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Fish Oil Supplementation Does Not Lower Plasma Cholesterol in Men with Hypercholesterolemia: Results of a Randomized, Placebo-Controlled Crossover Study

Timothy J. Wilt, MD; Richard P. Lofgren, MD, MPH; Kristin L. Nichol, MD, MPH; Anna E. Schorer, MD; Lori Crespin, MPH; Deborah Downes, BA, RD; and John Eckfeldt, MD, PhD
[+] Article and Author Information

Grant Support: Supported in part by grant 0325-2423-15 from the Graduate School of the University of Minnesota and by a special grant award from the Minnesota Medical Foundation.

Requests for Reprints: Timothy J. Wilt, MD, Minneapolis Veterans Administration Medical Center (111-0), 1 Veterans Drive, Minneapolis, MN 55417.

Current Author Addresses: Drs. Wilt, Nichol, and Schorer and Ms. Crespin and Mrs. Downes: Minneapolis Veterans Administration Medical Center, 1 Veterans Drive, Minneapolis, MN 55417.

Dr. Lofgren: University of Pittsburgh, Veterans Administration Medical Center (Oakland) (11G), University Drive C, Pittsburgh, PA 15240.

Dr. Eckfeldt: Box 198 University of Minnesota Health Center, Laboratory Medicine and Pathology, Harvard Street at East River Road, Minneapolis, MN 55455.


Ann Intern Med. 1989;111(11):900-905. doi:10.7326/0003-4819-111-11-900
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Study Objective: To determine the effects of fish oil supplementation on plasma cholesterol in middle-aged men with isolated hypercholesterolemia.

Design: Randomized double-blind placebo-controlled (safflower oil) two-period crossover trial with 12-week treatment periods.

Setting: Outpatient general medicine clinic at a university-affiliated Veterans Affairs hospital.

Patients: Thirty-eight men with plasma cholesterol between 5.68 and 7.76 mmol/L (220 to 300 mg/dL), triglyceride levels less than 3.39 mmol/L (300 mg/dL), and free of coexisting diseases.

Interventions: Fish oil and placebo (safflower oil) supplementation. After basal measurements and a 4-week lead-in period, twenty 1-g capsules of either fish oil or placebo oil were provided for 12 weeks (period 1). After a 4-week washout phase participants then received the other oil for an additional 12 weeks (period 2).

Measurements and Main Results: Blood was drawn at the beginning and end of each study period and analyzed for levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1, and apolipo-protein B. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. Total and LDL cholesterol increased from the before treatment values by 4.8% and 9.1%, respectively, after ingestion of fish oil. Compared with placebo, LDL cholesterol was significantly higher (4.5 compared with 4.1 mmol/L, P = 0.01) and triglycerides lower (1.3 compared with 1.8 mmol/L, P = 0.01) after fish oil. Total and HDL cholesterol and apolipoprotein A1 and B levels did not differ.

Conclusions: Fish oil supplements do not lower plasma cholesterol levels in middle-aged men with hypercholesterolemia without elevated triglycerides. They should not be recommended as a method to lower plasma cholesterol in these patients.

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