonstrated benefits, including decreased tender and swollen joint counts and less failure of concurrent triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine.”

Other randomized trials of omega-3 supplementation in RA have reported reductions in the duration of morning stiffness, time to fatigue, and use of nonsteroidal anti-inflammatory drugs.⁴ In 2015, Proudman et al published results from a 1-year randomized controlled trial of high-dose vs low-dose fish oil supplementation in patients with newly diagnosed RA that associated higher levels of plasma phospholipid EPA and DHA with a significantly greater likelihood of achieving remission per American College of Rheumatology criteria (but not disease activity score of 28 joints [DAS28] remission).⁵

Recently, an international team of scientists from Denmark, the United States, and Canada conducted a systematic review and meta-analysis to quantify the effects of marine oil supplementation in arthritides.⁶ After an exhaustive literature search, they identified 42 randomized trials eligible for inclusion. The primary outcome was pain, and secondary outcomes were function and inflammation in patients with RA, osteoarthritis, or other types of arthritis.

The meta-analysis for pain in RA included 22 trials. Coauthor Sabrina Mai Nielsen, MS, from the Parker Institute, Copenhagen University Hospital, Frederiksberg, Denmark, told Rheumatology Advisor that the research team found “moderate quality of evidence for our effect estimate on pain, indicating [marine oil had] a favorable effect in RA patients.”⁶ She emphasized that the effect was small and that they could not say for certain whether it was clinically meaningful. In addition, whereas marine oil had no effect on function in patients with RA, it significantly improved inflammation.⁶ The authors cautioned that most trials they reviewed had serious limitations and possible biases, which Nielsen said undermined the team’s confidence in the effect estimates.