TABLE 1.
Intervention studies investigating the effect of marine n–3 PUFA intake on circulating markers of low-grade inflammation1
| Authors, year (ref) | Subjects | Intake (source; duration) | Effect on low-grade inflammation |
| Blok et al., 1997 (84) | Healthy (n = 58; aged 21–87 y) | 0, 1.06, 2.13, 3.19 g/d EPA + DHA (FO capsules; up to 52 wk) | No effect: TNF-α, IL-1β, IL-1RA |
| Abe et al., 1998 (85) | Healthy and hyperlipidemic (n = 20; mean age = 51) | 0, 3.6 g/d EPA + DHA (EE capsules; up to 6 wk) | No effect: sICAM-1, sVCAM-1 |
| ↓ sE-selectin | |||
| Seljeflot et al., 1998 (86) | Hyperlipidemic smokers (n = 41; aged 41–57 y) | 0, 4.8 g/d EPA + DHA (EE capsules; 6 wk) | ↑ sVCAM-1, sE-selectin |
| No effect: sP-selectin, tissue plasminogen activator antigen | |||
| ↓ von Willibrand factor, thrombomodulin | |||
| Johansen et al., 1999 (87) | Patients with CHD (n = 54; aged 43–73 y) | 0, 5.1 g/d EPA + DHA (EE capsules; 24 wk) | ↑ sVCAM-1, sE-selectin |
| No effect: sP-selectin, tissue plasminogen activator antigen | |||
| ↓ von Willibrand factor, thrombomodulin | |||
| Sampson et al., 2001 (88) | Healthy (n = 21) and type 2 diabetics (n = 29); mean age = 55 y | 2.0 g/d EPA + DHA (FO capsules; 3 wk) | No effect: sICAM-1, sVCAM-1, sE-selectin, PAI-1 activity, PAI-1 antigen |
| Thies et al., 2001 (89) | Healthy (n = 24; aged 55–75 y) | 0, 0.7 g/d DHA (DHA-rich algal oil capsules; 12 wk), 1 g/d EPA + DHA (FO capsules; 12 wk) | EPA + DHA: No effect: sICAM-1, sE-selectin |
| ↓ sVCAM-1 | |||
| DHA: no effect: sICAM-1, sVCAM-1, sE-selectin | |||
| Chan et al., 2002 (90) | Obese (n = 48; mean age = 53 y) | 0, 3.5 g/d EPA + DHA (EE capsules; 6 wk) | No effect: CRP, IL-6, TNF-α |
| Berstad et al., 2003 (91) | Elderly at risk of CHD (n = 171; mean age = 70 y) | 0, 2.4 g/d EPA + DHA (FO capsules; 18 mo) | No effect: sICAM-1, sVCAM-1, sE-selectin, tissue plasminogen activator antigen |
| ↓ von Willibrand factor, thrombomodulin | |||
| Ciubotaru et al., 2003 (92) | Healthy on HRT (n = 30; mean age = 60 y) | 0, 1.09, 2.18 g/d EPA + DHA (FO capsules; 5 wk) | ↓ CRP, IL-6 |
| Madsen et al., 2003 (93) | Healthy (n = 60; ageds 21–57 y) | 0, 2.0, 6.6 g/d EPA + DHA (FO capsules; 12 wk) | No effect: CRP |
| Grundt et al., 2003 (94) | MI survivors (n = 300; aged 28–87 y) | 0, 3.5 g/d EPA + DHA (EE capsules; 12 mo) | No effect: sICAM-1, sVCAM-1, sE-selectin |
| Mori et al., 2003 (95), and Woodman et al., 2003 (96) | Type 2 diabetics (n = 59; aged 40–65 y) | 0, 4 g/d EPA, 4 g/d DHA (EPA EE or DHA EE capsules; 6 wk) | No effect: CRP, IL-6, TNF-α, von Willibrand factor, tissue plasminogen activator antigen, PAI-1 antigen, sP-selectin |
| Eschen et al., 2004 (97) | Healthy (n = 60; mean age = 38 y) | 0, 1.6, 5.8 g/d EPA + DHA (concentrated FO capsules; 3 y) | Low-dose: no effect: sVCAM-1, sP-selectin |
| ↓ sICAM-1 (especially in women) | |||
| High-dose: no effect: sICAM-1, sVCAM-1 | |||
| ↓ sP-selectin | |||
| Jellema et al., 2004 (98) | Obese (n = 11; age not given) | 1.1 g/d EPA + DHA (FO capsules; 6 wk) | No effect: CRP, IL-6, sTNFR1, sTNFR2, PAI-1 |
| Hjerkinn et al., 2005 (99) | Hyperlipidemic (n = 563; aged 64–76 y) | 0, 2.4 g/d EPA + DHA (FO capsules; 3 y) | No effect: sVCAM-1, sE-selectin, von Willibrand factor, tissue plasminogen activator antigen |
