1 All‐cause mortality (overall) |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
2 All‐cause mortality ‐ sensitivity analysis by fixed‐effect analysis |
10 |
4506 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.00 [0.89, 1.13] |
3 All‐cause mortality ‐ sensitivity analyses |
10 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
3.1 Studies at low risk of bias |
2 |
682 |
Risk Ratio (M‐H, Random, 95% CI) |
1.54 [0.98, 2.41] |
3.2 Pre‐2010 or prospective trials registry entry |
9 |
4306 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.89, 1.13] |
3.3 No commercial funding |
4 |
1208 |
Risk Ratio (M‐H, Random, 95% CI) |
1.19 [0.84, 1.69] |
3.4 Low risk of attention bias |
6 |
1489 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.83, 1.13] |
3.5 Randomised 250+ participants |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.01 [0.87, 1.17] |
3.6 Randomised 100+ participants |
8 |
4403 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.13] |
4 All‐cause mortality ‐ subgroup by LA or GLA |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
4.1 Mainly LA |
8 |
4341 |
Risk Ratio (M‐H, Random, 95% CI) |
1.01 [0.89, 1.14] |
4.2 GLA supplements |
2 |
165 |
Risk Ratio (M‐H, Random, 95% CI) |
0.76 [0.41, 1.39] |
5 All‐cause mortality ‐ subgroup by intervention type |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
5.1 Dietary advice |
3 |
2624 |
Risk Ratio (M‐H, Random, 95% CI) |
1.15 [0.82, 1.61] |
5.2 Supplements (capsules) |
2 |
165 |
Risk Ratio (M‐H, Random, 95% CI) |
0.76 [0.41, 1.39] |
5.3 Supplemental foods |
1 |
200 |
Risk Ratio (M‐H, Random, 95% CI) |
0.20 [0.01, 4.11] |
5.4 Dietary advice plus supplement |
2 |
447 |
Risk Ratio (M‐H, Random, 95% CI) |
0.94 [0.60, 1.46] |
5.5 Diet (all foods) provided |
2 |
1070 |
Risk Ratio (M‐H, Random, 95% CI) |
0.98 [0.84, 1.15] |
6 All‐cause mortality ‐ subgroup by replacement |
10 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
6.1 N‐6 replacing SFA |
6 |
4154 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.15] |
6.2 N‐6 replacing MUFA |
5 |
1698 |
Risk Ratio (M‐H, Random, 95% CI) |
1.13 [0.83, 1.53] |
6.3 N‐6 replacing nil, low n‐6 |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
6.4 N‐6 replacement unclear |
2 |
442 |
Risk Ratio (M‐H, Random, 95% CI) |
0.85 [0.58, 1.24] |
6.5 N‐6 replacing CHO |
1 |
133 |
Risk Ratio (M‐H, Random, 95% CI) |
1.97 [0.18, 21.21] |
6.6 N‐6 replacing protein |
1 |
133 |
Risk Ratio (M‐H, Random, 95% CI) |
1.97 [0.18, 21.21] |
7 All‐cause mortality ‐ subgroup by baseline CVD risk |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
7.1 Primary prevention ‐ low CVD risk |
5 |
1368 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.83, 1.13] |
7.2 Primary prevention ‐ moderate CVD risk |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
7.3 Secondary prevention ‐ existing CVD |
5 |
3138 |
Risk Ratio (M‐H, Random, 95% CI) |
1.06 [0.83, 1.35] |
8 All‐cause mortality ‐ subgroup by omega‐6 dose |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
8.1 N‐6 < 4% E |
4 |
2331 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.76, 1.19] |
8.2 N‐6 4% to 12% E |
2 |
1304 |
Risk Ratio (M‐H, Random, 95% CI) |
1.15 [0.76, 1.74] |
8.3 N‐6 > 12% E |
4 |
871 |
Risk Ratio (M‐H, Random, 95% CI) |
0.93 [0.60, 1.44] |
9 All‐cause mortality ‐ subgroup by duration |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
9.1 Medium duration 1 to < 2 years in study |
1 |
224 |
Risk Ratio (M‐H, Random, 95% CI) |
3.11 [0.17, 56.84] |
9.2 Medium‐long duration 2 to < 4 years |
6 |
2585 |
Risk Ratio (M‐H, Random, 95% CI) |
0.96 [0.76, 1.20] |
9.3 Long duration 4+ years in study |
3 |
1697 |
Risk Ratio (M‐H, Random, 95% CI) |
1.05 [0.81, 1.36] |
10 All‐cause mortality ‐ subgroup by statin use |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
