Comparison 4. High vs low ALA omega‐3 fat (primary outcomes).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality (overall) ‐ ALA	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.84, 1.20]
2 All‐cause mortality ‐ ALA ‐ sensitivity analysis (SA) fixed‐effect	5	16923	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.84, 1.34]
3 All‐cause mortality ‐ ALA ‐ SA by summary risk of bias	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.84, 1.20]
3.1 Low risk of bias	3	5213	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.72, 1.45]
3.2 Moderate/high risk of bias	2	14114	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.71, 1.67]
4 All‐cause mortality ‐ ALA ‐ SA by compliance and study size	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
4.1 SA ‐ low risk of compliance bias	3	5811	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.68, 1.63]
4.2 SA ‐ 100+ randomised	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.84, 1.20]
5 All‐cause mortality ‐ ALA ‐ subgroup by dose	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.84, 1.20]
5.1 ALA low < 5 g/d	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.80, 1.19]
5.2 ALA high ≥ 5 g/d	4	14490	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.77, 1.75]
6 All‐cause mortality ‐ ALA ‐ subgroup by replacement	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.1 ALA replacing SFA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.2 ALA replacing MUFA	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.80, 1.19]
6.3 ALA replacing n‐6	2	13672	Risk Ratio (M‐H, Random, 95% CI)	1.37 [0.48, 3.86]
6.4 ALA replacing CHO	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.5 ALA replacing nil/low n‐3 placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.6 ALA replacement unclear	2	818	Risk Ratio (M‐H, Random, 95% CI)	2.78 [0.29, 26.49]
7 All cause mortality ‐ ALA ‐ subgroup by intervention type	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.84, 1.20]
7.1 Dietary advice	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Supplemental foods	4	5921	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.82, 1.21]
7.3 Supplements (capsule)	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.70, 1.64]
7.4 Any combination	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 All‐cause mortality ‐ ALA ‐ subgroup by duration	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.84, 1.20]
8.1 Medium duration 1 to < 2 years in study	2	13516	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.71, 1.67]
8.2 Medium‐long duration: 2 to < 4 years in study	3	5811	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.68, 1.63]
8.3 Long duration: ≥ 4 years in study	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9 All‐cause mortality ‐ ALA ‐ subgroup by primary or secondary prevention	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.84, 1.20]
9.1 Primary CVD prevention	3	14380	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.75, 1.74]
9.2 Secondary CVD prevention	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.81, 1.19]
10 All‐cause mortality ‐ ALA ‐ subgroup by statin use	5	16923	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.84, 1.33]
10.1 ALA ‐ ≥ 50% of control group on statins	2	2543	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.77, 1.34]
10.2 ALA ‐ < 50% of control group on statins	3	14380	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.75, 1.74]
11 Cardiovascular mortality (overall) ‐ ALA	4	18619	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.74, 1.25]
12 CVD mortality ‐ ALA ‐ SA fixed‐effect	4	18619	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.74, 1.25]
13 CVD mortality ‐ ALA ‐ SA by summary risk of bias	4	18619	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.74, 1.25]
13.1 Low risk of bias	3	5213	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.70, 1.28]
13.2 Moderate/high risk of bias	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.58, 1.70]
14 CVD mortality ‐ ALA ‐ SA by compliance and study size	4	23722	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.78, 1.16]
14.1 SA ‐ low risk of compliance bias	2	5103	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.70, 1.27]
14.2 SA ‐ 100+ randomised	4	18619	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.74, 1.25]
15 CVD mortality ‐ ALA ‐ subgroup by dose	4	18619	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.74, 1.25]
15.1 ALA low < 5 g/d	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.69, 1.27]
15.2 ALA high ≥ 5 g/d	3	13782	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.62, 1.73]
16 CVD mortality ‐ ALA ‐ subgroup by replacement	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
16.1 N‐3 replacing SFA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
16.2 N‐3 replacing MUFA	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.69, 1.27]
16.3 N‐3 replacing n‐6	2	13672	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.60, 1.70]
16.4 N‐3 replacing carbohydrates/sugars	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
16.5 N‐3 replacing nil/low n‐3 placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
16.6 Replacement unclear	1	110	Risk Ratio (M‐H, Random, 95% CI)	2.69 [0.11, 64.74]
17 CVD mortality ‐ ALA ‐ subgroup by intervention type	4	18619	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.74, 1.25]
