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Meta-Analysis
. 2014 Feb 5;9(2):e88103.
doi: 10.1371/journal.pone.0088103. eCollection 2014.

Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on C-reactive Protein, Interleukin 6 and Tumor Necrosis Factor α: A Meta-Analysis

Kelei Li  1 , Tao Huang  1 , Jusheng Zheng  1 , Kejian Wu  1 , Duo Li  1
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Meta-Analysis

Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on C-reactive Protein, Interleukin 6 and Tumor Necrosis Factor α: A Meta-Analysis

Kelei Li et al. PLoS One. .
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Abstract

Background: Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α).

Methods and findings: A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m². The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α.

Conclusions: Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow chart for identifying eligible studies.
Figure 2
Figure 2. Pooled effect size of n-3 PUFAs supplementation on CRP in chronic non-autoimmune disease.
WMD, weighted mean difference.
Figure 3
Figure 3. Pooled effect size of n-3 PUFAs supplementation on IL-6 in chronic non-autoimmune disease.
WMD, weighted mean difference.
Figure 4
Figure 4. Pooled effect size of n-3 PUFAs supplementation on TNF-α in chronic non-autoimmune disease.
WMD, weighted mean difference.
Figure 5
Figure 5. Meta-regression for duration and effect size (n-3 PUFAs supplementation on IL-6 in chronic non-autoimmune disease).
WMD, weighted mean difference.
Figure 6
Figure 6. Meta-regression for age and effect size (n-3 PUFAs supplementation on IL-6 in chronic non-autoimmune disease).
WMD, weighted mean difference.
Figure 7
Figure 7. Meta-regression for baseline of TNF-α and effect size (n-3 PUFAs supplementation on TNF-α in chronic non-autoimmune disease).
WMD, weighted mean difference.
Figure 8
Figure 8. Meta-regression for duration and effect size (n-3 PUFAs supplementation on TNF-α in chronic non-autoimmune disease).
WMD, weighted mean difference.
Figure 9
Figure 9. Cubic relationship between BMI and effect size (n-3 PUFAs supplementation on IL-6 in chronic non-autoimmune disease).
WMD, weighted mean difference.
Figure 10
Figure 10. Pooled effect size of n-3 PUFAs from dietary intake on CRP in chronic non-autoimmune disease.
WMD, weighted mean difference.
Figure 11
Figure 11. Pooled effect size of n-3 PUFAs from dietary intake on TNF-α in chronic non-autoimmune disease.
WMD, weighted mean difference.
Figure 12
Figure 12. Pooled effect size of n-3 PUFAs from dietary intake on IL-6 in chronic non-autoimmune disease.
WMD, weighted mean difference.
Figure 13
Figure 13. Pooled effect size of n-3 PUFAs supplementation on CRP in chronic autoimmune disease.
WMD, weighted mean difference.
Figure 14
Figure 14. Pooled effect size of n-3 PUFAs supplementation on CRP in healthy subjects.
WMD, weighted mean difference.
Figure 15
Figure 15. Pooled effect size of n-3 PUFAs supplementation on TNF-α in healthy subjects.
WMD, weighted mean difference.
Figure 16
Figure 16. Pooled effect size of n-3 PUFAs supplementation on IL-6 in healthy subjects.
WMD, weighted mean difference.
Figure 17
Figure 17. Meta-regression for daily dose of EPA and effect size (n-3 PUFAs supplementation on CRP in healthy subjects).
WMD, weighted mean difference.
Figure 18
Figure 18. Meta-regression for duration and effect size (n-3 PUFAs supplementation on IL-6 in healthy subjects).
WMD, weighted mean difference.
Figure 19
Figure 19. Meta-regression for daily dose of DHA and effect size (n-3 PUFAs supplementation on IL-6 in healthy subjects).
WMD, weighted mean difference.
Figure 20
Figure 20. Cubic relationship between baseline of CRP and effect size (n-3 PUFAs supplementation on CRP in healthy subjects).
WMD, weighted mean difference.
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Grant support

The study was supported by a grant from National High Technology Research and Development Program of China (No. N20080753), the National Natural Science Foundation of China (No. 30972464) and the Ph.D. Programs Foundation of Ministry of Education of China (No. 20070335025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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