Dataset Information

Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial.

ABSTRACT:

Background

Recent posttrial analysis of a completed randomized trial found an increased risk of prostate cancer among healthy men taking high-dose vitamin E supplements. Trials that examined the effect of vitamin C supplements on cancer risk are few.

Objective

We examined whether vitamin E or vitamin C supplementation affects the risk of cancer events during posttrial follow-up of the Physicians' Health Study II.

Design

Beginning in 1997, a total of 14,641 US male physicians aged ≥50 y were randomly assigned to receive 400 IU of vitamin E every other day, 500 mg of vitamin C daily, or their respective placebos. The vitamin E and vitamin C treatment ended in 2007, and observational follow-up continued through June 2011.

Results

This study included an additional 356 cases of incident prostate cancer and 771 total cancers that developed during a mean (maximum) of 2.8 (3.8) y of posttrial observation. During an overall mean of 10.3 (13.8) y, there were a total of 1373 incident prostate cancers and 2669 total cancers documented. In comparison with placebo, vitamin E supplementation had no effect on the incidence of prostate cancer (HR: 0.99; 95% CI: 0.89, 1.10) or total cancers (HR: 1.02; 95% CI: 0.95, 1.10). There was also no effect of vitamin C supplementation on total cancers (HR: 1.02; 95% CI: 0.94, 1.10) or incident prostate cancer (HR: 1.03; 95% CI: 0.93, 1.15). Neither vitamin E nor vitamin C supplementation had effects on other site-specific cancers overall. Stratification by known cancer risk factors, history of cancer, other randomized treatment, and follow-up time showed no significant interactions.

Conclusion

In this large-scale randomized trial in men, vitamin E and C supplementation had no immediate or long-term effects on the risk of total cancers, prostate cancer, or other site-specific cancers.

SUBMITTER: Wang L

PROVIDER: S-EPMC4135500 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial.

Wang Lu L Sesso Howard D HD Glynn Robert J RJ Christen William G WG Bubes Vadim V Manson JoAnn E JE Buring Julie E JE Gaziano J Michael JM

The American journal of clinical nutrition 20140709 3

<h4>Background</h4>Recent posttrial analysis of a completed randomized trial found an increased risk of prostate cancer among healthy men taking high-dose vitamin E supplements. Trials that examined the effect of vitamin C supplements on cancer risk are few.<h4>Objective</h4>We examined whether vitamin E or vitamin C supplementation affects the risk of cancer events during posttrial follow-up of the Physicians' Health Study II.<h4>Design</h4>Beginning in 1997, a total of 14,641 US male physician ...[more]

PMID: 25008853

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Project description:BackgroundFindings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial demonstrated a positive effect of gestational cholecalciferol supplementation on offspring bone mineral density (BMD) at age 4 y. Demonstrating the persistence of this effect is important to understanding whether maternal vitamin D supplementation could be a useful public health strategy to improving bone health.ObjectivesWe investigated whether gestational vitamin D supplementation increases offspring BMD at ages 6-7 y in an exploratory post-hoc analysis of an existing trial.MethodsIn the MAVIDOS randomized controlled trial, pregnant females <14 wk' gestation with a singleton pregnancy and serum 25-hydroxyvitamin D 25-100nmol/l at 3 United Kingdom hospitals (Southampton, Sheffield, and Oxford) were randomly assigned to either 1000 IU/d cholecalciferol or placebo from 14 to 17-wk gestation until delivery. Offspring born at term to participants recruited in Southampton were invited to the childhood follow-up at ages 4 and 6-7 y. The children had a dual-energy X-ray absorptiometry (DXA, Hologic discovery) scan of whole-body-less-head (WBLH) and lumbar spine, from which bone area, bone mineral content (BMC), BMD, and bone mineral apparent density (BMAD) were derived. Linear regression was used to compare the 2 groups adjusting for age, sex, height, weight, duration of consumption of human milk, and vitamin D use at 6-7 y.ResultsA total of 454 children were followed up at ages 6-7 y, of whom 447 had a usable DXA scan. Gestational cholecalciferol supplementation resulted in higher WBLH BMC [0.15 SD, 95% confidence interval (CI): 0.04, 0.26], BMD (0.18 SD, 95% CI: 0.06, 0.31), BMAD (0.18 SD, 95% CI: 0.04, 0.32), and lean mass (0.09 SD, 95% CI: 0.00, 0.17) compared with placebo. The effect of pregnancy cholecalciferol on bone outcomes was similar at ages 4 and 6-7 y.ConclusionsSupplementation with cholecalciferol 1000 IU/d during pregnancy resulted in greater offspring BMD and lean mass in mid-childhood compared with placebo in this exploratory post-hoc analysis. These findings suggest that pregnancy vitamin D supplementation may be an important population health strategy to improve bone health.Trial registration numberThis trial was registered at the ISRCTN (https://doi.org/10.1186/ISRCTN82927713) as 82927713 and EUDRACT (https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001716-23/results) as 2007-001716-23.

