TABLE 1.
Summary RRs for the high vs. low and dose-response analyses of antioxidants and risk of coronary heart disease, stroke, cardiovascular disease, total cancer and mortality
| Outcome | Comparison | No. of studies | Cases, n | Participants, n | RR (95% CI) | I 2 | P heterogeneity | P (Egger' test) | References |
|---|---|---|---|---|---|---|---|---|---|
| Dietary vitamin C | |||||||||
| Coronary heart disease | High vs. low | 12 | 4297 | 241,579 | 0.83 (0.71, 0.98) | 50.7 | 0.02 | 0.97 | (13, 14, 33–41, 49) |
| Per 100 mg/d | 11 | 4167 | 240,824 | 0.88 (0.79, 0.98) | 65.1 | 0.001 | 0.007 | (13, 14, 33–41) | |
| Stroke | High vs. low | 13 | 7294 | 298,066 | 0.84 (0.77, 0.91) | 6.2 | 0.39 | 0.93 | (41, 44–52, 58, 61, 123) |
| Per 100 mg/d | 12 | 7049 | 296,596 | 0.92 (0.87, 0.98) | 68.0 | <0.0001 | 0.02 | (41, 44–52, 58, 123) | |
| Cardiovascular disease | High vs. low | 9 | 7986 | 246,711 | 0.84 (0.77, 0.91) | 0 | 0.53 | 0.71 | (19, 26, 41, 53, 55, 56, 80, 81) |
| Per 100 mg/d | 10 | 8175 | 247,765 | 0.89 (0.85, 0.94) | 27.2 | 0.19 | 0.81 | (19, 20, 26, 41, 53, 55, 56, 80, 81) | |
| Total cancer | High vs. low | 7 | 7068 | 181,318 | 0.87 (0.78, 0.95) | 17.7 | 0.30 | 0.91 | (14, 36, 53, 56, 57, 81) |
| Per 100 mg/d | 8 | 7208 | 181,318 | 0.93 (0.87, 0.99) | 45.5 | 0.08 | 0.28 | (14, 20, 36, 53, 56, 57, 81) | |
| Mortality | High vs. low | 16 | 38,079 | 315,214 | 0.86 (0.80, 0.92) | 68.5 | <0.0001 | 0.001 | (14, 19, 36, 38, 53, 54, 56, 58–60, 81–84, 127) |
| Per 100 mg/d | 14 | 36,404 | 295,152 | 0.89 (0.85, 0.94) | 80.2 | <0.0001 | <0.0001 | (14, 19, 20, 36, 38, 53, 54, 56, 58–60, 81, 84) | |
| Vitamin C in blood | |||||||||
| Coronary heart disease | High vs. low | 4 | 1368 | 6992 | 0.71 (0.59, 0.86) | 0.4 | 0.39 | 0.90 | (13, 14, 87, 92) |
| Per 50 µmol/L | 4 | 1420 | 7514 | 0.74 (0.65, 0.83) | 0 | 0.71 | 0.49 | (13–15, 92) | |
| Stroke | High vs. low | 5 | 957 | 27,843 | 0.60 (0.49, 0.73) | 0 | 0.86 | 0.70 | (16, 17, 58, 87, 98) |
| Per 50 µmol/L | 4 | 926 | 24,869 | 0.70 (0.61, 0.81) | 0 | 0.41 | 0.36 | (16, 17, 58, 98) | |
| Cardiovascular disease | High vs. low | 5 | 2792 | 45,273 | 0.61 (0.45, 0.83) | 55.6 | 0.06 | 0.22 | (18, 19, 21, 22, 103) |
| Per 50 µmol/L | 6 | 2981 | 46,327 | 0.76 (0.65, 0.87) | 55.7 | 0.05 | 0.31 | (18–22, 103) | |
| Total cancer | High vs. low | 5 | 1831 | 47,678 | 0.68 (0.57, 0.80) | 0 | 0.51 | 0.65 | (14, 18, 21, 22, 116) |
| Per 50 µmol/L | 5 | 1681 | 45,758 | 0.74 (0.66, 0.82) | 0 | 0.49 | 0.82 | (14, 18, 20–22) | |
| Mortality | High vs. low | 8 | 7528 | 47,238 | 0.68 (0.60, 0.77) | 43.1 | 0.09 | 0.07 | (14, 18, 19, 21–23, 58, 126) |
| Per 50 µmol/L | 8 | 8179 | 48,060 | 0.72 (0.66, 0.79) | 48.2 | 0.06 | 0.13 | (14, 18–23, 58) | |
