Related Articles

The prevalence of HCV infection was high among older citizens of Linxian, China, in 2000.

Bloodborne viruses may have spread in rural China during the past 25 years, but population-based prevalence estimates are lacking. We examined the frequency of hepatitis C virus (HCV) and HIV type 1 (HIV-1) among residents of Linxian, a rural community in Henan Province. In 2000, blood was collected from participants (>55 years of age) who had enrolled in a population-based nutritional intervention trial in 1985. We randomly selected 500 participants for HCV testing and 200 participants for HIV-1 testing. For HCV, 48 (9.6%) of 500 participants were positive by enzyme immunoassay and recombinant immunoblot assay (95% confidence interval [CI], 7.0%–12.2%), and prevalence was lowest in the most geographically isolated participants. Among the HCV-infected participants, 42 had a specimen available from1985, of which 16 (38.1%) were positive for HCV. For HIV-1, 0/200 participants were positive. We conclude that HCV is now a common infection among older adults in Linxian, China.

Background

Cancers of the upper gastrointestinal tract remain a significant cause of morbidity and mortality. Cysteine, known to be involved in a myriad of immuno-modulatory, anti-oxidant, and anti-carcinogenic pathways, has not been investigated in the aetiology of oesophageal or gastric cancers. To examine the relationship between serum cysteine concentration and risk of these cancers we conducted a nested case-cohort study within the General Population Nutrition Intervention Trial in Linxian, China.

Methods

498 oesophageal squamous cell carcinomas (OSCC) and 255 gastric cardia adenocarcinomas (GCA) were matched by age and sex to 947 individuals from the wider cohort. We calculated hazard ratios (HR) and 95% confidence intervals (95% CI) using the case-cohort estimator for the Cox proportional hazards models, stratified on age and sex, with adjustment for potential confounders.

Results

Higher concentrations of serum cysteine were significantly associated with a lower risk of both OSCC and GCA. For those in the highest quartile of serum cysteine, compared to those in the lowest, the multivariate HRs were 0.70 for OSCC (95% CI: 0.51, 0.98) and 0.59 for GCA (95% CI: 0.38, 0.91). These associations were dose dependent (P for trend = 0.006 and 0.008, respectively). These inverse associations were not significantly modified by other risk factors, with the exception of age, where a stronger association was noted among persons in the older age strata.

Conclusion

Higher serum concentrations of cysteine were associated with a significantly reduced risk of OSCC and GCA. Cysteine should be further investigated for its potential as a chemopreventive agent for upper gastrointestinal cancers.

OBJECTIVE

To evaluate the evidence of the supplements vitamin C and vitamin E for treatment and prevention of cancer.

METHODS

Systematic review of trials and meta-analysis.

DATA SOURCES AND MAIN RESULTS

Thirty-eight studies showed scant evidence that vitamin C or vitamin E beneficially affects survival. In the ATBC Cancer Prevention Study Group, no statistically significant effect of treatment was seen for any cancer individually, and our pooled relative risk (regardless of tumor type) for α-tocopherol alone was 0.91 (95% confidence interval [CI]: 0.74, 1.12). All cause mortality was not significant. In the Linxian General Population Trial, the relative risks for cancer death for vitamin C (combined with molybdenum) was 1.06 (95% CI: 0.92, 1.21) and for vitamin E (combined with β-carotene and selenium) was 0.87 (95% CI: 0.76, 1.00). We identified only 3 studies that reported statistically significant beneficial results: vitamin C (in combination with BCG) was found to be beneficial in a single trial of bladder cancer and vitamin E (in combination with ω-3 fatty acid) increased survival in patients with advanced cancer. In the ATBC trial, in analyses of 6 individual cancers, the prevention of prostate cancer in subjects treated with α-tocopherol was statistically significant (RR = 0.64, 95% CI: 0.44, 0.94).

CONCLUSIONS

The systematic review of the literature does not support the hypothesis that the use of supplements of vitamin C or vitamin E in the doses tested helps prevent and/or treat cancer in the populations tested. There were isolated findings of benefit, which require confirmation.

