Comparison 5. High vs low ALA omega‐3 fat (secondary outcomes).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 MACCEs ‐ ALA	1	110	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.32, 3.95]
2 Myocardial infarction (overall) ‐ ALA	3	18353	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.76, 1.32]
3 Total MI ‐ ALA ‐ subgroup by fatality	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
3.1 Fatal MI	2	4947	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.62, 1.46]
3.2 Non‐fatal MI	3	5213	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.15, 1.77]
4 Angina ‐ ALA	2	13516	Risk Ratio (M‐H, Random, 95% CI)	1.41 [0.75, 2.64]
5 Revascularisation ‐ ALA	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
5.1 CABG ‐ ALA	1	266	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.01, 5.93]
5.2 Angioplasty ‐ ALA	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
5.3 Any revascularisation ‐ ALA	1	266	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.07, 7.84]
6 Peripheral arterial disease ‐ ALA	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
7 Body weight, kg ‐ ALA	4	664	Mean Difference (IV, Random, 95% CI)	‐1.49 [‐4.17, 1.18]
8 Weight, kg ‐ ALA ‐ sensitivity analysis (SA) fixed‐effect	4	664	Mean Difference (IV, Fixed, 95% CI)	0.17 [‐0.61, 0.96]
9 Weight, kg ‐ ALA ‐ SA by summary risk of bias	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
9.1 Low risk of bias	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9.2 Moderate/high risk of bias	4	664	Mean Difference (IV, Random, 95% CI)	‐1.49 [‐4.17, 1.18]
10 Weight, kg ‐ ALA ‐ SA by compliance and study size	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
10.1 SA ‐ low risk of compliance bias	3	629	Mean Difference (IV, Random, 95% CI)	‐1.59 [‐4.47, 1.30]
10.2 SA ‐ 100+ randomised	3	629	Mean Difference (IV, Random, 95% CI)	‐1.59 [‐4.47, 1.30]
11 Weight, kg ‐ ALA ‐ subgroup by dose	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
11.1 ALA low < 5 g/d	3	485	Mean Difference (IV, Random, 95% CI)	‐0.71 [‐3.31, 1.90]
11.2 ALA high > 5 g/d	1	179	Mean Difference (IV, Random, 95% CI)	‐4.20 [‐7.61, ‐0.79]
12 Weight, kg ‐ ALA ‐ subgroup by intervention type	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
12.1 Dietary advice	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
12.2 Supplemental foods	3	526	Mean Difference (IV, Random, 95% CI)	‐1.23 [‐5.27, 2.80]
12.3 Supplement (capsule)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
12.4 Any combination	1	138	Mean Difference (IV, Random, 95% CI)	‐1.98 [‐5.89, 1.92]
13 Weight, kg ‐ ALA ‐ subgroup by replacement	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
13.1 ALA replacing SFA	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
13.2 ALA replacing MUFA	1	138	Mean Difference (IV, Random, 95% CI)	‐1.98 [‐5.89, 1.92]
13.3 ALA replacing n‐6	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
13.4 ALA replacing carbs/sugars	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
13.5 ALA replacing nil/low n‐3 placebo	1	35	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐10.57, 9.97]
13.6 Replacement unclear	2	491	Mean Difference (IV, Random, 95% CI)	‐1.43 [‐6.26, 3.39]
14 Weight, kg ‐ ALA ‐ subgroup by duration	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
14.1 Medium duration 1 to < 2 years in study	4	664	Mean Difference (IV, Random, 95% CI)	‐1.49 [‐4.17, 1.18]
14.2 Medium‐long duration: 2 to < 4 years in study	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
14.3 Long duration ≥ 4 years in study	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
15 Weight, kg ‐ ALA ‐ subgroup by statin use	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
15.1 ALA ‐ ≥ 50% of control group on statins	1	35	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐10.57, 9.97]
15.2 ALA ‐ < 50% of control group on statins	1	138	Mean Difference (IV, Random, 95% CI)	‐1.98 [‐5.89, 1.92]
15.3 ALA ‐ use of statins unclear	2	491	Mean Difference (IV, Random, 95% CI)	‐1.43 [‐6.26, 3.39]
16 Weight, kg ‐ ALA ‐ subgroup by primary or secondary prevention	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
16.1 Low CVD risk	3	629	Mean Difference (IV, Random, 95% CI)	‐1.59 [‐4.47, 1.30]
16.2 Moderate CVD risk	1	35	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐10.57, 9.97]