| Dietary total carotenoids | |||||||||
| Coronary heart disease | High vs. low | 5 | 1835 | 91,838 | 0.78 (0.67, 0.90) | 0 | 0.54 | 0.59 | (14, 34, 35, 37, 42) |
| Per 5000 µg/d | 5 | 1835 | 91,838 | 0.85 (0.77, 0.93) | 37.0 | 0.18 | 0.22 | (14, 34, 35, 37, 42) | |
| Stroke | High vs. low | 0 | — | — | — | — | — | — | — |
| Per 5000 µg/d | 0 | — | — | — | — | — | — | — | |
| Cardiovascular disease | High vs. low | 2 | 3198 | 134,358 | 0.87 (0.74, 1.01) | 0 | 0.51 | — | (81) |
| Per 5000 µg/d | 4 | 3584 | 135,971 | 0.80 (0.70, 0.90) | 0 | 0.76 | 0.93 | (20, 55, 81) | |
| Total cancer | High vs. low | 3 | 4441 | 135,038 | 0.93 (0.82, 1.06) | 0 | 0.59 | 0.42 | (14, 81) |
| Per 5000 µg/d | 4 | 4581 | 136,092 | 0.93 (0.82, 1.05) | 4.4 | 0.37 | 0.93 | (14, 20, 81) | |
| Mortality | High vs. low | 5 | 11,431 | 188,025 | 0.87 (0.80, 0.94) | 11.6 | 0.34 | 0.45 | (14, 42, 54, 81) |
| Per 5000 µg/d | 6 | 12,148 | 189,079 | 0.88 (0.83, 0.93) | 2.2 | 0.40 | 0.51 | (14, 20, 42, 54, 81) | |
| Carotenoids in blood | |||||||||
| Coronary heart disease | High vs. low | 4 | 634 | 6014 | 0.67 (0.53, 0.85) | 0 | 0.88 | 0.20 | (14, 87, 88, 90) |
| Per 100 µg/dL | 3 | 502 | 3040 | 0.83 (0.72, 0.95) | 0 | 0.56 | 0.69 | (14, 88, 90) | |
| Stroke | High vs. low | 1 | 31 | 2974 | 0.48 (0.18, 1.28) | — | — | — | — |
| Per 100 µg/dL | 0 | — | — | — | — | — | — | — | |
| Cardiovascular disease | High vs. low | 2 | 1386 | 14,324 | 0.81 (0.64, 1.03) | 0 | 0.34 | — | (108, 109) |
| Per 100 µg/dL | 3 | 1534 | 15,492 | 0.61 (0.33, 1.10) | 53.8 | 0.12 | — | (107, 109) | |
| Total cancer | High vs. low | 5 | 1178 | 20,231 | 0.74 (0.60, 0.90) | 0 | 0.99 | 0.39 | (14, 108, 110, 116, 118) |
| Per 100 µg/dL | 3 | 741 | 14,976 | 0.61 (0.36, 1.03) | 72.5 | 0.03 | 0.49 | (14, 107, 108) | |
| Mortality | High vs. low | 6 | 1578 | 17,391 | 0.75 (0.64, 0.88) | 0 | 0.80 | 0.65 | (14, 24, 25, 108, 121, 125) |
| Per 100 µg/dL | 7 | 1966 | 18,559 | 0.74 (0.62, 0.88) | 50.9 | 0.06 | 0.14 | (14, 24, 25, 107, 108, 121, 125) | |
| Dietary β-Carotene | |||||||||
| Coronary heart disease | High vs. low | 4 | 2104 | 99,345 | 0.73 (0.63, 0.85) | 0 | 0.46 | 0.29 | (36, 38, 39, 43) |
| Per 5000 µg/d | 4 | 2104 | 99,345 | 0.82 (0.68, 0.98) | 45.0 | 0.14 | 0.20 | (36, 38, 39, 43) | |
| Stroke | High vs. low | 7 | 5468 | 201,587 | 0.84 (0.75, 0.94) | 21.9 | 0.26 | 0.25 | (44, 45, 47, 48, 51, 52, 123) |
| Per 5000 µg/d | 7 | 5468 | 201,587 | 0.81 (0.66, 0.98) | 59.4 | 0.02 | 0.07 | (44, 45, 47, 48, 51, 52, 123) | |
| Cardiovascular disease | High vs. low | 4 | 1767 | 39,643 | 0.98 (0.84, 1.15) | 10.4 | 0.34 | 0.21 | (19, 53, 56, 80) |