10.1 ≥ 50% of control group on statins |
1 |
200 |
Risk Ratio (M‐H, Random, 95% CI) |
0.20 [0.01, 4.11] |
10.2 < 50% of control group on statins |
9 |
4306 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.89, 1.13] |
10.3 Statin use unclear |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
11 All‐cause mortality ‐ subgroup by baseline omega‐6 |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
11.1 ≥ 8% E from n‐6 |
1 |
133 |
Risk Ratio (M‐H, Random, 95% CI) |
1.97 [0.18, 21.21] |
11.2 5% to < 8% E from n‐6 |
2 |
2491 |
Risk Ratio (M‐H, Random, 95% CI) |
1.16 [0.77, 1.76] |
11.3 < 5% E from n‐6 |
2 |
1070 |
Risk Ratio (M‐H, Random, 95% CI) |
0.98 [0.84, 1.15] |
11.4 baseline n‐6 not reported |
5 |
812 |
Risk Ratio (M‐H, Random, 95% CI) |
0.85 [0.60, 1.22] |
12 All‐cause mortality ‐ subgroup by sex |
10 |
4506 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.88, 1.12] |
12.1 Men only |
5 |
3954 |
Risk Ratio (M‐H, Random, 95% CI) |
1.01 [0.89, 1.14] |
12.2 Women only |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
12.3 Men and women |
4 |
498 |
Risk Ratio (M‐H, Random, 95% CI) |
0.76 [0.43, 1.36] |
12.4 Sex not reported |
1 |
54 |
Risk Ratio (M‐H, Random, 95% CI) |
1.55 [0.41, 5.84] |
13 Cardiovascular mortality (overall) |
7 |
4019 |
Risk Ratio (M‐H, Random, 95% CI) |
1.09 [0.76, 1.55] |
14 CVD mortality ‐ sensitivity analysis by fixed‐effect analysis |
7 |
4019 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.05 [0.89, 1.25] |
15 CVD mortality ‐ sensitivity analyses |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
15.1 Studies at low risk of bias |
1 |
458 |
Risk Ratio (M‐H, Random, 95% CI) |
1.59 [0.99, 2.55] |
15.2 Pre‐2010 or prospective trials registry entry |
7 |
4019 |
Risk Ratio (M‐H, Random, 95% CI) |
1.09 [0.76, 1.55] |
15.3 No commercial funding |
4 |
1086 |
Risk Ratio (M‐H, Random, 95% CI) |
1.22 [0.67, 2.23] |
15.4 Low risk of attention bias |
2 |
900 |
Risk Ratio (M‐H, Random, 95% CI) |
0.79 [0.45, 1.39] |
15.5 Randomised 250+ participants |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.08 [0.76, 1.54] |
15.6 Randomised 100+ participants |
6 |
3965 |
Risk Ratio (M‐H, Random, 95% CI) |
1.06 [0.73, 1.55] |
16 CVD mortality ‐ subgroup by intervention type |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
16.1 Dietary advice |
4 |
2726 |
Risk Ratio (M‐H, Random, 95% CI) |
1.33 [0.86, 2.05] |
16.2 Supplements (capsules) |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
16.3 Supplemental foods |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
16.4 Dietary advice plus supplement |
2 |
447 |
Risk Ratio (M‐H, Random, 95% CI) |
1.11 [0.69, 1.78] |
16.5 Diet (all foods) provided |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.70 [0.51, 0.96] |
17 CVD mortality ‐ subgroup by replacement |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
17.1 N‐6 replacing SFA |
5 |
3832 |
Risk Ratio (M‐H, Random, 95% CI) |
1.04 [0.71, 1.52] |
17.2 N‐6 replacing MUFA |
3 |
1358 |
Risk Ratio (M‐H, Random, 95% CI) |
1.10 [0.56, 2.16] |
17.3 N‐6 replacing nil, low n‐6 |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
17.4 N‐6 replacement unclear |
1 |
393 |
Risk Ratio (M‐H, Random, 95% CI) |
1.05 [0.63, 1.75] |
17.5 N‐6 replacing CHO |
2 |
235 |
Risk Ratio (M‐H, Random, 95% CI) |
0.65 [0.01, 33.17] |
17.6 N‐6 replacing protein |
1 |
133 |
Risk Ratio (M‐H, Random, 95% CI) |
4.93 [0.24, 100.70] |
18 CVD mortality ‐ subgroup by baseline CVD risk |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
18.1 Primary prevention ‐ low CVD risk |
2 |
979 |
Risk Ratio (M‐H, Random, 95% CI) |
1.02 [0.22, 4.66] |
18.2 Primary prevention ‐ moderate CVD risk |
1 |
102 |
Risk Ratio (M‐H, Random, 95% CI) |
0.09 [0.01, 1.60] |
18.3 Secondary prevention ‐ existing CVD |
4 |
2938 |
Risk Ratio (M‐H, Random, 95% CI) |
