TABLE 1.
Characteristics of studies included in the meta-analysis1
| Reference | Study name and country | Total no. of participants (no. of cases) | Average follow-up duration | Study design | Male % | Baseline age | ALA measures | Baseline ALA concentration | Outcome | Adjustment |
| Dietary ALA intake as the exposure | ||||||||||
| Dolecek, 1992 (13) | The MRFIT study, United States | 6250 (232) | 10.5 y (1973–1985) | PC | 100 | Range: 35–57 y | Four 24-h dietary record (crude intake) | Mean2: 1.69 ± 0.74 g/d | CHD death | ++ |
| Ascherio et al, 1996 (14) | The HPFS study, United States | 43,757 (734) | 6 y (1986–1992) | PC | 100 | Range: 40–75 y | Validated FFQ (residual method adjusted) | Median: 1.1 g/d | Total MI, fatal MI | ++ |
| Pietinen et al, 1997 (15) | The Alpha-Tocopherol, Beta-Carotene Cancer Prevention study, Finland | 21,930 (1399) | 8 y (1985–1993); median: 6.1 y | PC | 100 | Range: 50–69 y | Dietary history (residual method adjusted) | Median: 1.5 g/d | Total MI, fatal MI | ++ |
| Hu et al, 1999 (16) | The NHS study, United States | 76,283 (829) | 10 y (1984–1994) | PC | 0 | Range: 38–63 y; mean: 50.3 y | Validated FFQ (residual method adjusted) | Mean: 1.10 ± 0.45 g/d | Fatal IHD | +++ |
| Oomen et al, 2001 (17) | Zutphen Elderly study, Netherlands | 667 (98) | 10 y (1985–1995) | PC | 100 | Range: 64–84 y; mean: 71.1 ± 5.2 y | Cross-check dietary history (percentage of energy) | Mean: 1.32 ± 0.47 g/d, or 0.53 ± 0.15% of total energy | CAD | +++ |
| He et al, 2002 (18) | The HPFS study, United States | 43,671 (608) | 12 y (1986–1998) | PC | 100 | Range: 40–75 y; mean: 53.4 y | Validated FFQ (residual method adjusted) | Mean: 1.07 g/d | Stroke | +++ |
| Albert et al, 2005 (19) | The NHS study, United States | 76,763 (2451) | 18 y (1984–2002) | PC | 0 | Range: 38–63 y; mean: 50.5 y | Validated FFQ (percentage of energy) | Median: 0.52% of total energy | Nonfatal MI | +++ |
| de Goede et al, 2011 (20) | The MORGEN study, Netherlands | 20,069 (581) | 13 y (1993/1997–2006); mean: 10.5 y | PC | 44.8 | Range: 20–65 y; mean: 41–42 y | Validated FFQ (residual method adjusted) | Mean: 1.3 ± 0.05 g/d | CHD, stroke | +++ |
| Vedtofte et al, 2011 (21) | Glostrup Population Studies, Denmark | 3277 (471) | Mean: 23.3 y | PC | 49.9 | Mean: 50.6 y | 7-d Weighted food records (crude intake) | Median: 1.2 g/d for women and 1.6 g/d for men | IHD | +++ |
| Larsson et al, 2012 (22) | Swedish Mammography Cohort, Sweden | 34,670 (1680) | Mean: 10.4 y | PC | 0 | Range: 49–83 y; mean: 61–62 y | Validated FFQ (residual method adjusted) | Median: 1.2 g/d | Stroke | +++ |
| ALA biomarker as the exposure | ||||||||||
| Simon et al, 1995 (23) | The MRFIT study, United States | 192 (96) | NA | NCC | 100 | Range: 35–57 y; mean: 50.3 ± 5.6 y | Serum CE and PL fatty acids | Mean: 0.39 ± 0.13% for CE and 0.12 ± 0.07% for PL in controls | Stroke | + |
| Simon et al, 1995 (24) | The MRFIT study, United States | 188 (94) | NA | NCC | 100 | Range: 35–57 y; mean: 49.8 ± 5.6 y | Serum CE and PL fatty acids | Mean: 0.40 ± 0.15% for CE and 0.14 ± 0.07% for PL in controls | CHD | + |
| Tornwall et al, 1996 (25) | The Alpha-Tocopherol, Beta-Carotene Cancer Prevention study, Finland | 670 (189) | NA | CC | 100 | Range: 50–69 y; mean: 58.1 y | Serum CE fatty acids | Mean: 0.68 ± 0.20% in controls | Acute MI | ++ |
| Guallar et al, 1999 (26) | The EURAMIC study, European countries and Israel | 1339 (639) | NA | CC | 100 | Range: ≤70 y; mean: 53.9 y | Adipose tissue | Mean: 0.80 ± 0.19% in controls | First-acute MI | +++ |
| Pedersen et al, 2000 (27) | Norway | 198 (100) | NA | CC | 72 | Range: 45–75 y; mean: 62.4 y | Adipose tissue | Mean: 0.71 ± 0.15% in controls | First-acute MI | +++ |
| Erkkila et al, 2003 (28) | Finnish cohort of the EUROASPIRE study, Finland | 398 (35) | 5 y (1995–2001) | PC | 68.7 | Range: 33–74 y; mean: 61 ± 8 y | Serum CE fatty acids | Median: 0.83% | Total CVD | ++ |