16.3 High CVD risk	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
17 Body mass index, kg/m² ‐ ALA	3	1581	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐1.53, 0.69]
18 BMI, kg/m² ‐ ALA ‐ SA fixed‐effect	3	1581	Mean Difference (IV, Fixed, 95% CI)	0.12 [‐0.06, 0.30]
19 BMI, kg/m² ‐ ALA ‐ SA by summary risk of bias	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
19.1 Low risk of bias	2	1402	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.04, 0.33]
19.2 Moderate/high risk of bias	1	179	Mean Difference (IV, Random, 95% CI)	‐1.5 [‐2.86, ‐0.14]
20 BMI, kg/m² ‐ ALA ‐ SA by compliance and study size	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
20.1 SA ‐ low risk of compliance bias	3	1581	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐1.53, 0.69]
20.2 SA ‐ 100+ randomised	3	1581	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐1.53, 0.69]
21 BMI, kg/m² ‐ ALA ‐ subgroup by dose	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
21.1 ALA low < 5 g/d	1	1260	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.03, 0.33]
21.2 ALA high > 5 g/d	2	321	Mean Difference (IV, Random, 95% CI)	‐1.12 [‐2.24, 0.01]
22 BMI, kg/m² ‐ ALA ‐ subgroup by intervention type	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
22.1 Dietary advice	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
22.2 Supplemental foods	3	1581	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐1.53, 0.69]
22.3 Supplement (capsule)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
22.4 Any combination	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
23 BMI, kg/m² ‐ ALA ‐ subgroup by replacement	3	1581	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐1.53, 0.69]
23.1 ALA replacing SFA	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
23.2 ALA replacing MUFA	1	1260	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.03, 0.33]
23.3 ALA replacing n‐6	1	142	Mean Difference (IV, Random, 95% CI)	‐0.3 [‐2.29, 1.69]
23.4 ALA replacing carbs/sugars	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
23.5 ALA replacing nil/low n‐3 placebo	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
23.6 Replacement unclear	1	179	Mean Difference (IV, Random, 95% CI)	‐1.5 [‐2.86, ‐0.14]
24 BMI, kg/m² ‐ ALA ‐ subgroup by duration	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
24.1 Medium duration 1 to < 2 years in study	1	179	Mean Difference (IV, Random, 95% CI)	‐1.5 [‐2.86, ‐0.14]
24.2 Medium‐long duration: 2 to < 4 years in study	2	1402	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.04, 0.33]
24.3 Long duration ≥ 4 years in study	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
25 BMI, kg/m² ‐ ALA ‐ subgroup by statin use	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
25.1 ALA ‐ ≥ 50% of control group on statins	1	1260	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.03, 0.33]
25.2 ALA ‐ < 50% of control group on statins	1	142	Mean Difference (IV, Random, 95% CI)	‐0.3 [‐2.29, 1.69]
25.3 ALA ‐ use of statins unclear	1	179	Mean Difference (IV, Random, 95% CI)	‐1.5 [‐2.86, ‐0.14]
26 BMI, kg/m² ‐ ALA ‐ subgroup by primary or secondary preventionA	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
26.1 Primary prevention of CVD	2	321	Mean Difference (IV, Random, 95% CI)	‐1.12 [‐2.24, 0.01]
26.2 Secondary prevention of CVD	1	1260	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.03, 0.33]
27 Other measures of adiposity ‐ ALA	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
27.1 Visceral adipose tissue, cm²	1	35	Mean Difference (IV, Fixed, 95% CI)	27.0 [‐21.28, 75.28]
27.2 Subcutaneous adipose tissue, cm²	1	35	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
27.3 Waist circumference, cm	3	629	Mean Difference (IV, Fixed, 95% CI)	‐1.59 [‐3.10, ‐0.07]
28 Total cholesterol, serum, mmoL/L ‐ ALA	6	2164	Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.23, 0.05]
29 TC, mmoL/L ‐ ALA ‐ SA fixed‐effect	6	2164	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.17, ‐0.03]
30 TC, mmoL/L ‐ ALA ‐ SA by summary risk of bias	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
30.1 Low risk of bias	3	1436	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.13, 0.14]
30.2 Moderate/high risk of bias	3	728	Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.36, ‐0.01]
