Omega-3 Fatty Acids Reduce Pain From AIs -- When BMI Is 30 or More

Second Study Suggests Omega-6 Fatty Acids May Be Better

Nick Mulcahy

June 14, 2018

CHICAGO — Omega-3 fatty acids significantly reduced pain among very overweight women who take aromatase inhibitors (AIs) for breast cancer, according to a new retrospective analysis from a major study on the subject.

The findings are potentially good news because, among postmenopausal women with hormone receptor–positive breast cancer, AIs prolong survival but are often discontinued because of arthralgia, including severe pain, said lead author Sherry Shen, MD, from Columbia University Medical Center in New York City, here at the American Society of Clinical Oncology (ASCO) 2108 annual meeting.

The new results come from the SWOG Study S0927, a 24-week randomized controlled trial of omega-3 fatty acids vs placebo for AI-related arthralgia. The original results, which were disappointing, showed no difference in pain reduction between the treatment and placebo groups.

However, the researchers suspected that heavier women were benefitting from the therapy. 

So, in the new study, they divided the women into two groups by their weight. Among the 249 participants, 139 had a body mass (BMI) less than 30 (56%) and 110 had a BMI of 30 or higher (44%).

"The objective of our study was to conduct a post hoc analysis of the patients enrolled in the SWOG Study S0927…and to see whether the effects of omega-3 fatty acids are related to body mass index," said Shen.

She reported that, among patients with a BMI of 30 or greater, once-a-day omega-3 fatty acid use was associated with a 2.89-point decrease in the Brief Pain Inventory (BPI) worst pain score at 24 weeks, which was the study's primary endpoint, compared with only a 1.49-point decrease with placebo use (P = .02). In other words, among the heavier women, the treatment significantly reduced pain vs placebo.

On the other hand, among women with a BMI less than 30, pain scores did not significantly differ between the omega-3 fatty acid and placebo groups (P = .40; interaction P = .05).

Joint-specific symptoms were also significantly lower at 24 weeks (compared to baseline) in the omega-3 fatty acid group  — but only in women with a BMI of 30 or more, said Shen.

Specifically, global change in joint pain was greater with omega-3 fatty acid use compared with placebo for the higher BMI group (0.98 vs 0.48, respectively, P = .05) but not the lower BMI group (0.57 vs 0.50. respectively; P = .80).

"Among nonobese patients, there really were no significant differences seen between the treatment arms," summarized Shen.

At a meeting "highlights of the day" session, Martin Stockler, MD, from the University of Sydney in Australia, said that the investigators gave a "measured" conclusion, which means the study results must be confirmed in a prospective trial in order for omega-3 fatty acids to be fully deemed beneficial. At the moment, the trial is "hypothesis-generating," he said.

Shen explained the appeal of omega-3 fatty acids as a possible treatment. They are inexpensive, are easy to take, and have low adverse events, which are all advantages over other currently proven arthralgia treatments, such as exercise, acupuncture, and the selective serotonin reuptake inhibitor duloxetine, she said.

Currently, nonsteroidal anti-inflammatory drugs are the most commonly used treatment for the joint pain, "but there's little data for their efficacy and they're associated with their own adverse effects of gastrointestinal toxicity and renal failure," she added.

Shen explained why heavier women might benefit from the fish oil supplements, in terms of AI-induced joint pain.

Omega-3 fatty acids are associated with decreased leukocyte chemotaxis, decreased production of reactive oxygen species, and decreased circulating levels of inflammatory cytokines — all of which lead to decreased joint inflammation, she said.

However, obesity is a risk factor for arthralgia and therefore those patients might have a greater need for any benefit generated by a treatment, Shen added. "Obese patients have a greater mechanical load on their joints…they also have increased bone stiffness and density, which can lead to cartilage breakdown. And obese patients have higher levels of systemic inflammation with higher levels of circulating leptin and inflammatory cytokines like IL1 [interleukin 1] and TNF [tumor necrosis factor] alpha, which promote local joint inflammation," she said.

"Omega-3 fatty acids are really thought to be targeting the systemic inflammation component here," she summarized.

Another Study on AI Pain and Omega-3 Fatty Acids

In a second study here, researchers reported that daily omega-6 fatty acid (soybean oil; high-dose) supplementation more effectively reduced pain levels compared with daily omega-3 fatty acid (fish oil; low- and high-dose) supplementation in breast cancer survivors.

The study was a multisite, blinded phase 2 randomized clinical trial examining the efficacy of the two agents for improving pain among 108 women receiving hormonal therapies, such as AIs and tamoxifen. Pain was assessed via the BPI before and after the intervention, which lasted 6 weeks.

The mean worst pain score did not significantly differ between the treatment groups, but the mean change in current pain score was more pronounced, indicating superiority with the higher doses, including that of omega-6 fatty acid. The researchers, led by Luke Joseph Peppone, MD, from the University of Rochester Medical Center in New York, called for further research on the effects of omega-6 fatty acid in patients with cancer.

University of Sydney's Stockler said that the supplements are worth trying because they are not harmful, but more data are needed to make any formal recommendation about use.

The SWOG study was funded by the National Cancer Institute. Multiple SWOG study authors have financial ties to the pharmaceutical industry. The second study's fatty acids were provided by Nordic Naturals. The study authors have disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2018. Presented June 3, 2018. Abstracts 10000 and 10118

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