LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women.
Open accessAbstract
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 approximately 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.
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One study reported using standard methods for estimating LDL-C, and one did not report its method.
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Cites
Clinical Trials: A Practical Approach.
Hill, I. D., & Pocock, S. (1984) · Biometrics · doi:10.2307/2531186 · Cited by 2,918 · see citing works
(1999) · PubMed · Cited by 2,062 · see citing works
n-3 fatty acids and serum lipoproteins: human studies
Harris, W. (1997) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/65.5.1645s · Cited by 1,243 · see citing works
Blood Levels of Long-Chain n–3 Fatty Acids and the Risk of Sudden Death
Albert, C. M., Campos, H., Stampfer, M. J., Ridker, P. M., Manson, J. E., Willett, W. C., & Ma, J. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012918 · Cited by 1,146 · see citing works
Fish and Omega-3 Fatty Acid Intake and Risk of Coronary Heart Disease in Women
Hu, F. B. (2002) · JAMA · doi:10.1001/jama.287.14.1815 · Cited by 1,018 · see citing works
Fish Consumption and Risk of Sudden Cardiac Death
Albert, C. M. (1998) · JAMA · doi:10.1001/jama.279.1.23 · Cited by 990 · see citing works
Gardner, C. D. (1996) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1996.03540110029028 · Cited by 843 · see citing works
MIETTINEN, T. A., TILVIS, R. S., & KESÄNIEMI, Y. A. (1990) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a115479 · Cited by 646 · see citing works
Mori, T. A., Burke, V., Puddey, I. B., Watts, G. F., O’Neal, D. N., Best, J. D., & Beilin, L. J. (2000) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.5.1085 · Cited by 588 · see citing works
Xu, J., Nakamura, M. T., Cho, H. P., & Clarke, S. D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.23577 · Cited by 499 · see citing works
Ou, J., Tu, H., Shan, B., Luk, A. Y., DeBose‐Boyd, R. A., Bashmakov, Y. K., Goldstein, J. L., & Brown, M. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111138698 · Cited by 474 · see citing works
Yoshikawa, T., Shimano, H., Yahagi, N., Ide, T., Amemiya-Kudo, M., Matsuzaka, T., Nakakuki, M., Tomita, S., Okazaki, H., Tamura, Y., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m105711200 · Cited by 426 · see citing works
Thurnham, D. I., Smith, E., & Flora, P. S. (1988) · Clinical Chemistry · doi:10.1093/clinchem/34.2.377 · Cited by 384 · see citing works
Grimsgaard, S., Bonaa, K., Hansen, J., & Nordøy, A. (1997) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/66.3.649 · Cited by 300 · see citing works
Nestel, P., Shige, H., Pomeroy, S., Cehun, M., Abbey, M., & Raederstorff, D. (2002) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.2.326 · Cited by 263 · see citing works
Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study
Humphries, S. E., Talmud, P. J., Hawe, E., Bolla, M. K., Day, I. N. M., & Miller, G. J. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05330-2 · Cited by 250 · see citing works
Self-citationApoE Polymorphism and Fish Oil Supplementation in Subjects With an Atherogenic Lipoprotein Phenotype
Minihane, A. M., Khan, S., Leigh-Firbank, E. C., Talmud, P., Wright, J. W., Murphy, M. C., Griffin, B. A., & Williams, C. M. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.8.1990 · Cited by 215 · see citing works
Conquer, J. A., & Holub, B. J. (1996) · The Journal of Nutrition · doi:10.1093/jn/126.12.3032 · Cited by 181 · see citing works
Sanders, T. A. B., Oakley, F. R., Miller, G. J., Mitropoulos, K. A., Crook, D., & Oliver, M. F. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.12.3449 · Cited by 122 · see citing works
Self-citationÅgren, J. J., Hänninen, O., Julkunen, A., Fogelholm, L., Vidgren, H. M., Schwab, U., Pynnönen, O., & Uusitupa, M. I. J. (1996) · PubMed · Cited by 117 · see citing works
Nelson, G. J., Schmidt, P. C., Bartolini, G. L., Kelley, D. S., & Kyle, D. J. (1997) · Lipids · doi:10.1007/s11745-997-0146-5 · Cited by 92 · see citing works
Davidson, M. H., Maki, K. C., Kalkowski, J., Schaefer, E. J., Torri, S. A., & Drennan, K. B. (1997) · Journal of the American College of Nutrition · doi:10.1080/07315724.1997.10718680 · Cited by 68 · see citing works
Surette, M., Whelan, J., Lu, G., Broughton, K. S., & Kinsella, J. E. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41546-9 · Cited by 65 · see citing works
Higgins, S., Carroll, Y. L., McCarthy, S., Corridan, B. M., Roche, H. M., Wallace, J. M. W., O’Brien, N. M., & Morrissey, P. A. (2001) · British Journal Of Nutrition · doi:10.1079/bjn2000220 · Cited by 62 · see citing works
Sanders, T. A. B., Dean, T. S., Grainger, D., Miller, G. J., & Wiseman, H. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.2.373 · Cited by 61 · see citing works
Self-citationLindsey, S., Pronczuk, A., & Hayes, K. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41429-4 · Cited by 56 · see citing works
Salen, G., Xu, G., Tint, G. S., et al. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31982-9 · Cited by 23 · see citing works
Rapid determination of apolipoprotein E genotype using a heteroduplex generator
Bolla, M. K., Wood, N., & Humphries, S. E. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32109-x · Cited by 21 · see citing works
Self-citationDietary fish oil decreases low-density-lipoprotein clearance in nonhuman primates
Schectman, G., Boerboom, L. E., Hannah, J. S., Howard, B. V., Mueller, R., & Kissebah, A. H. (1996) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/64.2.215 · Cited by 18 · see citing works
Hamazaki, T., Sawazaki, S., Asaoka, E., Itomura, M., Mizushima, Y., Yazawa, K., Kuwamori, T., & Kobayashi, M. (1996) · Journal of Nutrition · doi:10.1093/jn/126.11.2784 · Cited by 17 · see citing works
8 Polyunsaturated fatty acids and coronary heart disease
Sanders, T. A. B. (1990) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(05)80083-7 · Cited by 15 · see citing works
Self-citation(1997) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/s0952-3278(97)90133-2 · Cited by 11 · see citing works
Flagged first, then by citations
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Sorted by citations
Distribution, interconversion, and dose response of n-3 fatty acids in humans.