31 TC, mmoL/L ‐ ALA ‐ SA by compliance and study size	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
31.1 SA ‐ low risk of compliance bias	4	2045	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.25, 0.05]
31.2 SA ‐ 100+ randomised	4	2045	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.25, 0.05]
32 TC, mmoL/L ‐ ALA ‐ subgroup by dose	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
32.1 ALA low < 5 g/d	3	1759	Mean Difference (IV, Random, 95% CI)	‐0.07 [‐0.24, 0.09]
32.2 ALA high > 5 g/d	3	405	Mean Difference (IV, Random, 95% CI)	‐0.13 [‐0.47, 0.21]
33 TC, mmoL/L ‐ ALA ‐ subgroup by intervention type	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
33.1 Dietary advice	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
33.2 Supplemental foods	6	2164	Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.23, 0.05]
33.3 Supplement (capsule)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
33.4 Any combination	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
34 TC, mmoL/L ‐ ALA ‐ subgroup by replacement	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
34.1 ALA replacing SFA	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
34.2 ALA replacing MUFA	1	1210	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.13, 0.09]
34.3 ALA replacing n‐6	1	142	Mean Difference (IV, Random, 95% CI)	0.14 [‐0.10, 0.38]
34.4 ALA replacing carbs/sugars	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
34.5 ALA replacing nil/low n‐3 placebo	1	35	Mean Difference (IV, Random, 95% CI)	0.30 [‐0.30, 0.90]
34.6 Replacement unclear	3	777	Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.31, ‐0.11]
35 TC, mmoL/L ‐ ALA ‐ subgroup by duration	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
35.1 Medium duration 1 to < 2 years in study	4	812	Mean Difference (IV, Random, 95% CI)	‐0.20 [‐0.33, ‐0.07]
35.2 Medium‐long duration: 2 to < 4 years in study	2	1352	Mean Difference (IV, Random, 95% CI)	0.02 [‐0.12, 0.16]
35.3 Long duration ≥ 4 years in study	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
36 TC, mmoL/L ‐ ALA ‐ subgroup by statin use	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
36.1 ALA ‐ ≥ 50% of control group on statins	3	1329	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.15, 0.11]
36.2 ALA ‐ < 50% of control group on statins	1	142	Mean Difference (IV, Random, 95% CI)	0.14 [‐0.10, 0.38]
36.3 ALA ‐ use of statins unclear	2	693	Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.30, ‐0.11]
37 TC, mmoL/L ‐ ALA ‐ subgroup by primary or secondary preventionA	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
37.1 Primary prevention of CVD	4	870	Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.30, 0.12]
37.2 Secondary prevention of CVD	2	1294	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.14, 0.08]
38 Triglycerides, fasting, serum, mmoL/L ‐ ALA	6	1776	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.11, 0.05]
39 TG, fasting, mmoL/L ‐ ALA ‐ SA fixed‐effect	6	1776	Mean Difference (IV, Fixed, 95% CI)	‐0.03 [‐0.11, 0.05]
40 TG, fasting, mmoL/L‐ ALA ‐ SA by summary risk of bias	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
40.1 Low risk of bias	3	1436	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.13, 0.19]
40.2 Moderate/high risk of bias	3	340	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.18, 0.09]
41 TG, fasting, mmoL/L‐ ALA ‐ SA by compliance and study size	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
41.1 SA ‐ low risk of compliance bias	4	1657	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.13, 0.04]
41.2 SA ‐ 100+ randomised	4	1657	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.13, 0.04]
42 TG, fasting, mmoL/L ‐ ALA ‐ subgroup by dose	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
42.1 ALA low < 5 g/d	3	1371	Mean Difference (IV, Random, 95% CI)	‐0.07 [‐0.16, 0.03]
42.2 ALA high > 5 g/d	3	405	Mean Difference (IV, Random, 95% CI)	0.05 [‐0.09, 0.19]
43 TG, fasting, mmoL/L‐ ALA ‐ subgroup by intervention type	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
43.1 Dietary advice	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
43.2 Supplemental foods	5	1650	Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.10, 0.07]
43.3 Supplement (capsule)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
