Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet

BACKGROUND: An adverse hematological interaction between vitamins E and K has been reported, primarily in patients on anticoagulants. However, little is known regarding circulating levels or tissue concentrations of vitamin K in response to vitamin E supplementation. The purpose of this study was to examine the effect of different levels of dietary α-tocopherol on phylloquinone and menaquinone-4 concentrations, while maintaining a constant intake of phylloquinone, in rat tissues. METHODS: Male 4-wk old Fischer 344 rats (n = 33) were fed one of 3 diets for 12 wk: control (n = 13) with 30 mg all-rac-α-tocopherol acetate/kg diet; vitamin E-supplemented (n = 10) with 100 mg all-rac-α-tocopherol acetate/kg diet; and vitamin E-restricted (n = 10) with <10 mg total tocopherols/kg diet. All 3 diets contained 470 ± 80 μg phylloquinone/kg diet. RESULTS: Phylloquinone concentrations were lower (P ≤ 0.05) in the vitamin E-supplemented compared to the vitamin E-restricted group (mean ± SD spleen: 531 ± 58 vs.735 ± 77; kidney: 20 ± 17 vs. 94 ± 31, brain: 53 ± 19 vs.136 ± 97 pmol/g protein respectively); no statistically significant differences between groups were found in plasma, liver or testis. Similar results were noted with menaquinone-4 concentrations in response to vitamin E supplementation. CONCLUSION: There appears to be a tissue-specific interaction between vitamins E and K when vitamin E is supplemented in rat diets. Future research is required to elucidate the mechanism for this nutrient-nutrient interaction

Plasma Carotenoids and Biomarkers of Oxidative Stress in Patients with prior Head and Neck Cancer

Diets high in fruits and vegetables are generally believed protective against several chronic diseases. One suggested mechanism is a reduction in oxidative stress. The carotenoids, nutrients found in colored fruits and vegetables, possess antioxidant properties in vitro, but their role in humans is less well documented. The aim of this cross-sectional study was to explore the relationships between the most abundant plasma carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin and beta-cryptoxanthin), as well as grouped carotenoids (total xanthophylls, carotenes and carotenoids), and urinary excretion of the F2-isoprostanes (F2-IsoPs), stable and specific biomarkers of oxidative damage to lipids. Two F2-IsoP measures were utilized: total F2-IsoPs and 8-iso-PGF2α. The study population (N = 52) was drawn from a study among patients curatively treated for early-stage head and neck cancer. Unadjusted linear regression analyses revealed significant inverse associations between plasma lutein, total xanthophylls and both F2-IsoP measures at baseline. After control for potential confounders, all individual and grouped xanthophylls remained inversely associated with the F2-IsoP measures, but none of these associations achieved significance. The carotenes were not inversely associated with total F2-IsoPs or 8-iso-PGF2a concentrations. The finding of consistent inverse associations between individual and grouped xanthophylls, but not individual and grouped carotenes, and F2-IsoPs is intriguing and warrants further investigation

Hidden Hunger: Solutions for America’s Aging Populations

The global population, including the United States, is experiencing a demographic shift with the proportion of older adults (aged ≥ 65 years) growing faster than any other age group. This demographic group is at higher risk for developing nutrition-related chronic conditions such as heart disease and diabetes as well as infections such as influenza and pneumonia. As a result, an emphasis on nutrition is instrumental for disease risk reduction. Unfortunately, inadequate nutrient status or deficiency, often termed hidden hunger, disproportionately affects older adults because of systematic healthcare, environmental, and biological challenges. This report summarizes the unique nutrition challenges facing the aging population and identifies strategies, interventions, and policies to address hidden hunger among the older adults, discussed at the scientific symposium “Hidden Hunger: Solutions for America’s Aging Population”, on March 23, 2018

Hidden Hunger:Solutions for America's Aging Populations

The global population, including the United States, is experiencing a demographic shift with the proportion of older adults (aged 65 years) growing faster than any other age group. This demographic group is at higher risk for developing nutrition-related chronic conditions such as heart disease and diabetes as well as infections such as influenza and pneumonia. As a result, an emphasis on nutrition is instrumental for disease risk reduction. Unfortunately, inadequate nutrient status or deficiency, often termed hidden hunger, disproportionately affects older adults because of systematic healthcare, environmental, and biological challenges. This report summarizes the unique nutrition challenges facing the aging population and identifies strategies, interventions, and policies to address hidden hunger among the older adults, discussed at the scientific symposium Hidden Hunger: Solutions for America's Aging Population, on March 23, 2018

Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

SummarySomatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk

The Use of Multivitamin/Multimineral Supplements:A Modified Delphi Consensus Panel Report

PURPOSE: Evidence supporting the use of dietary supplements, in particular, multivitamin/multimineral supplements (MVMS), has been mixed, complicating the ability of health care professionals to recommend their use. To clarify the role that MVMS can play in supporting human health, a series of consensus statements was developed based on expert opinion. METHODS: A panel of 14 international experts in nutritional science and health care was convened to develop consensus statements related to using MVMS in supporting optimal human health. The modified Delphi process included 2 rounds of remote voting and a final round of voting at a roundtable meeting where evidence summaries were presented and discussed. The level of agreement with each of 9 statements was rated on a 5-point Likert scale: agree strongly; agree with reservation; undecided; disagree; or disagree strongly. Consensus was predefined as ≥80% of the panel agreeing strongly or agreeing with reservation to a given statement. FINDINGS: Consensus was reached for all statements. The panel determined that MVMS can broadly improve micronutrient intakes when they contain at least the micronutrients that are consumed insufficiently or have limited bioavailability within a specified population. MVMS formulations may also be individualized according to age, sex, life cycle, and/or other selected characteristics. There are specific biological processes and health outcomes associated with deficient, inadequate, and adequate micronutrient levels. Adequate intake is necessary for normal biological functioning required for good health; in some instances, higher than recommended micronutrient intakes have the potential to provide additional health benefits. Meeting daily intakes established by dietary reference values should be an explicit public health goal for individuals and populations. Use of MVMS is one approach to ensure that adequate micronutrient needs are met in support of biological functions necessary to maintain health. Long-term use of MVMS not exceeding the upper limit of recommended intakes has been determined to be safe in healthy adults. There is insufficient evidence to indicate that MVMS are effective for the primary prevention of chronic medical conditions, including cardiovascular disease and cancer. However, for certain otherwise healthy subpopulations (eg, pregnant women, older adults) and some individuals with existing medical conditions who experience inadequacies in micronutrient intake, addressing inadequacies by using MVMS can provide health benefits. IMPLICATIONS: This consensus panel has described key issues related to the use of MVMS among individuals at risk of or presenting with inadequacies in micronutrient intake or biomarker status

Reexamination of a Meta-Analysis of the Effect of Antioxidant Supplementation on Mortality and Health in Randomized Trials

A recent meta-analysis of selected randomized clinical trials (RCTs), in which population groups of differing ages and health status were supplemented with various doses of β-carotene, vitamin A, and/or vitamin E, found that these interventions increased all-cause mortality. However, this meta-analysis did not consider the rationale of the constituent RCTs for antioxidant supplementation, none of which included mortality as a primary outcome. As the rationale for these trials was to test the hypothesis of a potential benefit of antioxidant supplementation, an alternative approach to a systematic evaluation of these RCTs would be to evaluate this outcome relative to the putative risk of greater total mortality. Thus, we examined these data based on the primary outcome of the 66 RCTs included in the meta-analysis via a decision analysis to identify whether the results provided a positive (i.e., benefit), null or negative (i.e., harm) outcome. Our evaluation indicated that of these RCTs, 24 had a positive outcome, 39 had a null outcome, and 3 had a negative outcome. We further categorized these interventions as primary (risk reduction in healthy populations) or secondary (slowing pathogenesis or preventing recurrent events and/or cause-specific mortality) prevention or therapeutic (treatment to improve quality of life, limit complications, and/or provide rehabilitation) studies, and determined positive outcomes in 8 of 20 primary prevention studies, 10 of 34 secondary prevention studies, and 6 out of 16 therapeutic studies. Seven of the eight RCTs with a positive outcome in primary prevention included participants in a population where malnutrition is frequently described. These results suggest that analyses of potential risks from antioxidant supplementation should be placed in the context of a benefit/risk ratio

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701