| Supple- ment |
Study, Publication
(Jadad Score) |
Setting/ population |
Treatment
(dose, formulation, frequency);
Other interventions |
Duration of follow-up;
Follow-up rate |
Myocardial Infarction |
Cardio- vascular Disease Events |
Cardio- vascular Disease mortality |
All-cause mortality |
| Vitamin E |
ATBC, ATBC Study Group, 199432 |
29,133 Finnish male smokers age 50-69 with no current use of vitamin A, E, or beta-carotene; no severe angina, malignancy, or other medical problems. |
50 IU/day vitamin E and 20 mg/day beta-carotene in 2x2 factorial design. |
5-8 years, median 6.1 years; case ascertainment essentially complete. |
|
|
|
1.02
(0.95-1.09) |
ATBC
Rapola, 199633
(5) |
Same as above. |
See above. |
Maximum 7 years, median 4.7 years; 73%. |
|
(Angina)
0.91
(0.83-0.99) |
|
|
ATBC
Virtamo, 199834
(5) |
27,271 men, Same as above except patients with prior MI excluded. |
See above. |
5-8 years, median 6.1 years; case ascertainment essentially complete. |
1.04
(0.89-1.22) |
0.98
(0.87-1.10) |
0.90
(0.75-1.08) |
|
HOPE Study
Yusuf, 200035
(5) |
9,541 men and women at 129 centers in 19 countries, over age 55, with a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes, plus one cardiovascular risk factor. |
400 IU/day vitamin E from natural sources and ACE inhibitor (10 mg ramipril) in 2x2 factorial design. |
5 years; 99.9%. |
1.02
(0.90-1.15) |
1.05
(0.95-1.22) |
1.05
(0.90-1.22) |
1.00
(0.89-1.13) |
Primary Prevention Project
Collaborative Group of the Primary Prevention Project, 200136
(3) |
4,495 Italian men and women attending general practitioner's office or outpatients attending hospital-based hypertension clinic; > age 50 with one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, diabetes mellitus, obesity, family history of early MI (< age 55), or age >64. |
300 IU/day synthetic alpha-tocopherol and 100 mg/day aspirin in 2x2 factorial design. |
Mean 3.6 years + 1.0 years; median 4 years 99.3%. |
0.89
(0.52-1.58) |
0.94
(0.77-1.16) |
0.86
(0.49-1.52) |
1.07
(0.77-1.49) |
Vitamin E Atherosclerosis Prevention Study (VEAPS Trial)
Hodis, 200239
(5) |
353 subjects >40 years with high LDL and no symptoms or signs of cardiovascular disease; no history of hypertriglyceridemia, diabetes or regular vitamin E. Primary outcome measure was change in carotid artery intima-media thickness. |
400 IU/day tocopherol. |
3 years
73% followed for 3 years. |
Vitamin: 5
Placebo: 4
p value not cited |
Vitamin: 8
Placebo: 10
p=0.81 |
Vitamin: 1
Placebo: 1
p value not cited |
Vitamin: 2
Placebo: 1
p value not cited |
| Beta-Carotene |
ATBC
ATBC Study Group, 199432
(5) |
29,133 Finland male smokers age 50-69 with no current use of vitamin A, E, or beta-carotene; no severe angina, malignancy, or other medical problems. |
20 mg/day beta-carotene and 50 IU/day vitamin E in 2x2 factorial design. |
5-8 years, median 6.1 years; case ascertainment "essentially complete." |
|
|
|
1.08
(1.01-1.16) |
ATBC
Rapola, 199633
(5) |
Same as above. |
Same as above. |
Maximum 7 years, median 4.7 years; 73%. |
|
(Angina)
1.06
(0.97-1.16) |
|
|
ATBC
Virtamo, 199834
(5) |
27,271 men, Same as above except patients with prior MI excluded. |
Same as above. |
5-8 years, median 6.1 years; case ascertainment "essentially complete." |
1.06
(0.90-1.24) |
1.03
(0.91-1.16) |
0.99
(0.83-1.19) |
|
Physician's Health Study
Hennekens, 199629
(4) |
22,071 US male physicians age 40-84, with no history of cancer, MI, stroke, or cerebral ischemia. |
50 mg beta-carotene on alternate days; cointervention with 325 mg aspirin in 2x2 factorial design. |
Mean 12 years; 99.99%. |
0.96
(0.84-1.09) |
1.0
(0.91-1.09) |
1.09
(0.93-1.27) |
1.02
(0.93-1.11) |
Skin Cancer Prevention Study
Greenberg, 199631
(3) |
1,188 US men and 532 women with prior non-melanoma skin cancer, < age 85. Multicenter trial to prevent skin cancer recurrence. |
50 mg/day beta-carotene. |
Median 8.2 years; 98%. |
|
|
1.16
(0.82-1.64) |
1.03
(0.82-1.30) |
Women's Health Study
I-M Lee, 199930
(4) |
39,876 US female health professionals, > age 45; no history of cancer, coronary heart disease, or cerebrovascular disease. |
50 mg beta-carotene on alternate days; co-intervention with 100 mg aspirin and 600 IU/day vitamin E in 2x2x2 factorial design. |
Median 2.1 years of treatment plus 2 years of follow-up; 100%. |
0.84
(0.56-1.27) |
1.14
(0.87-1.49) |
1.17
(0.54-2.53) |
1.07
(0.74-1.56) |
CARET
Omenn, 199637
(4) |
4,060 West Coast US male asbestos workers, age 45-74, first exposure to asbestos >15 yrs ago, plus asbestos-related lung disease or high-risk job for 5 years, and 14,254 US male and female heavy smokers age 50-69, >20 pack-years, current smokers or quit <6 years ago. |
30 mg/day beta-carotene and 25,000 IU/day retinol (retinyl palmitate). |
5.5 years; 98% for mortality. |
|
|
1.26 (0.99-1.61) |
1.17 (1.03-1.33) |
AREDS
AREDS Study Group, 200138
(5) |
4,757 US participants, age 55-80 years recruited from ophthalmology clinics, without major cardiovascular disease or cancer in recent past. |
500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene per day. Some patients with age-related macular degeneration also assigned to receive 80 mg zinc and 2 mg copper versus placebo. 66% of the cohort chose to take a multivitamin (Centrum*) in addition. |
Mean 6.3 years
97.7% completed the trial. |
Reported chest pain:
Vitamins: 19.8%
Placebo: 22.8%
(p=0.01) |
1.06
(0.84-1.33) |
|
|
Heart Protection Study
Heart Protection Collaborative Group, 200240
(5) |
20,536 adults 40-80 years in UK with blood cholesterol >3.5 mmol/L and history of coronary artery disease, other occlusive arterial disease, diabetes, or treated hypertension; excluded with prior high dose vitamin E supplementation or life-threatening disease. Must have shown compliance in 2 month prerandomization compliance period. |
600 mg synthetic vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily in 2x2 factorial trial. Cointervention with simvastatin. |
5 years; 99.7% followed for morbidity. |
|
|
(Vascular Mortality)
1.05
(0.95-1.15) |
1.04
(0.97-1.12) |
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