Vitamins in Aging, Health, and Longevity

Figures & data

Table 1 Examples of epidemiological associations with diet, vitamins, or supplements with specific diseases

Study	Population	Condition	Association	Results	95% CI
Kittner et al 1999	167 women aged 15–44 years vs 328 women without a stroke	First ischemic stroke	Plasma homocysteine level ≥ 7.3 μmol/L	Odds ratio 1.6	1.1–2.5
Cancer Prevention Study 2000 – Hirvonen et al 2000	26 593 male smokers,aged 50–69 years	Cerebral infarction	Dietary intake of p-carotene	Relative risk 0.77	0.61–0.99
Cancer Prevention Study 2002 – Hirvonen et al 2000	26 593 male smokers, aged 50–69 years	Cerebral infraction	Lycopene, lutein,zeaxanthin, Vitamin C, flavonols, flavones, vitamin E	No association
Robinson et al 1998	750 patients vs 800 controls	Coronary artery, disease	Homocysteine concentrations >80th percentile of control subjects	Increased risk
Robinson et al 1998	750 patients vs 800 controls	Coronary artery disease	Red cell folate < 10th percentile of controls	Increased risk
Robinson et al 1998	750 patients vs 800 controls	Coronary artery disease	Vitamin B6 < 20th percentil of controls	Increased risk
Anderson et al 2000	1412 patients	Coronary artery disease	Plasma total homocysteine levels	Higher 3-year mortality	15.7% vs 9.6%
Muntwyler et al 2002	83 639 male US physicians with no history of cardiovascular disease (CVD) or cancer	Cardiovascular disease or cardiovascular mortality	Self-reported use of vitamins E, C, or multivitamins	No association
Hung et al 2004	71 910 female participants in the Nurses' Health Study and 37 725 male participants in the Health Professionals' Follow-Up Study, free of chronic disease	Incidence of cardiovascular disease, cancer, or death	Total fruit and vegetable intake by dietary questionnaire	Relative risk for major chronic disease of 0.95 for highest quintile vs lowest, Relative risk for greater than 5 servings daily 0.88 for cardiovascular disease and 1.00 for cancer	0.89–1.01 for major chronic disease; 0.81–0.95 for cardiovascular disease; 0.95–1.05 for cancer
Chen et al 2002	15 317 men and women > 20 years of age	Hypertension	Lower levels of vitamin A and vitamin E	Higher risk of hypertension	43% vs 18%
Chen et al 2002	15 317 men and women > 20 years of age	Hypertension	Higher levels of alphacarotene and betacarotene	Lower risk of hypertension	16% vs 11%
Chen et al 2002	15 317 men and women >20 years of age	Hypertension	Higher levels of vitamin C	Lower diastolic pressure
Tabak et al 1999	Finland (n = 1248), Italy (n = 1386), and the Netherlands (n = 691) middle-aged men	Pulmonary	Higher intake of fruits, vegetables	Higher forced vital capacity	53 mL–118 mL
Tabak et al 1999	Finland (n = 1248), Italy (n = 1386), and the Netherlands (n = 691) middle-aged men	Pulmonary	Higher intake of vitamin C, betacarotene	No association
Tabak et al 1999	Finland (n = 1248),Italy (n = 1386), and the Netherlands (n = 691) middle-aged men	Pulmonary	Higher intake of vitamin E	No association
Nomura et al 2003	9345 Japanese-American men	Bladder cancer	Alphacarotene, betacarotene, lutein plus zeaxanthin, betacryptoxanthin and total carotenoids	No association after adjusting for smoking
Luchsinger et al 2003	980 elderly subjects free of dementia at baseline, followed for mean 4 years	Alzheimer disease	Carotenes and vitamin C, or vitamin E in supplemental or dietary (nonsupplemental) form or in both forms	No association

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

KittnerSJGilesWHMackoRFHomocyst(e)ine and risk of cerebral infarction in a biracial population – the stroke prevention in young women studyStroke19993015546010436100

 PubMed Web of Science ®Google Scholar

HirvonenTVirtamoJKorhonenPIntake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokersStroke2000312301611022054

 PubMed Web of Science ®Google Scholar

RobinsonKArheartKRefsumHLow circulating folate and vitamin B6 concentrations – risk factors for stroke, peripheral vascular disease, and coronary artery diseaseCirculation199897437439490237

 PubMed Web of Science ®Google Scholar

AndersonJLMuhlesteinJBHorneBDPlasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery diseaseCirculation200010212273210982535

 PubMed Web of Science ®Google Scholar

MuntwylerJHennekensCHMansonJEVitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortalityArch Intern Med20021621472612090883