1.28 [1.04, 1.57] |
19 CVD mortality ‐ subgroup by omega‐6 dose |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
19.1 N‐6 < 4% E |
2 |
2166 |
Risk Ratio (M‐H, Random, 95% CI) |
1.26 [0.97, 1.64] |
19.2 N‐6 4% to 12% E |
3 |
1406 |
Risk Ratio (M‐H, Random, 95% CI) |
0.87 [0.38, 1.99] |
19.3 N‐6 > 12% E |
2 |
447 |
Risk Ratio (M‐H, Random, 95% CI) |
1.11 [0.69, 1.78] |
20 CVD mortality ‐ subgroup by duration |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
20.1 Medium duration 1 to < 2 years in study |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
20.2 Medium‐long duration 2 to < 4 years |
3 |
2220 |
Risk Ratio (M‐H, Random, 95% CI) |
1.27 [0.98, 1.64] |
20.3 Long duration 4+ years in study |
4 |
1799 |
Risk Ratio (M‐H, Random, 95% CI) |
0.96 [0.56, 1.63] |
21 CVD mortality ‐ subgroup by baseline omega‐6 |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
21.1 ≥ 8% E from n‐6 |
1 |
133 |
Risk Ratio (M‐H, Random, 95% CI) |
4.93 [0.24, 100.70] |
21.2 5% to < 8% E from n‐6 |
2 |
2491 |
Risk Ratio (M‐H, Random, 95% CI) |
1.32 [1.05, 1.66] |
21.3 < 5% E from n‐6 |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.70 [0.51, 0.96] |
21.4 Baseline n‐6 not reported |
3 |
549 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.38, 2.34] |
22 CVD mortality ‐ subgroup by sex |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
22.1 Men only |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.08 [0.76, 1.54] |
22.2 Women only |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
22.3 Men and women |
2 |
235 |
Risk Ratio (M‐H, Random, 95% CI) |
0.65 [0.01, 33.17] |
22.4 Sex not reported |
1 |
54 |
Risk Ratio (M‐H, Random, 95% CI) |
1.55 [0.41, 5.84] |
23 Any cardiovascular event (overall) |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
24 CVD events ‐ sensitivity analysis by fixed‐effect analysis |
7 |
4962 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.97 [0.89, 1.05] |
25 CVD events ‐ sensitivity analyses |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
25.1 Studies at low risk of bias |
2 |
1525 |
Risk Ratio (M‐H, Random, 95% CI) |
1.62 [1.02, 2.57] |
25.2 Pre‐2010 or prospective trials registry entry |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
25.3 No commercial funding |
3 |
1918 |
Risk Ratio (M‐H, Random, 95% CI) |
1.16 [0.64, 2.12] |
25.4 Low risk of attention bias |
4 |
2078 |
Risk Ratio (M‐H, Random, 95% CI) |
0.90 [0.66, 1.22] |
25.5 Randomised 250+ participants |
5 |
4797 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.78, 1.16] |
25.6 Randomised 100+ participants |
6 |
4908 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.79, 1.14] |
26 CVD events ‐ subgroup by LA or GLA |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
26.1 Mainly LA |
6 |
4851 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.17] |
26.2 GLA supplements |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
27 CVD events ‐ subgroup by intervention type |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
27.1 Dietary advice |
2 |
2491 |
Risk Ratio (M‐H, Random, 95% CI) |
1.18 [0.76, 1.85] |
27.2 Supplements (capsules) |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
27.3 Supplemental foods |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
27.4 Dietary advice plus supplement |
2 |
447 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.63, 1.42] |
27.5 Diet (all foods) provided |
2 |
1913 |
Risk Ratio (M‐H, Random, 95% CI) |
0.80 [0.64, 1.01] |
28 CVD events ‐ subgroup by replacement |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
28.1 N‐6 replacing SFA |
5 |
4797 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.78, 1.16] |
28.2 N‐6 replacing MUFA |
4 |
2425 |
Risk Ratio (M‐H, Random, 95% CI) |
1.15 [0.73, 1.81] |
