Skip to main content
. 2018 Nov 29;2018(11):CD011094. doi: 10.1002/14651858.CD011094.pub4

Comparison 1. Primary outcomes ‐ higher omega‐6 vs lower omega‐6.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
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]