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Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank.

ABSTRACT: Prospective studies and randomized controlled trials elucidating the impact of antioxidants supplementation on mortality risk are inconclusive. The present analysis determined association between regular antioxidants use and all-cause (primary objective), as well as cause-specific, mortality in 345,626 participants of the UK Biobank cohort using Cox proportional hazard models. All models were adjusted for confounders and multiple testing. Antioxidants users were defined as participants who indicated to regularly use at least one of the following: multivitamins, vitamin C, vitamin E, selenium, and zinc. Median age of antioxidants users (n = 101,159) and non-users (n = 244,467) at baseline was 57 years. During 3.9 million person-years and a median follow-up of 11.5 years, 19,491 deaths occurred. Antioxidants use was not significantly associated with all-cause, cancer, and non-cancer mortality including several cancer and non-cancer subtypes. Interestingly, mortality risk from respiratory disease was significantly 21% lower among antioxidants users as compared to non-users (hazard ratio: 0.79; 95% confidence interval: 0.67, 0.92). In conclusion, the present study findings do not support recommendations for antioxidants supplementation to prevent all-cause, cancer, or non-cancer mortality on a population level. The significant inverse association between antioxidants use and respiratory disease mortality needs further study.

SUBMITTER: Behrendt I

PROVIDER: S-EPMC7766648 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank.

Behrendt Inken I Eichner Gerrit G Fasshauer Mathias M

Antioxidants (Basel, Switzerland) 20201216 12

Prospective studies and randomized controlled trials elucidating the impact of antioxidants supplementation on mortality risk are inconclusive. The present analysis determined association between regular antioxidants use and all-cause (primary objective), as well as cause-specific, mortality in 345,626 participants of the UK Biobank cohort using Cox proportional hazard models. All models were adjusted for confounders and multiple testing. Antioxidants users were defined as participants who indic ...[more]

PMID: 33339307

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Project description:Study questionWhat is the association between menopausal hormone therapy (MHT) and cause-specific mortality?Summary answerSelf-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes.What is known alreadyEvidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality.Study design, size, durationCohort study (the UK Biobank), 178 379 women, recruited in 2006-2010.Participants/materials, setting, methodsPostmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality.Main results and the role of chanceAmong the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74).Limitations, reasons for cautionSelf-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT.Wider implications of the findingsThe current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation.Study funding/competing interest(s)This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests.Trial registration numberN/A.

Project description:BackgroundOpioids have, at most, small benefits for non-cancer pain in the medium and long-term but there is good evidence that they cause harm. The current study describes the characteristics and clinical status of people taking regular opioids in Great Britain and determines whether use is associated with mortality risk.MethodsAn analysis of participants in UK Biobank, a prospective population-based study. At recruitment (2006-10) participants reported medicines which they regularly used in addition to lifestyle and health-related factors. Information was available on deaths until October 2016.FindingsThere were 466 486 participants (54% women) aged 40-69 years and without a prior history of cancer of whom 5.5% were regularly using opioids. Use increased with age-group, was more common in females (6.3% v. 4.6%) and 87% of persons using them reported chronic pain. The highest rates of use (~1 in 9) were in people with low household income, who left school <16 years and lived in areas with high deprivation. Amongst 15,032 people who could not work because of ill-health, 1 in 3 were regularly taking opioids. Regular users reported insomnia (88.7%), a recent major recent life event (57.3%) and were much more likely than non-users to rate their health as poor (RR 5.5, 99% CI (4.9, 6.1)). Those taking weak (4.2% of participants) or strong (1.4%) opioids were more likely to die during follow-up (6.9% and 9.1% respectively v. 3.3% in non-users) an excess which remained after adjustment for demographic, socio-economic, health and lifestyle factors (MRR 1.18 99% CI (1.06, 1.32) and 1.20 99% CI (1.01, 1.43)) respectively.InterpretationRegular use of opioids is common in Great Britain, particularly in groups of low socio-economic status. Most users still report chronic pain, poor health generally and are at increased risk of premature death although it is not established that this relationship is causal.FundingThere were no external sources of funding obtained for the current analyses.

Project description:BackgroundThe World Health Organization proposed the concept of intrinsic capacity (IC; the composite of all the physical and mental capacities of the individual) as central for healthy ageing. However, little research has investigated the interaction and joint associations of IC with cardiovascular disease (CVD) incidence and CVD mortality in middle- and older-aged adults.MethodsUsing data from 443 130 UK Biobank participants, we analysed seven biomarkers capturing the level of functioning of five domains of IC to calculate a total IC score (ranging from 0 [better IC] to +4 points [poor IC]). Associations between IC score and incidence of six long-term CVD conditions (hypertension, stroke/transient ischaemic attack stroke, peripheral vascular disease, atrial fibrillation/flutter, coronary artery disease and heart failure), and grouped mortality from these conditions were estimated using Cox proportional models, with a 1-year landmark analysis to triangulate the findings.ResultsOver 10.6 years of follow-up, CVD morbidity grouped (n = 384 380 participants for the final analytic sample) was associated with IC scores (0 to +4): mean hazard ratio (HR) [95% confidence interval, CI] 1.11 [1.08-1.14], 1.20 [1.16-1.24], 1.29 [1.23-1.36] and 1.56 [1.45-1.59] in men (C-index = 0.68), and 1.17 [1.13-1.20], 1.30 [1.26-1.36], 1.52 [1.45-1.59] and 1.78 [1.67-1.89] in women (C-index = 0.70). In regard to mortality, our results indicated that the higher IC score (+4 points) was associated with a significant increase in subsequent CVD mortality (mean HR [95% CI]: 2.10 [1.81-2.43] in men [C-index = 0.75] and 2.29 [1.85-2.84] in women [C-index = 0.78]). Results of all sensitivity analyses by full sample, sex and age categories were largely consistent independent of major confounding factors (P < 0.001).ConclusionsIC deficit score is a powerful predictor of functional trajectories and vulnerabilities of the individual in relation to CVD incidence and premature death. Monitoring an individual's IC score may provide an early-warning system to initiate preventive efforts.

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Dataset Information

Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank.

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Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank.

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