 PubMed Web of Science ®Google Scholar

HungHCJoshipuraKJJiangRFruit and vegetable intake and risk of major chronic diseaseJ Natl Cancer Inst20049615778415523086

 PubMed Web of Science ®Google Scholar

ChenJHeJHammLSerum antioxidant vitamins and blood pressure in the United States populationHypertension2002408101612468562

 PubMed Web of Science ®Google Scholar

TabakCSmitHARasanenLDietary factors and pulmonary function: a cross sectional study in middle aged men from three European countriesThorax1999541021610525562

 PubMed Web of Science ®Google Scholar

NomuraAMYLeeJStemmermannGNSerum vitamins and the subsequent risk of bladder cancerJ Urol20031704 Part 111465014501712

 PubMed Web of Science ®Google Scholar

LuchsingerJATangMXSheaSAntioxidant vitamin intake and risk of Alzheimer diseaseArch Neurol200360203812580704

 PubMed Web of Science ®Google Scholar

Heart Protection Study Collaborative GroupMRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals – a randomized controlled trialLancet2002360233312114037

 PubMed Web of Science ®Google Scholar

HercbergSGalanPPreziosiPThe SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and mineralsArch Intern Med200416423354215557412

 PubMed Web of Science ®Google Scholar

HOPE and HOPE-TOO Trial InvestigatorsEffects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trialJAMA2005293133815769967

 PubMed Web of Science ®Google Scholar

MillerER3rdPastor-BarriusoRDalalDMeta-analysis: high-dosage vitamin E supplementation may increase all-cause mortalityAnn Intern Med2005142374615537682

 PubMed Web of Science ®Google Scholar

MullanBAYoungISFeeHAscorbic acid reduces blood pressure and arterial stiffness in type 2 diabetesHypertension200240804912468561

 PubMed Web of Science ®Google Scholar

KimMKSasakiSSasazukiSLack of long-term effect of vitamin C supplementation on blood pressureHypertension20024079780312468560

 PubMed Web of Science ®Google Scholar

PfeiferMBegerowBMinneHWEffects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly womenJ Clin Endocrinol Metab2001861633711297596

 PubMed Web of Science ®Google Scholar

RamFSFRoweBHKaurBVitamin C supplementation for asthmaCochrane Database Syst Rev20033

 Google Scholar

CaraballosoMSacristanMSerraCDrugs for preventing lung cancer in healthy peopleCochrane Database of Syst Rev20033

 Google Scholar

OmennGSGoodmanGEThornquistMDEffects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular diseaseN Engl J Med1996334115058602180

 PubMed Web of Science ®Google Scholar

VirtamoJPietinenPHuttunenJKIncidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-upJAMA20032904768512876090

 PubMed Web of Science ®Google Scholar

GreenbergERBaronJATostesonTDA clinical trial of antioxidant vitamins to prevent colorectal adenomaNEJM199433114178008027

 PubMed Web of Science ®Google Scholar

Rodriguez-MartinJLQizilbashNLopez-ArrietaJMThiamine for Alzheimer's diseaseCochrane Database Syst Rev20033

 Google Scholar

SanoMErnestoCThomasRGA controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative StudyN Engl J Med19973361216229110909

 PubMed Web of Science ®Google Scholar

LernerVMiodownikCKaptsanAVitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients: a double-blind, placebo-controlled studyJ Clin Psychiatry20026354811838627

 PubMed Web of Science ®Google Scholar

TaylorMJCarneySGeddesJFolate for depressive disordersCochrane Database Syst Rev20033

 Web of Science ®Google Scholar

ChristenWGMansonJEGlynnRJA randomized trial of beta carotene and age-related cataract in US physiciansArch Ophthalmol2003121372812617708

 PubMedGoogle Scholar

EvansJRAntioxidant vitamin and mineral supplements for age-related macular degenerationCochrane Database Syst Rev20033

 Google Scholar

GirodonFGalanPMongetALImpact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients – a randomized controlled trialArch Intern Med19991597485410218756

 PubMed Web of Science ®Google Scholar

ChandraRKEffect of vitamin and trace-element supplementation on immune responses and infection in elderly subjectsLancet1992340112471359211

 PubMed Web of Science ®Google Scholar

El-KadikiASuttonAJRole of multivitamins and mineral supplements in preventing infections in elderly people: systematic review and meta-analysis of randomized controlled trialsBMJ200533087115805125

 PubMed Web of Science ®Google Scholar

GillespieWJAvenellAHenryDAVitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosisCochrane Database Syst Rev20033

 Web of Science ®Google Scholar