Omega-3 & Lipid Membrane Health — References

Mirrored Reference Dossier

Parent Topic: Omega-3 & Lipid Membrane Health | References Hub: 02 - Compounds & Molecules References MOC

Landmark Peer-Reviewed Studies

Citation: Harris, W. S., & Von Schacky, C. (2004). The Omega-3 Index: a new risk factor for death from coronary heart disease? Preventive Medicine, 39(1), 212–220.
Identifiers: PMID: 15208005 (PubMed · Europe PMC) | DOI: 10.1016/j.ypmed.2004.02.030 (DOI · SciDB · Scholar)
Study Design & Sample Size: Prospective biomarker validation and clinical meta-synthesis across epidemiological cohorts and randomized intervention trials.
Key Quantitative Outcomes: Defined the Omega-3 Index as the percentage of EPA + DHA in erythrocyte cell membranes. Demonstrated that an Omega-3 Index $\geq 8%$ confers the highest cardioprotection (associated with up to a $90%$ relative risk reduction for sudden cardiac death compared to an Omega-3 Index $\leq 4%$ ), with erythrocyte EPA+DHA correlating strongly with human myocardial tissue EPA+DHA ( $r = 0.81, p < 0.001$ ).

Citation: Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., Tardif, J. C., & Ballantyne, C. M. (2019). Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. New England Journal of Medicine, 380(1), 11–22.
Identifiers: PMID: 30415628 (PubMed · Europe PMC) | DOI: 10.1056/NEJMoa1812792 (DOI · SciDB · Scholar)
Study Design & Sample Size: Multicenter, randomized, double-blind, placebo-controlled trial ( $N = 8, 179$ , median follow-up $4.9 years$ ) in statin-treated patients with elevated triglycerides ( $135 - 499 mg/dL$ ).
Key Quantitative Outcomes: $4 g/day$ purified EPA (icosapent ethyl, $2 g$ twice daily) reduced the primary composite endpoint of cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina by $- 25%$ ( $17.2%$ vs. $22.0%$ ; $HR 0.75, 95% CI 0.68 - 0.83, p < 0.001$ ), reduced cardiovascular death by $- 20%$ ( $HR 0.80, p = 0.03$ ), and lowered median triglycerides by $- 18.3%$ ( $p < 0.001$ ).

Citation: Dyerberg, J., Madsen, P., Møller, J. M., Aardestrup, I., & Schmidt, E. B. (2010). Bioavailability of marine n-3 fatty acid formulations. Prostaglandins, Leukotrienes and Essential Fatty Acids, 83(3), 137–141.
Identifiers: PMID: 20638827 (PubMed · Europe PMC) | DOI: 10.1016/j.plefa.2010.06.007 (DOI · SciDB · Scholar)
Study Design & Sample Size: Double-blind, randomized, parallel-group bioavailability trial in healthy human subjects ( $N = 72$ ) comparing equal doses ( $3.1 - 3.6 g/day$ EPA+DHA for 2 weeks) across re-esterified triglycerides (rTG), ethyl esters (EE), free fatty acids (FFA), fish body oil, cod liver oil, and krill oil.
Key Quantitative Outcomes: Re-esterified triglycerides (rTG) demonstrated the highest relative bioavailability at $124%$ compared to natural fish oil ( $100%$ ), whereas ethyl esters (EE) demonstrated the lowest bioavailability at $73%$ ( $p < 0.0001$ ), giving rTG a $+ 70%$ superior systemic incorporation over EE.

Citation: Serhan, C. N. (2014). Pro-resolving lipid mediators are leads for resolution physiology. Nature, 510(7503), 92–101.
Identifiers: PMID: 24899309 (PubMed · Europe PMC) | DOI: 10.1038/nature13479 (DOI · SciDB · Scholar)
Study Design & Sample Size: Foundational biochemical and lipidomic mechanistic synthesis of specialized pro-resolving mediators (SPMs).
Key Quantitative Outcomes: Characterized stereospecific enzymatic conversion of EPA and DHA via 15-LOX, 5-LOX, and acetylated COX-2 into picogram-to-nanogram active mediators (Resolvins RvE1/RvD1/RvD2, Protectin D1, Maresin 1) that act at GPCRs (ChemR23, GPR32, ALX/FPR2) with $EC_{50}$ values in the $1 - 10 nM$ range to halt polymorphonuclear neutrophil transmigration and accelerate tissue repair without immunosuppression.