FNS  Vol.5 No.4 , February 2014
Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized, Placebo-Controlled, Double-Blind Clinical Trial in Healthy Volunteers
Abstract: 22 healthy volunteers were included in a randomized, placebo-controlled pilot study in order to investigate immunomodulatory effects of a concentrated juice, containing the ingredients of a total of 80 different fruits, vegetables, herbs, mushrooms, oils, and others (Cellagon aurum?, “CA”). 11 subjects received the concentrated juice while 11 were allocated to the placebo group. Stimulated whole-blood cultures were used to assess any treatment-related changes in the response of leukocytes towards experimental immune cell activation. For each of the individuals, 5 cultures were performed either immediately before, during, or 3 days after termination of the 7 weeks treatment. Leukocyte activities were determined by measuring cytokine levels in the supernatants at the end of the 48 h of stimulation (induced by the addition of LPS + SE-B + anti-CD28 antibodies). Despite the relatively small number of volunteers, multiplexed cytokine assays revealed a typical T-cell signature of cytokines that were increased significantly in the course of CA treatment compared to placebo (GM-CSF, IFNγ, IL-4, IL-10, IL-17, TNFβ, all p < 0.05). These preliminary results suggest that CA is able to support leukocyte activation, in particular that of T-lymphocytes.
Cite this paper: M. Schmolz, R. März, M. Schaudt, C. Schaudt and C. Lauster, "Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized, Placebo-Controlled, Double-Blind Clinical Trial in Healthy Volunteers," Food and Nutrition Sciences, Vol. 5 No. 4, 2014, pp. 341-350. doi: 10.4236/fns.2014.54041.

[1]   J. L. Rios, M. C. Recio, J. M. Escandell and I. Andujar, “Inhibition of Transcription Factors by Plant-Derived Compounds and Their Implications in Inflammation and Cancer,” Current Pharmaceutical Design, Vol. 15, No. 11, 2009, pp. 1212-1237.

[2]   S. A. Stanner, J. Hughes, C. N. Kelly and J. Buttriss, “A Review of the Epidemiological Evidence for the ‘Antioxidant Hypothesis’,” Public Health Nutrition, Vol. 7, No. 3, 2004, pp. 407-422.

[3]   M. Dell’Agli, C. Di Lorenzo, M. Badea, E. Sangiovanni, L. Dima, E. Bosisio and P. Restani, “Plant Food Supplements with Anti-Inflammatory Properties: A Systematic Review (I),” Critical Reviews in Food Science and Nutrition, Vol. 53, No. 4, 2013, pp. 403-413.

[4]   C. Di Lorenzo, M. Dell’agli, E. Colombo, E. Sangiovanni and P. Restani, “Metabolic Syndrome and Inflammation: A Critical Review of in Vitro and Clinical Approaches for Benefit Assessment of Plant Food Supplements,” Evidence-Based Complementary and Alternative Medicine, Vol. 2013, 2013, Article ID: 782461.

[5]   N. Iyer, S. A. Marathe, D. Chaudhuri, P. Garai and D. Chakravortty, “Immunomodulation Using Agonists and Antagonists: Potential Clinical Applications,” Expert Opinion on Investigational Drugs, Vol. 21, No. 1, 2012, pp. 67-81.

[6]   J. M. van Dieren, E. J. Kuipers, J. N. Samsom, E. E. Nieuwenhuis and C. J. van der Woude, “Revisiting the Immunomodulators Tacrolimus, Methotrexate, and Mycophenolate Mofetil: Their Mechanisms of Action and Role in the Treatment of IBD,” Inflammatory Bowel Diseases, Vol. 12, No. 4, 2006, pp. 311-327.

[7]   M. Ramadan, S. Goeters, B. Watzer, E. Krause, K. Lohmann, R. Bauer, B. Hempel and P. Imming, “Chamazulene Carboxylic Acid and Matricin: A Natural Profen and Its Natural Prodrug, Identified through Similarity to Synthetic Drug Substances,” Journal of Natural Products, Vol. 69, No. 7, 2006, pp. 1041-1045.

