TABLE 1.

The effects of supplementation of α-tocopherol on PCa (primary or secondary end point) in randomized, placebo-controlled intervention trials

Study and duration	Characteristics of participants	Intervention	Major end points/outcomes
The α-Tocopherol, β-Carotene Cancer Prevention Study (ATBC), Southwestern, Finland [35]: 5–8 y (1985 to 1993)	29,133 men, 50–69 y, all heavy smokers, healthy (no previous cancer or other serious diseases)	50 mg/d dl-α-tocopheryl acetate (dl-α-TA), 20 mg/d β-carotene, or their combination	1': Lung cancer. 2': Prostate, bladder, colon and rectum, stomach cancer. Outcomes: dl-α-TA ↓ PCa death; ↑deaths from hemorrhagic stroke
Heart Protection Study MRC/BHF (HPS), United Kingdom [36]; 5 y (1994–2001)	20,536 individuals, 40–80 y with coronary disease, other occlusive arterial disease, or diabetes	600 mg synthetic vitamin E, 250 mg vitamin C, 20 mg β-carotene daily	1': Coronary events and fatal or nonfatal vascular events 2': Cancer and other major morbidity Outcomes: no benefit
The Heart Outcomes Prevention Evaluation (HOPE) and The Ongoing Outcomes (HOPE-TOO), multi-European countries and United States [37]; median 7 y (1993–2003)	7030 patients aged 55 y or older with vascular disease or diabetes mellitus from the initial HOPE trial (1993–1999) and the HOPE-TOO extension (1999–2003)	400 IU/d RRR-α-tocopherol acetate	1': Cancer incidence, cancer-related deaths, and major cardiovascular events Outcomes: no benefits (including PCa incidence) and ↑ rates of heart failure
Physician’s Health Study II (PHS-II), United States [38]; 8 y (1997–2007)	14,641 physicians, men aged 50 y or older including 1307 men with a history of cancer including PCa	400 IU synthetic α-tocopherol every other day and vitamin C 500 mg daily	1': PCa for vitamin E and total cancer for vitamin C 2': Total cancer for vitamin E Outcomes: no effects on prostate or total cancer incidence or death
Progression from HGPIN to PCa, Canada [39]; 3 y of supplements plus 3-y follow-up (2003–2010)	303 patients (the median age of 62.8 y), confirmed with HGPIN, median PSA ∼5.41 ng/mL	Soy (40 g), dl-α-tocopherol (800 IU), selenium (200 μg) daily vs. placebo	1': Progression from HGPIN to invasive PCa Outcomes: supplementation did not show beneficial effects
Selenium and Vitamin E Cancer Prevention Trial (SELECT), Canada, Puerto Rico, United States [40,41]; 7–12 y (2001–2011)	35,533 men, 50 y or older for African American and 55 y or older among other races. PSA ≤ 4 ng/mL and not diagnosed or suspicious for PCa based on DRE screening	400 mg IU dl-α-TA, 200 μg/d L-selenomethionine, or their combination	1': PCa. 2': Lung, colorectal, and overall primary cancer. Outcomes: ↑ incidence of early-stage PCa; no effects on other types of cancer

Abbreviations: 1', primary end point; 2', secondary end point; DRE, digital rectal examination; HGPIN, high-grade prostatic intraepithelial neoplasia; PCa, prostate cancer; RCT, randomized controlled trial; Se, selenium; ↓, suppress or inhibit; ↑, increase or enhance.