Efficacy of n-3 fatty acid supplementation on rheumatoid arthritis’ disease activity indicators: a systematic review and meta-analysis of randomized placebo-controlled trials

Abstract

Theoretical evidence and previous studies suggest that oralnutrient supplementation (ONS) with n-3 fatty acids for rheumatoid arthritis (RA) has the potential to lower disease activity indicators and non-steroidal anti-inflammatory drug (NSAID) uptake. A systematic search was conducted on five databases/registries from inception until May 23, 2021 with the aim to identify randomized placebo-controlled trials comparing n-3 supplements to placebo on disease-specific outcomes. A total of 23 studies matched the criteria (PROSPERO: CRD42019137041). Pooled analyses revealed that n-3 ONS provided a small effect in reducing pain [standardized mean difference (SMD): −0.16, 95% confidence intervals (CI): −0.40 to 0.09], and tender (SMD: −0.20, 95% CI: −0.46 to 0.05) and swollen joint count (SMD: −0.10, 95% CI: −0.28 to 0.07). In sensitivity analyses, there was a small effect in the reduction of NSAIDs intake (SMD: −0.22, 95% CI: −0.90 to 0.46), and c-reactive protein was reduced only by 0.21 mg/dL (95% CI: −0.75 to 0.33). Similar findings were observed regarding other objective/subjective outcomes. The certainty of the evidence was mostly of “very low/low” quality. Overall, n-3 ONS in RA might have a limited clinical benefit. Previous findings suggesting a reduction in NSAID intake may have been biased from the inadequate blinding of interventions.

Keywords:

• Autoimmune disease
• rheumatic disease
• omega-3 fatty acids
• docosahexaenoic acid
• eicosapentaenoic acid
• EPA
• DHA
• dietary supplements

Acknowledgements

The authors are thankful to Professor Leslie G. Cleland and Professor Surat Komindr for sharing methodological details regarding their randomized clinical trials. Also, authors wish to express their gratitude to: (1) Ms. Anastasia Diolintzi, PhD candidate, Rutgers University–New Brunswick, for her aid during the systematic literature search, (2) Associate Professor Anna-Bettina Haidich, Aristotle University of Thessaloniki, for her statistical suggestions, (3) Dr. Elena Ismyrli, PhD candidate, Aristotle University of Thessaloniki, for her advice in laboratory assessments. A summary of this work was presented as an e-poster at the 3rd Polythematic Panhellenic Congress of Autoimmune Diseases, Rheumatology and Clinical Immunology, 24th–26th September 2021, Nafplio, Greece, receiving a research award.

Authors’ contributions

The authors’ contributions were as follows—KG and DPB: substantial contributions to the conception or design of the work. KG: systematic search, data extraction, data analysis, risk of bias and quality assessment of the included studies, and drafting the manuscript. MGG: data extraction, quality assessment of the included studies, and drafting the manuscript. IM: systematic search and risk of bias assessment of the included studies. TP and EIG: data extraction and interpretation of laboratory parameters. DPB: systematic search. DPB and LIS: risk of bias and quality assessment of studies. All authors: data interpretation; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Disclosure statement

During the study, K.G. and M.G.G. were funded by the Greek World Wild Fund (WWF) for the promotion of sustainable diets. Their individual funding source was unrelated to the present study.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Data availability statement

The data that support the findings of this study are available from the corresponding author, MGG, upon reasonable request.