Serum levels of interleukin-18 are reduced by diet and n-3 fatty acid intervention in elderly high-risk men
Abstract
Inflammation plays a central role in the development and progression of atherosclerosis, and inflammatory markers have been reported to predict cardiovascular events. Mediterranean-like diet and very long chain omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation have been reported to reduce the risk of cardiovascular mortality and morbidity, but the mechanisms are not fully clarified. The aims of the present study were to investigate the effect of such interventions on serum levels of inflammatory markers, and potential associations with changes in serum fatty acids and anthropometric measures. This was a randomized 2 x 2 factorial-designed trial comparing the effect of 3 years of dietary counseling, n-3 PUFA supplementation (2.4 g/d), or both on different measures of atherosclerosis in elderly high-risk men (N = 563). Levels of interleukin-18 (IL-18) were decreased by diet (-10.5% vs baseline, P = .012 compared with no diet) and by n-3 PUFA supplementation (-9.9% vs baseline, P = .008 compared with placebo). Other measured inflammatory markers were not affected. Changes in IL-18 were significantly correlated to changes in triglycerides (r = 0.20, P < .001), eicosapentaenoic acid (r = -0.14, P = .030), docosahexaenoic acid (r = -0.14, P = .034), body mass index (r = 0.16, P < .001), and waist circumference (r = 0.12, P = .007). In conclusion, levels of IL-18 were significantly reduced by Mediterranean-like diet and n-3 PUFA supplementation. However, the changes correlated only weakly to changes in triglycerides, serum fatty acids, and anthropometric measures. The cardioprotective effects of both interventions might thus in part be explained by reduced levels of IL-18, but probably beyond changes in serum fatty acids and body composition.
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Chronic low-grade inflammation is associated with poor iron status in obese persons.
“past and emerging evidence indicates that chronic low-grade inflammation is associated with poor Fe status in obese persons (716 -721) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [721]
Cites
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725 · see citing works
de Lorgeril, M., Salen, P., Martin, J.-L., Monjaud, I., Delaye, J., & Mamelle, N. (1999) · Circulation · doi:10.1161/01.cir.99.6.779 · Cited by 2,910 · see citing works
Esposito, K., Marfella, R., Ciotola, M., Di Palo, C., Giugliano, F., Giugliano, G., D'Armiento, M., D'Andrea, F., & Giugliano, D. (2004) · JAMA · doi:10.1001/jama.292.12.1440 · Cited by 2,126 · see citing works
(1999) · PubMed · Cited by 2,062 · see citing works
Endres, S., Ghorbani, R., Kelley, V. E., Georgilis, K., Lonnemann, G., van der Meer, J. W. M., Cannon, J. G., Rogers, T. S., Klempner, M. S., Weber, P. C., et al. (1989) · New England Journal of Medicine · doi:10.1056/nejm198902023200501 · Cited by 1,898 · see citing works
The Opposing Effects of N-3 and n-6 Fatty Acids
Schmitz, G., & Ecker, J. (2008) · Progress in Lipid Research · doi:10.1016/j.plipres.2007.12.004 · Cited by 1,245 · see citing works
EFFECT OF DIET AND SMOKING INTERVENTION ON THE INCIDENCE OF CORONARY HEART DISEASE
Hjermann, I., Holme, I., Byre, K. V., & Leren, P. (1981) · The Lancet · doi:10.1016/s0140-6736(81)91338-6 · Cited by 1,045 · see citing works
The Effects of Diet on Inflammation
Giugliano, D., Ceriello, A., & Esposito, K. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.03.052 · Cited by 842 · see citing works
Interleukin-18 Binding Protein
Novick, D., Kim, S. H., Fantuzzi, G., Reznikov, L. L., Dinarello, C. A., & Rubinstein, M. (1999) · Immunity · doi:10.1016/s1074-7613(00)80013-8 · Cited by 781 · see citing works
REGULATION OF GENE EXPRESSION BY DIETARY FAT
Jump, D. Β., & Clarke, S. D. (1999) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.19.1.63 · Cited by 664 · see citing works
NAKANISHI, K., YOSHIMOTO, T., Tsutsui, H., & Okamura, H. (2001) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(00)00015-0 · Cited by 658 · see citing works
