Fatty Fish Versus Gout: A Potential Winner

But no benefit seen with fish oil sans fish

by Nancy Walsh, Senior Staff Writer, MedPage Today

March 27, 2019

Consumption of omega-3 polyunsaturated fatty acids (n-3 PUFA), which are contained in fatty fish such as salmon, mackerel, and sardines, was associated with a significant decrease in the risk of gout flares, a large online survey found.

Among patients with gout, consuming any quantity of fatty fish in the previous 48 hours lowered the risk of an acute gout attack by 33%, with an adjusted odds ratio of 0.77 (95% CI 0.61-0.96, P=0.02), according to Tuhina Neogi, MD, PhD, of Boston University School of Medicine, and colleagues.

However, risk was not lowered with use of dietary supplements such as fish oil in the previous 48 hours, with an adjusted odds ratio of 1.01 (95% CI 0.63-1.60, P=0.98), the researchers reported online in Arthritis & Rheumatology.

That discrepancy may be explained by the fact that the usual levels of the biologically active n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in commercially available supplements, are “far below that which is required for significant anti-inflammatory effect,” they observed.

Despite the availability of effective treatments for gout, flares of the disease remain common, and additional approaches to prevention and treatment are clearly needed.

Considerable interest exists in the anti-inflammatory properties of n-3 PUFA in other arthritic disorders such as rheumatoid arthritis. “Certain n-3 PUFAs have been shown to have multiple anti-inflammatory effects through rapid and selective inhibition of the NLRP3 inflammasome via G-protein coupled receptors, specifically GPR120 and GPR140 through arrestin-β,” with results such as blocking neutrophil chemotaxis, toll-like receptor activation, and synthesis of prostaglandins, Neogi and colleagues explained.

In contrast, n-6 PUFAs such as linoleic acid and arachidonic acid, which are found in vegetable oils and other animal products, exert pro-inflammatory effects, and the ratio of n-3 to n-6 PUFAs is believed to be critical in triggering inflammation.

Therefore, to explore the potential effects of these dietary factors on the acute inflammation of gout flares, the researchers conducted the Boston University Online Gout Study from 2003 to 2012, enrolling 724 individuals with gout who responded to questionnaires every 3 months and at the time of flares. Details obtained included anatomic location, symptoms, and treatments used, as well as dietary and supplement exposures in the 24 and 48 hours prior to the flare.

The quantity of fatty fish was classified as none, one serving, or two or more 5-oz servings.

The mean age of the participants was 55, and most were obese white men. Fewer than half were on urate-lowering or prophylactic medications. During the 1-year follow-up, there were 1,434 flares.

A total of 22% of patients reported n-3 PUFA consumption within the 48 hours before the acute attack, with 4.6% of these using supplements and the remainder consuming fatty fish.

The risk analysis was adjusted for other dietary factors such as alcohol and purine intake, as well as the use of medications such as allopurinol, nonsteroidal anti-inflammatory drugs, and diuretics.

The researchers noted that for fish consumption, there was a dose-response effect: For a single serving of fatty fish, the adjusted odds ratio of a flare was 0.79 (95% CI 0.61-1.03, P=0.08) compared with no fish consumption, and for two or more servings, the adjusted odds ratio was 0.74 (95% CI 0.54-0.99, P=0.04).

The researchers further examined the potentially negative effects of n-6 PUFAs. Whereas fatty fish have a high n-3:n-6 ratio, consuming foods with a neutral n-3:n-6 ratio such as spinach had no decrease in flare risk (OR 1.19, 95% CI 0.85-1.66) and consuming foods with a low n-3:n-6 ratio such as eggs raised the risk (OR 1.34, 95% CI 1.10-1.63).

In previous studies of n-3 PUFA consumption for rheumatoid arthritis, anti-inflammatory effects were seen with daily doses of at least 3.4 g, which is approximately 10 times higher than what is contained in typical commercial fish oil supplements. The levels of EPA and DHA in fatty fish typically range from 0.7 to 5.6 g per serving, with variations according to the specific type of fish and how it is prepared.

“The results of our study suggest that n-3 PUFA supplements, when administered at adequate doses, may provide a prophylactic effect,” Neogi and co-authors stated. Side effects of high-dose fish oil supplements have been reported to include nausea and loose stools, and while excessive bleeding times have been reported in Inuit populations whose diet is high in n-3 PUFAs, studies have not found risks of bleeding with fish oil supplements, the researchers added.

In fact, they added, dietary supplements might actually be more beneficial than fish consumption, because fatty fish also contain purines, which can trigger gout flares.

“These results provide support for future clinical trials examining n-3 PUFA supplementation at appropriate anti-inflammatory doses for gout flare prevention,” the researchers concluded.

Limitations of the study, the team said, included self-report of dietary exposures and flares and a lack of information about serum urate levels.

LAST UPDATED 03.27.2019