Highlights
- •Fish oil supplements contain omega-3 fatty acids from which specialized pro-resolving mediators (SPM) are derived, including resolvins, protectins, and maresins. These have potential as therapy for human rheumatic inflammatory disease, however, little is known about the effect of fish oil supplementation on SPM blood levels in rheumatoid arthritis patients. But, previous research has shown that fish oil supplementation is associated with a lower risk of RA. Thus, we investigated associations between over-the-counter omega-3 fatty acid FO supplementation and circulating SPMs among patients with and without RA.
- •Among all patients, both with and without RA, oral over-the-counter fish oil supplementation was associated with higher blood levels of pro-resolving lipid mediators including 17-HDHA (from DHA) and 15- and 18-HEPE (from EPA), precursors of both protectins and resolvins.
- •RA patients have the ability to augment their SPM precursor reserves, which may be important in resolving RA inflammation.
Abstract
Objective
Little is known about the effects of over-the-counter fish oil (FO) supplements on
circulating omega-3 polyunsaturated fatty acid (n-3 PUFA)-derived specialized pro-resolving
mediators (SPMs), nor about whether having a chronic inflammatory disease such as
rheumatoid arthritis (RA) influences SPM levels. We investigated associations between
over-the-counter n-3 PUFA FO supplementation and circulating SPMs among patients with
vs. without RA.
Methods
We studied 104 participants: 26 with RA taking FO matched by age and sex to 26 with
RA not taking FO, 26 without RA taking FO, and 26 without RA not taking FO. Targeted-liquid
chromatography-tandem mass spectroscopy was performed on patient plasma to identify
and quantify 27 lipid mediators (including eicosanoids and SPMs). We performed t-tests
and then multivariable linear regression analyses to assess whether having RA or taking
FO supplements was associated with circulating lipid mediator concentrations, adjusting
for age, race, sex, smoking, body mass index, and current medication use (statins,
prednisone and immunomodulators among RA cases only). We tested for interactions between
FO supplementation and RA status. We also conducted Spearman's correlations between
EPA, DHA, and ARA and their downstream metabolites.
Results
Among patients who were taking FO compared to those who were not, in multivariable-
adjusted analyses, SPM substrates EPA and DHA were both elevated as were several of
their pro-resolving bioactive products, including 15- and 18-HEPE from EPA, and 14-
and 17-HDHA from DHA, which are substrates for specific SPMs. While E-series and D-series
resolvins were present and identified, we did not find statistical elevations of other
SPMs. Results were similar among patients with RA and patients without RA, taking
vs. not taking FO supplementation (no formal statistical interaction observed). There
was a strong positive correlation between EPA and DHA and their immediate downstream
SPM precursors (18-HEPE and15-HEPE from EPA; 17-HDHA and 14-HDHA from DHA) among all
patients.
Conclusion
Patients taking FO supplements, regardless of RA status, not only had higher blood
levels of EPA and DHA, but also of their enzymatic products 18-HEPE (E-series resolvin
precursors), 15-HEPE and 17-HDHA (D-series resolvin and protectin precursors). Patients
with RA, an inflammatory autoimmune disease, may be able to augment some SPM precursor
reserves, similarly to matched controls without RA, by taking oral FO supplements.
Keywords
Abbreviations:
ARA (Arachidonic acid), EPA (Eicosapentaenoic acid), DHA (Docosahexaenoic acid), LTB4 (Leukotriene B4), LXA4 (Lipoxin A4), LXB4 (Lipoxin B4), Mar1 and Mar2 (Maresin 1 and Maresin 2), PGD2 (Prostaglandin D2), PGE2 (Prostaglandin E2), PGF2a (Prostaglandin F2 alpha), TXB2 (Thromboxane B2), PD1 (Protectin D1), RA (Rheumatoid arthritis), RvD1, RvD2, RvD3, RvD4, RvD5, and RvD6 (D-series resolvins), RvE1, RvE2, RvE3, and RvE4 (E-series resolvins), 14-HDHA (14-hydroxy-docosahexaenoic acid), 15-HEPE (15-hydroxyeicosapentaenoic acid), 17-HDHA (17-hydroxy-docosahexaenoic acid), 18-HEPE (18-hydroxyeicosapentaenoic acid)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 25, 2023
Accepted:
January 22,
2023
Received in revised form:
January 17,
2023
Received:
October 8,
2022
Identification
Copyright
© 2023 Elsevier Ltd. All rights reserved.