Project description:BackgroundWe examined the effect of maternal vitamin D supplementation during pregnancy and lactation on risk of acute respiratory infection (ARI) in infants up to 6 months of age in Bangladesh.MethodsThis study was nested in a randomized, double-blind, placebo-controlled, 5-arm dose-ranging trial of prenatal and postpartum vitamin D supplementation. One group of women received 0 IU vitamin D per week during pregnancy and for 26 weeks post delivery ("placebo" group), one group received high-dose prenatal vitamin D supplementation of 28 000 IU per week and 26 weeks post delivery, and there were 3 additional dose-ranging groups receiving vitamin D supplementation during pregnancy only (4200, 16 800, and 28 000 IU per week, respectively). Episodes of ARI were identified by active and passive surveillance. The primary outcome was microbiologically confirmed ARI, and the primary analysis compared the high-dose prenatal plus postpartum vitamin D vs placebo groups.ResultsIn total, 1174 mother-infant pairs were included. Among infants born to mothers in the placebo group, 98% had a venous umbilical cord 25(OH)D level below 30 nmol/L compared with none in the high-dose prenatal plus postdelivery vitamin D group. Incidence of microbiologically confirmed ARI in the high-dose prenatal plus postpartum vitamin D (1.21 episodes per 6 person-months; N = 235) and placebo groups (1.07 episodes per 6 person-months; N = 234) was not significantly different (hazard ratio of 1.12 [95% confidence intervals: 0.90-1.40]). There were no differences in the incidence of microbiologically confirmed or clinical ARI, upper, lower, or hospitalized lower respiratory tract infection between high-dose prenatal plus postpartum vitamin D and placebo groups.ConclusionsDespite a high prevalence of maternal baseline vitamin D deficiency and significant effects of maternal vitamin D supplementation on infant vitamin D status, the intervention did not reduce the risk of microbiologically confirmed ARI in infants up to 6 months of age.