17.1 Dietary advice	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
17.2 Supplemental foods	3	5213	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.70, 1.28]
17.3 Supplements (capsule)	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.58, 1.70]
17.4 Any combination	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
18 CVD mortality ‐ ALA ‐ subgroup by duration	4	18619	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.74, 1.25]
18.1 Medium duration 1 to < 2 years in study	2	13516	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.61, 1.73]
18.2 Medium‐long duration: 2 to < 4 years in study	2	5103	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.70, 1.27]
18.3 Long duration: ≥ 4 years in study	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
19 CVD mortality ‐ ALA ‐ subgroup by primary or secondary prevention	4	18619	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.74, 1.25]
19.1 Primary prevention	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.58, 1.70]
19.2 Secondary prevention	3	5213	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.70, 1.28]
20 CVD mortality ‐ ALA ‐ subgroup by statin uses	4	18619	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.74, 1.25]
20.1 ALA ‐ ≥ 50% of control group on statins	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.70, 1.28]
20.2 ALA ‐ < 50% of control group on statins	2	13672	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.60, 1.70]
21 Cardiovascular events (overall) ‐ ALA	5	19327	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.07]
22 CVD events ‐ ALA ‐ SA fixed‐effect	5	19327	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.84, 1.07]
23 CVD events ‐ ALA ‐ SA by summary risk of bias	5	19327	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.07]
23.1 Low risk of bias	3	5213	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.79, 1.04]
23.2 Moderate/high risk of bias	2	14114	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.84, 1.48]
24 CVD events ‐ ALA ‐ SA by compliance and study size	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
24.1 SA ‐ low risk of compliance bias	3	5811	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.79, 1.04]
24.2 SA ‐ 100+ randomised	5	19327	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.07]
25 CVD events ‐ ALA ‐ subgroup by dose	5	19327	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.07]
25.1 ALA low < 5 g/d	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.79, 1.05]
25.2 ALA high ≥ 5 g/d	4	14490	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.82, 1.40]
26 CVD events ‐ ALA ‐ subgroup by replacement	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
26.1 N‐3 replacing SFA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
26.2 N‐3 replacing MUFA	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.79, 1.05]
26.3 N‐3 replacing n‐6	2	13672	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.24, 2.41]
26.4 N‐3 replacing carbohydrates/sugars	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
26.5 N‐3 replacing nil/low n‐3 placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
26.6 Replacement unclear	2	818	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.36, 2.43]
27 CVD events ‐ ALA ‐ subgroup by intervention type	6	19526	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.07]
27.1 Dietary advice	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
27.2 Supplemental foods	5	6120	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.79, 1.04]
27.3 Supplements (capsule)	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.85, 1.51]
27.4 Any combination	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
28 CVD events ‐ ALA ‐ subgroup by duration	5	19327	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.07]
28.1 Medium duration 1 to < 2 years in study	2	13516	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.86, 1.50]
28.2 Medium‐long duration: 2 to < 4 years in study	3	5811	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.79, 1.04]
28.3 Long duration: ≥ 4 years in study	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
29 CVD events ‐ ALA ‐ subgroup by primary or secondary prevention	5	19327	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.07]
29.1 Primary prevention	3	14380	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.46, 1.67]
29.2 Secondary prevention	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.80, 1.05]
30 CVD events ‐ ALA ‐ subgroup by statin use	5	19327	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.07]
30.1 ALA ‐ ≥ 50% of control group on statins	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.80, 1.05]
30.2 ALA ‐ < 50% of control group on statins	3	14380	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.46, 1.67]
31 Coronary heart disease mortality (overall) ‐ ALA	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
32 CHD mortality ‐ ALA ‐ SA fixed‐effect	3	18353	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.72, 1.26]
33 CHD mortality ‐ ALA ‐ SA by summary risk of bias	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
33.1 Low risk of bias	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.67, 1.30]
33.2 Moderate/high risk of bias	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.58, 1.70]