Arterburn, L. M., Hall, E. B., & Oken, H. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.6.1467s · Cited by 1,162 · see citing works
Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus
Hartweg, J., Perera, R., Montori, V. M., Dinneen, S. F., Neil, A. H., & Farmer, A. J. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003205.pub2 · Cited by 282 · see citing works
Wei, M. Y., & Jacobson, T. A. (2011) · Current Atherosclerosis Reports · doi:10.1007/s11883-011-0210-3 · Cited by 284 · see citing works
Jacobson, T. A., Glickstein, S. B., Rowe, J. D., & Soni, P. N. (2012) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2011.10.018 · Cited by 263 · see citing works
The differential effects of EPA and DHA on cardiovascular risk factors
Cottin, S. C., Sanders, T. A., & Hall, W. L. (2011) · Proceedings of the Nutrition Society · doi:10.1017/s0029665111000061 · Cited by 247 · see citing works
Self-citationKelley, D. S., Siegel, D., Vemuri, M., & Mackey, B. E. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.2.324 · Cited by 179 · see citing works
Bernstein, A. M., Ding, E. L., Willett, W. C., & Rimm, E. B. (2012) · The Journal of Nutrition · doi:10.3945/jn.111.148973 · Cited by 148 · see citing works
AbuMweis, S., Jew, S., Tayyem, R., & Agraib, L. (2018) · Journal of Human Nutrition and Dietetics · doi:10.1111/jhn.12493 · Cited by 122 · see citing works
Neff, L. M., Culiner, J., Cunningham-Rundles, S., Seidman, C., Meehan, D., Maturi, J., Wittkowski, K. M., Levine, B., & Breslow, J. L. (2011) · The Journal of Nutrition · doi:10.3945/jn.110.130021 · Cited by 121 · see citing works
Jones, P. J., Senanayake, V. K., Pu, S., Jenkins, D. J., Connelly, P. W., Lamarche, B., Couture, P., Charest, A., Baril-Gravel, L., West, S. G., et al. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.081133 · Cited by 115 · see citing works
Docosahexaenoic acid (DHA) and cardiovascular disease risk factors
Holub, B. J. (2009) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2009.05.016 · Cited by 100 · see citing works
Geppert, J., Kraft, V., Demmelmair, H., & Koletzko, B. (2006) · British Journal of Nutrition · doi:10.1079/bjn20051720 · Cited by 96 · see citing works
Ryan, A. S., Keske, M. A., Hoffman, J. P., & Nelson, E. B. (2009) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e31817fe2be · Cited by 72 · see citing works
Ouguerram, K., Maugeais, C., Gardette, J., Magot, T., & Krempf, M. (2006) · British Journal of Nutrition · doi:10.1079/bjn20061806 · Cited by 31 · see citing works
- Authors
- Theobald, H. E., Chowienczyk, P. J., Whittall, R., Humphries, S. E., & Sanders, T. A.
- Affiliations
- King's College London (GB)
- St Thomas' Hospital (GB)
- Corresponding author
- Sanders, Thomas AB
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 79
- Issue
- 4
- Pages
- 558-563
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2128858609
- Cited by
- 101
- References
- 33
- Citations by year
- 2025: 2 · 2023: 6 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 7 · 2013: 2 · 2012: 4
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- docosahexaenoic acid, LDL cholesterol, omega-3 fatty acids, dietary supplementation, serum lipids, apolipoprotein B, LDL particle size, serum cholesterol, middle-aged adults, erythrocyte fatty acids
- MeSH terms
- Adult, Aged, Docosahexaenoic Acids, Double-Blind Method, Female, Humans, Lipids, Lipoproteins, Cholesterol, LDL, Male, Middle Aged, Cross-Over Studies
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