Study: Omega-3 Levels May Play Causal Role in SLE

A new study probing the causes of polyunsaturated fatty acids (PUFAs) in patients with systemic lupus erythematosus (SLE) has found a potentially causal relationship between omega-3 fatty acid levels and risk of the disease.

SLE is believed to be caused by a combination of genetic and environmental factors. However, although several associations have been found that appear to affect the risk of SLE, investigators have yet to zero in on which genetic associations might specifically trigger the disease.

One area of investigation is nutrition. PUFAs can be divided into omega-3 and omega-6 fatty acids. The former has been shown to have anti-inflammatory properties that can benefit patients with rheumatic diseases, and the latter was shown in a mouse model of SLE to increase autoantibodies and cause proteinuria and glomerulonephritis.

In the new study published in Frontiers in Nutrition, the team of investigators incorporated Mendelian randomization (MR) to evaluate potential causal relationships between omega-3 and omega-6 PUFAs and SLE.

They used genome-wide association studies of circulating omega-3 and omega-6 levels in order to obtain single-nucleotide polymorphisms to analyze and conducted a genome-wide meta-analysis of SLE, the latter of which involved more than 5000 cases and 9000 controls. They then performed 2-sample MR, which is designed to replicate the objectivity of a randomized controlled trial, in order to estimate genetic effects and causal correlations.

Using the inverse-variance weighted method, the investigators’ analysis showed that increases in omega-3 levels appeared to be causally linked with an increased risk for SLE, (odds ratio [OR], 1.49, 95% CI, 1.07-2.08; P = .021). Omega-6, on the other hand, had no such causal relationship. (OR, 1.06, 95% CI, 0.72-1.57; P = .759)

The authors also could not find any significant causal associations in genetic predisposition to SLE with changes in omega-3 and omega-6 levels, which they say differs from some previous studies—although they posited a couple of possible reasons for the change.

“First, the levels of omega-3 and omega-6 in the current study were defined as circulating metabolites, while omega-3 in previous studies was used as supplements,” they said. “The supplements of omega-3 could not be equal to the circulating omega-3 levels, and it may cause the contrasting associations with SLE.”

In addition, they said their MR study looked at the lifetime effects of the single-nucleotide polymorphisms, while other studies have focused on short periods of time.

The investigators noted a few limitations to their research: They did not have the data necessary to stratify risk by age or sex; their study was based on people of European ancestry, and thus may not reflect associations in other popoulations; and quality control methods varied between individual genome-wide association studies.

Nonetheless, the investigators said they appear to have hit on a possible culprit in the pathogenesis of SLE that warrants more investigation.

“Our findings provided the evidence that omega-3 might increase the risk for SLE, which would be insightful for the current dietary fish oil supplements,” they said, noting that fish oil supplements are often used to boost omega-3. “However, due to the study limitations, further large-scale studies or longitudinal studies are required to validate this finding.”

Reference

Wang P, Xiang K, Xu Y-Y, et al. Genetically predicted circulating omega-3 fatty acids levels are causally associated with increased risk for systemic lupus erythematosus. Front Nutr. Published online February 9, 2022. doi:10.3389/fnut.2022.783338