Table 2.

Examples of controlled trials of vitamins or supplements on specific diseases

Study	Population	Condition	Intervention	Results	Effect
Heart Protection Study Collaborative Group 2002	20 536 subjects followed 5 years	Coronary heart disease, vascular occlusive disease, diabetes mellitus, hyper tension	Vitamin E 600 mg/d, plus vitamin C 250 mg/d, plus betacarotene 20 mg/d or placebo	All-cause, vascular, or nonvascular mortality, or secondary measures including major coronary events, stroke, revascularization, and cancer	No difference
The SU.VI.MAX Study 2004 – Hercberg et al 2004	13 017 persons, age 45–60, followed 7.5 years	Cancer, cardiovascular disease or cardiovascular mortality	120 mg ascorbic acid, 30 mg of vitamin E, 6 mg of betacarotene, 100 μg of selenium, 20 mg of zinc vs placebo	Total cancer incidence 4.1% vs 4.5%; ischemic cardiovascular disease incidence 2.1% vs 2.1%, all-cause mortality 1.2% vs 1.5%	No difference; may have small protective effect in men
HOPE and Hope-TOO Trial 2005	3994 persons, > 55 years with CVD or cardiovascular disease; diabetes mellitus followed 7 years	Cardiovascular events and cancer	Vitamin E 400 IU/d vs placebo	Cancer incidence 11.6% vs 12.3%; cancer deaths 3.3% vs 3.7%; major cardiovascular events 21.5% vs 20.6%	No difference. Higher risk of congestive heart failure (CHF) and hospitalization for CHF
Heart Protection Study Collaborative Group 2002	15 000 men aged 40–80, followed 5 years	Cardiovascular disease	Daily combination of vitamin E (600 mg) vitamin C (250 mg), and betacarotene (20 mg)	Incidence	No significant reduction
Meta-analysis 2005 – Miller et al 2005	135 967 participants in 19 clinical trials	All-cause mortality	Vitamin E≥400 IU/d	39 deaths per 10 000 persons (3–74 per 10 000 persons; p = 0.035)	Higher mortality
Mullan et al 2002	30 patients, 45–70 years old, with type 2 diabetes, followed 4 weeks	Hypertension	500 mg of ascorbic acid daily	Mean systolic 9.9 mmHg, mean diastolic 6.0 mmHg	Reduced systolic blood pressure
Kim et al 2002	439 subjects followed 5 years	Hypertension	500 mg of vitamin C daily	Blood pressure	No reduction
Pfeifer et al 2001	148 women, mean age 74 years	Hypertension	1200 mg calcium plus 800 IU vitamin D3 or 1200 mg calcium/day	Decrease in systolic blood pressure of 9.3%	Improved
Ram et al 2003	Six trials	Asthma	Vitamin C supplementation	Asthma outcome	No difference
Caraballoso et al 2003	109 394 subjects	Lung cancer	Betacarotene, alone or combination with alphatocopherol or retinol, or alphatocopherol alone	Cancer incidence	No reduction
The Betacarotene and Retional Efficacy Trial 1996 – Omenn et al 1996	18 314 subjects, 45–74 years, at high risk, followed 4 years	Lung cancer	Betacarotene and retinyl palmitate compared with placebo	28% (4%–57%) higher cancer incidence and 17% (3%–33%) higher total mortality in the supplemented group	Worse outcome
Virtamo et al 2003	25 390 persons followed 6 years	Prostate cancer	Alphatocopherol	Relative risk 0.88 (0.76–1.03)	No difference
Virtamo et al 2003	25 390 persons followed 6 years	Prostate cancer	Betacarotene	Relative risk 1.06 (0.91–1.23)	No difference
Greenberg et al 1994	864 subjects	Incidence of colon polyps	Placebo, betacarotene (25 mg daily), vitamin C (1 g daily) and vitamin E (400 mg daily), or betacarotene plus vitamins C and E	Relative risk 1.01 (0.85–1.20) for betacarotene and 1.08 (0.91 to 1.29) for vitamin C and E	No difference