| ↓ sICAM-1, thrombomodulin | |||
| Cazzola et al., 2007 (100) | Healthy young (n = 93; mean age = 24 y); healthy older (n = 62; mean age = 61 y) | 0, 1.35, 2.7, 4.05 g/d EPA + DHA (EPA-rich oil; 12 wk) | No effect: sICAM-1, sVCAM-1 |
| ↑sE-selectin (young only) | |||
| Fujioka et al., 2006 (101) | Healthy (n = 141; mean age = 47 y) | 0, 0.96 g/d EPA + DHA (FO in soya milk; 12 wk) | No effect: CRP, sTNFR1, sTNFR2 |
| Krebs et al., 2006 (102) | Overweight and insulin resistant (n = 116; aged 21–69 y) | 0, 0 + weight-loss program, 4.2 g/d EPA + DHA + weight-loss program (concentrated FO capsules; 24 wk) | ↑Adiponectin |
| No effect: CRP, TNF-α, IL-6 | |||
| Sanders et al., 2006 (103) | Healthy (n = 80; mean age = 30 y) | 0, 1.5 g/d DHA (DHA-rich algal oil; 4 wk) | No effect: CRP, fibrinogen, PAI-1 activity, von Willibrand factor |
| Kabir et al., 2007 (104) | Overweight type 2 diabetics (n = 27; mean age = 55 y) | 0, 1.8 g/d EPA + DHA (FO capsules; 8 wk) | No effect:IL-6, TNF-α, SAA, adiponectin |
| ↓ PAI-1 activity, inflammatory gene expression in adipose tissue | |||
| Browning et al., 2007 (105) | Overweight and obese (n = 30; age not given) | 0, 4.2 g/d EPA + DHA (DHA-rich TAG capsules; 12 wk; crossover) | No effect: sialic acid, fibrinogen, PAI-1 activity |
| ↓ CRP, IL-6 | |||
| Rasic-Milutinovic et al., 2007 (106) | Insulin resistant with chronic renal failure (n = 35; mean age = 55 y) | 2.4 g/d EPA + DHA (FO capsules; 8 wk) | ↓ CRP, IL-6, TNF-α |
| Madsen et al., 2007 (107) | MI survivors (n = 41; mean age = 63 y) | 0, 5.2 g/d EPA + DHA (EPA-rich TAG capsules; 12 wk) | No effect: CRP |
| Murphy et al., 2007 (108) | Overweight (n = 86; age not given) | 0, 1 g/d EPA + DHA (enriched foods; 6 mo) | No effect: CRP |
| Yamada et al., 2008 (109) | Metabolic syndrome (n = 23; mean age = 50 y) | 0, 1.8 g/d EPA (EPA capsules; 12 wk) | ↓ sICAM-1, sVCAM-1 |
| Yusof et al., 2008 (110) | Healthy (n = 20; aged 35–60 y) | 0, 1.8 g/d EPA + DHA (EPA-rich oil; 8 wk) | No effect: CRP, IL-6, sVCAM-1, sE-selectin, sP-selectin |
| ↓ sICAM-1 | |||
| Kelley et al., 2009 (111) | Moderately hyperlipidemic (n = 34; aged 39–66 y) | 0, 3 g/d DHA (DHA-rich algal oil; 90 d) | No effect: SAA, TNF-α, IL-1β, IL-8, IL-10, sVCAM-1, sICAM-1, sE-selectin |
| ↓ Leukocytes, CRP, IL-6, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor | |||
| Pot et al., 2009 (112) | Healthy (n = 77; aged 50–70 y) | 0, 1.5 g/d EPA + DHA (FO capsules; 12 wk) | No effect: 19 cytokines, chemokines, and adhesion molecules |
| Trøseid et al., 2009 (113) | Elderly at risk of CHD (n = 563; mean age = 70 y) | 0, 2.4 g/d EPA + DHA (FO capsules; 3 y) | No effect: CRP, IL-6, TNF-α, adiponectin |
| ↓ IL-18 |
1
Adapted from reference 51 with permission. CHD, coronary heart disease; CRP, C-reactive protein; EE, ethyl ester; FO, fish oil; HRT, hormone replacement therapy; IL-1RA, IL-1 receptor antagonist; MI, myocardial infarction; PAI-1, plasminogen activator inhibitor 1; ref, reference; SAA, serum amyloid A; sE-selectin, soluble E-selectin; sICAM-1, soluble intercellular adhesion molecule 1; sP-selectin, soluble P-selectin; sTNFR, soluble TNF receptor; sVCAM-1, soluble vascular cell adhesion molecule 1; TAG, triacylglycerol; ↓, decreased; ↑, increased.