Novel Marine Oil Supplement Alters HDL Lipid Mediator Profile

by Lewis Chang, PhD and Annalouise O’Connor, PhD, RD

High-density lipoprotein (HDL) is best known for its ability to carry cholesterol from the blood to the liver for elimination. HDL also facilitates other cardioprotective effects in the body through anti-inflammatory, anti-oxidative, and antithrombotic actions.^1,2 However, for HDL to have these benefits, it needs to be functional. Loss of HDL function, or worse, gain of HDL dysfunction can negatively impact cardiometabolic health.³ In addition to cholesterol, HDL can accumulate other molecules, several of which have been linked to HDL function.^4,5

Researchers from Vascular and Endovascular Surgery at University of California, San Francisco, Brigham and Women’s Hospital, and Harvard Medical School recently conducted a short-term, dose escalation study of a novel marine oil supplement in 6 patients with peripheral arterial disease (PAD) and 6 healthy volunteers.⁶

The study supplement contained fractionated marine lipid concentrate standardized to 18-hydroxyeicosapentaenoic acid (18-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDHA), two lipid mediators that are important in the production of specialized pro-resolving mediators (SPMs), such as resolvins, and in the resolution phase of inflammation.⁷

HDL particles were isolated from blood specimens obtained at baseline and the end of the study, and lipid mediator and inflammatory cytokines profile within the HDL particle were assessed. Therefore, this study offered an opportunity for the researchers to compare HDL profile of these 2 groups of subjects before and after supplement intervention. Specifically, they were interested in whether the profile differed by health status and whether the marine oil supplement might affect the profile.

The investigators found that:⁶

• The HDL lipid mediator profile differed significantly between the two groups at baseline, and was altered in both groups following supplement intervention
• The supplementation led to a significant increase in levels of pro-resolving mediators 15R-lipoxin B₄ and 17-HDHA in the HDL particles
• The HDL cytokine profile differed significantly between the two groups at baseline, but the supplementation did not alter the cytokine profile

These data suggest that PAD is associated with altered cytokine and lipid mediator content in the HDL particles, and a novel marine oil supplementation standardized to 18-HEPE and 17-HDHA may increase the levels of pro-resolving mediators in HDL. Whether these lipid mediators help ameliorate vascular inflammation associated with PAD requires further investigations. However, one previous study linked lipid mediator profile of HDL particles with aspects of its antithrombotic action,⁵ suggesting that modifying the lipid mediator profile of HDL has the potential to support its protective functional effect.

 Why is this Clinically Relevant?

• Accumulating scientific evidence indicates that HDL has anti-inflammatory, anti-oxidative, and anti-thrombotic effects in addition to transporting circulating cholesterol to the liver for elimination^1,2
• This study demonstrated that certain pro-resolving lipid mediators are increased in HDL particles after receiving a novel marine oil supplement⁶
• These lipid mediators transported by HDL particles may represent an important new signaling paradigm in vascular disease that warrants further investigation

Link to abstract

Citations

1. Zhang H, Reilly MP. Anti-inflammatory effects of high-density lipoprotein through activating transcription factor 3: benefit beyond cholesterol transport-dependent processes. Arterioscler Thromb Vasc Biol. 2014;34(6):e11-12.
2. Rosenson RS, Brewer HB, Jr., Ansell BJ, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol. 2016;13(1):48-60.
3. Kontush A, Chapman MJ. Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev. 2006;58(3):342-374.
4. Kajani S, Curley S, McGillicuddy FC. Unravelling HDL—Looking beyond the Cholesterol Surface to the Quality Within. Int J Mol Sci. 2018;19(7):E1971.
5. Garcia C, Montee N, Faccini J, et al. Acute coronary syndrome remodels the antiplatelet aggregation properties of HDL particle subclasses. J Thromb Haemost. 2018;16(5):933-945.
6. Sorrentino TA, Creasy KT, Schaller MS, et al. Abstract 12919: Effects of marine oil supplementation on cytokine and lipid mediator content of HDL in patients with peripheral arterial disease. Circulation. 2018;138(Suppl_1):A12919-A12919.
7. Spite M, Claria J, Serhan CN. Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. Cell Metab. 2014;19(1):21-36.