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Clin Nutr. 2014 Feb;33(1):130-5. doi: 10.1016/j.clnu.2013.03.012. Epub 2013 Mar 26.

Orange juice and its major polyphenol hesperidin consumption do not induce immunomodulation in healthy well-nourished humans.

Author information

  • 1Clermont Université, Université d'Auvergne, UMR 1019, Unité de Nutrition Humaine, CRNH-Auvergne, CLARA, BP 10448, F-63000 Clermont-Ferrand, France.
  • 2Centre de recherche INRA, UMR 1019 INRA Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand Theix, France.
  • 3CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, Inserm, CIC 501, Univ Clermont 1, Faculté de Médecine, F-63001 Clermont-Ferrand, France.
  • 4Centre anticancéreux Jean-Perrin, CHU, Unité de Nutrition, CLARA, F-63000 Clermont-Ferrand, France. Electronic address:



Polyphenols exert a variety of biological properties, including antioxidant, immunomodulatory and antigenotoxic effects. In a randomized crossover study in healthy men, we investigated the effects of orange juice and its major polyphenolic compound hesperidin on a panel of immune cell functions, including cytokine secretion by leukocytes, lytic activity of NK cells, and the Reactive Oxygen Species (ROS) burst by polymorphonuclear neutrophil cells (PMN).


The protocol design was divided into three 4-week treatment periods separated by 3-week wash-out intervals, for total study duration of 18 weeks. During treatment periods, volunteers (n = 24) consumed daily 500 mL of orange juice, or an isocaloric control beverage with hesperidin (292 mg in a capsule), or of the same control beverage with a placebo.


Whatever the intake was, no variations were recorded on leukocyte subset distributions (PMN, B and T lymphocytes, NK cells and monocytes), ROS production by stimulated PMNs, lytic activity of NK cells or cytokine production capacity of leukocytes in well-nourished healthy volunteers.


We show that consumption within the usual daily intake range of orange juice and its major polyphenol hesperidin do not induce immunomodulation of cell immune function in healthy well-nourished humans.

Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.


Anti-oxidant status; Cytokines; ECD; EGFP; Enhanced Green Fluorescent Protein; FITC; Fluorescein IsothioCyanate; Leukocyte functions; NK; NK cells; Natural Killer; Oxidative response; PBMC; PC5; PE; PE-Cyanine 5; PE-Texas red; PHA; PMA; PMN; Peripheral Blood Mononuclear Cells; Phorbol Myristate Acetate; PhycoErythrine; PhytoHemAgglutinin; PolyMorphoNuclear neutrophil cells; ROS; Reactive Oxygen Species

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