Project description:AimsVitamin D supplementation is widely used in the clinical setting, but its effects on mortality and cardiovascular outcomes in patients with heart failure are unclear. This paper reports outcome data that were collected during follow-up of 3 years after closure of the EVITA trial (a 3 year randomized, placebo-controlled, intervention study with 4000 IU vitamin D daily in patients with advanced heart failure), to capture potential latency effects of vitamin D supplementation on clinical outcomes.Methods and resultsThe prespecified primary endpoint was overall mortality. Secondary endpoints included hospitalization, mechanical circulatory support implantation, high urgent listing for heart transplantation, and heart transplantation. For group comparisons, we used Cox regression models with a time-dependent categorical covariate. The calculated net difference in circulating 25-hydroxyvitamin D between the vitamin D and placebo groups dropped from 60.9 nmol/L at the end of the active study period to 3.2 nmol/L at the end of the post-intervention period. During the entire 6 year period, 73 patients (36.5%) died in the placebo group and 76 (38.8%) in the vitamin D group. Out of these 149 patients, 36 and 39 died during the first 3 years, and 37 and 37 during the second 3 years, respectively. The hazard ratio (HR) for mortality in the vitamin D versus the placebo group was 1.06 [95% confidence interval (CI): 0.68-1.66] for the first 3 years and 1.07 (95% CI: 0.68-1.70) for the 3 year post-intervention follow-up. Compared with the placebo group, the HRs for hospitalization and for mechanical circulatory support implant were significantly higher in the vitamin D group during vitamin D supplementation (HR = 1.31, 95% CI: 1.01-1.68 and HR = 2.01, 95% CI: 1.08-3.76, respectively) but not after vitamin D discontinuation (HR = 1.10, 95% CI: 0.62-1.94 and HR = 0.99, 95% CI: 0.38-2.56, respectively). There was no significant time-dependent effect on the risk of high urgent listing for heart transplantation and heart transplantation.ConclusionsNo beneficial latency effects of vitamin D supplementation on overall mortality could be demonstrated. Instead, the disappearance of unfavourable findings in the vitamin D group (higher HRs for hospitalization and for mechanical circulatory support implant) after vitamin D discontinuation supports the assumption of adverse vitamin D effects on the cardiovascular system at doses of 4000 IU daily.

Project description:ContextMultivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality.ObjectiveTo determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men.Design, setting, and participantsA large-scale, randomized, double-blind, placebo controlled trial (Physicians" Health Study II) of 14 641 male US physicians initially aged 50 years or older (mean [SD] age, 64.3 [9.2] years), including 1312 men with a history of cancer at randomization, enrolled in a common multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011.InterventionDaily multivitamin or placebo.Main outcome measuresTotal cancer (excluding nonmelanoma skin cancer), with prostate, colorectal, and other site-specific cancers among the secondary end points.ResultsDuring a median (interquartile range) follow-up of 11.2 (10.7-13.3) years, there were 2669 men with confirmed cancer, including 1373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (multivitamin and placebo groups, 17.0 and 18.3 events, respectively, per 1000 person-years; hazard ratio [HR], 0.92; 95% CI, 0.86-0.998; P=.04). There was no significant effect of a daily multivitamin on prostate cancer (multivitamin and placebo groups, 9.1 and 9.2 events, respectively, per 1000 person-years; HR, 0.98; 95% CI, 0.88-1.09; P=.76), colorectal cancer (multivitamin and placebo groups, 1.2 and 1.4 events, respectively, per 1000 person-years; HR, 0.89; 95% CI, 0.68-1.17; P=.39), or other site-specific cancers. There was no significant difference in the risk of cancer mortality (multivitamin and placebo groups, 4.9 and 5.6 events, respectively, per 1000 person-years; HR, 0.88; 95% CI, 0.77-1.01; P=.07). Daily multivitamin use was associated with a reduction in total cancer among 1312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56-0.96; P=.02), but this did not differ significantly from that among 13 329 men initially without cancer (HR, 0.94; 95% CI, 0.87-1.02; P=.15; P for interaction=.07). Conclusion In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.Trial registrationclinicaltrials.gov Identifier: NCT00270647.

Project description:ObjectiveTo assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer.DesignBlinded randomized placebo controlled trial.SettingLinqu County, Shandong province, China.Participants3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design.InterventionsH pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003).Main outcome measuresPrimary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease.Results151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease.ConclusionsH pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer.Trial registrationClinicalTrials.gov NCT00339768.

