Table 1.
Characteristics of the trials included in the meta-analyses trials presenting complete outcome data on pain are presented in the upper part of the panel.
| Author, Year [Reference Number], (Trial Registry Number) | N Total | Study Design | Duration of Intervention (Weeks) | Diagnosis | Mean Age (Years) | % Females | Mean Disease Duration (Years) | No. of Patients Receiving Intervention | Intervention | Dose of EPA + DHA (g/Day) | No. of Patients Receiving Control | Control Treatment |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Trials with complete data for pain | ||||||||||||
| Belch et al. 1986 [43] | 34 | Three-arm, parallel | 52 | RA | na | na | na | 11 c | MO (whole fish), and EPO (480 mg GLA) | 0.24 + na | 12 c | Oil (unspecified) k |
| 11 c | EPO (540 mg GLA) | |||||||||||
| Belch et al. 1988 [44] | 49 | Three-arm, parallel | 52 | RA | 49.0 | 29.3 | 5.0 | 15 | MO (whole fish), and EPO (450 mg GLA) | 0.24 + na | 18 | Paraffin k |
| 16 | EPO (540 mg GLA) | |||||||||||
| Cleland et al. 1988 [45] | 60 | Two-arm, parallel | 12 | RA | 50.5 | 53.3 | 8.3 | 30 | MO (whole fish) | 3.20 + 2.00 | 30 | Olive oil |
| Stammers et al. 1989 [46] | 26 | Two-arm, parallel | 26 | OA | 52–84 | 80.8 | na | na | MO (unspecified) | na | na | Oil (unspecified) |
| Kremer et al. 1990 [47] | 64 | Three-arm, parallel c | 24 | RA | 58.3 | 51.6 | 13.8 | 19 | MO (whole fish), high dose | 4.05 e + 2.70 e | 23 | Olive oil j |
| 22 | MO (whole fish), low dose | 2.03 e + 1.35 e | ||||||||||
| Tulleken et al. 1990 [48] | 28 | Two-arm, parallel | 13 | RA | 55.0 | 85.7 | 18.0 | 14 | MO (whole fish) | 2.04 + 1.32 | 14 | Coconut oil w/fish flavor |
| van der Tempel et al. 1990 [49,50] | 16 | Cross-over, no WO | 12 a | RA | 53.0 | 56.3 | 12.0 | 16 | MO (whole fish) | 2.04 + 1.32 | 16 | Coconut oil w/fish aroma |
| Espersen et al. 1992 [51] | 32 | Two-arm parallel | 12 | RA | na | na | na | 18 c | MO (whole fish) | 2.00 + 1.20 | 14 c | Mix (38% MUFA and 21% PUFA) |
| Kjeldsen-Kragh et al. 1992 [52,53] | 79 | Three-arm, parallel | 16 | RA | 57.3 | 21.5 | 8.5 | 26 | MO (whole fish), and declining NSAID | 3.78 + 1.96 | 28 | Corn oil and declining NSAID |
| 25 | MO (whole fish), and NSAID k | 3.78 + 1.96 | ||||||||||
| Magarò et al. 1992 [54] | 20 | Two-arm, parallel | 6 | RA | 25–45 | 100.0 | na | 10 | MO (whole fish) | 1.60 + 1.10 | 10 | None |
| Nielsen et al. 1992 [55,56,57] | 57 | Two-arm, parallel | 12 | RA | 61.0 b | na | 5.0 b | 29 | MO (whole fish) | 2.00 + 1.20 | 28 | Mix of FA |
| Sköldstam et al. 1992 [58] | 46 | Two-arm, parallel | 26 | RA | 57.0 | 73.9 | 18.0 | 23 | MO (whole fish) | 1.80 + 1.20 | 23 | Maize oil, olive oil and peppermint oil |
| Stammers et al. 1992 [59] | 86 | Two-arm, parallel | 24 | OA | 68.0 | 72.1 | 15.5 | 44 | MO (cod liver oil) | 0.79 + 0.70 g | 42 | Olive oil |
| Geusens et al. 1994 [60] | 90 | Three-arm, parallel | 52 | RA | 57.3 | 52.2 | 10.1 | 30 | MO (whole fish), high dose | 1.68 + 0.36 | 30 | Olive oil j |
| 30 | MO (whole fish), low dose | 0.84 + 0.18 | ||||||||||
| Kremer et al. 1995 [61] | 66 | Four-arm, parallel | 26 or 30 | RA | 57.5 | 40.9 | 10.5 | 33 c | MO (whole fish), diclofenac, and diclofenac placebo | 4.29 e + 2.34 e | 33 c | Corn oil, diclofenac, and diclofenac placebo |