Iodine concentrates in gastric tissue and may act as an antioxidant for the stomach. We previously showed that self-reported goiter was associated with significantly increased risk of gastric noncardia adenocarcinoma (GNCA) and non-significantly increased risks of gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC) in a prospective case-cohort study in a high-risk population in China. Negatively correlated with iodine levels, serum thyroglobulin (Tg) is a more sensitive biomarker of iodine deficiency than goiter. This study aimed to determine whether baseline serum Tg was also associated with development of GNCA, GCA, and ESCC in the same cohort, the Linxian General Population Nutrition Intervention Trial. Sera from approximately 200 subjects of each case type and 400 non-cases were tested for serum Tg concentration using appropriate assays. Tg was modeled as sex- and assay-specific quartiles in Cox regression models adjusted for age, smoking, alcohol, Helicobacter pylori status, pepsinogens I/II ratio, family history, and commune of residence. In the final combined analysis, participants in the highest quartile of serum Tg, compared to those in the lowest quartile, had adjusted Hazard Ratios of 0.88 (95% confidence interval 0.50–1.52), 1.14 (0.63–2.05), and 0.78 (0.47–1.31) for GNCA, GCA, and ESCC, respectively. Using serum Tg, a sensitive biomarker of iodine deficiency, we found no association between serum Tg concentrations and risk of these upper gastrointestinal (UGI) cancers in the study population. Our results do not support the hypothesis that iodine deficiency, as assessed by serum Tg, is associated with an increased risk of UGI cancers.

Background

Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma (ESCC), and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures of vitamin D exposure have reached different conclusions about the association between vitamin D and risk of developing esophageal cancer.

Methods

We measured serum 25-hydroxyvitamin D (25(OH)D) concentrations in a cross-sectional analysis of 720 subjects from Linxian, China, a population at high risk for developing ESCC. All subjects underwent endoscopy and biopsy and were categorized by presence or absence of histologic squamous dysplasia. We used crude and multivariate adjusted generalized linear models to estimate the relative risk (RR) and 95% confidence intervals (CI) for the association between squamous dysplasia and sex-specific quartiles of serum 25(OH)D concentration.

Results

Two hundred and thirty (32%) of 720 subjects had squamous dysplasia. Subjects with dysplasia had significantly higher median serum 25(OH)D concentrations then subjects without dysplasia, 36.5 and 31.5 nmol/L respectively (Wilcoxon two-sample test p = 0.0004). In multivariate adjusted models, subjects in the highest compared to the lowest quartile were at significantly increased risk of squamous dysplasia, RR (95% CI) = 1.86 (1.35–2.62). Increased risks were similar when examined in men and women separately: Men RR (95% CI) = 1.74 (1.08–2.93); Women RR (95% CI) = 1.96 (1.28–3.18).

Conclusions

Higher serum 25(OH)D concentration was associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding.

In a cohort of 29 584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case–cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26–2.14, and 1.60; 1.15–2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88–1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies.

Background

Stroke is the leading cause of death in Linxian, China. Although there is evidence of DNA damage in experimental stroke, no data exist on DNA repair and stroke in human populations.

Aim

To assess the risk of stroke conferred by polymorphisms in the DNA repair genes, XRCC1, XPD23 and APE/ref‐1 in a cohort of individuals originally assembled as subjects in two cancer prevention trials in Linxian, China.

Methods

The subjects for this prospective study were sampled from a cohort of 4005 eligible subjects who were alive and cancer free in 1991 and had blood samples available for DNA extraction. Using real‐time Taqman analyses, all incident cases of stroke (n = 118) that developed from May 1996, and an age‐ and a sex‐stratified random sample (n = 454) drawn from all eligible subjects were genotyped. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% CIs.

Results

No association was observed between polymorphisms in APE/ref‐1 codon 148 and XRCC1*6 codon 194, and stroke. Polymorphisms in XRCC1*10 codon 399 were associated with a significantly reduced risk of stroke (RR 0.59, 95% CI 0.36 to 0.96, p = 0.033), whereas XPD23 codon 312 was associated with a significantly increased risk of stroke (RR 2.18, 95% CI 1.14 to 4.17, p = 0.010).