28.3 N‐6 replacing nil, low n‐6 |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
28.4 N‐6 replacement unclear |
1 |
393 |
Risk Ratio (M‐H, Random, 95% CI) |
0.82 [0.62, 1.07] |
28.5 N‐6 replacing CHO |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
28.6 N‐6 replacing protein |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
29 CVD events ‐ subgroup by baseline CVD risk |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
29.1 Primary prevention ‐ low CVD risk |
2 |
1913 |
Risk Ratio (M‐H, Random, 95% CI) |
0.80 [0.64, 1.01] |
29.2 Primary prevention ‐ moderate CVD risk |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
29.3 Secondary prevention ‐ existing CVD |
4 |
2938 |
Risk Ratio (M‐H, Random, 95% CI) |
1.04 [0.83, 1.29] |
30 CVD events ‐ subgroup by primary vs secondary prevention |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
30.1 Primary prevention ‐ low or mod CVD risk |
3 |
2024 |
Risk Ratio (M‐H, Random, 95% CI) |
0.80 [0.64, 1.00] |
30.2 Secondary prevention ‐ existing CVD |
4 |
2938 |
Risk Ratio (M‐H, Random, 95% CI) |
1.04 [0.83, 1.29] |
31 CVD events ‐ subgroup by omega‐6 dose |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
31.1 N‐6 < 4% E |
2 |
2144 |
Risk Ratio (M‐H, Random, 95% CI) |
0.99 [0.90, 1.09] |
31.2 N‐6 4% to 12% E |
3 |
2371 |
Risk Ratio (M‐H, Random, 95% CI) |
1.15 [0.61, 2.16] |
31.3 N‐6 > 12% E |
2 |
447 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.63, 1.42] |
32 CVD events ‐ subgroup by duration |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
32.1 Medium duration 1 to < 2 years in study |
2 |
1178 |
Risk Ratio (M‐H, Random, 95% CI) |
1.30 [0.22, 7.67] |
32.2 Medium‐long duration 2 to < 4 years |
2 |
2087 |
Risk Ratio (M‐H, Random, 95% CI) |
1.00 [0.91, 1.09] |
32.3 Long duration 4+ years in study |
3 |
1697 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.68, 1.33] |
33 CVD events ‐ subgroup by baseline omega‐6 |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
33.1 ≥ 8% E from n‐6 |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
33.2 5% to < 8% E from n‐6 |
2 |
2491 |
Risk Ratio (M‐H, Random, 95% CI) |
1.18 [0.76, 1.85] |
33.3 < 5% E from n‐6 |
2 |
1913 |
Risk Ratio (M‐H, Random, 95% CI) |
0.80 [0.64, 1.01] |
33.4 baseline n‐6 not reported |
3 |
558 |
Risk Ratio (M‐H, Random, 95% CI) |
0.90 [0.67, 1.21] |
34 CVD events ‐ subgroup by sex |
7 |
4962 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.81, 1.15] |
34.1 Men only |
5 |
4797 |
Risk Ratio (M‐H, Random, 95% CI) |
0.95 [0.78, 1.16] |
34.2 Men and women |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
34.3 Sex not reported |
1 |
54 |
Risk Ratio (M‐H, Random, 95% CI) |
1.27 [0.72, 2.23] |
35 Coronary heart disease events (overall): myocardial infarction (fatal or non‐fatal) or angina |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
36 CHD events ‐ sensitivity analysis by fixed‐effect analysis |
7 |
3997 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.91 [0.82, 1.00] |
37 CHD events ‐ sensitivity analyses |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
37.1 Studies at low risk of bias |
1 |
458 |
Risk Ratio (M‐H, Random, 95% CI) |
1.63 [1.00, 2.67] |
37.2 Pre‐2010 or prospective trials registry entry |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
37.3 No commercial funding |
3 |
953 |
Risk Ratio (M‐H, Random, 95% CI) |
0.78 [0.33, 1.82] |
37.4 Low risk of attention bias |
3 |
1011 |
Risk Ratio (M‐H, Random, 95% CI) |
0.83 [0.62, 1.09] |
37.5 Randomised 250+ participants |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.78, 1.19] |
37.6 Randomised 100+ participants |
6 |
3943 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.61, 1.15] |
38 CHD events ‐ subgroup by LA or GLA |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
38.1 Mainly LA |
6 |
3886 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.19] |
