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] |