Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers

Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
BMC Medicine (Impact Factor: 7.25). 09/2010; 8(1):54. DOI: 10.1186/1741-7015-8-54
Source: PubMed


Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are not elucidated. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells. Trial registration number: NCT00520819
In an 8-week dietary intervention study, 102 healthy male smokers were randomised to either a diet rich in various antioxidant-rich foods, a kiwifruit diet (three kiwifruits/d added to the regular diet) or a control group. Blood cell gene expression profiles were obtained from 10 randomly selected individuals of each group. Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis (GSEA) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays.
Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group. Groups of genes involved in regulation of cellular stress defence, such as DNA repair, apoptosis and hypoxia, were significantly upregulated (GSEA, FDR q-values < 5%) by both diets compared to the control group. Genes with common regulatory motifs for aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (AhR/ARNT) were upregulated by both interventions (FDR q-values < 5%). Plasma antioxidant biomarkers (polyphenols/carotenoids) increased in both groups.
The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes.

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Available from: Asim K Duttaroy, Oct 04, 2015
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    • "In fact, recent studies suggest that this indirect effect of plant antioxidants may be more relevant than a direct effect on ROS and RNS [18]. Blood cell gene expression associated with cellular stress defence is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers [18]. "
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    ABSTRACT: Fruit and vegetable intake has been found to reduce the risk of cardiovascular disease, certain types of cancer and diabetes mellitus. It is possible that antioxidants play a large part in this protective effect. However, which foods account for the variation in antioxidant intake in a population is not very clear. We used food frequency data from a population-based sample of women to identify the food items that contributed most to the variation in antioxidant intake in Norwegian diet. We used data from a study conducted among participants in the Norwegian Breast Cancer Screening Program (NBCSP), the national program which invites women aged 50-69 years to mammographic screening every 2 years. A subset of 6514 women who attended the screening in 2006/2007 completed a food frequency questionnaire (FFQ). Daily intake of energy, nutrients and antioxidant intake were estimated. We used multiple linear regression analysis to capture the variation in antioxidant intake. The mean (SD) antioxidant intake was 23.0 (8.5) mmol/day. Coffee consumption explained 54 % of the variation in antioxidant intake, while fruits and vegetables explained 22 %. The twenty food items that contributed most to the total variation in antioxidant intake explained 98 % of the variation in intake. These included different types of coffee, tea, red wine, blueberries, walnuts, oranges, cinnamon and broccoli. In this study we identified a list of food items which capture the variation in antioxidant intake among these women. The major contributors to dietary total antioxidant intake were coffee, tea, red wine, blueberries, walnuts, oranges, cinnamon and broccoli. These items should be assessed in as much detail as possible in studies that wish to capture the variation in antioxidant intake.
    BMC Public Health 01/2014; 14(1):45. DOI:10.1186/1471-2458-14-45 · 2.26 Impact Factor
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    • "Moreover, it has been described that hypoxiainducible factors act as essential regulators of inflammation [54], and that hypoxia modulates lipopolysaccharide-induced TNFa expression in murine macrophages via HIF-1alpha [55]. Furthermore , in an 8-week dietary intervention study with a diet rich in antioxidant foods, the gene expression profiles related with common regulatory motifs for AhR and AhR/ARNT were upregulated in blood cells from healthy male smokers [56]. Finally, it has been described that Arnt activity determines ABCA1 expression and cholesterol efflux under hypoxia in human macrophages [57]. "
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    ABSTRACT: The aim of this article is to assess the potential relationships between TNFα gene promoter methylation in peripheral white blood cells and central adiposity (truncal fat), metabolic features and dietary fat intake. A group of 40 normal-weight young women (21±3y; BMI 21.0±1.7kg/m(2)) was included in this cross-sectional study. Anthropometric, biochemical and dietary data were assessed using validated procedures. DNA from white blood cells was isolated and 5-methylcytosine levels of the CpGs sites present in TNFα gene promoter (from -170 to +359 pb) were analyzed by Sequenom EpiTyper. Those women with high truncal fat (⩾52.3%) showed lower 5-methylcytosine levels (P<0.05) in the site CpG13 (at position +207) and CpG19 (+317 pb) of the TNFα gene promoter when were compared to women with lower truncal adiposity. The methylation levels of CpG13 were also correlated with circulating TNFα levels, which were higher in those women with greater truncal adiposity. In a linear regression model, truncal fat, HDL-cholesterol, insulin, plasma TNFα, and daily n-6 PUFA intake explained the methylation levels of CpG13 site +207 by 48% and the average of CpG13 and CpG19 by 43% (P<0.001). In conclusion, women with higher truncal fat showed lower methylation levels of TNFα promoter in peripheral white blood cells and higher plasma TNFα concentrations. DNA methylation levels of TNFα promoter were associated with some metabolic features and with n-6 PUFA intake, suggesting a complex nutriepigenomic network in the regulation of this recognized pro-inflammatory marker.
    Cytokine 06/2013; 64(1). DOI:10.1016/j.cyto.2013.05.028 · 2.66 Impact Factor
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    • "There is some evidence that consumption of one to three kiwifruit per d reduces endogenous levels of oxidised pyrimidines and purines in the DNA of healthy individuals( 25 , 27 ) and affects DNA repair activity( 25 , 27 , 46 ). Bohn et al. demonstrated up-regulation of a number of DNA repair genes in blood cells from male smokers supplemented with three kiwifruit per d for 8 weeks( 47 ). Consumption of Gold kiwifruit has also been shown to improve Fe absorption in women with low-Fe status( 28 ), probably due to the ability of vitamin C to enhance the absorption of non-haem Fe. "
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    ABSTRACT: Vitamin C is an essential nutrient in humans and must be obtained through the diet. The aim of this study was to determine vitamin C uptake in healthy volunteers after consuming kiwifruit (Actinidia chinensis var. Hort. 16A), and to determine the amount of fruit required to raise plasma vitamin C to ‘healthy’ (i.e. >50 µmol/l) and ‘optimal’ or saturating levels (i.e. >70 µmol/l). Leucocyte and urinary vitamin C levels were also determined. A total of fifteen male university students with below average levels of plasma vitamin C were selected for the study. Weekly fasting blood samples were obtained for a 4-week lead-in period and following supplementation with, sequentially, half, one, two and three Gold kiwifruit per d for 4–6 weeks each, followed by a final 4-week washout period. The results showed that addition of as little as half a kiwifruit per d resulted in a significant increase in plasma vitamin C. However, one kiwifruit per d was required to reach what is considered healthy levels. Increasing the dose of kiwifruit to two per d resulted in further increases in plasma vitamin C levels as well as increased urinary output of the vitamin, indicating that plasma levels were saturating at this dosage. Dividing the participants into high and low vitamin C groups based on their baseline plasma and leucocyte vitamin C levels demonstrated that it is critical to obtain a study population with low initial levels of the vitamin in order to ascertain a consistent effect of supplementation.
    10/2012; 1. DOI:10.1017/jns.2012.15
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