43.4 Any combination	1	126	Mean Difference (IV, Random, 95% CI)	‐0.12 [‐0.33, 0.09]
44 TG, fasting, mmoL/L‐AL ‐ subgroup by replacementA	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
44.1 ALA replacing SFA	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
44.2 ALA replacing MUFA	2	1336	Mean Difference (IV, Random, 95% CI)	‐0.07 [‐0.17, 0.02]
44.3 ALA replacing n‐6	1	142	Mean Difference (IV, Random, 95% CI)	0.13 [‐0.16, 0.42]
44.4 ALA replacing carbs/sugars	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
44.5 ALA replacing nil/low n‐3 placebo	1	35	Mean Difference (IV, Random, 95% CI)	0.30 [‐0.39, 0.99]
44.6 Replacement unclear	2	263	Mean Difference (IV, Random, 95% CI)	0.04 [‐0.15, 0.23]
45 TG, fasting, mmoL/L‐ ALA ‐ subgroup by duration	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
45.1 Medium duration 1 to < 2 years in study	4	424	Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.15, 0.12]
45.2 Medium‐long duration: 2 to < 4 years in study	2	1352	Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.17, 0.15]
45.3 Long duration ≥ 4 years in study	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
46 TG, fasting, mmoL/L ‐ ALA ‐ subgroup by statin use	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
46.1 ALA ‐ ≥ 50% of control group on statins	3	1329	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.17, 0.23]
46.2 ALA ‐ < 50% of control group on statins	2	268	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.26, 0.23]
46.3 ALA ‐ use of statins unclear	1	179	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.20, 0.16]
47 TG, fasting, mmoL/L‐ ALA ‐ subgroup by primary or secondary prevention	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
47.1 Primary prevention	4	482	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.14, 0.11]
47.2 Secondary prevention	2	1294	Mean Difference (IV, Random, 95% CI)	0.02 [‐0.22, 0.25]
48 High‐density lipoprotein, serum, mmoL/L ‐ ALA	6	1776	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.08, 0.03]
49 HDL, mmoL/L ‐ ALA ‐ SA fixed‐effect	6	1776	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.05, 0.00]
50 HDL, mmoL/L ‐ ALA ‐ SA by summary risk of bias	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
50.1 Low risk of bias	3	1436	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.06, 0.00]
50.2 Moderate/high risk of bias	3	340	Mean Difference (IV, Random, 95% CI)	0.04 [‐0.14, 0.22]
51 HDL, mmoL/L ‐ ALA ‐ SA by compliance and study size	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
51.1 SA ‐ low risk of compliance bias	4	1657	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.08, 0.04]
51.2 SA ‐ 100+ randomised	4	1657	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.08, 0.04]
52 HDL, mmoL/L ‐ ALA ‐ subgroup by dose	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
52.1 ALA low < 5 g/d	3	1371	Mean Difference (IV, Random, 95% CI)	0.06 [‐0.08, 0.19]
52.2 ALA high > 5 g/d	3	405	Mean Difference (IV, Random, 95% CI)	‐0.07 [‐0.12, ‐0.01]
53 HDL, mmoL/L ‐ ALA ‐ subgroup by intervention type	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
53.1 Dietary advice	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
53.2 Supplemental foods	5	1650	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.06, ‐0.00]
53.3 Supplement (capsule)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
53.4 Any combination	1	126	Mean Difference (IV, Random, 95% CI)	0.15 [0.01, 0.29]
54 HDL, mmoL/L ‐ ALA ‐ subgroup by replacement	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
54.1 ALA replacing SFA	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
54.2 ALA replacing MUFA	2	1336	Mean Difference (IV, Random, 95% CI)	0.05 [‐0.11, 0.22]
54.3 ALA replacing n‐6	1	142	Mean Difference (IV, Random, 95% CI)	‐0.04 [‐0.11, 0.03]
54.4 ALA replacing carbs/sugars	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
54.5 ALA replacing nil/low n‐3 placebo	1	35	Mean Difference (IV, Random, 95% CI)	0.10 [‐0.17, 0.37]
54.6 Replacement unclear	2	263	Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.17, ‐0.02]
55 HDL, mmoL/L ‐ ALA ‐ subgroup by duration	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
55.1 Medium duration 1 to < 2 years in study	4	424	Mean Difference (IV, Random, 95% CI)	‐0.00 [‐0.13, 0.13]