| Per 5000 µg/d | 4 | 1851 | 38,988 | 0.91 (0.74, 1.11) | 36.6 | 0.19 | 0.47 | (53, 55, 56, 80) | |
| Total cancer | High vs. low | 4 | 2797 | 46,280 | 0.90 (0.81, 1.00) | 0 | 0.55 | 0.02 | (36, 53, 56, 57) |
| Per 5000 µg/d | 4 | 2797 | 46,280 | 0.96 (0.90, 1.02) | 24.9 | 0.26 | 0.006 | (36, 53, 56, 57) | |
| Mortality | High vs. low | 8 | 11,729 | 142,798 | 0.82 (0.78, 0.87) | 0 | 0.51 | 0.57 | (19, 36, 38, 53, 54, 56, 60, 127) |
| Per 5000 µg/d | 6 | 11,120 | 143,140 | 0.92 (0.85, 0.98) | 66.2 | 0.01 | 0.008 | (36, 38, 53, 54, 56, 60) | |
| β-Carotene in blood | |||||||||
| Coronary heart disease | High vs. low | 4 | 1128 | 3179 | 0.73 (0.57, 0.94) | 0 | 0.61 | 0.11 | (89, 91, 93, 95) |
| Per 25 µg/dL | 3 | 1005 | 2933 | 0.80 (0.66, 0.97) | 10.4 | 0.33 | 0.90 | (91, 93, 95) | |
| Stroke | High vs. low | 3 | 1548 | 30,144 | 0.85 (0.71, 1.01) | 0 | 0.66 | 0.52 | (97, 99, 100) |
| Per 25 µg/dL | 3 | 1548 | 30,144 | 0.85 (0.74, 0.97) | 0 | 0.50 | 0.27 | (97, 99, 100) | |
| Cardiovascular disease | High vs. low | 7 | 3232 | 34,090 | 0.71 (0.57, 0.88) | 17.7 | 0.30 | 0.13 | (19, 21, 27, 103, 105, 106, 109) |
| Per 25 µg/dL | 8 | 3451 | 24,428 | 0.86 (0.78, 0.96) | 3.1 | 0.41 | 0.38 | (19–21, 27, 102, 103, 106, 109) | |
| Total cancer | High vs. low | 6 | 2654 | 66,892 | 0.76 (0.65, 0.89) | 0 | 0.80 | 0.22 | (21, 27, 28, 105, 115, 118) |
| Per 25 µg/dL | 8 | 2519 | 56,773 | 0.76 (0.68, 0.85) | 0 | 0.74 | 0.17 | (20, 21, 27, 28, 102, 115, 117, 120) | |
| Mortality | High vs. low | 7 | 5659 | 23,141 | 0.68 (0.55, 0.83) | 43.5 | 0.10 | 0.15 | (19, 21, 27, 117, 121, 122, 124) |
| Per 25 µg/dL | 7 | 5659 | 23,141 | 0.81 (0.72, 0.90) | 46.5 | 0.08 | 0.20 | (19–21, 27, 102, 117, 121, 124) | |
| α-Carotene in blood | |||||||||
| Coronary heart disease | High vs. low | 4 | 1963 | 18,251 | 0.88 (0.71, 1.10) | 0 | 0.63 | 0.64 | (91, 93–95) |
| Per 10 µg/dL | 4 | 1963 | 18,251 | 0.87 (0.71, 1.07) | 0 | 0.89 | 0.60 | (91, 93–95) | |
| Stroke | High vs. low | 3 | 784 | 16,943 | 0.74 (0.48, 1.14) | 0 | 0.73 | 0.58 | (94, 99, 100) |
| Per 10 µg/dL | 3 | 784 | 16,943 | 0.80 (0.55, 1.18) | 0 | 0.80 | 0.39 | (94, 99, 100) | |
| Cardiovascular disease | High vs. low | 4 | 3556 | 30,640 | 0.80 (0.58, 1.09) | 68.2 | 0.02 | 0.25 | (94, 106, 108, 109) |
| Per 10 µg/dL | 5 | 3745 | 31,694 | 0.83 (0.62, 1.10) | 68.2 | 0.01 | 0.81 | (20, 94, 106, 108, 109) | |
| Total cancer | High vs. low | 2 | 878 | 17,671 | 0.62 (0.40, 0.96) | 0 | 0.56 | — | (94, 118) |
| Per 10 µg/dL | 4 | 1177 | 19,043 | 0.58 (0.45, 0.74) | 0 | 0.66 | 0.95 | (20, 94, 117, 120) | |
| Mortality | High vs. low | 4 | 4285 | 18,928 | 0.76 (0.59, 0.98) | 49.9 | 0.12 | 0.08 | (24, 94, 117, 121) |
| Per 10 µg/dL | 5 | 5002 | 19,982 | 0.71 (0.64, 0.79) | 0 | 0.86 | 0.07 | (20, 24, 94, 117, 121) | |