Bagga, D., Wang, L., Farias‐Eisner, R., Glaspy, J. A., & Reddy, S. T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0334211100 · Cited by 639 · see citing works
Expression of Interleukin-18 in Human Atherosclerotic Plaques and Relation to Plaque Instability
Mallat, Z., Corbaz, A., Scoazec, A., Besnard, S., Lesèche, G., Chvatchko, Y., & Tedgui, A. (2001) · Circulation · doi:10.1161/hc3901.096721 · Cited by 632 · see citing works
Gustafson, B., Hammarstedt, A., Andersson, C. X., & Smith, U. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.147835 · Cited by 434 · see citing works
Dietary fat intake and prevention of cardiovascular disease: systematic review
Hooper, L., Summerbell, C., Higgins, J., Thompson, R. L., Capps, N., Smith, G., Riemersma, R., & Ebrahim, S. (2001) · British medical journal · doi:10.1136/bmj.322.7289.757 · Cited by 409 · see citing works
C-Reactive Protein, Interleukin-6, and Fibrinogen as Predictors of Coronary Heart Disease
Luc, G., Bard, J., Juhan-Vague, I., Ferrières, J., Evans, A., Amouyel, P., Arveiler, D., Fruchart, J., & Ducimetière, P. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000079512.66448.1d · Cited by 378 · see citing works
Effect of Diet and Smoking Intervention on the Incidence of Coronary Heart Disease
Hjermann, I. (1984) · Springer eBooks · doi:10.1007/978-1-4757-1824-9_66 · Cited by 372 · see citing works
Meydani, S. N., Lichtenstein, A. H., Cornwall, S., Meydani, M., Goldin, B. R., Rasmussen, H., Dinarello, C. A., & Schaefer, E. J. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116537 · Cited by 357 · see citing works
Dietary modulation of endothelial function: implications for cardiovascular disease
Brown, A. A., & Hu, F. B. (2001) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/73.4.673 · Cited by 350 · see citing works
Interleukin-18 and the Risk of Coronary Heart Disease in European Men
Blankenberg, S., Luc, G., Ducimetière, P., Arveiler, D., Ferrières, J., Amouyel, P., Evans, A., Cambien, F., & Tiret, L. (2003) · Circulation · doi:10.1161/01.cir.0000099509.76044.a2 · Cited by 327 · see citing works
Weight loss reduces interleukin-18 levels in obese women
Esposito, K., Pontillo, A., Ciotola, M., Di Palo, C., Grella, E., Nicoletti, G., & Giugliano, D. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.8.8781 · Cited by 254 · see citing works
Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency
Eritsland, J., Arnesen, H., Grønseth, K., Fjeld, N. B., & Abdelnoor, M. (1996) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)89130-8 · Cited by 252 · see citing works
Self-citationBeneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?
Das, U. N. (2000) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1054/plef.2000.0226 · Cited by 238 · see citing works
Dona, M., Fredman, G., Schwab, J. M., Chiang, N., Arita, M., Goodarzi, A., Cheng, G., von Andrian, U. H., & Serhan, C. N. (2008) · Blood · doi:10.1182/blood-2007-11-122598 · Cited by 228 · see citing works
Kahlenberg, J. M., Lundberg, K. C., Kertesy, S. B., Qu, Y., & Dubyak, G. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.11.7611 · Cited by 211 · see citing works
Follow-up of preterm children: important to document dropouts
Wolke, D., Söhne, B., Ohrt, B., et al. (1995) · The Lancet · doi:10.1016/s0140-6736(95)90425-5 · Cited by 178 · see citing works
Johansen, O., Seljeflot, I., Høstmark, A. T., & Arnesen, H. (1999) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.19.7.1681 · Cited by 169 · see citing works
Self-citationInterleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss
Bruun, J. M., Stallknecht, B. M., Helge, J. W., & Richelsen, B. (2007) · European Journal of Endocrinology · doi:10.1530/eje-07-0206 · Cited by 149 · see citing works
Michalsen, A., Lehmann, N., Pithan, C., Knoblauch, N. T. M., Moebus, S., Kannenberg, F., Binder, L., Budde, T., & Dobos, G. (2005) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602340 · Cited by 146 · see citing works
Hjerkinn, E. M., Seljeflot, I., Ellingsen, I., Berstad, P. M., Hjermann, I., Sandvik, L., & Arnesen, H. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.3.583 · Cited by 113 · see citing works
Self-citationMarine n-3 polyunsaturated fatty acids and coronary heart disease