55.2 Medium‐long duration: 2 to < 4 years in study	2	1352	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.05, 0.00]
55.3 Long duration ≥ 4 years in study	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
56 HDL, mmoL/L ‐ ALA ‐ subgroup by statin use	6		Mean Difference (IV, Random, 95% CI)	Subtotals only
56.1 ALA ‐ ≥ 50% of control group on statins	3	1329	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.09, 0.03]
56.2 ALA ‐ < 50% of control group on statins	2	268	Mean Difference (IV, Random, 95% CI)	0.05 [‐0.14, 0.23]
56.3 ALA ‐ use of statins unclear	1	179	Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.20, 0.02]
57 HDL, mmoL/L ‐ ALA ‐ subgroup by primary or secondary prevention	7		Mean Difference (IV, Random, 95% CI)	Subtotals only
57.1 Low CVD risk	2	305	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.21, 0.26]
57.2 Moderate CVD risk	2	177	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.10, 0.04]
57.3 High CVD risk	3	1368	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.08, 0.03]
58 Low‐density lipoprotein, serum, mmoL/L ‐ ALA	7	2201	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.15, 0.04]
59 LDL, mmoL/L ‐ ALA ‐ SA fixed‐effect	7	2201	Mean Difference (IV, Fixed, 95% CI)	‐0.05 [‐0.11, 0.00]
60 LDL, mmoL/L ‐ ALA ‐ SA by summary risk of bias	7		Mean Difference (IV, Random, 95% CI)	Subtotals only
60.1 Low risk of bias	3	1350	Mean Difference (IV, Random, 95% CI)	0.02 [‐0.05, 0.10]
60.2 Moderate/high risk of bias	4	851	Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.22, ‐0.06]
61 LDL, mmoL/L ‐ ALA ‐ SA by compliance and study size	5		Mean Difference (IV, Random, 95% CI)	Subtotals only
61.1 SA ‐ low risk of compliance bias	5	2085	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.16, 0.06]
61.2 SA ‐ 100+ randomised	5	2085	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.16, 0.06]
62 LDL, mmoL/L ‐ ALA ‐ subgroup by dose	7		Mean Difference (IV, Random, 95% CI)	Subtotals only
62.1 ALA low < 5 g/d	4	1796	Mean Difference (IV, Random, 95% CI)	‐0.06 [‐0.17, 0.05]
62.2 ALA high > 5 g/d	3	405	Mean Difference (IV, Random, 95% CI)	‐0.04 [‐0.28, 0.19]
63 LDL, mmoL/L ‐ ALA ‐ subgroup by intervention type	7		Mean Difference (IV, Random, 95% CI)	Subtotals only
63.1 Dietary advice	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
63.2 Supplemental foods	6	2075	Mean Difference (IV, Random, 95% CI)	‐0.06 [‐0.17, 0.05]
63.3 Supplement (capsule)	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
63.4 Any combination	1	126	Mean Difference (IV, Random, 95% CI)	0.0 [‐0.25, 0.25]
64 LDL, mmoL/L ‐ ALA ‐ subgroup by replacement	7		Mean Difference (IV, Random, 95% CI)	Subtotals only
64.1 ALA replacing SFA	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
64.2 ALA replacing MUFA	2	1250	Mean Difference (IV, Random, 95% CI)	0.01 [‐0.07, 0.09]
64.3 ALA replacing n‐6	1	142	Mean Difference (IV, Random, 95% CI)	0.14 [‐0.08, 0.36]
64.4 ALA replacing carbs/sugars	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
64.5 ALA replacing nil/low n‐3 placebo	1	32	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.59, 0.39]
64.6 Replacement unclear	3	777	Mean Difference (IV, Random, 95% CI)	‐0.16 [‐0.24, ‐0.07]
65 LDL, mmoL/L ‐ ALA ‐ subgroup by duration	7		Mean Difference (IV, Random, 95% CI)	Subtotals only
65.1 Medium duration 1 to < 2 years in study	5	935	Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.22, ‐0.06]
65.2 Medium‐long duration: 2 to < 4 years in study	2	1266	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.06, 0.13]
65.3 Long duration ≥ 4 years in study	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
66 LDL, mmoL/L ‐ ALA ‐ subgroup by statin use	7		Mean Difference (IV, Random, 95% CI)	Subtotals only
66.1 ALA ‐ ≥ 50% of control group on statins	3	1240	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.08, 0.08]
66.2 ALA ‐ < 50% of control group on statins	2	268	Mean Difference (IV, Random, 95% CI)	0.08 [‐0.09, 0.24]
66.3 ALA ‐ use of statins unclear	2	693	Mean Difference (IV, Random, 95% CI)	‐0.16 [‐0.25, ‐0.07]
67 LDL, mmoL/L ‐ ALA ‐ subgroup by primary or secondary prevention	7		Mean Difference (IV, Random, 95% CI)	Subtotals only
67.1 Primary prevention of CVD	5	993	Mean Difference (IV, Random, 95% CI)	‐0.08 [‐0.20, 0.05]
67.2 Secondary prevention of CVD	2	1208	Mean Difference (IV, Random, 95% CI)	0.01 [‐0.08, 0.09]