Table 1. Randomized Controlled Trials of Vitamin Supplementation to Prevent Cancer and Outcomes

Table 1a. Randomized Controlled Trials of Vitamin Supplementation to Prevent Cancer^A

Study, Publication	Setting/Population	Treatment	Duration of Followup; Followup Rate
*Beta-carotene*
Hennekens, 1996⁸ Physicians' Health Study	22,071 U.S. male physicians aged 40-84 years; no history of: Cancer. Myocardial infarction. Stroke. Cerebral ischemia. Noncompliance in run-in phase.	50 mg beta-carotene on alternate days; cointervention with 325 mg aspirin on alternate days in 2 x 2 factorial design	Mean 12 years; 99.99%
Alpha-Tocopherol Beta-Carotene (ATBC) Study Group, 1994⁹	SW Finland; 29,133 male smokers aged 50-69 years	20 mg/day beta-carotene; 50 mg/day alpha-tocopherol in 2 x 2 factorial design	5-8 years; median 6.1 years
Greenberg 1994¹¹ Polyp Prevention Study	6 U.S. gastroenterology clinics; 864 subjects; 79% male <80 years; at least one polyp	25 mg/day beta-carotene vs placebo; cointervention with combination of 1 g/day vitamin C and 400 mg/day vitamin E or placebo in 2 x 2 factorial design	3 years between year 1 and year 4 colonoscopies (mean 36.6 months; no difference between groups)
MacLennan, 1995¹² Australian Polyp Prevention Study	Australian gastrointestinal clinics; 424 subjects; 67% male; aged 30-74 years; at least one polyp	20 mg/day beta-carotene; fat reduction (25% of total energy target); wheat bran fiber (25 g/day of finely milled raw wheat bran) in 2 x 2 x 2 factorial design	2-4 years
I-M Lee, 1999¹⁰ Women's Health Study	39,876 U.S. female health professionals >45 years	50 mg beta-carotene on alternate days vs placebo; cointervention with 100 mg aspirin or placebo on alternate days and 600 IU vitamin E or placebo on alternate days in 2x2x2 factorial design. Beta-carotene study terminated early.	4 years
DeKlerk, 1998¹⁵ Mesothelioma Prevention Study	1024 Australian male (92%) and female (8%) asbestos mine workers; mean age 57; 21% current smokers, 52% ex-smokers, 27% never smokers	30 mg/day beta-carotene (n=512) or 25,000 IU/day retinol (n=512); No placebo group	Through 5/95; mean FU 4.5 years
*Vitamin E*
ATBC Study Group, 1994⁹	SW Finland; 29,133 aged 50-69 years male smokers	20 mg/day beta-carotene; 50 mg/day alpha-tocopherol in a 2 x 2 factorial design	5-8 years; median 6.1 years
*Multivitamin and antioxidant combinations*
Greenberg, 1994¹¹ Polyp Prevention Study	6 U.S. gastroenterology clinics; 864 subjects; 79% male; <80 years; at least one polyp	1 g/day vitamin C and 400 mg/day vitamin E vs placebo; cointervention 25 mg/day beta-carotene or placebo in a 2 x 2 factorial design	3 years between year 1 and year 4; colonoscopies (mean=36.6 months, no difference between groups)
Omenn 1996¹⁴ CARET	4060 West Coast male asbestos workers; 14,254 U.S. male and female heavy smokers (66% male overall)	30 mg/day beta-carotene and 25,000 IU/day retinol or placebo	5.5 years
McKeown-Eyssen 1998²⁵	Toronto hospital; 185 subjects; 60% male; at least one polyp	400 mg/day vitamin C and 400 mg/day vitamin E or placebo	2 years
Ponz de Leon 1997²⁶ Italian Polyp Prevention Study	Italy; 255 subjects; % male not known; at least one polyp	Antioxidant vitamins (30,000 IU vitamin A, 70 mg vitamin E, 1 g vitamin C per day); lactulose (crystalline powder or syrup); placebo	36 months
^A For more details about the trials, go to Appendix 3. Note: ATBC indicates Alpha-Tocopherol Beta-Carotene;g, gram; mg, milligram; n, number; FU, followup; NR, not reported; CARET, Beta-Carotene and Retinol Efficacy Trial.