Schmidt, E. B., Arnesen, H., Caterina, R. D., Rasmussen, L. H., & Kristensen, S. D. (2004) · Thrombosis Research · doi:10.1016/j.thromres.2004.09.006 · Cited by 106 · see citing works
Self-citationHjerkinn, E. M., Abdelnoor, M., Breivik, L., Bergengen, L., Ellingsen, I., Seljeflot, I., Aase, O., Klemsdal, T. O., Hjermann, I., & Arnesen, H. (2006) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1097/01.hjr.0000209817.28444.fb · Cited by 94 · see citing works
Self-citationVilarrasa, N., Vendrell, J. J., Sánchez‐Santos, R., Broch, M., Megía, A., Masdevall, C., Gomez, N., Soler, J., Pujol, J., Bettónica, C., et al. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02945.x · Cited by 87 · see citing works
Schernthaner, G.-H., Kopp, H.-P., Kriwanek, S., Krzyzanowska, K., Satler, M., Koppensteiner, R., & Schernthaner, G. (2006) · Obesity Surgery · doi:10.1381/096089206777346763 · Cited by 83 · see citing works
Fain, J. N., Tichansky, D. S., & Madan, A. K. (2006) · Metabolism · doi:10.1016/j.metabol.2006.04.008 · Cited by 73 · see citing works
Gangemi, S. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00061-5 · Cited by 73 · see citing works
Doi, T., Sakoda, T., Akagami, T., Naka, T., Mori, Y., Tsujino, T., Masuyama, T., & Ohyanagi, M. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00148.2008 · Cited by 45 · see citing works
Marine n−3 polyunsaturated fatty acids and coronary heart disease
Schmidt, E. B., Arnesen, H., Christensen, J., Rasmussen, L. H., Kristensen, S., & Caterina, R. D. (2004) · Thrombosis Research · doi:10.1016/j.thromres.2004.09.007 · Cited by 43 · see citing works
Self-citationProstaglandins E1 and E2 inhibit lipopolysaccharide-induced interleukin-18 production in monocytes
Takahashi, H. K., Iwagaki, H., Mori, S., et al. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.05.020 · Cited by 12 · see citing works
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Calder, P. C., Ahluwalia, N., Brouns, F., Buetler, T., Clement, K., Cunningham, K., Esposito, K., Jönsson, L. S., Kolb, H., Lansink, M., et al. (2011) · British Journal of Nutrition · doi:10.1017/s0007114511005460 · Cited by 1,098 · see citing works
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Abdelhamid, A. S., Brown, T. J., Brainard, J. S., Biswas, P., Thorpe, G. C., Moore, H. J., Deane, K. H., Summerbell, C. D., Worthington, H. V., Song, F., et al. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003177.pub5 · Cited by 295 · see citing works
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Trøseid, M., Seljeflot, I., & Arnesen, H. (2010) · Cardiovascular Diabetology · doi:10.1186/1475-2840-9-11 · Cited by 155 · see citing works
Self-citationLandberg, R., Sun, Q., Rimm, E. B., Cassidy, A., Scalbert, A., Mantzoros, C. S., Hu, F. B., & van Dam, R. M. (2011) · The Journal of Nutrition · doi:10.3945/jn.110.133843 · Cited by 121 · see citing works
Dewell, A., Marvasti, F. F., Harris, W. S., Tsao, P., & Gardner, C. D. (2011) · The Journal of Nutrition · doi:10.3945/jn.111.142240 · Cited by 98 · see citing works
- Authors
- Trøseid, M., Arnesen, H., Hjerkinn, E. M., & Seljeflot, I.
- Affiliations
- Oslo University Hospital (NO)
- Corresponding author
- Seljeflot, Ingebjørg
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 58
- Issue
- 11
- Pages
- 1543-1549
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2033737104
- Cited by
- 73
- References
- 39
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 1 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 2 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 6
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- IL-18, omega-3 fatty acids, omega-3 supplementation, nutrition counseling, atherosclerosis, inflammation, older men, cardiovascular risk, triglycerides, eicosapentaenoic acid, docosahexaenoic acid, body mass index, waist circumference, serum fatty acids
- MeSH terms
- Aged, Anthropometry, C-Reactive Protein, Fatty Acids, Nonesterified, Follow-Up Studies, Humans, Inflammation, Lipids, Male, Risk, Biomarkers, Fatty Acids, Omega-3, Body Mass Index, Interleukin-18, Diet, Mediterranean, Atherosclerosis, Adipokines, Waist Circumference
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