Project description:ContextAlthough multivitamins are used to prevent vitamin and mineral deficiency, there is a perception that multivitamins may prevent cardiovascular disease (CVD). Observational studies have shown inconsistent associations between regular multivitamin use and CVD, with no long-term clinical trials of multivitamin use.ObjectiveTo determine whether long-term multivitamin supplementation decreases the risk of major cardiovascular events among men.Design, setting, and participantsThe Physicians' Health Study II, a randomized, double-blind, placebo-controlled trial of a common daily multivitamin, began in 1997 with continued treatment and follow-up through June 1, 2011. A total of 14,641 male US physicians initially aged 50 years or older (mean, 64.3 [SD, 9.2] years), including 754 men with a history of CVD at randomization, were enrolled.InterventionDaily multivitamin or placebo.Main outcome measuresComposite end point of major cardiovascular events, including nonfatal myocardial infarction (MI), nonfatal stroke, and CVD mortality. Secondary outcomes included MI and stroke individually.ResultsDuring a median follow-up of 11.2 (interquartile range, 10.7-13.3) years, there were 1732 confirmed major cardiovascular events. Compared with placebo, there was no significant effect of a daily multivitamin on major cardiovascular events (11.0 and 10.8 events per 1000 person-years for multivitamin vs placebo, respectively; hazard ratio [HR], 1.01; 95% CI, 0.91-1.10; P = .91). Further, a daily multivitamin had no effect on total MI (3.9 and 4.2 events per 1000 person-years; HR, 0.93; 95% CI, 0.80-1.09; P = .39), total stroke (4.1 and 3.9 events per 1000 person-years; HR, 1.06; 95% CI, 0.91-1.23; P = .48), or CVD mortality (5.0 and 5.1 events per 1000 person-years; HR, 0.95; 95% CI, 0.83-1.09; P = .47). A daily multivitamin was also not significantly associated with total mortality (HR, 0.94; 95% CI, 0.88-1.02; P = .13). The effect of a daily multivitamin on major cardiovascular events did not differ between men with or without a baseline history of CVD (P = .62 for interaction).ConclusionAmong this population of US male physicians, taking a daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up.Trial registrationclinicaltrials.gov Identifier: NCT00270647.

Project description:BackgroundMaternal vitamin D status during pregnancy and lactation is a modifiable factor that may influence offspring musculoskeletal outcomes. However, few randomized trials have tested the effects of prenatal or postpartum vitamin D supplementation on offspring bone and muscle development.ObjectivesThe aim was to examine hypothesized effects of improvements in early-life vitamin D status on childhood musculoskeletal health in Dhaka, Bangladesh.MethodsIn a previously completed, double-blind, dose-ranging trial, healthy pregnant women (n = 1300) were recruited at 17-24 weeks' gestation and randomly assigned to a prenatal/postpartum regimen of 0/0, 4200/0, 16,800/0, 28,000/0, or 28,000/28,000 IU cholecalciferol (vitamin D3)/wk until 26 wk postpartum. In this new report, we describe additional follow-up at 4 y of age (n = 642) for longer-term outcomes. Bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by DXA. Grip strength was tested using a hand-held dynamometer. The primary comparison was children of women assigned to 28,000 IU/wk prenatally compared with placebo. Differences are expressed as means and 95% CIs.ResultsTotal-body-less-head (TBLH) BMC, TBLH aBMD, and grip strength were similar in the combined high-dose prenatal (28,000/0 and 28,000/28,000 IU/wk) compared with placebo groups (mean difference [95% CI] = 0.61 g [-10.90, 12.13], 0.0004 g/cm2 [-0.0089, 0.0097], and 0.02 kg [-0.26, 0.31], respectively). In dose-ranging analyses, TBLH BMC and aBMD, whole-body BMC and aBMD, and grip strength in each of the prenatal vitamin D groups were not significantly different from placebo (P > 0.05 for all comparisons). Only head aBMD was greater in children of women assigned to the 28,000/28,000-IU regimen compared with placebo (mean difference [95% CI] = 0.024 g/cm2 [0.0009, 0.047], P = 0.042); the effect was attenuated upon adjustment for child height, weight, and sex (P = 0.11).ConclusionsMaternal prenatal, with or without postpartum, vitamin D supplementation does not improve child BMC, aBMD, or grip strength at 4 y of age. The MDIG trial and present follow-up study were registered prospectively at www.clinicaltrials.gov as NCT01924013 and NCT03537443, respectively.

Dataset Information

Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial.

Background

Objective

Design

Results

Conclusion

Publications

Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial.

Similar Datasets

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