38.2 GLA supplements |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
39 CHD events ‐ subgroup by intervention type |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
39.1 Dietary advice |
3 |
2593 |
Risk Ratio (M‐H, Random, 95% CI) |
0.78 [0.38, 1.61] |
39.2 Dietary advice plus supplement |
2 |
447 |
Risk Ratio (M‐H, Random, 95% CI) |
1.02 [0.76, 1.38] |
39.3 Supplemental foods |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
39.4 Supplements (capsules) |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
39.5 Diet (all foods) provided |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.77 [0.56, 1.04] |
40 CHD events ‐ subgroup by replacement |
7 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
40.1 N‐6 replacing SFA |
5 |
3832 |
Risk Ratio (M‐H, Random, 95% CI) |
0.85 [0.61, 1.17] |
40.2 N‐6 replacing MUFA |
3 |
1358 |
Risk Ratio (M‐H, Random, 95% CI) |
1.38 [1.07, 1.77] |
40.3 N‐6 replacing nil, low n‐6 |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
40.4 N‐6 replacement unclear |
1 |
393 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.69, 1.37] |
40.5 N‐6 replacing CHO |
1 |
102 |
Risk Ratio (M‐H, Random, 95% CI) |
0.27 [0.14, 0.52] |
40.6 N‐6 replacing protein |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
41 CHD events ‐ subgroup by baseline CVD risk |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
41.1 Primary prevention ‐ low CVD risk |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.77 [0.56, 1.04] |
41.2 Primary prevention ‐ moderate CVD risk |
2 |
213 |
Risk Ratio (M‐H, Random, 95% CI) |
0.27 [0.14, 0.52] |
41.3 Secondary prevention ‐ existing CVD |
4 |
2938 |
Risk Ratio (M‐H, Random, 95% CI) |
1.05 [0.84, 1.32] |
42 CHD events ‐ subgroup by omega‐6 dose |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
42.1 N‐6 < 4% E |
2 |
2144 |
Risk Ratio (M‐H, Random, 95% CI) |
0.93 [0.82, 1.05] |
42.2 N‐6 4% to 12% E |
3 |
1406 |
Risk Ratio (M‐H, Random, 95% CI) |
0.72 [0.31, 1.64] |
42.3 N‐6 > 12% E |
2 |
447 |
Risk Ratio (M‐H, Random, 95% CI) |
1.02 [0.76, 1.38] |
43 CHD events ‐ subgroup by duration |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
43.1 Medium duration 1 to < 2 years in study |
1 |
111 |
Risk Ratio (M‐H, Random, 95% CI) |
0.35 [0.01, 8.45] |
43.2 Medium‐long duration 2 to < 4 years |
2 |
2087 |
Risk Ratio (M‐H, Random, 95% CI) |
0.94 [0.83, 1.05] |
43.3 Long duration 4+ years in study |
4 |
1799 |
Risk Ratio (M‐H, Random, 95% CI) |
0.79 [0.46, 1.35] |
44 CHD events ‐ subgroup by baseline omega‐6 |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
44.1 ≥ 8% E from n‐6 |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
44.2 5% to < 8% E from n‐6 |
2 |
2491 |
Risk Ratio (M‐H, Random, 95% CI) |
1.17 [0.68, 2.01] |
44.3 < 5% E from n‐6 |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.77 [0.56, 1.04] |
44.4 Baseline omega 6 not reported |
4 |
660 |
Risk Ratio (M‐H, Random, 95% CI) |
0.68 [0.31, 1.47] |
45 CHD events ‐ subgroup by sex |
7 |
3997 |
Risk Ratio (M‐H, Random, 95% CI) |
0.88 [0.66, 1.17] |
45.1 Men only |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.78, 1.19] |
45.2 Women only |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
45.3 Men and women |
2 |
213 |
Risk Ratio (M‐H, Random, 95% CI) |
0.27 [0.14, 0.52] |
45.4 Sex not reported |
1 |
54 |
Risk Ratio (M‐H, Random, 95% CI) |
1.24 [0.63, 2.44] |
46 Major adverse cardiac and cerebrovascular events (MACCEs), overall |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
47 MACCEs ‐ sensitivity analysis by fixed‐effect analysis |
2 |
2879 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.92 [0.82, 1.04] |
48 MACCEs ‐ sensitivity analyses |
2 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
48.1 Low risk of bias |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
