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LDL cholesterol–raising effect of low-dose docosahexaenoic acid in middle-aged men and women^1,2,3

¹ From the Nutrition Food and Health Research Centre (HET and TABS) and the Department of Clinical Pharmacology, St Thomas’ Hospital, Centre for Cardiovascular Biology and Medicine (PJC), King’s College London, and the Centre for the Genetics of Cardiovascular Disease, British Heart Foundation Laboratories, Royal Free and University College London Medical School (RW and SEH), London.

Background: Long-chain n-3 polyunsaturated fatty acids have variable effects on LDL cholesterol, and the effects of docosahexaenoic acid (DHA) are uncertain.

Objective: The objective of the study was to determine the effect on blood lipids of a daily intake of 0.7 g DHA as triacylglycerol in middle-aged men and women.

Design: Men and women aged 40–65 y (n = 38) underwent a double-blind, randomized, placebo-controlled, crossover trial of treatment with 0.7 g DHA/d for 3 mo.

Results: DHA supplementation increased the DHA concentration in plasma by 76% (P < 0.0001) and the proportion in erythrocyte lipids by 58% (P < 0.0001). Values for serum total cholesterol, LDL cholesterol, and plasma apolipoprotein B concentrations were 4.2% (0.22 mmol/L; P = 0.04), 7.1% (0.23 mmol/L; P = 0.004), and 3.4% (P = 0.03) higher, respectively, with DHA treatment than with placebo. In addition, the LDL cholesterol:apolipoprotein B ratio was 3.1% higher with DHA treatment than with placebo (P = 0.04), which suggested an increase in LDL size. Plasma lathosterol and plant sterol concentrations were unaffected by treatment.

Conclusion: A daily intake of 0.7 g DHA increases LDL cholesterol by 7% in middle-aged men and women. It is suggested that DHA down-regulates the expression of the LDL receptor.

Key Words: Lipids • docosahexaenoic acid • LDL

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