| β-Cryptoxanthin in blood | |||||||||
| Coronary heart disease | High vs. low | 2 | 811 | 1902 | 1.01 (0.43, 2.37) | 70.8 | 0.06 | — | (91, 93) |
| Per 15 µg/dL | 2 | 811 | 1902 | 1.12 (0.33, 3.79) | 67.3 | 0.08 | — | (91, 93) | |
| Stroke | High vs. low | 0 | — | — | — | — | — | — | — |
| Per 15 µg/dL | 0 | — | — | — | — | — | — | — | |
| Cardiovascular disease | High vs. low | 3 | 2246 | 42,636 | 0.83 (0.67, 1.03) | 0 | 0.77 | 0.38 | (104, 106, 108) |
| Per 15 µg/dL | 4 | 2435 | 43,690 | 0.90 (0.76, 1.06) | 0 | 0.70 | 0.79 | (20, 104, 106, 108) | |
| Total cancer | High vs. low | 2 | 777 | 16,421 | 0.83 (0.60, 1.15) | 0 | 0.56 | — | (108, 118) |
| Per 15 µg/dL | 3 | 944 | 14,665 | 0.74 (0.60, 0.91) | 0 | 0.99 | 0.16 | (20, 108, 120) | |
| Mortality | High vs. low | 2 | 3104 | 13,931 | 0.81 (0.64, 1.03) | 27.0 | 0.24 | — | (108, 121) |
| Per 15 µg/dL | 3 | 3821 | 14,985 | 0.84 (0.76, 0.94) | 0 | 0.99 | 0.84 | (20, 108, 121) | |
| Dietary lycopene | |||||||||
| Coronary heart disease | High vs. low | 2 | 1199 | 111,731 | 0.88 (0.71, 1.10) | 11.1 | 0.29 | — | (43, 78) |
| Per 12,000 µg/d | 2 | 1199 | 111,731 | 0.91 (0.76, 1.08) | 19.9 | 0.26 | — | (43, 78) | |
| Stroke | High vs. low | 3 | 1371 | 108,776 | 0.80 (0.63, 1.01) | 35.1 | 0.21 | 0.36 | (45, 47, 78) |
| Per 12,000 µg/d | 3 | 1371 | 108,776 | 0.72 (0.39, 1.34) | 83.7 | 0.002 | 0.31 | (45, 47, 78) | |
| Cardiovascular disease | High vs. low | 1 | 719 | 39,876 | 0.90 (0.69, 1.17) | — | — | — | (78) |
| Per 12,000 µg/d | 2 | 916 | 40,435 | 0.94 (0.79, 1.12) | 0 | 0.32 | — | (55, 78) | |
| Total cancer | High vs. low | 0 | — | — | — | — | — | — | — |
| Per 12,000 µg/d | 0 | — | — | — | — | — | — | — | |
| Mortality | High vs. low | 2 | 881 | 48,805 | 0.74 (0.54, 1.02) | 48.1 | 0.17 | — | (54, 127) |
| Per 12,000 µg/d | 0 | — | — | — | — | — | — | — | |
| Lycopene in blood | |||||||||
| Coronary heart disease | High vs. low | 4 | 1128 | 3179 | 0.90 (0.62, 1.29) | 52.9 | 0.10 | 0.47 | (89, 91, 93, 95) |
| Per 25 µg/dL | 3 | 1005 | 2933 | 1.11 (0.32, 3.85) | 72.7 | 0.03 | 0.15 | (91, 93, 95) | |
| Stroke | High vs. low | 2 | 491 | 1625 | 0.59 (0.36, 0.96) | 0 | 0.35 | — | (99, 100) |
| Per 25 µg/dL | 2 | 491 | 1625 | 0.49 (0.19, 1.25) | 59.7 | 0.12 | — | (99, 100) | |
| Cardiovascular disease | High vs. low | 4 | 1749 | 43,667 | 0.88 (0.70, 1.10) | 8.0 | 0.35 | 0.24 | (104, 106, 108, 109) |
| Per 25 µg/dL | 5 | 1938 | 44,721 | 0.81 (0.63, 1.06) | 34.8 | 0.19 | 0.15 | (20, 104, 106, 108, 109) | |
| Total cancer | High vs. low | 3 | 918 | 17,418 | 0.81 (0.54, 1.21) | 65.5 | 0.06 | 0.13 | (108, 118, 119) |