[8]   V. M. Chandrashekhar, K. S. Halagali, R. B. Nidavani, M. H. Shalavadi, B. S. Biradar, D. Biswas and I. S. Muchchandi, “Anti-Allergic Activity of German Chamomile (Matricaria recutita L.) in Mast Cell Mediated Allergy Model,” Journal of Ethnopharmacology, Vol. 137, No. 1, 2011, pp. 336-340.

[9]   X. Gao, D. Deeb, Y. Liu, S. Gautam, S. A. Dulchavsky and S. C. Gautam, “Immunomodulatory Activity of Xanthohumol: Inhibition of T Cell Proliferation, Cell-Mediated Cytotoxicity and Th1 Cytokine Production through Suppression of NF-KappaB,” Immunopharmacology and Immunotoxicology, Vol. 31, No. 3, 2009, pp. 477-484.

[10]   U. Svajger and M. Jeras, “Anti-Inflammatory Effects of Resveratrol and Its Potential Use in Therapy of Immune-Mediated Diseases,” International Reviews of Immunology, Vol. 31, No. 3, 2012, pp. 202-222.

[11]   J. H. Park, J. W. Kim, C. M. Lee, Y. D. Kim, S. W. Chung, I. D. Jung, K. T. Noh, J. W. Park, D. R. Heo, Y. K. Shin, J. K. Seo and Y. M. Park, “Sulforaphane Inhibits the Th2 Immune Response in Ovalbumin-Induced Asthma,” BMB Reports, Vol. 45, No. 5, 2012, pp. 311-316.

[12]   Y. Zhang, D. Y. Leung, B. N. Richers, Y. Liu, L. K. Remigio, D. W. Riches and E. Goleva, “Vitamin D Inhibits Monocyte/Macrophage Proinflammatory Cytokine Production by Targeting MAPK Phosphatase-1,” Journal of Immunology, Vol. 188, No. 5, 2012, pp. 2127-2135.

[13]   J. M. Carcamo, O. Borquez-Ojeda and D. W. Golde, “Vitamin C Inhibits Granulocyte Macrophage-Colony-Stimulating Factor-Induced Signaling Pathways,” Blood, Vol. 99, No. 9, 2002, pp. 3205-3212.

[14]   C. Hartel, T. Strunk, P. Bucsky and C. Schultz, “Effects of Vitamin C on Intracytoplasmic Cytokine Production in Human Whole Blood Monocytes and Lymphocytes,” Cytokine, Vol. 27, No. 4-5, 2004, pp. 101-106.

[15]   J. J. Casciari, H. D. Riordan, N. Mikirova and J. Austin, “Effect of Vitamin C Supplementation on ex Vivo Immune Cell Functioning,” Journal of Orthomolecular Medicine, Vol. 18, No. 2, 2003, pp. 83-92.

[16]   J. Tamura, K. Kubota, H. Murakami, M. Sawamura, T. Matsushima, T. Tamura, T. Saitoh, H. Kurabayshi and T. Naruse, “Immunomodulation by Vitamin B12: Augmentation of CD8+ T Lymphocytes and Natural Killer (NK) Cell Activity in Vitamin B12-Deficient Patients by Methyl-B12 Treatment,” Clinical & Experimental Immunology, Vol. 116, No. 1, 1999, pp. 28-32.

[17]   H. K. Kwak, C. M. Hansen, J. E. Leklem, K. Hardin and T. D. Shultz, “Improved Vitamin B-6 Status Is Positively Related to Lymphocyte Proliferation in Young Women Consuming a Controlled Diet,” Journal of Nutrition, Vol. 132, No. 11, 2002, pp. 3308-3313.

[18]   S. C. Mueller, R. Marz, M. Schmolz and B. Drewelow, “Intraindividual Long Term Stability and Response Corridors of Cytokines in Healthy Volunteers Detected by a Standardized Whole-Blood Culture System for Bed-Side Application,” BMC Medical Research Methodology, Vol. 12, 2012, p. 112.

