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Ann Pharmacother. 2007 Jul;41(7):1296-300. Epub 2007 Jul 3.

Elevation of low-density lipoprotein cholesterol concentration with over-the-counter fish oil supplementation.

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Nesbitt School of Pharmacy and Nursing, Wilkes University, Wilkes-Barre, PA 18766, USA.



To report a case of elevated low-density lipoprotein cholesterol (LDL-C) concentration in a patient taking fish oil supplements for hypertriglyceridemia.


A 63-year-old white woman had been taking 2.7 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily in 9 g of over-the-counter (OTC) fish oil capsules for triglyceride lowering. Prior to the adverse event, she had baseline fasting triglyceride (TG) and LDL-C concentrations of 278 mg/dL and 106 mg/dL, respectively. After 6 weeks of treatment with fish oil, fasting TG levels decreased by 47.5% (-132 mg/dL) and the LDL-C increased by 75% (+80 mg/dL). Discontinuation of therapy for 6 weeks resulted in TG returning to high concentrations (334 mg/dL; +56 mg/dL change from baseline) and LDL-C decreasing toward baseline (143 mg/dL; +37 mg/dL change from baseline).


Fish oil, an omega-3 polyunsaturated fatty acid, consists of EPA and DHA. EPA and DHA are thought to inhibit the synthesis of triglycerides in the liver. Type IV dyslipidemic patients may develop increased LDL-C levels while taking fish oil to lower triglycerides due to possible down-regulation of the LDL-C receptor in hepatic cells and formation of larger LDL particles. Use of the Naranjo probability scale indicates a probable relationship between elevations in LDL-C from baseline and initiation of fish oil treatment for hypertriglyceridemia. It is unknown whether any component within this particular product could have contributed to such an unusual elevation in LDL-C.


This case documents a much higher LDL-C elevation associated with OTC fish oil supplementation than has been previously identified in the literature. Healthcare providers should be advised that LDL-C levels may increase with use of OTC fish oil and should monitor patients periodically for such elevations. The significance of this increase on clinical outcomes is not known.

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