48.2 Pre‐2010 or prospective trials registry entry |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
48.3 No commercial funding |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
48.4 Low risk of attention bias |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.69 [0.51, 0.93] |
48.5 Randomised 250+ participants |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
48.6 Randomised 100+ participants |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
49 MACCEs ‐ subgroup by intervention type |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
49.1 Dietary advice |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
0.99 [0.87, 1.12] |
49.2 Supplements (capsules) |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
49.3 Supplemental foods |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
49.4 Dietary advice plus supplement |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
49.5 Diet (all foods) provided |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.69 [0.51, 0.93] |
50 MACCEs ‐ subgroup by replacement |
2 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
50.1 N‐6 replacing SFA |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
50.2 N‐6 replacing MUFA |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.69 [0.51, 0.93] |
50.3 N‐6 replacing nil, low n‐6 |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
50.4 N‐6 replacement unclear |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
50.5 N‐6 replacing CHO |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
50.6 N‐6 replacing protein |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
51 MACCEs ‐ subgroup by baseline CVD risk |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
51.1 Primary prevention ‐ low CVD risk |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.69 [0.51, 0.93] |
51.2 Primary prevention ‐ moderate CVD risk |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
51.3 Secondary prevention ‐ existing CVD |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
0.99 [0.87, 1.12] |
52 MACCEs ‐ subgroup by omega‐6 dose |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
52.1 N‐6 < 4% E |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
0.99 [0.87, 1.12] |
52.2 N‐6 4% to 12% E |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.69 [0.51, 0.93] |
52.3 N‐6 > 12% E |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
53 MACCEs ‐ subgroup by duration |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
53.1 Medium duration 1 to < 2 years in study |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
53.2 Medium‐long duration 2 to < 4 years |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
0.99 [0.87, 1.12] |
53.3 Long duration 4+ years in study |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.69 [0.51, 0.93] |
54 MACCEs ‐ subgroup by baseline omega‐6 |
2 |
2879 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.59, 1.20] |
54.1 ≥ 8% E from n‐6 |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
54.2 5% to < 8% E from n‐6 |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
0.99 [0.87, 1.12] |
54.3 < 5% E from n‐6 |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.69 [0.51, 0.93] |
54.4 Baseline n‐6 not reported |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
55 Stroke: fatal or non‐fatal (overall) |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
56 Stroke ‐ sensitivity analysis by fixed‐effect analysis |
4 |
3730 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.00 [0.59, 1.68] |
57 Stroke ‐ sensitivity analyses |
4 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
57.1 Low risk of bias |
1 |
458 |
Risk Ratio (M‐H, Random, 95% CI) |
1.07 [0.15, 7.55] |
57.2 Pre‐2010 or prospective trials registry entry |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