[19]   M. Triantafilou and K. Triantafilou, “Lipopolysaccharide Recognition: CD14, TLRs and the LPS-Activation Cluster,” Trends in Immunology, Vol. 23, No. 6, 2002, pp. 301-304.

[20]   T. Nagashima, T. Aranami, C. Iclozan and K. Onoé, “Analysis of T Cell Responses to a Superantigen, Staphylococcal Enterotoxin-B,” Journal of Clinical and Experimental Hematopathology, Vol. 44, No. 1, 2004, pp. 25-32.

[21]   M. E. van Berkel and M. A. Oosterwegel, “CD28 and ICOS: Similar or Separate Costimulators of T Cells?” Immunology Letters, Vol. 105, No. 2, 2006, pp. 115-122.

[22]   M. M. Wurfel, W. Y. Park, F. Radella, J. Ruzinski, A. Sandstrom, J. Strout, R. E. Bumgarner and T. R. Martin, “Identification of High and Low Responders to Lipopolysaccharide in Normal Subjects: An Unbiased Approach to Identify Modulators of Innate Immunity,” Journal of Immunology, Vol. 175, No. 4, 2005, pp. 2570-2578.

[23]   N. Serhan, “Resolvins and Protectins: Novel Lipid Mediators in Anti-Inflammation and Resolution,” Scandinavian Journal of Food and Nutrition, Vol. 50, No. S2, 2006, pp. 68-78.

[24]   Z. Huang, A. H. Rose and P. R. Hoffmann, “The Role of selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities,” Antioxidants & Redox Signaling, Vol. 16, No. 7, 2012, pp. 705-743.

[25]   G. Fortin, “L-Carnitine and Intestinal Inflammation,” Vitamins & Hormones, Vol. 86, 2011, pp. 353-366.

[26]   H. Haase and L. Rink, “Zinc Signals and Immune Function,” Biofactors, 2013.

[27]   A. M. Sullivan, J. G. Laba, J. A. Moore and T. D. Lee, “Echinacea-Induced Macrophage Activation,” Immunopharmacology and Immunotoxicology, Vol. 30, No. 3, 2008, pp. 553-574.

[28]   M. R. Ritchie, J. Gertsch, P. Klein and R. Schoop, “Effects of Echinaforce (R) Treatment on ex Vivo-Stimulated Blood Cells,” Phytomedicine, Vol. 18, No. 10, 2011, pp. 826-831.

[29]   A. P. Moreira, T. F. Texeira, A. B. Ferreira, C. Peluzio Mdo and C. Alfenas Rde, “Influence of a High-Fat Diet on Gut Microbiota, Intestinal Permeability and Metabolic Endotoxaemia,” British Journal of Nutrition, Vol. 108, No. 5, 2012, pp. 801-809.

[30]   N. D. Pugh, C. R. Jackson and D. S. Pasco, “Total Bacterial Load within Echinacea Purpurea, Determined Using a New PCR-Based Quantification Method, Is Correlated with LPS Levels and in Vitro Macrophage Activity,” Planta Medica, Vol. 79, No. 1, 2013, pp. 9-14.

[31]   T. R. Mosmann and S. Sad, “The Expanding Universe of T-Cell Subsets: Th1, Th2 and More,” Immunology Today, Vol. 17, No. 3, 1996, pp. 138-146.

[32]   E. Maier, A. Duschl and J. Horejs-Hoeck, “STAT6-Dependent and -Independent Mechanisms in Th2 Polarization,” European Journal of Immunology, Vol. 42, No. 11, 2012, pp. 2827-2833.

[33]   T. L. Geiger and S. Tauro, “Nature and Nurture in Foxp3(+) Regulatory T Cell Development, Stability, and Function,” Human Immunology, Vol. 73, No. 3, 2012, pp. 232-239.

[34]   S. O. Yoon, X. Zhang, P. Berner and Y. S. Choi, “IL-21 and IL-10 Have Redundant Roles but Differential Capacities at Different Stages of Plasma Cell Generation from Human Germinal Center B Cells,” Journal of Leukocyte Biology, Vol. 86, No. 6, 2009, pp. 1311-1318.