| Vargová et al. 1998 [62] | 23 | Two-arm, parallel | 21 | JCA | 10.1 | na | na | 13 | “diet with increased content of omega-3 PUFA” | na | 10 | Unspecified |
| Volker et al. 2000 [63] | 50 | Two-arm, parallel | 15 | RA | 57.0 | n | 13.5 | 25 | MO (whole fish) | 0.90 e,g +0.63 e,g | 25 | 50:50 corn oil and olive oil |
| Adam et al. 2003 [64] | 68 | Two parallel cross-over studies, 8.7 weeks. WO | 13 a | RA | 56.8 | 41.2 | 9.6 | 34 | MO (whole fish), and WD | 0.80 e + 0.60 e | 34 | Corn oil, and WD |
| 58.0 | 41.2 | 9.5 | 34 | MO (whole fish), and AID | 0.84 e + 0.63 e | 34 | Corn oil, and AID | |||||
| Lau et al. 2004 [65] | 80 | Two-arm, parallel | 24 | Knee OA | 62.5 | 86.3 | 8.9 | 40 | MO (GLM extract) | na | 40 | Olive oil |
| Sundrarjun et al. 2004 [66] | 60 | Three-arm, parallel | 12 | RA | 46.9 | 85.0 | 4.4 | 23 | MO (whole fish) | 1.88 + 1.48 | 23 | Unspecified |
| na | 14 | None k | ||||||||||
| Berbert et al. 2005 [67] | 55 | Three-arm, parallel | 24 | RA | 49.0 | 61.8 | 15.3 | 18 | MO (whole fish) | 1.80 + 1.20 | 17 | Soy oil |
| 20 | MO (whole fish), and olive oil k | 1.80 + 1.20 | ||||||||||
| Madland et al. 2006 [68] | 43 | Two-arm, parallel | 2 | p.a. PsA | 55.0 | 51.2 | 13.0 b | 22 | MO (seal oil) | 2.40 + 2.60 | 21 | Soy oil (bottle) |
| Deutsch 2007 [69] | 90 | Two-arm, parallel | 4 | RA/CVD/OA | 55.0 | 47.8 | na | 45 | MO (krill oil) | 0.05 + 0.03 | 45 | Microcrystalline cellulose |
| Galarraga et al. 2008 [70] | 97 | Two-arm, parallel | 36 | RA | 59.5 | 71.1 | 13.0 | 49 | MO (mix of oil from cod liver and whole fish) | 1.50 + 0.70 | 48 | Air filled capsule |
| Das Gupta et al. 2009 [71] | 100 | Two-arm, parallel | 12 | RA | 47.3 | na | na | 50 | MO (whole fish), and indomethacin | 1.80 g + 1.20 g | 50 | Indomethacin |
| Gruenwald et al. 2009 [72] (EUCTR200500366918DE) | 177 | Two-arm, parallel | 26 | Knee/hip OA | 62.3 | 63.8 | na | 90 | MO (mix of oil from cod liver and whole fish), and glucosamine sulfate | 0.60 i | 87 | Mix of oils, and glucosamine sulfate |
| Park et al. 2013 [73] (NCT01618019) | 109 | Two-arm, parallel | 16 | RA | 48.4 | 34.4 | 8.4 | 55 | MO (whole fish) | 2.09 + 1.17 | 54 | Sunflower oil w/oleic acid |
| Araújo et al. 2014 [74] | 37 | Three-arm, parallel | 26 | RA | na | na | na | 11 c | MO (unspecified) | na | 15 c | na |
| 8 | Mediterranean diet k | na | ||||||||||
| Stebbings et al. 2014 [75] | 80 | Two-arm, parallel | 12 | Knee or hip OA | 66.4 | 55.0 | na | 39 | MO (GLM) | 0.01 +0.01 | 41 | Corn oil |
| Fu et al. 2015 [76] (NCT02173587) | 50 | Two-arm, parallel | 26 | RA | 57.5 | 60.0 | 7.6 | 25 | 50:50 MO (HMLE) and corn oil | 0.07 f + 0.10 f | 25 | Corn oil |
| Trials with incomplete data or no data for pain | ||||||||||||
| Kremer et al. 1986 [77] | 36 | Cross-over, 4 weeks WO | 14 a | RA | na | na | na | 36 | MO (whole fish) | 2.70 + na | 36 | Unspecified |
| Darlington & Ramsey 1987 [40] | 35 | Two-arm, parallel | 12 | RA | na | na | na | (17) d | MO (whole fish) | 3.24 + 2.16 | (18) d | Olive oil |
| Hernández-Cruz et al. 1988 [78] | 90 | Two-arm, parallel | 52 | RA | 43.2 | 89.0 | 3.4 | 45 | MO (whole fish) | 1.50 + na | 45 | Sunflower oil |
| Kremer et al. 1988 [79] | 55 | Three-arm, parallel | 24 | RA | na | na | na | (18) d | MO (whole fish), high dose | 4.05 e + 2.70 e | (19) d | Olive oil j |