34 CHD mortality ‐ ALA ‐ SA by compliance and study size	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
34.1 SA ‐ low risk of compliance bias	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]
34.2 SA ‐ 100+ randomised	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
35 CHD mortality ‐ ALA ‐ subgroup by dose	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
35.1 ALA low < 5 g/d	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]
35.2 ALA high ≥ 5 g/d	2	13516	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.61, 1.73]
36 CHD mortality ‐ ALA ‐ subgroup by replacement	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
36.1 N‐3 replacing SFA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
36.2 Coronary heart mortality‐ ALA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
36.3 N‐3 replacing MUFA	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]
36.4 N‐3 replacing n‐6	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.58, 1.70]
36.5 N‐3 replacing carbohydrates/sugars	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
36.6 N‐3 replacing nil/low n‐3 placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
36.7 Replacement unclear	1	110	Risk Ratio (M‐H, Random, 95% CI)	2.69 [0.11, 64.74]
37 CHD mortality ‐ ALA ‐ subgroup by intervention type	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
37.1 Dietary advice	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
37.2 Supplemental foods	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.67, 1.30]
37.3 Supplements (capsule)	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.58, 1.70]
37.4 Any combination	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
38 CHD mortality ‐ ALA ‐ subgroup by duration	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
38.1 Medium duration 1 to < 2 years in study	2	13516	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.61, 1.73]
38.2 Medium‐long duration: 2 to < 4 years in study	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]
38.3 Long duration: ≥ 4 years in study	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
39 CHD mortality ‐ ALA ‐ subgroup by primary or secondary prevention	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
39.1 Primary prevention of CVD	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.58, 1.70]
39.2 Secondary prevention of CVD	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.67, 1.30]
40 CHD mortality ‐ ALA ‐ subgroup by statin use	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
40.1 ALA ‐ ≥ 50% of control group on statins	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.67, 1.30]
40.2 ALA ‐ < 50% of control group on statins	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.58, 1.70]
41 CHD mortality ‐ ALA ‐ subgroup by CAD history	3	18353	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.72, 1.26]
41.1 Previous CAD	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]
41.2 No previous CAD	2	13516	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.61, 1.73]
42 Coronary heart disease events (overall) ‐ ALA	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
43 CHD events ‐ ALA ‐ SA fixed‐effect	4	19061	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.82, 1.21]
44 CHD events ‐ ALA ‐ SA by summary risk of bias	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
44.1 Low risk of bias	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.71, 1.15]
44.2 Moderate/high risk of bias	2	14114	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.86, 1.67]
45 CHD events ‐ ALA ‐ SA by compliance and study size	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
45.1 SA ‐ low risk of compliance bias	2	5545	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.73, 1.17]
45.2 SA ‐ 100+ randomised	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
46 CHD events ‐ ALA ‐ subgroup by dose	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
46.1 ALA low < 5 g/d	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.72, 1.17]
46.2 ALA high ≥ 5 g/d	3	14224	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.84, 1.61]
47 CHD events ‐ ALA ‐ subgroup by replacement	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
47.1 N‐3 replacing SFA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
47.2 N‐3 replacing MUFA	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.72, 1.17]
47.3 N‐3 replacing n‐6	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.85, 1.65]
47.4 N‐3 replacing carbohydrates/sugars	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
47.5 N‐3 replacing nil/low n‐3 placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
47.6 Replacement unclear	2	818	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.08, 5.81]
48 CHD events ‐ ALA ‐ subgroup by intervention type	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
48.1 Dietary advice	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
48.2 Supplemental foods	3	5655	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.72, 1.16]
48.3 Supplements (capsule)	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.85, 1.65]
48.4 Any combination	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
49 CHD events ‐ ALA ‐ subgroup by duration	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
