The effects of vitamin E supplementation on malondialdehyde as a biomarker of oxidative stress in haemodialysis patients: a systematic review and meta-analysis.

BACKGROUND: Haemodialysis (HD) patients tend to have higher levels of oxidative stress (OS), associated with increased morbidity and premature mortality, compared to the general population. Levels of malondialdehyde (MDA), a biomarker of OS, are reduced by the antioxidant properties of vitamin E (VE) but outcomes from randomised control trials of VE supplementation on MDA in HD patients have been inconsistent. METHODS: We undertook a systematic review and meta-analysis of adult HD patients from VE supplementation studies with measures of MDA. The following search criteria of MEDLINE and EMBASE were considered from inception to January 2020: 'dialysis' AND 'Vitamin E OR tocopherol' AND 'malondialdehyde OR MDA'. Two reviewers independently extracted study data and assessed risk of bias. Mean MDA levels and standard deviation were determined before and after VE supplementation. Standardised mean difference (SMD) and standard error were calculated as the within person difference and units of measure were not consistently recorded across all studies. The SMD were pooled using random effects meta-analysis. RESULTS: The SMD of MDA levels from 18 comparisons was significantly lower in HD patients following VE supplementation (- 1.55; confidence interval: - 2.17 to - 0.94, P < 0.00001). There were significant levels of heterogeneity between studies (I2 value = 91%; P < 0.00001) with evidence of potential publication bias toward smaller studies. CONCLUSIONS: Our findings support the use of VE to reduce the effects of OS in HD patients although high levels of heterogeneity and variation in the methodological approaches used by some studies highlight the need for further investigation.

Coffee consumption by type and risk of digestive cancer: a large prospective cohort study.

BACKGROUND: Inverse associations have been observed between coffee consumption and liver cancer, but associations for other digestive cancers are unclear. Few previous studies have investigated coffee type (specifically instant or ground coffee) or a range of digestive cancer types within one cohort. We therefore investigated coffee consumption by type and digestive cancer risks in a population-based cohort. METHODS: The UK Biobank captured self-reported coffee consumption and cancer-registry recorded incident digestive cancers. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. The risk of every type of digestive cancer was investigated in association with coffee consumption by dose-response and by coffee type (decaffeinated, instant and ground). RESULTS: Over 7.5 years of follow-up, 3567 developed digestive cancer among 471,779 participants. There were 88 cases of hepatocellular carcinoma and a marked association was observed for hepatocellular carcinoma in coffee drinkers (HR 0.50, 95% CI 0.29, 0.87), which was similar for instant (HR 0.51, 95% CI 0.28, 0.93) and ground coffee (HR 0.47, 95% CI 0.20, 1.08). We did not observe significant consistently reduced risks of other individual digestive cancers amongst coffee drinkers. CONCLUSIONS: We found some evidence that coffee consumption was inversely associated with hepatocellular carcinoma which was similar by coffee type.

Plasma Antioxidant Status in Patients with Alzheimer's Disease and Cognitively Intact Elderly: A Meta-Analysis of Case-Control Studies.

Serum antioxidants may afford neuroprotection against Alzheimer's disease (AD) via correction of the pro-oxidative imbalance but findings reported have been inconsistent. We compared the pooled mean difference in serum levels of ten dietary antioxidants between patients with AD and cognitively intact controls from 52 studies in meta-analyses using random-effects models. Patients with AD had significantly lower plasma levels of α-carotene, ß-carotene, lycopene, lutein, vitamin A, C, and E, and uric acid. No significant difference was observed for plasma levels of ß-cryptoxanthin and zeaxanthin. Considerable heterogeneity was detected across studies. The lower serum levels of dietary antioxidants from the carotene and vitamin subclasses observed in individuals with AD suggest reduced systemic availability of these subclasses in this prevalent form of dementia. To our knowledge, these are the first meta-analyses to demonstrate lower serum lycopene and to evaluate ß-cryptoxanthin, lutein, and zeaxanthin levels in AD. In light of the significant heterogeneity detected across studies, caution should be exercised in the interpretation of the data and therapeutic intervention approaches considered through supplementation measures. Our data may better inform interventions to improve antioxidant status in a condition of major public health importance.

