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

Siv K Bøhn, Mari C Myhrstad, Magne Thoresen, Marit Holden, Anette Karlsen, Siv Haugen Tunheim, Iris Erlund, Mette Svendsen, Ingebjørg Seljeflot, Jan O Moskaug, Asim K Duttaroy, Petter Laake, Harald Arnesen, Serena Tonstad, Andrew Collins, Christan A Drevon, Rune Blomhoff, Siv K Bøhn, Mari C Myhrstad, Magne Thoresen, Marit Holden, Anette Karlsen, Siv Haugen Tunheim, Iris Erlund, Mette Svendsen, Ingebjørg Seljeflot, Jan O Moskaug, Asim K Duttaroy, Petter Laake, Harald Arnesen, Serena Tonstad, Andrew Collins, Christan A Drevon, Rune Blomhoff

Abstract

Background: 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 http://clinicaltrials.gov.

Methods: 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.

Results: 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.

Conclusions: 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.

Figures

Figure 1
Figure 1
Overview of the experimental approach and strategy for data analyses. (Images courtesy of Affymetrix Inc.).
Figure 2
Figure 2
Participant flow.
Figure 3
Figure 3
Hypothetical model suggesting how plant food phytochemicals influence protective cellular defence systems (yellow box) in a similar manner as an optimal level of reactive oxygen species (ROS). It is possible that phytochemicals work by modulating ROS levels while regulating inducible defence systems.

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