Conclusions

Polymorphisms in DNA repair genes may be important in the aetiology of stroke. These data should stimulate research on DNA damage and repair in stroke.

Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR=1.10, 95%CI=0.64–1.89) or in Linxian (OR=1.47, 95%CI=0.70–3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79–1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC.

Objective

To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidant (SUVIMAX) study which reported a four-fold higher melanoma risk among women who were randomized to a supplement with nutritionally appropriate doses of antioxidants.

Design

Prospective study (VITamins And Lifestyle (VITAL) cohort).

Setting

Population-based study targeting supplement users recruited from Western Washington State.

Participants

69,671 men and women who self-reported intake of multivitamins and supplemental antioxidants including selenium and beta-carotene over the past 10 years as well as melanoma risk factors on a baseline questionnaire.

Main Outcome Measure

incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry.

Results

Cox regression models were used to estimate multivariate relative risks (RR) and 95% confidence intervals (CI) for multivitamins, supplemental selenium and supplemental beta-carotene use. After adjusting for melanoma risk factors, we did not detect a significant association between multivitamins and melanoma risk for women (RR=1.14, CI = 0.78–1.66) or men (RR=1.09, CI =0.83–1.43). Moreover, we did not observe increased melanoma risk for supplemental beta-carotene (RR=0.87, CI=0.48, 1.56) or selenium (RR=0.98, CI=0.69–1.41) at doses comparable to the SUVIMAX study.

Conclusion

Antioxidants in nutritional doses do not appear to increase the melanoma risk.

In the Shandong Intervention Trial, 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions, whereas 7.3 years of oral supplementation with garlic extract and oil (garlic treatment) or vitamin C, vitamin E, and selenium (vitamin treatment) did not. Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 randomly assigned subjects in this masked factorial placebo-controlled trial. Conditional logistic regression was used to estimate the odds of gastric cancer incidence, and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality. All statistical tests were two-sided. Gastric cancer was diagnosed in 3.0% of subjects who received H pylori treatment and in 4.6% of those who received placebo (odds ratio = 0.61, 95% confidence interval = 0.38 to 0.96, P = .032). Gastric cancer deaths occurred among 1.5% of subjects assigned H pylori treatment and among 2.1% of those assigned placebo (hazard ratio [HR] of death = 0.67, 95% CI = 0.36 to 1.28). Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality. Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer, a secondary endpoint (HR = 0.51, 95% CI = 0.30 to 0.87; P = .014).

Forty-seven corn samples were collected in 1989 from Linxian and Shangqiu Counties in Henan Province, the high- and low-risk areas, respectively, for human esophageal cancer in the People's Republic of China. The samples were analyzed for fumonisin (fumonisin B1 [FB1] and FB2) contamination. Of the fumonisin-positive samples, the mean levels in Linxian corn were found to be 872 ng/g for FB1 and 448 ng/g for FB2, while the Shangqiu corns had 890 ng of FB1 and 330 ng of FB2 per g. The incidence of fumonisin contamination of Linxian corn (48%) was about two times higher than that of Shangqiu corn (25%), and the former corn samples were frequently cocontaminated with trichothecenes. Fusarium species isolated from corn from Linxian County produced FB1 at levels ranging from 1,280 to 11,300 micrograms/g.

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (1985–1993) recruited 29,133 Finnish male cigarette smokers, finding that vitamin E supplementation had no overall effect on mortality. The authors of this paper found that the effect of vitamin E on respiratory infections in ATBC Study participants was modified by age, smoking, and dietary vitamin C intake; therefore, they examined whether the effect of vitamin E supplementation on mortality is modified by the same variables. During a median follow-up time of 6.1 years, 3,571 deaths occurred. Age and dietary vitamin C intake had a second-order interaction with vitamin E supplementation of 50 mg/day. Among participants with a dietary vitamin C intake above the median of 90 mg/day, vitamin E increased mortality among those aged 50–62 years by 19% (95% confidence interval: 5, 35), whereas vitamin E decreased mortality among those aged 66–69 years by 41% (95% CI: −56, −21). Vitamin E had no effect on participants who had a dietary vitamin C intake below the median. Smoking quantity did not modify the effect of vitamin E. This study provides strong evidence that the effect of vitamin E supplementation on mortality varies between different population groups. Further study is needed to confirm this heterogeneity.