57.3 No commercial funding |
2 |
851 |
Risk Ratio (M‐H, Random, 95% CI) |
1.67 [0.32, 8.62] |
57.4 Low risk of attention bias |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.59 [0.30, 1.15] |
57.5 Randomised 250+ participants |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
57.6 Randomised 100+ participants |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
58 Stroke ‐ subgroup by intervention type |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
58.1 Dietary advice |
2 |
2491 |
Risk Ratio (M‐H, Random, 95% CI) |
2.36 [0.81, 6.91] |
58.2 Supplements (capsules) |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
58.3 Supplemental foods |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
58.4 Dietary advice plus supplement |
1 |
393 |
Risk Ratio (M‐H, Random, 95% CI) |
4.88 [0.24, 100.89] |
58.5 Diet (all foods) provided |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.59 [0.30, 1.15] |
59 Stroke ‐ subgroup by replacement |
4 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
59.1 N‐6 replacing SFA |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
59.2 N‐6 replacing MUFA |
2 |
1304 |
Risk Ratio (M‐H, Random, 95% CI) |
0.63 [0.33, 1.18] |
59.3 N‐6 replacing nil, low n‐6 |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
59.4 N‐6 replacement unclear |
1 |
393 |
Risk Ratio (M‐H, Random, 95% CI) |
4.88 [0.24, 100.89] |
59.5 N‐6 replacing CHO |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
59.6 N‐6 replacing protein |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
60 Stroke ‐ subgroup by baseline CVD risk |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
60.1 Primary prevention ‐ low CVD risk |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.59 [0.30, 1.15] |
60.2 Primary prevention ‐ moderate CVD risk |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
60.3 Secondary prevention ‐ existing CVD |
3 |
2884 |
Risk Ratio (M‐H, Random, 95% CI) |
2.56 [0.93, 7.04] |
61 Stroke ‐ subgroup by omega‐6 dose |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
61.1 N‐6 < 4% E |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
3.32 [0.92, 12.04] |
61.2 N‐6 ≥ 4% to < 12% E |
2 |
1304 |
Risk Ratio (M‐H, Random, 95% CI) |
0.63 [0.33, 1.18] |
61.3 N‐6 ≥ 12% E |
1 |
393 |
Risk Ratio (M‐H, Random, 95% CI) |
4.88 [0.24, 100.89] |
62 Stroke ‐ subgroup by duration |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
62.1 Medium duration 1 to < 2 years in study |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
62.2 Medium‐long duration 2 to < 4 years |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
3.32 [0.92, 12.04] |
62.3 Long duration 4+ years in study |
3 |
1697 |
Risk Ratio (M‐H, Random, 95% CI) |
0.69 [0.36, 1.33] |
63 Stroke ‐ subgroup by baseline omega‐6 |
4 |
3730 |
Risk Ratio (M‐H, Random, 95% CI) |
1.36 [0.45, 4.11] |
63.1 ≥ 8% E from n‐6 |
0 |
0 |
Risk Ratio (M‐H, Random, 95% CI) |
0.0 [0.0, 0.0] |
63.2 5% to < 8% E from n‐6 |
2 |
2491 |
Risk Ratio (M‐H, Random, 95% CI) |
2.36 [0.81, 6.91] |
63.3 < 5% E from n‐6 |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.59 [0.30, 1.15] |
63.4 Baseline n‐6 not reported |
1 |
393 |
Risk Ratio (M‐H, Random, 95% CI) |
4.88 [0.24, 100.89] |
64 Stroke ‐ subgroup by stroke type |
1 |
4066 |
Risk Ratio (M‐H, Random, 95% CI) |
2.93 [0.64, 13.49] |
64.1 Ischaemic stroke |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
6.98 [0.86, 56.62] |
64.2 Haemorrhagic stroke |
1 |
2033 |
Risk Ratio (M‐H, Random, 95% CI) |
1.50 [0.25, 8.93] |
65 Stroke ‐ subgroup by fatality |
2 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
65.1 Fatal stroke |
2 |
1304 |
Risk Ratio (M‐H, Random, 95% CI) |
0.48 [0.16, 1.40] |
65.2 Non‐fatal stroke |
1 |
846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.77 [0.34, 1.73] |