Olano-Martin, E., Anil, E., Caslake, M.J., Packard, C.J. , Bedford, D., Stewart, G., Peiris, D., Williams, C.M. and Minihane, A.M. (2010) Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil. Atherosclerosis, 209(1), pp. 104-110. (doi: 10.1016/j.atherosclerosis.2009.08.024)
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Abstract
<b>Objectives</b>: To investigate the impact of apolipoprotein E (apoE) genotype on the response of the plasma lipoprotein profile to eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) intervention in humans. <b>Methods and results</b>: 38 healthy normolipidaemic males, prospectively recruited on the basis of apoE genotype (n = 20 E3/E3 and n = 18 E3/E4), completed a double-blind placebo-controlled cross-over trial, consisting of 3 × 4 week intervention arms of either control oil, EPA-rich oil (ERO, 3.3 g EPA/day) or DHA-rich oil (DRO, 3.7 g DHA/day) in random order, separated by 10 week wash-out periods. A significant genotype-independent 28% and 19% reduction in plasma triglycerides in response to ERO and DRO was observed. For total cholesterol (TC), no significant treatment effects were evident; however a significant genotype by treatment interaction emerged (P = 0.045), with a differential response to ERO and DRO in E4 carriers. Although the genotype × treatment interaction for LDL-cholesterol (P = 0.089) did not reach significance, within DRO treatment analysis indicated a 10% increase in LDL (P = 0.029) in E4 carriers with a non-significant 4% reduction in E3/E3 individuals. A genotype-independent increase in LDL mass was observed following DRO intervention (P = 0.018). Competitive uptake studies in HepG2 cells using plasma very low density lipoproteins (VLDL) from the human trial, indicated that following DRO treatment, VLDL2 fractions obtained from E3/E4 individuals resulted in a significant 32% (P = 0.002) reduction in LDL uptake relative to the control. <b>Conclusions</b>: High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers, which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Bedford, Mrs Dorothy and Stewart, Mrs Grace and Caslake, Professor Muriel and Packard, Professor Chris |
| Authors: | Olano-Martin, E., Anil, E., Caslake, M.J., Packard, C.J., Bedford, D., Stewart, G., Peiris, D., Williams, C.M., and Minihane, A.M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences |
| Journal Name: | Atherosclerosis |
| ISSN: | 0021-9150 |
| ISSN (Online): | 1879-1484 |
| Published Online: | 21 August 2009 |
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