We investigated dietary supplement use and prostate cancer risk in the Carotene and Retinol Efficacy Trial (CARET). CARET was a randomized, double-blinded placebo-controlled trial testing a daily dose of 30 mg β-carotene + 25,000 IU retinyl palmitate for lung cancer prevention (1985-1996; active follow-up occurred through 2005). Secondary outcomes, including prostate cancer, were also assessed. Participants were queried about dietary supplements, health history, family history of cancer, smoking and lifestyle habits. Cox proportional hazards regression estimated multivariate-adjusted relative risk (and 95% confidence intervals) of prostate cancer for dietary supplement users and non-users with or without the high-dose CARET vitamins during the intervention and post-intervention phases. After an average of 11 years of follow-up, 890 prostate cancer cases were reported. Neither the CARET nor other supplements were associated with total prostate cancer risk. For aggressive prostate cancer, men in the CARET intervention arm who used additional supplements had a relative risk for aggressive prostate cancer (Gleason ≥ 7 or stage III/IV) of 1.52 (95% CI, 1.03-2.24, p<0.05), relative to all others. These associations disappeared in the post-intervention period (0.75, 95%CI 0.51, 1.09). Conversely, there was no association of CARET + other supplements with non-aggressive disease, relative to all others. There was no effect modification by smoking or time on CARET intervention in any analyses. CARET only included smokers so findings reported here may not apply to non-smokers. Our results are consistent with other studies suggesting that dietary supplements may influence prostate cancer risk.

A comparative study on the natural occurrence of Fusarium toxins was done with 47 corn and 30 wheat samples collected in 1989 from Linxian and Shangqiu Counties in Henan Province, People's Republic of China, high- and low-risk areas, respectively, for esophageal cancer. Three trichothecenes (deoxynivalenol [DON], 15-acetyldeoxynivalenol [15-ADON], and nivalenol [NIV]) and zearalenone (ZEA) were detected in corn samples, and DON, NIV, and ZEA were found in wheat samples. Compared with Shangqiu corn, the incidence and mean level of DON in Linxian were 2.4 and 5.8 times higher, respectively, and those of 15-ADON were 16.3 and 2.6 times higher, respectively. The incidence and level of trichothecenes in wheat samples were significantly lower than those in corn. However, the level of DON in Linxian wheat was 3.3 times higher than in Shangqiu wheat. This is the first report indicating a significant difference in the natural occurrence of Fusarium toxins in main staple foods between high- and low-risk areas for esophageal cancer in the People's Republic of China.

Purpose

Urothelial Carcinoma (UC) has the highest lifetime treatment cost of any cancer making it an ideal target for preventative therapies. Previous work has suggested that certain vitamin and mineral supplements may reduce the risk of UC. We sought to use the prospective VITamins And Lifestyle (VITAL) cohort to examine the association of all commonly taken vitamin and mineral supplements as well as 6 common anti-inflammatory supplements with incident UC in a United States population.

Materials&Methods

77,050 eligible VITAL participants completed a detailed questionnaire at baseline on supplement use and cancer risk factors. . After 6 years of follow-up, 330 incident UC cases occurring in the cohort were identified via linkage to the Seattle-Puget Sound Surveillance, Epidemiology and End Results (SEER) cancer registry. We analyzed use of supplemental vitamins (multivitamins, beta-carotene, retinol, folic acid, vitamins B1, B3, B6, B12, C, D and E), minerals (calcium, iron, magnesium, zinc, and selenium), and anti-inflammatory supplements (glucosamine, chondroitin, saw-palmetto, ginko-biloba, fish oil and garlic). For each supplement, the hazard ratios (risk ratios) for UC comparing each category of users to nonusers, and 95% confidence intervals, were determined using Cox proportional hazards regression., adjusted for potential confounders.