Table 1b. Outcomes^B of Randomized Controlled Trials of Vitamin Supplementation to Prevent Cancer

Study, Publication	Lung Cancer	Prostate Cancer	Breast Cancer	Colon Cancer	Other Cancer	All-cause Mortality
*Beta-carotene*
Hennekens, 1996 ⁸ Physicians' Health Study	Incidence: 0.93 (0.69-1.25; NS)	Incidence: 0.99 (0.88-1.11)	NR	Colon/Rectum Incidence: 0.96 (0.78-1.18)	Incidence: Stomach: 0.90 (0.49-1.67) Pancreas: 1.38 (0.79-2.40) Brain: 0.81 (0.48-1.36) Melanoma: 0.88 (0.63-1.22) Leukemia: 0.83 (0.53 -1.30) Lymphoma: 1.07 (0.79-1.45) Bladder: 1.51 (1.02-2.24) Thyroid: 8.00 (2.05-31.23) All cancer mortality: 1:02 (0.88-1.17)	1.01 (0.93-1.10)
ATBC Study Group, 1994⁹	Incidence: 1.19 (1.03-1.36)	Incidence: 1.23 (0.95-1.60)	NR	Incidence: 1.05 (0.75-1.47) Adenomatous polyps recurrence: 0.98 (0.71-1.35)	Pancreatic incidence: 0.75 (0.49-1.14) Pancreatic mortality: 0.81 (0.53-1.26)	1.08 (1.01-1.16)
Greenberg, 1994¹¹ Polyp Prevention Study	NR	NR	NR	Adenomatous polyps recurrence: 1.01 (0.85-1.20)	NR	1.03 (0.82-1.30)
MacLennan, 1995¹² Australian Polyp Prevention Study	NR	NR	NR	Incidence: 1.5 (0.9-2.5)^c	NR	NR
I-M Lee, 1999¹⁰ Women's Health Study	Incidence: 1.43 (0.82-2.48)	NR	Incidence: 1.01 (0.81-1.24)	Incidence: 0.99 (0.62-1.60)	Incidence: Uterus: 1.15 (0.69-1.91;NS) Ovary: 1.33 (0.73-2.43) Thyroid: 0.75 (0.32-1.74;NS) Bladder: 0.83 (0.27-2.57) Brain: 0.67 (0.20-2.20) Pancreas: 1.50 (0.45-4.94) Cervix: 0.67 (0.13-3.33) Stomach: 0.99 (0.10-9.58) All cancer: 1.03 (0.89-1.18) All cancer mortality: 1.11 (0.67-1.85)	1.07 (0.74-1.56)
DeKlerk, 1998¹⁵ Mesothelioma Prevention Study	Incidence: 0.66 (0.19-2.32)	NR	NR	NR	Malignant mesothelioma incidence: 0.24 (0.07-0.86) Other cancer mortality: 0.97(0.24-3.90)	0.56 (0.33-0.95)
*Vitamin E*
ATBC Study Group, 1994⁹	0.98 (0.86-1.12)	Incidence: 0.68 (0.53-0.88) Mortality: 0.59 (0.35-0.99)	NR	Incidence: 0.78 (0.55-1.09) Adenomatous polyps recurrence: 1.66 (1.19-2.32)	Cancer mortality: 1.05 Pancreatic cancer incidence: 1.34 (0.88-2.05) Pancreatic cancer mortality: 1.11 (0.72-1.72)	1.02 (0.95-1.09)
*Multivitamin and antioxidant combinations*
Greenberg, 1994¹¹ Polyp Prevention Study	NR	NR	NR	Adenomatous polyps recurrence: 1.08 (0.91-1.29)	NR	NR
Omenn, 1996¹⁴ CARET	Incidence: 1.28 (1.04-1.57) Mortality: 1.46 (1.07-2.00)	Incidence: 1.01 (0.80-1.27)	Incidence: 0.78 (0.55-1.12)	Incidence: 1.02 (0.70-1.50)	Incidence: Urinary/bladder: .08 (0.69-1.70) Head/neck: 1.26 (0.73-2.19) Leukemia: 2.18 (0.95-5.03) Lymphoma: 0.91 (0.42-1.98) Mesothelioma: 1.52 (0.66-3.52)	1.17 (1.03-1.33)
McKeown-Eyssen, 1998²⁵	NR	NR	NR	Adenomatous polyps recurrence: 0.86 (0.51-1.45)	NR	NR
Ponz de Leon, 1997²⁶ Italian Polyp Prevention Study	NR	NR	NR	Adenomatous polyps recurrence: 0.16 0.04-0.46)	NR	NR
^A For more details about the trials, go to Appendix 3. ^B All confidence intervals .95%. ^c Unadjusted odds ratio. Note: ATBC indicates Alpha-Tocopherol Beta-Carotene;g, gram; mg, milligram; n, number; FU, followup; NR, not reported; CARET, Beta-Carotene and Retinol Efficacy Trial.

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