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Effects of n-3 Polyunsaturated Fatty Acids on Glucose Homeostasis and Blood Pressure in Essential Hypertension: A Randomized, Controlled Trial

Ingrid Toft, MD; Kaare H. Bonaa, MD, PhD; Ole C. Ingebretsen, MD, PhD; Arne Nordoy, MD, PhD; and Trond Jenssen, MD, PhD
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From the University of Tromso and Tromso University Hospital, Tromso, Norway. Acknowledgments: The authors thank the staff of the General Clinical Research Centre and thank Jorunn Ekrem, Angstromse Lund Bendiksen, Gro Bolstad, and Hege Iversen for technical assistance. Grant Support: In part by the Norwegian Diabetes Association, Nordic Research Funding, and the Research Council of Norway. Pronova Biocare provided the test medication. Requests for Reprints: Ingrid Toft, MD, Department of Internal Medicine, Tromso University Hospital, N-9038 Tromso, Norway. Current Author Addresses: Drs. Toft, Nordoy, and Jenssen: Department of Internal Medicine, Tromso University Hospital, N-9038 Tromso, Norway. Dr. Bonaa: Institute of Community Medicine, University of Tromso, N-9037 Tromso, Norway. Dr. Ingebretsen: Department of Clinical Chemistry, Tromso University Hospital, N-9038 Tromso, Norway.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;123(12):911-918. doi:10.7326/0003-4819-123-12-199512150-00003
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Objective: To determine whether dietary supplementation with fish oil adversely affects glycemic control in patients with hypertension.

Design: Randomized, double-blind, placebo-controlled study.

Patients: 78 persons with untreated hypertension recruited from a population survey.

Intervention: Participants were randomly assigned to receive eicosapentaenoic and docosahexaenoic acids, 4 g/d, or corn oil placebo, 4 g/d, for 16 weeks.

Measurements: An oral glucose tolerance test; assessments of insulin release, glucose disposal, and insulin sensitivity done using the hyperglycemic clamp technique to keep plasma glucose levels at 10 mmol/L for 180 minutes; assessment of insulin sensitivity done using a euglycemic hyperinsulinemic clamp technique (infusing insulin and glucose to keep plasma glucose levels at 5 mmol/L); assessments of lipid levels and blood pressure. Measurements were done before and after intervention.

Results: Changes in integrated glucose and insulin response after the oral glucose challenge did not differ between the fish oil and corn oil groups after intervention (−0.6 ± 0.7 compared with −1.0 ± 0.6 mmol/L [P > 0.3] for integrated glucose and 143 ± 76 compared with 169 ± 84 pmol/L [P > 0.3] for insulin response). Changes in first-phase insulin release (34 ± 72 pmol/L in the fish oil group compared with 191 ± 112 pmol/L in the corn oil group [P > 0.3]), second-phase insulin release (179 ± 66 pmol/L compared with 257 ± 122 pmol/L [P > 0.3]), and insulin sensitivity index (−0.03 ± 0.01 compared with −0.01 ± 0.01 [µmol/kg · min ÷ pmol/L]; P > 0.3) were also similar in both groups after treatment. Fish oil lowered systolic blood pressure by 3.8 mm Hg more than control (P = 0.04) and lowered diastolic blood pressure by 2.0 mm Hg more than control (P = 0.10). After fish oil treatment, triglyceride levels decreased by 0.28 ± 0.08 mmol/L more than control (P = 0.01), and very-low-density lipoprotein cholesterol levels decreased by 0.13 ± 0.04 mmol/L more than control (P = 0.01).

Conclusion: Fish oil, in doses that reduce blood pressure and lipid levels in hypertensive persons, does not adversely affect glucose metabolism.


Grahic Jump Location
Figure 1.
Change in mean arterial blood pressure during fish oil treatment.

The change in mean arterial pressure during treatment was associated with baseline levels of plasma phospholipid eicosapentaenoic and docosahexaenoic acids.

Grahic Jump Location




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