Results

None of the vitamin, mineral or anti-inflammatory supplements was significantly associated with UC risk in either age-adjusted or multivariate models.

Conclusions

The results of this study do not support the use of commonly taken vitamin or mineral supplements or 6 common anti-inflammatory supplements for chemoprevention of UC.

High-dose β-carotene supplementation in high-risk persons has been linked to increased lung cancer risk in clinical trials; whether effects are similar in the general population is unclear. The authors examined associations of supplemental β-carotene, retinol, vitamin A, lutein, and lycopene with lung cancer risk among participants, aged 50–76 years, in the VITamins And Lifestyle (VITAL) cohort Study in Washington State. In 2000–2002, eligible persons (n = 77,126) completed a 24-page baseline questionnaire, including detailed questions about supplement use (duration, frequency, dose) during the previous 10 years from multivitamins and individual supplements/mixtures. Incident lung cancers (n = 521) through December 2005 were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. Longer duration of use of individual β-carotene, retinol, and lutein supplements (but not total 10-year average dose) was associated with statistically significantly elevated risk of total lung cancer and histologic cell types; for example, hazard ratio = 2.02, 95% confidence interval: 1.28, 3.17 for individual supplemental lutein with total lung cancer and hazard ratio = 3.22, 95% confidence interval: 1.29, 8.07 for individual β-carotene with small-cell lung cancer for >4 years versus no use. There was little evidence for effect modification by gender or smoking status. Long-term use of individual β-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers.

Background

Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.

Method

This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted.

Results

The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels.

The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.

Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R2 = 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora.

Conclusions

Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism.

Trial Registration

Clinical Trial Registration Number: NCT01225198

Background

We had found a 14% higher incidence of pneumonia with vitamin E supplementation in a subgroup of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study cohort: participants who had initiated smoking by the age of 20 years. In this study, we explored the modification of vitamin E effect by body weight, because the same dose could lead to a greater effect in participants with low body weight.

Methods

The ATBC Study recruited males aged 50–69 years who smoked at least 5 cigarettes per day at the baseline; it was conducted in southwestern Finland in 1985–1993. The current study was restricted to 21,657 ATBC Study participants who initiated smoking by the age of 20 years; the median follow-up time was 6.0 years. The hospital-diagnosed pneumonia cases were retrieved from the national hospital discharge register (701 cases).

Results

Vitamin E supplementation had no effect on the risk of pneumonia in participants with body weight in a range from 70 to 89 kg (n = 12,495), risk ratio (RR) = 0.99 (95% CI: 0.81 to 1.22). Vitamin E increased the risk of pneumonia in participants with body weight less than 60 kg (n = 1054), RR = 1.61 (1.03 to 2.53), and in participants with body weight over 100 kg (n = 1328), RR = 2.34 (1.07 to 5.08). The harm of vitamin E supplementation was restricted to participants with dietary vitamin C intake above the median.

Conclusion

Vitamin E supplementation may cause harmful effects on health in certain groups of male smokers. The dose of vitamin E used in the ATBC Study, 50 mg/day, is substantially smaller than conventional vitamin E doses that are considered safe. Our findings should increase caution towards taking vitamin E supplements.

Trial registration

ClinicalTrials.gov NCT00342992.

Objective To examine the impact of antenatal supplementation with multiple micronutrients or iron and folic acid compared with folic acid alone on birth weight, duration of gestation, and maternal haemoglobin concentration in the third trimester.

Design Cluster randomised double blind controlled trial.

Setting Two rural counties in north west China.

Participants 5828 pregnant women and 4697 live births.

Interventions Villages were randomised for all pregnant women to take either daily folic acid (control), iron with folic acid, or multiple micronutrients with a recommended allowance of 15 vitamins and minerals.

Main outcome measures Birth weight, length, and head circumference measured within 72 hours after delivery. Neonatal survival assessed at the six week follow-up visit.