Serum concentrations of vitamin E and carotenoids are altered in Alzheimer's disease: A case-control study.

INTRODUCTION: Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). We investigated associations between serum levels of lipophilic antioxidants and AD. METHODS: Serum concentrations of retinol, two forms of vitamin E (α- and γ-tocopherol) and six carotenoids were quantified by high-performance liquid chromatography from patients with AD (n = 251) and cognitively intact controls (n = 308) and assessed by regression analyses. RESULTS: Serum levels of α-tocopherol and all six carotenoids were significantly lower in patients with AD compared with cognitively intact controls (P < .001). In contrast, γ-tocopherol was significantly higher in the serum of patients with AD (odds ratio = 1.17 [confidence intervals: 1.05-1.31]). DISCUSSION: Our findings implicate compromised serum antioxidant defenses in AD pathogenesis and differing biological roles for vitamin E isoforms. This highlights the need for improved understanding in the balanced upregulation of exogenous antioxidants related to dietary intake or supplement use in future nutritional intervention studies.

Cardiac glycosides and breast cancer risk: A systematic review and meta-analysis of observational studies.

Cardiac glycosides are phytoestrogens and have been linked to the risk of estrogen sensitive cancers such as uterus cancer. However, the association between use of cardiac glycosides and risk of breast cancer remains unclear. We investigated the association between cardiac glycosides use and the risk of breast cancer by systematically reviewing the published literature and performing meta-analyses. A comprehensive literature search was performed using MEDLINE, EMBASE, Web of Science and SCOPUS to identify all relevant articles published up to November 2015. Risk estimates, and accompanying standard errors, for the association between cardiac glycoside use and breast cancer were extracted from identified studies. Meta-analysis models were used to calculate a combined hazard ratio (HR), and 95% confidence interval (CI), and to investigate heterogeneity between studies. In total, nine studies were identified investigating cardiac glycosides use and risk of developing breast cancer. Overall, there was evidence to suggest an association between cardiac glycosides use and breast cancer risk (HR = 1.34; 95% CI 1.25, 1.44; p < 0.001) with little variation in the association between studies (I2 = 16%, p for heterogeneity = 0.30). Results were little altered when analysis was restricted to studies with high quality scores or cohort studies. Overall, there was a 34% increase in breast risk with use of cardiac glycosides but it is unclear whether this association reflects confounding or is causal. Further observational studies are required to examine this association particularly for estrogen receptor positive breast cancer and to explore the role of potential confounding variables.

Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment.

BACKGROUND: It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis. OBJECTIVES: To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments). SEARCH METHODS: We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied. DATA COLLECTION AND ANALYSIS: Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes. MAIN RESULTS: Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I(2)= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I(2) = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I(2) = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I(2) = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear. AUTHORS' CONCLUSIONS: Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

Neonatal jaundice is associated with a small increase in the risk of childhood type 1 diabetes: a meta-analysis of observational studies.

Published data on the role of neonatal jaundice as a risk factor for childhood type 1 diabetes mellitus is inconsistent. We aimed to review systematically, the evidence for an increased risk of type 1 diabetes in children diagnosed with neonatal jaundice. A comprehensive search of the published literature was performed to identify studies that had recorded the occurrence of neonatal jaundice in a group of children with type 1 diabetes and in a group of control children. Odds ratios (ORs) were extracted from reports or derived from tabulated data and then combined using a random effects meta-analysis. Data were available from 12 case-control studies and one retrospective cohort study. Overall, there was only weak evidence of an increase in the risk of type 1 diabetes in children who had neonatal jaundice (OR 1.14, 95% CI 0.99-1.32; P = 0.07), and there was some evidence of heterogeneity (I(2) = 53%, P = 0.01) mainly attributable to one study. An analysis restricted to studies not relying on parental recall showed a stronger, significant relationship (OR = 1.25, 95% CI 1.03-1.51; P = 0.02), although heterogeneity remained. This analysis found evidence of a small but statistically significant increase in childhood type 1 diabetes risk associated with neonatal jaundice but only for studies which used data from obstetric records. Jaundice caused by blood group incompatibility or requiring phototherapy may be associated with a greater increase in type 1 diabetes risk and deserves further study.