| Per 25 µg/dL | 5 | 1129 | 18,015 | 0.95 (0.68, 1.33) | 65.9 | 0.02 | 0.13 | (20, 108, 117, 119, 120) | |
| Mortality | High vs. low | 4 | 3233 | 16,438 | 0.91 (0.77, 1.07) | 0 | 0.60 | 0.08 | (108, 117, 121, 124) |
| Per 25 µg/dL | 5 | 3950 | 17,492 | 0.87 (0.74, 1.02) | 25.5 | 0.25 | 0.07 | (20, 108, 117, 121, 124) | |
| Dietary vitamin E | |||||||||
| Coronary heart disease | High vs. low | 9 | 3010 | 239,610 | 0.86 (0.65, 1.05) | 68.2 | 0.001 | 0.81 | (14, 34, 35, 37–39, 41, 49, 77) |
| Per 5 µg/d | 8 | 2880 | 238,855 | 0.94 (0.87, 1.02) | 67.6 | 0.003 | 0.18 | (14, 34, 35, 37–39, 41, 77) | |
| Stroke | High vs. low | 10 | 7003 | 311,965 | 0.89 (0.78, 1.02) | 34.4 | 0.13 | 0.58 | (41, 44–49, 51, 61, 123) |
| Per 5 µg/d | 8 | 6688 | 292,966 | 0.97 (0.93, 1.02) | 54.4 | 0.03 | 0.18 | (41, 44–48, 51, 123) | |
| Cardiovascular disease | High vs. low | 8 | 7852 | 233,310 | 0.90 (0.78, 1.03) | 55.5 | 0.03 | 0.05 | (19, 41, 53, 55, 56, 80, 81) |
| Per 5 µg/d | 8 | 7928 | 233,130 | 0.99 (0.96, 1.01) | 41.6 | 0.10 | 0.06 | (20, 41, 53, 55, 56, 80, 81) | |
| Total cancer | High vs. low | 5 | 5578 | 168,182 | 1.01 (0.92, 1.10) | 0 | 0.69 | 0.72 | (14, 53, 56, 81) |
| Per 5 µg/d | 6 | 5718 | 169,236 | 0.97 (0.93, 1.02) | 61.1 | 0.03 | 0.07 | (14, 20, 53, 56, 81) | |
| Mortality | High vs. low | 9 | 15,321 | 229,830 | 0.98 (0.93, 1.04) | 2.9 | 0.41 | 0.92 | (14, 19, 38, 53, 54, 56, 81, 127) |
| Per 5 µg/d | 8 | 15,429 | 222,223 | 1.00 (0.99, 1.01) | 0 | 0.59 | 0.07 | (14, 20, 38, 53, 54, 56, 81) | |
| α-Tocopherol in blood | |||||||||
| Coronary heart disease | High vs. low | 8 | 1407 | 47,374 | 1.22 (0.96, 1.57) | 0 | 0.80 | 0.18 | (14, 85, 86, 89–91, 95, 96) |
| Per 500 µg/dL | 5 | 1182 | 42,882 | 1.05 (0.95, 1.15) | 18.6 | 0.30 | 0.51 | (14, 90, 91, 95, 96) | |
| Stroke | High vs. low | 5 | 1966 | 69,569 | 0.71 (0.58, 0.85) | 0 | 0.70 | 0.61 | (85, 96, 97, 99, 100) |
| Per 500 µg/dL | 4 | 1951 | 69,386 | 0.90 (0.86, 0.95) | 0 | 0.43 | 0.61 | (96, 97, 99, 100) | |
| Cardiovascular disease | High vs. low | 6 | 8053 | 47,012 | 0.79 (0.56, 1.10) | 68.8 | 0.007 | 0.69 | (19, 21, 70, 79, 85, 103) |
| Per 500 µg/dL | 8 | 8607 | 51,283 | 0.92 (0.82, 1.03) | 69.9 | 0.002 | 0.97 | (19–21, 70, 79, 102, 103, 107) | |
| Total cancer | High vs. low | 10 | 7201 | 56,258 | 0.80 (0.74, 0.87) | 0 | 0.73 | 0.34 | (14, 21, 70, 110–114, 116, 118) |
| Per 500 µg/dL | 10 | 6919 | 51,210 | 0.91 (0.83, 0.99) | 70.1 | <0.0001 | 0.77 | (14, 20, 21, 70, 102, 107, 111–114) | |
| Mortality | High vs. low | 6 | 18,316 | 47,853 | 0.89 (0.72, 1.08) | 59.6 | 0.03 | 0.79 | (14, 19, 21, 70, 121, 124) |
| Per 500 µg/dL | 9 | 20,051 | 52,376 | 0.94 (0.89,0.99) | 56.3 | 0.02 | 0.97 | (14, 19–21, 70, 102, 107, 121, 124) | |