Rodriguez-Martin et al 2003	50 subjects, followed 1 year	Alzheimer dementia	Thiamine supplementation	Cognitive status	No benefit
Alzheimer's Disease Cooperative Study 1997 – Sano et al 1997	341 subjects followed 2 years	Alzheimer dementia	Vitamin E 1000 mg twice a day, selegiline 5 mg twice a day, both or placebo	Time to either death, institutionalization, decline in activities of daily living, or progression to severe dementia	Reduced in vitamin E group (670 days) and selegiline group (655 days) compared with placebo group (440 days), higher mortality 1.08 (1.01–1.14)
Lerner et al 2002	15 subjects	Schizophrenia	Vitamin B6 400 mg vs placebo	Mental status	No difference
Taylor et al 2003	247 subjects	Depression	Folic acid	Reduction in depression scores	2.65 points, CI 0.38–4.93
Christen et al 2003	22 071 male US physicians aged 40–84 years, followed 1 year	Cataract	Betacarotene 50 mg on alternate days vs placebo	Incidence	No benefit
Evans 2003	4119 subjects in 7 trials	Age-related macular degeneration, progression to advanced disease	Antioxidant and zinc supplementation	Risk ratio 0.72 (0.52–0.98)	Less risk
Evans 2003	4119 subjects in 7 trials	Age-related macular degeneration	Vitamin E, betacarotene or both	Prevention	No benefit
Girodon et al 1999	725 institutionalized elderly subjects > 65 years, followed 2 years	Antibody titers, respiratory infections, urinary tract infections, survival rate	Trace elements (zinc and selenium sulfide) or vitamins (betacarotene, ascorbic acid, and vitamin E) or a placebo	Antibody titers after influenza vaccine were higher in group that received trace elements alone or associated with vitamins, but the vitamin group had significantly lower antibody titers	Higher titers with minerals but low with vitamins
Chandra 1992	96 subjects	Infection-related illness, days taking antibiotics, nutritional deficiencies	Vitamin A 400 units, betacarotene 16 mg; thiamine 2.2 mg; riboflavin 1.5 mg; niacin 16 mg; vitamin B6 3.0 mg; folate 400 μg; vitamin C 80 mg; vitamin D 4 μg; vitamin E 44 mg; iron 16 mg; zinc 14 mg; copper 1.4 mg; selenium 20 μg; iodine 0.2 mg; calcium 200 mg; and magnesium 100 mg vs placebo (calcium, 200 mg, and magnesium, 100 mg)	23 (23–28) vs 48 fewer infection-related illness days; 18 (12–16) vs 32 fewer days taking antibiotics	Improved
El-Kadiki et al 2005	8 trials in older adults	Days with infection, at least one infection, incident infections	Any combination of vitamin or mineral supplements	14(10–18) fewer days with infection; at least one infection 1.10 (0.81–1.50); incident infections 0.89 (0.78–1.03)	Fewer days with infection, no difference in incident infections
Gillespie et al 2003	Frail elderly subjects	Hip fracture and vertebral fracture incidence	Vitamin D3 supplementation along with calcium	Risk ratio 0.74 (0.60–0.91)	Less risk
Gillespie et al 2003	Frail elderly subjects	Hip fracture and vertebral fracture incidence	Vitamin D3 supplementation alone without calcium	Risk ratio 1.20 (0.83–1.75)	No difference
Gillespie et al 2003	In healthy younger, ambulatory subjects	Hip fracture	Vitamin D3 supplementation along with calcium	Risk ratio 0.36 (0.01–8.78)	No difference
Gillespie et al 2003	In healthy younger, ambulatory subjects	Nonvertebral fracture	Vitamin D3 supplementation alone with calcium	Risk ratio 0.46 (0.23–0.90)	Less risk