49.1 Medium duration 1 to < 2 years in study	2	13516	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.34, 2.58]
49.2 Medium‐long duration: 2 to < 4 years in study	2	5545	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.73, 1.17]
49.3 Long duration: ≥ 4 years in study	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
50 CHD events ‐ ALA ‐ subgroup by primary or secondary prevention	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
50.1 Primary prevention	2	14114	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.86, 1.67]
50.2 Secondary prevention	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.71, 1.15]
51 CHD events ‐ ALA ‐ subgroup by statin use	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
51.1 ALA ‐ ≥ 50% of control group on statins	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.71, 1.15]
51.2 ALA ‐ < 50% of control group on statins	2	14114	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.86, 1.67]
52 CHD events ‐ ALA ‐ subgroup by CAD history	4	19061	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
52.1 Previous CAD	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.72, 1.17]
52.2 No previous CAD	3	14224	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.84, 1.61]
53 Stroke (overall) ‐ ALA	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.66, 2.01]
54 Stroke ‐ ALA ‐ SA fixed‐effect	5	19327	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.71, 2.13]
55 Stroke ‐ ALA ‐ SA by summary risk of bias	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.66, 2.01]
55.1 Low risk of bias	3	5213	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.45, 2.09]
55.2 Moderate/high risk of bias	2	14114	Risk Ratio (M‐H, Random, 95% CI)	1.39 [0.62, 3.13]
56 Stroke ‐ ALA ‐ SA by compliance and study size	5	25138	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.66, 1.64]
56.1 SA ‐ low risk of compliance bias	3	5811	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.39, 1.87]
56.2 SA ‐ 100+ randomised	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.66, 2.01]
57 Stroke ‐ ALA ‐ subgroup by dose	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
57.1 ALA low < 5 g/d	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.39, 2.15]
57.2 ALA high ≥ 5 g/d	4	14490	Risk Ratio (M‐H, Random, 95% CI)	1.36 [0.65, 2.85]
58 Stroke ‐ ALA ‐ subgroup by replacement	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
58.1 N‐3 replacing SFA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
58.2 N‐3 replacing MUFA	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.39, 2.15]
58.3 N‐3 replacing n‐6	2	13672	Risk Ratio (M‐H, Random, 95% CI)	1.26 [0.53, 3.01]
58.4 N‐3 replacing carbohydrates/sugars	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
58.5 N‐3 replacing nil/low n‐3 placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
58.6 Replacement unclear	2	818	Risk Ratio (M‐H, Random, 95% CI)	1.79 [0.31, 10.17]
59 Stroke ‐ ALA ‐ subgroup by intervention type	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.66, 2.01]
59.1 Dietary advice	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
59.2 Supplemental foods	4	5921	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.46, 2.03]
59.3 Supplements (capsule)	1	13406	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.62, 3.36]
59.4 Any combination	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
60 Stroke ‐ ALA ‐ subgroup by duration	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.66, 2.01]
60.1 Medium duration 1 to < 2 years in study	2	13516	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.70, 3.44]
60.2 Medium‐long duration: 2 to < 4 years in study	3	5811	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.39, 1.87]
60.3 Long duration: ≥ 4 years in study	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
61 Stroke ‐ ALA ‐ subgroup by primary or secondary prevention	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.66, 2.01]
61.1 Primary prevention	3	14380	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.57, 2.74]
61.2 Secondary prevention	2	4947	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.47, 2.34]
62 Stroke ‐ ALA ‐ subgroup by statin use	5	19327	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.71, 2.18]
62.1 ALA ‐ ≥ 50% of control group on statins	2	4947	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.56, 2.77]
62.2 ALA ‐ < 50% of control group on statins	3	14380	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.57, 2.74]
63 Stroke ‐ ALA ‐ subgroup by stroke type	3	13782	Risk Ratio (M‐H, Random, 95% CI)	1.40 [0.65, 3.01]
63.1 Ischaemic stroke ‐ ALA	3	13782	Risk Ratio (M‐H, Random, 95% CI)	1.40 [0.65, 3.01]
63.2 Haemorrhagic stroke ‐ ALA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
64 Arrythmia (overall) ‐ ALA	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.57, 1.10]
64.1 ALA ‐ new arrhythmias	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.57, 1.10]
64.2 ALA ‐ recurrent arrhythmias	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
65 Arrhythmia ‐ ALA ‐ SA by summary risk of bias	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.57, 1.10]
65.1 Low risk of bias	1	4837	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.57, 1.10]
65.2 Moderate/high risk of bias	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]