Association of very high intakes of Fish Oil and Chronic Disease Risk

Associations of very high intakes of eicosapentaenoic and docosahexaenoic acids with biomarkers of chronic disease risk among Yup’ik Eskimos1,2,3,4
Zeina Makhoul, Alan R Kristal, Roman Gulati, Bret Luick, Andrea Bersamin, Bert Boyer and Gerald V Mohatt

1 From the Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA (ZM ARKRG)the Center for Alaska Native Health Research Institute of Arctic Biology University of Alaska-Fairbanks Fairbanks AK (BL AB BBGVM).

2 The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Research Resources, the National, or the National Science Foundation.

3 Supported by a Centers for Biomedical Research Excellence grant (P20 RR16430) from the National Center for Research Resources, a component of the National Institutes of Health.

4 Address correspondence to Z Makhoul, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M4-B402, PO Box 19024, Seattle, WA 98109-4433. E-mail:

Background: Few studies have examined the associations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with biomarkers of chronic disease risk in populations with high intakes.

Objective: We examined the associations of red blood cell (RBC) EPA and DHA, as percentages of total fatty acids, with biomarkers of chronic disease risk across a wide range of EPA and DHA intakes.

Design: In a cross-sectional study of 357 Yup’ik Eskimos, generalized additive models were used to plot covariate-adjusted associations of EPA and DHA with chronic disease biomarkers. Linear regression models were used to test for the statistical significance of these associations.

Results: Means (5th–95th percentiles) for RBC EPA and DHA were 2.8% (0.5–5.9%) and 6.8% (3.3–9.0%), respectively. Associations of EPA and DHA were inverse and linear for triglycerides (β ± SE = –0.10 ± 0.01 and –0.05 ± 0.01, respectively) and positive and linear for HDL cholesterol (β ± SE = 2.0 ± 0.5 and 0.9 ± 0.6, respectively) and apolipoprotein A-I (β ± SE = 2.6 ± 0.8 and 1.7 ± 0.8, respectively). Positive linear associations of DHA with LDL and total cholesterol (β ± SE = 7.5 ± 1.4 and 6.80 ± 1.57, respectively) were observed; for EPA, these associations were nonlinear and restricted to concentrations {approx}3% of total fatty acids; for DHA, it was observed only at concentrations {approx}>7% of total fatty acids.

Conclusion: Increasing EPA and DHA intakes to amounts well above those consumed by the general US population may have strong beneficial effects on chronic disease risk.

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