| (18) d | MO (whole fish), low dose | 2.03 e + 1.35 e | ||||||||||
| Kremer et al. 1993 [80] | 50 | Two-arm, parallel | 26 or 30 | RA | na | na | na | (25) d | MO (whole fish), diclofenac, and diclofenac placebo | 9.75 e,h | (25) d | Corn oil, diclofenac, and diclofenac placebo |
| Lau et al. 1993 [81,82] | 64 | Two-arm, parallel | 52 | RA | 51.4 | 70.3 | 4.2 | 32 | MO (whole fish) | 1.71 + 1.14 | 32 | Air-filled capsule |
| Lau et al. 1995 [83] | 45 | Two-arm, parallel | 26 | RA | 51.0 b | 71.1 | 2.3 b | 25 | MO (whole fish) | 1.70 + 1.10 | 20 | Air-filled capsule |
| Kolahi et al. 2010 [84] | 90 | Three-arm, parallel | na | RA | na | Na | na | (30) d | MO (whole fish), and vitamin E-placebo | na | (30) d | MO placebo (unspecified) and vitamin E placebo |
| (30) d | MO (whole fish), and vitamin E k | |||||||||||
| Kolahi et al. 2010 [85,86,87,88] (IRCT138902073812N1) | 90 | Two-arm, parallel | 13 | RA | 50.0 b | 92.2 | 4.6 b | 45 | MO (whole fish) | 0.18 + 0.12 | 45 | Paraffin |
| Dawczynski et al. 2011 [89] (NCT01179971) | 60 | Four-arm, parallel | 12 | RA (or PsA) | 56.2 | 71.7 | na | 15 | MO (unspecified) | 3.00 l | 15 | Olive oil |
| 15 | MO (unspecified), and GLA (1800 mg) | 1.58 l | 15 | GLA (3150 mg) | ||||||||
| Reed et al. 2014 [90,91] (NCT00072982) | 150 | Three-arm, parallel | 78 | RA | 59.2 | 81.3 | 8.6 b | 53 | MO (whole fish), and borage seed oil | 2.10 + 1.40 | 52 | Borage seed oil, and sunflower seed oil |
| 45 | MO (whole fish), and sunflower seed oil k | 2.10 + 1.40 | ||||||||||
| Yazdanpanah et al. 2014 [92] (IRCT2012102610799N2) | 114 | Six-arm, parallel | 6 | Knee OA | na | na | na | 19 | Omega-3, and acetaminophen and naproxen | 1.00 h | 19 | Acetaminophen and naproxen |
| 19 | Omega-3 and acetaminophen | 1.00 h | 19 | Acetaminophen | ||||||||
| 19 | Omega-3 and naproxen | 1.00 h | 19 | Naproxen | ||||||||
AID: anti-inflammatory diet; CVD: cardiovascular disease; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; EPO: evening primrose oil; FA: fatty acid; GLA: gamma-linolenic acid; GLM: green-lipped mussel; HMLE: hard-shelled mussel lipid extract; JCA: juvenile chronic arthritis; MO: marine oil; MUFA: monounsaturated fatty acid; N: number; na: not available; NSAID: nonsteroidal anti-inflammatory drugs, OA: osteoarthritis; p.a. PSA: polyarticular psoriatic arthritis; PUFA: polyunsaturated fatty acid; RA: rheumatoid arthritis; WD: western diet; WO: wash out; Note that the use of the term MO refers to all oils of marine origin (e.g., oil from whole fish, seal, or mussel); a Duration of first period of cross-over study; b Median; c The numbers of participants receiving the interventions are not clearly stated in the publication, but other information suggests the numbers reported; d No group sample sizes reported. Assumed equal distribution among groups; e Based on mean body weight of participants or, if not available, on 75 kg; f Mean dose given over 26 weeks; g Estimated from information about EPA/DHA ratio or content in similar products; h Dose of omega-3; i Dose of fish oil; j Placebo group used twice in meta-analysis for two comparisons. Number of patients in the control group divided by two in the analysis; k Group excluded from the meta-analysis.