Modification of the effect of vitamin E supplementation on the mortality of male smokers by age and dietary vitamin C.
ABSTRACT: 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.
Project description: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.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).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.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.ClinicalTrials.gov NCT00342992.
Project description:The Dietary Reference Intakes (DRI)-monograph (USA/Canada) states that the estimated average requirement (EAR) of vitamin E for men and women of any age is 12 mg/day. The EAR value is based on in vitro hemolysis in young males; a surrogate endpoint without any direct validity. The EAR is then extrapolated to females and older males. The validity of the EAR level is therefore questionable. Total mortality is an outcome of direct clinical relevance. Investigating the effect of long-term dietary vitamin E intake level on mortality in a randomized trial is, however, not feasible. Nevertheless, the effect of dietary vitamin E intake can be investigated indirectly from the effects of a fixed-level vitamin E supplement administered to participants on variable levels of dietary vitamin E intake. If vitamin E intake below the EAR is harmful, then vitamin E supplement should be beneficial to those people who have dietary vitamin E intake level below the EAR. The purpose of this study was to analyze the association between dietary vitamin E intake and the effect of 25 mg/day of vitamin E supplement on total mortality in Finnish male smokers aged 50-69 years in the Alpha-Tocopherol-Beta-Carotene (ATBC) Study. The effect of vitamin E supplement was estimated by Cox regression. Among participants who had dietary vitamin C intake of 90 mg/day and above, vitamin E supplement increased mortality by 19% (p = 0.006) in those aged 50-62 years, but decreased mortality by 41% (p = 0.0003) in those aged 66-69 years. No association between vitamin E supplement effect and dietary vitamin E intake was found in these two groups, nor in participants who had dietary vitamin C intake less than 90 mg/day. There is no evidence in any of the analyzed subgroups that there is a difference in the effect of the 25 mg/day vitamin E supplement on males on dietary vitamin E intakes below vs. above the EAR of 12 mg/day. This analysis of the ATBC Study found no support for the 'estimated average requirement' level of 12 mg/day of vitamin E for older males. Trial registration: ClinicalTrials.gov, identifier: NCT00342992.
Project description:A previous analysis of the Alpha-Tocopherol Beta-Carotene (ATBC) Study on male smokers found that ?-carotene supplementation increased the risk of pneumonia 4-fold in those who started smoking at the age of ?21 years and smoked ?21 cigarettes/d (a subgroup of 7 % of the study population). The present study hypothesised that ?-carotene increases mortality in the same subgroup. The ATBC Study (1985-1993) recruited 29 133 Finnish male smokers (?5 cigarettes/d) aged 50-69 years. Cox regression models were constructed to estimate the effect of ?-carotene supplementation in subgroups. ?-Carotene increased mortality (risk ratio 1·56; 95 % CI 1·06, 2·3) in those who started to smoke at ?21 years and smoked ?21 cigarettes/d. Within this subgroup, there was strong evidence of further heterogeneity. The effect of ?-carotene supplementation was further modified by dietary vitamin C intake, fruit and vegetable intake (P = 0·0004), and by vitamin E supplementation (P = 0·011). Thus, harm from ?-carotene was not uniform within the study population. Interactions between ?-carotene and vitamins C and E were seen only within a subgroup of 7 % of the ATBC participants, and therefore should not be extrapolated to the general population. Heterogeneity of the ?-carotene effect on mortality challenges the validity of previous meta-analyses that have pooled many diverse antioxidants for one single estimate of effect using the assumption that a single estimate equally applies to all antioxidants and all people. Trial registration: ClinicalTrials.gov NCT00342992.
Project description:Significant reductions in prostate cancer incidence and mortality were observed in men randomized to receive 50 mg supplemental vitamin E (alpha-tocopherol) per day in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We hypothesized that variation in key vitamin E transport genes might directly affect prostate cancer risk or modify the effects of vitamin E supplementation. Associations between prostate cancer risk and 13 polymorphisms in two genes, TTPA and SEC14L2, were examined in 982 incident prostate cancer cases and 851 controls drawn from the ATBC Study. There was no association between the genetic variants and prostate cancer risk. Significant interactions were observed, however, between two variants in SEC14L2 (IVS11+931A>G and IVS11-896A>T) and the trial alpha-tocopherol supplement such that vitamin E supplementation reduced prostate cancer risk among men who were homozygous for either common allele [odds ratios (OR) and 95% confidence intervals (95% CI), 0.52 (0.30-0.90) and 0.64 (0.46-0.88), respectively] and nonsignificantly increased risk among those who carried one or two copies of either variant allele [ORs and 95% CIs, 1.27 (0.90-1.79) and 1.21 (0.96-1.52), respectively; both P for interaction < 0.05]. Genotype-phenotype analyses revealed significant but modest differences in baseline circulating concentrations of alpha-tocopherol and serum responses to the vitamin E supplementation for several polymorphisms. This study shows that genetic variation in TTPA and SEC14L2 is associated with serum alpha-tocopherol but does not have a direct effect on prostate cancer. Our results do, however, suggest that polymorphisms in SEC14L2 may modify the effect of vitamin supplementation regimens on prostate cancer risk.
