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Bilberry juice modulates plasma concentration of NF-κB related inflammatory markers in subjects at increased risk of CVD

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Abstract

Purpose

Bilberries are abundant in polyphenols. Dietary polyphenols have been associated with strategies for prevention and treatment of chronic inflammatory diseases. We investigated the effect of bilberry juice on serum and plasma biomarkers of inflammation and antioxidant status in subjects with elevated levels of at least one risk factor for cardiovascular disease (CVD).

Methods

In a randomized controlled trial, participants consumed either bilberry juice (n = 31) or water (n = 31) for 4 weeks.

Results

Supplementation with bilberry juice resulted in significant decreases in plasma concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-15, and monokine induced by INF-γ (MIG). Unexpectedly, an increase in the plasma concentration of tumor nuclear factor-α (TNF-α) was observed in the bilberry group. CRP, IL-6, IL15, MIG, and TNF-α are all target genes of nuclear factor- kappa B (NF-κB), —a transcription factor that is crucial in orchestrating inflammatory responses. Plasma quercetin and p-coumaric acid increased in the bilberry group, otherwise no differences were observed for clinical parameters, oxidative stress or antioxidant status. Furthermore, we studied the effect of polyphenols from bilberries on lipopolysaccharide (LPS)-induced NF-κB activation in a monocytic cell line. We observed that quercetin, epicatechin, and resveratrol inhibited NF-κB activation.

Conclusions

These findings suggest that supplementation with bilberry polyphenols may modulate the inflammation processes. Further testing of bilberry supplementation as a potential strategy in prevention and treatment of chronic inflammatory diseases is warranted.

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Abbreviations

CVD:

Cardiovascular disease

CRP:

C-reactive protein

IL:

Interleukin

MIG:

Monokine induced by INF-γ

RANTES:

Regulated upon activation, normal T cell expressed and secreted

TNF-α:

Tumor nuclear factor-α

NF-κB:

Nuclear factor-kappa B

LPS:

Lipopolysaccharide

BP:

Blood pressure

LDL:

Low-density lipoprotein

HDL:

High density lipoprotein

SRM:

Standardized reference materials

FRAP:

Ferric reducing/antioxidant power

TRAP:

Total peroxyl-radical trapping activity

TE:

Trolox equivalents

ORAC:

Oxygen radical absorbance capacity

PCA:

Perchloric acid

AA:

Ascorbic acid

DHAA:

Dehydroascorbic acid

TAA:

Total ascorbic acid

HPLC:

High performance liquid chromatography

GSH:

Glutathione

D-ROM:

Diacrons reactive oxygen metabolites

WBC:

White blood cells

γ-GT:

γ-glutamyltransferase

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Acknowledgments

This research received grants from the Norwegian Research Council and the Throne–Holst Foundation. The participation of study subjects recruited through an advertisement in a local newspaper and from the Department of Preventive Cardiology, Ullevål University Hospital, Oslo, Norway, is greatly appreciated. The enthusiastic support of Lisa Flakk at the Department of Preventive Cardiology at Ullevål University Hospital in coordinating the study is highly appreciated. Kari Holte has provided valuable help in the laboratory. We are also grateful to Dr Janne Reseland at Institute of Clinical Dentistry, University of Oslo, Norway, for providing their facilities for cytokine analysis. RB and ST formulated the present hypothesis. IP was responsible for the cell culture experiments, and the data handling and statistical analysis associated with these. ST was the overall principal investigator of the clinical study. RB and AK contributed to the clinical study design, intervention, sample handling and data collection. SKB was responsible for the analysis of inflammatory mediators in plasma samples. AKS was responsible for analysis of glutathione in plasma samples. GIB was responsible for the analysis of ORAC in plasma. MS was responsible for the analysis of TRAP in plasma. IE was responsible for the analysis of polyphenols in plasma. AK was responsible for analysis of additional parameters in plasma samples. AK and PL were responsible for the statistical analysis for the clinical study. AK and IP were responsible for writing the manuscript. All authors approved the final version of the manuscript before submission.

Conflict of interest statement

RB has interests in Cgene AS, Bioindex AS and Vitas AS. Cgene AS and Bioindex AS were established by Birkeland Innovation, the Technology transfer office at the University of Oslo while Vitas AS was established by the Oslo Innovation Center. No competing financial interests exist for AK, IP, SKB, AKS, GIB, IE, MS, PL or ST.

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Authors and Affiliations

  1. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1046, Blindern, 0316, Oslo, Norway

    Anette Karlsen, Ingvild Paur, Siv K. Bøhn, Amrit K. Sakhi & Rune Blomhoff

  2. Nofima Mat AS, Osloveien 1, Ås, Norway

    Grethe I. Borge

  3. Antioxidant Research Laboratory, Unit of Human Nutrition, INRAN, Rome, Italy

    Mauro Serafini

  4. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

    Iris Erlund

  5. Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Petter Laake

  6. Department of Preventive Cardiology, Ullevaal University Hospital, Oslo, Norway

    Serena Tonstad

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  1. Anette Karlsen
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  2. Ingvild Paur
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  3. Siv K. Bøhn
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  4. Amrit K. Sakhi
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  5. Grethe I. Borge
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  6. Mauro Serafini
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  7. Iris Erlund
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  8. Petter Laake
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  9. Serena Tonstad
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  10. Rune Blomhoff
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Corresponding author

Correspondence to Rune Blomhoff.

Additional information

A. Karlsen and I. Paur contributed equally to this work.

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Karlsen, A., Paur, I., Bøhn, S.K. et al. Bilberry juice modulates plasma concentration of NF-κB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr 49, 345–355 (2010). https://doi.org/10.1007/s00394-010-0092-0

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  • DOI: https://doi.org/10.1007/s00394-010-0092-0

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