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ApoE Polymorphism and Fish Oil Supplementation in Subjects With an Atherogenic Lipoprotein Phenotype
Open accessAbstract
Abstract —The study assessed the efficacy of fish oil supplementation in counteracting the classic dyslipidemia of the atherogenic lipoprotein phenotype (ALP). In addition, the impact of the common apolipoprotein E (apoE) polymorphism on the fasting and postprandial lipid profile and on responsiveness to the dietary intervention was established. Fifty-five ALP males (aged 34 to 69 years, body mass index 22 to 35 kg/m 2 , triglyceride [TG] levels 1.5 to 4.0 mmol/L, high density lipoprotein cholesterol [HDL-C] <1.1 mmol/l, and percent low density lipoprotein [LDL]-3 >40% total LDL) completed a randomized placebo-controlled crossover trial of fish oil (3.0 g eicosapentaenoic acid/docosahexaenoic acid per day) and placebo (olive oil) capsules with the 6-week treatment arms separated by a 12-week washout period. In addition to fasting blood samples, at the end of each intervention arm, a postprandial assessment of lipid metabolism was carried out. Fish oil supplementation resulted in a reduction in fasting TG level of 35% ( P <0.001), in postprandial TG response of 26% (TG area under the curve, P <0.001), and in percent LDL-3 of 26% ( P <0.05). However, no change in HDL-C levels was evident ( P =0.752). ANCOVA showed that baseline HDL-C levels were significantly lower in apoE4 carriers ( P =0.035). The apoE genotype also had a striking impact on lipid responses to fish oil intervention. Individuals with an apoE2 allele displayed a marked reduction in postprandial incremental TG response (TG incremental area under the curve, P =0.023) and a trend toward an increase in lipoprotein lipase activity relative to non-E2 carriers. In apoE4 individuals, a significant increase in total cholesterol and a trend toward a reduction in HDL-C relative to the common homozygous E3/E3 profile was evident. Our data demonstrate the efficacy of fish oil fatty acids in counteracting the proatherogenic lipid profile of the ALP but also that the apoE genotype influences responsiveness to this dietary treatment.
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“Although most trials presented in Table 4 specified direct LDL-C measurement in cases when triglycerides >400 mg/dL (as is standard for clinical practice), only 3 trials reported LDL-C results obtained from direct LDL measurement throughout the triglyceride range.28,30,45”
From Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association (2019) · cites this paper as [45]
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“On average, the triglyceride reduction was ≈27% (range, 21%-35%), apart from the study of a medical food (3.2 g/d EPA+DHA), which specifically recruited people with very low blood levels of n-3 FA and reported a 48% reduction.”
From Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association (2019) · cites this paper as [45]
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“Total cholesterol levels increased in APOE4 carriers and, although not statistically significant, LDL-C levels tended to increase more in APOE4 carriers than in APOE2 or APOE3 carriers following OM3FA treatment.”
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“However, small dense LDL levels decreased similarly in the different APOE genotypes [59].”
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“Minihane et al. were the first to show that the effect of OM3FAs on LDL was dependent on APOE genotype [59].”
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Metadata
- Authors
- Minihane, A. M., Khan, S., Leigh-Firbank, E. C., Talmud, P., Wright, J. W., Murphy, M. C., Griffin, B. A., & Williams, C. M.
- Affiliations
- University of Surrey (GB)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2000-08
- Volume
- 20
- Issue
- 8
- Pages
- 1990-1997
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2133738729
- Cited by
- 215
- References
- 70
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 13 · 2016: 7 · 2015: 5 · 2014: 12 · 2013: 12 · 2012: 12
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- APOE polymorphism, fish oil supplementation, eicosapentaenoic acid, docosahexaenoic acid, atherogenic lipoprotein phenotype, dyslipidemia, postprandial triglyceride response, HDL cholesterol, LDL cholesterol, lipoprotein lipase activity, APOE ε4 carriers, ApoE2 allele, olive oil placebo
- MeSH terms
- Adult, Aged, Apolipoproteins E, Arteriosclerosis, Double-Blind Method, Fasting, Fatty Acids, Nonesterified, Fish Oils, Food, Genotype, Humans, Lipoproteins, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Phenotype, Placebos, Polymorphism, Genetic, Triglycerides, Cross-Over Studies
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