| Kark et al, 2003 (29) | Israel | 672 (180) | NA | CC | 72 | Range: 25–64 y; mean: 52.6 y | Adipose tissue | Mean: 1.23 ± 0.42% in controls | First-acute MI | +++ |
| Lemaitre et al, 2003 (30) | The CHS study, United States | 108 (54) | NA | NCC | 57.4 | Range: ≥65 y; mean: 78.5 y | Plasma PL fatty acids | Mean: 0.17 ± 0.06% in controls | Fatal IHD | ++ |
| Lemaitre et al, 2003 (30) | The CHS study, United States | 250 (125) | NA | NCC | 64 | Range: ≥65 y | Plasma PL fatty acids | Mean: 0.17 ± 0.06% in controls | Nonfatal MI | ++ |
| Wang et al, 2003 (31) | The ARIC study, United States | 3591 (282) | 12 y (1987/1989–1999); mean: 10.7 y | PC | 46 | Range: 45–64 y; mean: 54 y | Plasma CE and PL fatty acids | Median: 0.41% for CE and 0.14% for PL | Total CHD | ++ |
| Wiberg et al, 2006 (32) | The ULSAM study, Sweden | 2313 (421) | 32 y (1970/1972–2002); mean: 29.3 y | PC | 100 | Mean: 50 y | Serum CE fatty acids | Mean: 0.7 ± 0.2% | Stroke | ++ |
| Warensjö et al, 2008 (33) | The ULSAM study, Sweden | 2009 (1012) | 33.7 y (1970/1972–2003); mean: 30.7 y | PC | 100 | Mean: 50 y | Serum CE fatty acids | Mean: 0.66 ± 0.16% | CVD death | ++ |
| Lemaitre et al, 2009 (34) | United States | 680 (265) | NA | CC | 81 | Range: 25–74 y; mean: 57.6 y | Red blood cell membrane fatty acids | Mean: 0.13 ± 0.04% in controls | Sudden cardiac arrest | +++ |
| Shearer et al, 2009 (35) | United States | 898 (445) | NA | CC | 66.5 | Mean: 59 y | Red blood cell membrane fatty acids | Median: 0.44% in controls | Acute coronary syndrome | ++ |
| Khaw et al, 2012 (36) | EPIC-Norfolk study, United Kingdom | 7354 (2424) | NA | NCC | 52.2 | Mean: 61.6 y | Plasma PL fatty acids | Mean: 0.24% | Total CHD | +++ |
| Studies reporting both diet and biomarker results | ||||||||||
| Laaksonen et al, 2005 (37) | The KIHD study, Finland | 1551 (78) | 17.8 y (1984/1989–2001); median: 14.6 y | PC | 100 | Range: 42–60 y; mean: 52.0 ± 5.5 y | 4-d Food records (residual method adjusted); serum esterified fatty acids | Mean: 0.79 ± 0.23% for serum; 1.6 ± 0.5 g/d for diet | CVD death | +++ |
| Lopes et al, 2007 (38) | Portugal | 607 (297) | NA | CC | 100 | Range: ≥40 y; mean: 57.0 y | Validated FFQ (residual method adjusted); subset study of adipose tissue | Mean: 1.61 ± 0.59 g/d for diet; 0.36 ± 0.09% for adipose tissue in controls | First-acute MI | ++ |
| Campos et al, 2008 (39) | Costa Rica | 3638 (1819) | NA | CC | 73 | Mean: 58 ± 11 y | Adipose tissue and validated FFQ (residual method adjusted) | Mean: 1.63 ± 0.63 g/d for diet; 0.65 ± 0.21% for adipose tissue in controls | Nonfatal acute MI | +++ |
Degree of covariate adjustment indicated by +: sociodemographics (eg, age, sex, race, education, and income); ++: sociodemographics, other CVD risk factors (eg, BMI, smoking, alcohol intake, physical activity, family history, blood pressure, and blood lipids), and certain dietary variables (total energy, fiber intake etc., not including other fatty acids); +++: sociodemographics, other CVD risk factors, and dietary variables (including other fatty acids). ALA, α-linolenic acid; ARIC, Atherosclerosis Risk in Communities; CAD, coronary artery disease; CC, case-control study; CE, cholesterol ester; CHD, coronary heart disease; CHS, Cardiovascular Health Study; CVD, cardiovascular disease; EPIC, European Prospective Investigation into Cancer; EURAMIC, EURopean multicenter case-control study on Antioxidants, Myocardial Infarction and breast Cancer; EUROASPIRE, European Action on Secondary Prevention through Intervention to Reduce Events; FFQ, food-frequency questionnaire; HPFS, Health Professionals Follow-Up Study; IHD, ischemic heart disease; KIHD, Kuopio Ischemic Heart Disease Risk Factor; MI, myocardial infarction; MRFIT, Multiple Risk Factor Intervention Trial; MORGEN, Monitoring Project on Risk Factors for Chronic Diseases; NA, not available; NCC, nested case-control study; NHS, Nurses’ Health Study; PC, prospective cohort study; PL, phospholipids; ULSAM, Uppsala Longitudinal Study of Adult Men.
±SD (all such values).