Project description:To assess the relationship between antioxidant vitamin intake and all-cause mortality in older adults, we examined these associations using data from the Leisure World Cohort Study, a prospective study of residents of the Leisure World retirement community in Laguna Hills, California. In the early 1980s, participants (who were aged 44-101 years) completed a postal survey, which included details on use of vitamin supplements and dietary intake of foods containing vitamins A and C. Age-adjusted and multivariate-adjusted (for factors related to mortality in this cohort—smoking, alcohol intake, caffeine consumption, exercise, body mass index, and histories of hypertension, angina, heart attack, stroke, diabetes, rheumatoid arthritis, and cancer) hazard ratios for death were calculated using Cox regression for 8,640 women and 4,983 men (median age at entry, 74 years). During follow-up (1981-2013), 13,104 participants died (median age at death, 88 years). Neither dietary nor supplemental intake of vitamin A or vitamin C nor supplemental intake of vitamin E was significantly associated with mortality after multivariate adjustment. A compendium that summarizes previous findings of cohort studies evaluating vitamin intake and mortality is provided. Attenuation in the observed associations between mortality and antioxidant vitamin use after adjustment for confounders in our study and in previous studies suggests that such consumption identifies persons with other mortality-associated lifestyle and health risk factors.
Project description:End-stage renal disease (ESRD) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation, low dietary intake and inadequate sun exposure. Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality. ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein (APP) synthesis. Our aim was to look for associations between lifestyle factors, diet, and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism. The study included 59 ESRD patients treated with maintenance hemodialysis. A 24-hour dietary recall was conducted in the post-summer (November 2018, PS) and post-winter (February/March 2019, PW) period, and blood was collected for the measurements of serum total vitamin D, ?1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin, prealbumin (PRE), parathormone, calcium and phosphate. A self-constructed questionnaire gathered information on vitamin D supplementation, sun exposure and physical activity. Higher caloric intake was observed PW compared PS. Less than 15% of participants met the dietary recommendations for energy, protein, fiber, vitamin D and magnesium intake. Vitamin D supplementation was associated with higher serum vitamin D regardless of season. AGP, PRE, albumin, and vitamin D presented seasonal changes (higher values PS). In patients with serum vitamin D below 25 ng/mL, vitamin D seasonal change correlated with CRP and prealbumin change. Phosphate and Ca × P correlated positively with AGP. A low vitamin D serum level could impact the inflammatory process; however, more studies are needed to confirm the relationship.
Project description:UNLABELLED:Nitrosatable drugs, such as secondary or tertiary amines and amides react with nitrite in an acidic environment to form N-nitroso compounds, teratogens in animal models. Vitamin C is a known nitrosation inhibitor. METHODS:Using data from the National Birth Defects Prevention Study, we assessed nitrosatable drug exposure and vitamin C intake during the first trimester among 11,606 case-mothers of infants with oral clefts, limb deficiencies (LDs), or congenital heart defects and 6807 control-mothers of infants without major birth defects during 1997-2005. Daily intake of vitamin C was estimated from maternal interviews that elicited information about supplement use and dietary intake. RESULTS:With no reported use of nitrosatable drugs as the referent group, a lower odds ratio (OR) was observed for transverse LDs among births to mothers exposed to secondary amine drugs and daily vitamin C supplementation (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 0.83-1.8) compared with women taking these drugs and no supplementation (aOR 2.7, 95% CI 1.5-4.6). The OR for longitudinal LDs associated with secondary amine exposure was lower with daily dietary vitamin C intake ?85 mg (aOR 1.2, 95% CI 0.68-2.0) compared with <85 mg (aOR 1.9, 95% CI 1.2-3.1). Daily vitamin C supplementation in combination with higher dietary vitamin C intake reduced associations between nitrosatable drug exposures and limb deficiencies and atrial septal defects not otherwise specified. CONCLUSION:Prenatal dietary and vitamin C supplement intake may diminish the association between nitrosatable drug exposure during pregnancy and selected birth defects.