Results Birth weight was 42 g (95% confidence interval 7 to 78 g) higher in the multiple micronutrients group compared with the folic acid group. Duration of gestation was 0.23 weeks (0.10 to 0.36 weeks) longer in the iron-folic acid group and 0.19 weeks (0.06 to 0.32 weeks) longer in the multiple micronutrients group. Iron-folic acid was associated with a significantly reduced risk of early preterm delivery (<34 weeks) (relative risk 0.50, 0.27 to 0.94, P=0.031). There was a significant increase in haemoglobin concentration in both iron-folic acid (5.0 g/l, 2.0 to 8.0 g/l, P=0.001) and multiple micronutrients (6.9 g/l, 4.1 to 9.6 g/l, P<0.001) groups compared with folic acid alone. In post hoc analyses there were no significant differences for perinatal mortality, but iron-folic acid was associated with a significantly reduced early neonatal mortality by 54% (relative risk 0.46, 0.21 to 0.98).

Conclusion In rural populations in China antenatal supplementation with iron-folic acid was associated with longer gestation and a reduction in early neonatal mortality compared with folic acid. Multiple micronutrients were associated with modestly increased birth weight compared with folic acid, but, despite this weight gain, there was no significant reduction in early neonatal mortality. Pregnant women in developing countries need sufficient doses of iron in nutrient supplements to maximise reductions in neonatal mortality.

Trial registration ISRCTN08850194.

Background and Objectives

Linxian in Henan Province, China, has among the highest rates of esophageal cancer worldwide. Little is known about long-term survival after esophagectomy for early neoplastic lesions found during early detection screening. A long-term survival analysis was performed for 315 patients from Linxian who received esophagectomy for early esophageal squamous cell carcinoma.

Methods

Cases that received esophagectomy for early esophageal squamous cell carcinoma were age- and gender-matched with two healthy controls, and Kaplan-Meier survival analyses were performed for both groups.

Results

10-year survival was 77% for cases and 64% for controls, and this difference was not statistically significant (p = 0.33). There were no significant differences in survival based on age or gender (p>0.05). Cases with esophageal squamous cell carcinoma-in-situ had significantly better survival than cases with invasive esophageal squamous cell carcinoma (p=0.035).

Conclusions

Survival of cases who received esophagectomy for early esophageal squamous cell carcinoma was not significantly different from survival of age- and gender-matched controls. Early intervention probably improved survival rates for these patients who otherwise would most likely have developed advanced esophageal carcinoma. Early screening and intervention are highly relevant in areas with a high risk of esophageal cancer such as Linxian, China.

Background

Although many patients take antioxidant dietary supplements during breast cancer treatment, the benefits of such supplementation are unproven. We analyzed the prevalence of and factors associated with antioxidant supplement use during breast cancer treatment among women who participated in the Long Island Breast Cancer Study Project.

Methods

In 2002–2004, women with breast cancer (BC) who had participated in the 1996–1997 case-control study were invited to participate in a follow-up interview. We defined antioxidant supplement use as any self-reported intake of supplemental vitamin C, vitamin E, beta-carotene, or selenium, in individual supplements or multivitamins.

Results

Follow-up interview participants were younger, more predominantly white, and of higher socioeconomic status, than women who did not respond. Among 764 participants who completed the follow-up interview, 663 (86.8%) reported receiving adjuvant treatment for their BC. Of these 663 women, 401 (60.5%) reported using antioxidants during adjuvant treatment: 120/310 (38.7%) during chemotherapy, 196/464 (42.2%) during radiation, and 286/462 (61.9%) during tamoxifen therapy. Of the 401 antioxidant users, 278 (69.3%) used high doses (doses higher than those contained in a Centrum multivitamin). Factors associated with high antioxidant supplement use during treatment were higher fruit and vegetable intake at diagnosis (RR 1.71, 95% CI 1.13–2.59), tamoxifen use (RR 3.66, 95% CI 2.32–5.78), ever using herbal products (RR 3.49, 95% CI 2.26–5.38), and ever engaging in mind-body practices (RR 1.72, 95% CI 1.13–2.64).

Conclusions

Given the common use of antioxidant supplements during BC treatment, often at high doses and in conjunction with other complementary therapies, future research should address the effects of antioxidant supplementation on BC outcomes.

