No Evidence of Anti-Inflammatory Mediator Increase From Fish Oil Ingestion

Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of PennsylvaniaMedicalResearch.com Interview with:
Carsten C. Skarke MD
Research Assistant Professor of Medicine
McNeil Fellow in Translational Medicine
Institute for Translational Medicine and Therapeutics
Perelman School of Medicine
University of Pennsylvania

Medical Research: What is the background for this study? What are the main findings?

Dr. Skarke: A growing body of publications suggests anti-inflammatory actions of fish oils. These health benefits are proposed to emerge from lipids called specialized pro-resolving mediators, (SPMs), which can be formed from omega-3 polyunsaturated fatty acids found in fish. A limitation to date, though, in this field is that there is little evidence of their formation in humans. And the cases where presence of these lipids is reported in humans, less rigorous analytical approaches, such as enzyme immunoassay (EIA), radioimmunoassay (RIA) or mass spectrometry without internal authentic standards, have been used. Thus, the specific aim for our study was to use state-of-the-art mass spectrometry to identify and quantify these specialized pro-resolving mediators.

Several aspects of our study design set us apart from what was done in previous studies.

  • First, we biased our ability to detect SPMs formed in healthy volunteers by giving fish oil in high doses which had been previously shown to influence blood pressure and platelet aggregation under placebo-controlled conditions.
  • Second, we also looked at lower doses of fish oil, those more commonly consumed by the general public, for the formation of SPMs during an acute inflammatory response and its resolution.
  • Third, we relied in our measurements of SPMs on authentic internal standards. These deuterated lipids, d4-resolvin E1 for example, facilitate distinct identification of the naturally formed lipid.
  • And fourth, we achieved very low limit of detection levels, below 10 pg/ml for resolvin E1, for example.

The surprising finding of our studies is that we failed to detect a consistent signal of SPM formation in urine or plasma of healthy volunteers who had taken fish oil. Even more surprising was that we found no alteration in the formation of SPMs during the resolution of inflammation. These results let us question the relevance of endogenous specialized pro-resolving mediators to the putative anti-inflammatory effects of fish oils in humans.

Medical Research: What should clinicians and patients take away from your report?

Dr. Skarke: Our study provides no evidence supporting the role of SPMs in mediating an anti-inflammatory action of fish oil. Thus, we invite both clinician and patient to treat this supposed mechanism of benefit from fish oils with a healthy amount of curiosity and to take our studies as an opportunity to revisit the reasons why fish oil is prescribed or taken.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Skarke: Despite the substantial interest of the research and patient communities in the field of SPMs, it is noteworthy that the community has been slow in adopting authentic internal standards for unbiased analytical methods such as mass spectrometry. The family of lipids with a suggested link to inflammation and its resolution is growing fast. Corresponding authentic internal standards need to be developed promptly with analytical methods refined. All of this needs to get disseminated broadly in the research community. These are not trivial endeavors. Hopefully, to give these developments more momentum, the funding agencies, foremost NIH, decide to incentivize such efforts. Less rigorous analytical approaches have been quantitatively misleading in the past in the much more developed, but closely related, field of prostaglandin measurements.

Citation:

J Lipid Res. 2015 Jul 15. pii: jlr.M060392. [Epub ahead of print]

Bioactive products formed in humans from fish oils.

Skarke C1, Alamuddin N2, Lawson JA2, Ferguson JF2, Reilly MP2, FitzGerald GA2.

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Our study provides no evidence supporting the role of SPMs in mediating an anti-inflammatory action of fish oil. (2015). No Evidence of Anti-Inflammatory Mediators From Fish Oil Ingestion MedicalResearch.com

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