Project description:The aim of the study was to assess the relationships between individual-level dietary intakes of antioxidant vitamins C, E and beta-carotene with all-cause and cause-specific mortality in three Central and Eastern European (CEE) populations.Data from the Health, Alcohol and Psychosocial factors in Eastern Europe cohort study were used. At the baseline survey, between 2002 and 2005, 28,945 men and women aged 45-69 years were examined in Novosibirsk (Russia), Krakow (Poland) and seven Czech towns. Deaths in the cohorts were identified through mortality registers. Cox regression was used to estimate the association between vitamin consumption and all-cause, cardiovascular (CVD) disease and cancer mortality.In multivariable-adjusted analyses, there were no clear inverse associations between antioxidant vitamin intakes and mortality, although in some groups, several hazard ratios (HRs) were significant. For example, in men, compared with the lowest quintile of vitamin C intake, all-cause mortality in the third and fourth quintiles was lower by 28 % (HR 0.72; 95 % CI 0.61-0.85) and by 20 % (HR 0.80; 95 % CI 0.68-0.95), respectively. CVD mortality was lower by 35 % (HR 0.65; 95 % CI 0.50-0.84) and by 23 % (HR 0.77; 95 % CI 0.59-0.99) in third and fourth quintile of vitamin C intake, respectively. In women, the third and fourth quintiles of dietary intake of vitamin E were associated with reduced risk of all-cause death by 33 % (HR 0.67; 95 % CI 0.53-0.84) and by 23 % (HR 0.77; 95 % CI 0.61-0.97), respectively. Consumption of vitamin C, vitamin E and beta-carotene was not related to CVD mortality in women and to cancer mortality in either gender.This large prospective cohort study in CEE populations with low prevalence of vitamin supplementation did not find a strong, dose-response evidence for protective effects of antioxidant vitamin intake.
Project description:BACKGROUND:The purpose of this study was to test the hypothesis that decreased dietary intake of Vitamin D contributes to Vitamin D deficiency in end-stage renal disease (ESRD) patients on hemodialysis (HD). METHODS:We performed a cross-sectional study of 58 hemodialysis outpatients from two Mount Sinai Medical Center (MSMC)-affiliated outpatient HD units in New York City and 648 outpatients at MSMC with CKD stages I-IV. Serum 25(OH)D concentrations were measured from August 2010 to July of 2011 in recruited hemodialysis patients (n=58) and linked with results of dietary and lifestyle surveys. The Mount Sinai Data Warehouse (electronic medical record) was used to capture 25(OH) Vitamin D levels for outpatients with CKD stages I-IV who had Vitamin D testing during the same time period. RESULTS:The prevalence of Vitamin D insufficiency/deficiency in the HD cohort was 96.6%. Mean (SD) and median (IQR) 25(OH)D concentrations were 15.65 (6.82) and 13.55 (10.15) ng/mL, respectively. Dietary surveys showed a median weekly Vitamin D intake of 1044 IU (IQR=808, vs. a recommended weekly allowance of 4200 IU) and specific avoidance of foods containing both Vitamin D and phosphorus. In contrast, mean and median 25(OH)D concentrations in patients with CKD stages I-IV were 25.66 (13.44) and 23.60 (15.48) ng/mL (p<0.001 vs. HD patients). CONCLUSIONS:Vitamin D deficiency is more prevalent in HD patients than in pre-dialysis patients with CKD and is associated with decreased dietary intake of Vitamin D. Dialysis restrictions imposed to reduce dietary phosphorus intake likely contributes to the development of hypovitaminosis D in ESRD patients.
Project description:Arctic populations are at an increased risk of vitamin D inadequacy due to geographic latitude and a nutrition transition. This study aimed to assess the adequacy of dietary vitamin D and calcium among women of child-bearing age in Arctic Canada.This study collected data from 203 randomly selected women of child-bearing age (19-44 years) in Nunavut and the Northwest Territories of Arctic Canada. Cross-sectional surveys using a validated quantitative food frequency questionnaire were analysed to determine the dietary adequacy of vitamin D and calcium and summarize the top foods contributing to vitamin D and calcium intake among traditional food eaters (TFE) and non-traditional food eaters (NTFE).The response rate was between 69-93% depending on the community sampled. Mean BMIs for both TFE and NTFE were above the normal range. Traditional food eaters had a significantly higher median vitamin D intake compared with non-traditional eaters (TFE=5.13 ± 5.34 µg/day; NTFE=3.5 ± 3.22 µg/day, p=0·004). The majority of women (87%) were below the Estimated Average Requirements (EAR) for vitamin D. Despite adequate median daily calcium intake in both TFE (1,299 ± 798 mg/day) and NTFE (992 ± 704 mg/day; p=0.0005), 27% of the study population fell below the EAR for calcium. Dairy products contributed the most to intake of vitamin D (TFE=30.7%; NTFE=39.1%) and calcium (TFE=25.5%; NTFE=34.5%).Inadequate dietary vitamin D intake is evident among Inuit and Inuvialuit women of child-bearing age in Arctic Canada. Promotion of nutrient-rich sources of traditional foods, supplementation protocols and/or expanded food fortification should be considered to address this nutrition concern.