In the United States, 40 – 50% of the men and women 50 years of age or older regularly use multivitamin/mineral (MVM) supplements, making the annual sales of these supplements over $11 billion. However, the question remains whether using MVM supplements is beneficial to health. This article reviews the results of randomized studies of MVM supplements and individual vitamins/mineral supplements in relation to overall mortality and incidence of chronic diseases, particularly cancer and ischemic heart disease. The results of large-scale randomized trials show that, for the majority of the population, there is no overall benefit from taking MVM supplements. Indeed, some studies have shown increased risk of cancers in relation to using certain vitamins.

Purpose

Vitamin D deficiency is associated with increased breast cancer risk and decreased breast cancer survival. The purpose of this study was to determine the prevalence of vitamin D deficiency, as measured by serum 25-hydroxyvitamin D (25-OHD), in premenopausal women at initiation of adjuvant chemotherapy for breast cancer and after 1 year of vitamin D supplementation.

Patients and Methods

The study included 103 premenopausal women from the northeastern United States with stages I to III breast cancer who received adjuvant chemotherapy and participated in a 1-year zoledronate intervention trial. All patients were prescribed vitamin D3 (cholecalciferol) 400 IU and calcium carbonate 1,000 mg daily. At baseline and at 6 and 12 months, bone mineral density (BMD) measurements were obtained and blood was collected and analyzed in batches for serum 25-OHD. Vitamin D deficiency was defined as serum 25-OHD less than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as 30 ng/mL or greater.

Results

At baseline, 74% of women were vitamin D deficient (median, 17 ng/mL). Vitamin D deficiency was slightly less common in white women (66%) compared with black (80%) and Hispanic (84%) women. After vitamin D supplementation for 1 year, less than 15% of white and Hispanic women, and no black women, achieved sufficient 25-OHD levels. Vitamin D levels did not correlate with baseline BMD and were not altered by chemotherapy or bisphosphonate use.

Conclusion

Vitamin D deficiency is highly prevalent in women with breast cancer. The current recommended dietary allowance of vitamin D is too low to increase serum 25-OHD greater than 30 ng/mL. Optimal dosing for bone health and, possibly, improved survival has yet to be determined.

Background:

Biology is complex and the effects of many interventions may vary between population groups. Subgroup analysis can give estimates for specific populations, but trials are usually too small for such analyses.

Purpose:

To test whether the effect of vitamin E on pneumonia risk is uniform over subgroups defined by smoking and exercise.

Methods:

The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study examined the effects of vitamin E (50 mg per day) and β-carotene (20 mg per day) on lung cancer in 29,133 male smokers aged 50–69 years using a 2 × 2 factorial design. The trial was conducted among the general community in Finland during 1985–1993; the intervention lasted for 6.0 years (median). In the present study, we tested the uniformity of vitamin E effect on the risk of hospital-treated pneumonia (898 cases) by adding a dummy variable to allow each subgroup its own vitamin E effect in a Cox model covering all participants.

Results:

Vitamin E effect was not uniform over eight subgroups defined by baseline smoking (5–19 vs ≥20 cigarettes per day), age of smoking initiation (≤20 vs ≥21 years), and exercise during leisure time (yes vs no). Vitamin E decreased pneumonia risk by 69% (95% CI: 43% to 83%) among participants who had the least exposure to smoking and exercised during leisure time. Vitamin E increased pneumonia risk by 79% (95% CI: 27% to 150%) among those who had the highest exposure to smoking and did not exercise.

Limitations:

Although the evidence of heterogeneity is strong, it is not evident to what extent the estimates of effect or the limits between the subgroups can be extrapolated to other populations.

Conclusion:

Subgroup analysis of large trials should be encouraged, though caution is needed in the interpretation of findings. The role of vitamin E in susceptibility to pneumonia in physically active nonsmokers warrants further study.

Trial registration:

ClinicalTrials.gov NCT00342992.

Summary

The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D3 daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.

Introduction

This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality.

Methods

WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS).

Results

Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38–1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44–0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive.

Conclusion

Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.

Electronic supplementary material

The online version of this article (doi:10.1007/s00198-012-2224-2) contains supplementary material, which is available to authorized users.