Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil

Olano-Martin, Estibaliz; Anil, Eliz; Caslake, Muriel J.; Packard, Chris J.; Bedford, Dorothy; Stewart, Grace; Peiris, Dammika; Williams, Christine M.; Minihane, Anne M.

doi:10.1016/j.atherosclerosis.2009.08.024

Cited by 83Fatty Acid Research and HealthLipoproteins and Cardiovascular HealthNutrition, Genetics, and Disease

Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil

Olano-Martin, Estibaliz, Anil, Eliz, Caslake, Muriel J., Packard, Chris J., Bedford, Dorothy, Stewart, Grace, Peiris, Dammika, Williams, Christine M. +1 more·2010·Atherosclerosis

DOI 10.1016/j.atherosclerosis.2009.08.024

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Abstract

Objectives 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.Methods and results 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 x 4 week intervention arms of either control oil, EPA-rich oil (ERO, 3.3g EPA/day) or DHA-rich oil (DRO, 3.7g 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 x 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, VLDL(2) fractions obtained from E3/E4 individuals resulted in a significant 32% (P=0.002) reduction in LDL uptake relative to the control.Conclusions 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.

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A greater conversion of VLDL to LDL occurs in APOE4 carriers, as shown in kinetic studies.
“Another likely explanation for the increase in LDL-C in APOE4 carriers is a greater conversion of VLDL to LDL, which has been shown to occur in APOE4 carriers in kinetic studies [60].”
From Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review (2017) · cites this paper as [60]

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Effect of sex and genotype on cardiovascular biomarker response to fish oils
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Effect of a Novel Eicosapentaenoic Acid‐Rich Oil on Serum Cholesterol in Man: Comparison to Docosahexaenoic Acid
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Authors: Olano-Martin, E., Anil, E., Caslake, M. J., Packard, C. J., Bedford, D., Stewart, G., Peiris, D., Williams, C. M., & Minihane, A. M.
Affiliations: University of Reading (GB)
Glasgow Royal Infirmary (GB)
Corresponding author: Minihane, Anne M.
ORCID: Packard, Chris J.
Minihane, Anne M.
Venue: Atherosclerosis
Publisher: Elsevier BV
Published: 2010-03
Volume: 209
Issue: 1
Pages: 104-110
ISSN: 0021-9150 (ISSN-L)
DOI: 10.1016/j.atherosclerosis.2009.08.024
OpenAlex: W1987968562
Cited by: 83
References: 40
Citations by year: 2025: 2 · 2024: 1 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 7 · 2017: 8 · 2016: 7 · 2015: 5 · 2014: 8 · 2013: 12 · 2012: 8
FWCI: 5.49
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Atherosclerosis (publishedVersion)
PubMed (publishedVersion)
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
UEA Digital Repository (University of East Anglia) (submittedVersion)
Funders: Biological Sciences Research Council (BBSRC), UK
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Keywords: APOE genotype, docosahexaenoic acid, eicosapentaenoic acid, fish oil supplementation, LDL cholesterol, serum lipoproteins, triglycerides, total cholesterol, genotype × treatment interaction, cardioprotection
MeSH terms: Adolescent, Adult, Aged, Apolipoproteins E, Cell Line, Docosahexaenoic Acids, Fish Oils, Genotype, Humans, Cholesterol, LDL, Male, Middle Aged, Eicosapentaenoic Acid, Cholesterol, VLDL, Young Adult

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Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil

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