Supplementation with aged garlic extract improves both NK and γδ-T cell function and reduces the severity of cold and flu symptoms: A randomized, double-blind, placebo-controlled nutrition intervention

Published:December 12, 2011DOI:


      Background & aims

      Earlier studies show that dietary bioactive compounds can modify proliferation of γδ-T cells. Garlic contains numerous compounds that have this potential and, in addition, has been shown to influence NK cell function. Our primary aim was to demonstrate that aged garlic extract could modify these immune cells.


      A randomized, double-blind, placebo-controlled parallel intervention study recruited 120 healthy subjects (60 per group) to determine the effect of aged garlic extract supplementation (2.56 g/d) on immune cell proliferation and cold and flu symptoms.


      After 45 d of consuming an encapsulated aged garlic extract, γδ-T cells (p = 0.039, n = 56) and NK cells (p = 0.043, n = 56) were shown to proliferate better compared to placebo. After 90 d of supplementation, illness diary entries showed that the incidence of colds and flu, a secondary outcome, were not statistically different; however, the group consuming the aged garlic extract appeared to have reduced severity as noted by a reduction in the number of symptoms reported (21% fewer, p < 0.001, z-test of proportions), a reduction in the number of days (61% fewer, p < 0.001, z-test) and incidences (58% fewer p < 0.001, z-test) where the subjects functioned sub-optimally and the number of work/school days missed due to illness (58% fewer, p = 0.035, z-test).


      These results suggest that supplementation of the diet with aged garlic extract may enhance immune cell function and that this may be responsible, in part, for reduced severity of colds and flu.



      AGE (aged garlic extract), PAMP (pathogen-associated molecular pattern), PRR (pattern recognition receptors), SAC (S-allyl-l-cysteine)
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        • Chandrashekar P.M.
        • Venkatesh Y.P.
        Identification of the protein components displaying immunomodulatory activity in aged garlic extract.
        J Ethnopharmacol. 2009; 124: 384-390
        • Chandrashekar P.M.
        • Prashanth K.V.H.
        • Venkatesh Y.P.
        Isolation, structural elucidation and immunomodulatory activity of fructans from aged garlic extract.
        Phytochemistry. 2011; 72: 255-264
        • Ryu K.
        • Ide N.
        • Matsuura H.
        • Itakura Y.
        N alpha-(1-deoxy-D-fructos-1-yl)-L-arginine, an antioxidant compound identified in aged garlic extract.
        J Nutr. 2001; 131: 972S-976S
        • Ichikawa M.
        • Ryu K.
        • Yoshida J.
        • Ide N.
        • Yoshida S.
        • Sasaoka T.
        • et al.
        Antioxidant effects of tetrahydro-beta-carboline derivatives identified in aged garlic extract.
        Biofactors. 2002; 16: 57-72
        • Hedges J.F.
        • Lubick K.J.
        • Jutila M.A.
        Gamma delta T cells respond directly to pathogen-associated molecular patterns.
        J Immunol. 2005; 174: 6045-6053
        • Jutila M.A.
        • Holderness J.
        • Graff J.C.
        • Hedges J.F.
        Antigen-independent priming: a transitional response of bovine gammadelta T-cells to infection.
        Anim Health Res Rev. 2008; 9: 47-57
        • Kabelitz D.
        • Glatzel A.
        • Wesch D.
        Antigen recognition by human γδ lymphocytes.
        Int Arch Allergy Immunol. 2000; 122: 1-7
        • Morita C.T.
        • Mariuzza R.A.
        • Brenner M.B.
        Antigen recognition by human gamma delta T cells: pattern recognition by the adaptive immune system.
        Springer Semin Immunopathol. 2000; 22: 191-217
        • Tanaka Y.
        • Morita C.T.
        • Tanaka Y.
        • Nieves E.
        • Brenner M.B.
        • Bloom B.R.
        Natural and synthetic non-peptide antigens recognized by human gamma delta T cells.
        Nature. 1995; 375: 155-158
        • Lowdell M.W.
        • Lamb L.
        • Hoyle C.
        • Velardi A.
        • Prentice H.G.
        Non-MHC-restricted cytotoxic cells: their roles in the control and treatment of leukaemias.
        Br J Haematol. 2001; 114: 11-24
        • Rowe C.A.
        • Nantz M.P.
        • Bukowski J.F.
        • Percival S.S.
        Specific formulation of Camellia sinensis prevents cold and flu symptoms and enhances γδ T cell function: a randomized, double-blind, placebo-controlled study.
        J Am Coll Nutr. 2007; 26: 445-452
        • Bukowski J.F.
        • Morita C.T.
        • Brenner M.B.
        Human γδ T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity.
        Immunity. 1999; 11: 57-65
        • Kamath A.B.
        • Wang L.
        • Das H.
        • Li L.
        • Reinhold V.N.
        • Bukowski J.F.
        Antigens in tea-beverage prime human Vgamma 2Vdelta 2 T cells in vitro and in vivo for memory and nonmemory antibacterial cytokine responses.
        Proc Natl Acad Sci U S A. 2003; 100: 6009-6014
        • Holderness J.
        • Jackiw L.
        • Kimmel E.
        • Kerns H.
        • Radke M.
        • Hedges J.F.
        • et al.
        Select plant tannins induce IL-2Ralpha up-regulation and augment cell division in gammadelta T cells.
        J Immunol. 2007; 179: 6468-6478
        • Graff J.C.
        • Jutila M.A.
        Differential regulation of CD11b on gammadelta T cells and monocytes in response to unripe apple polyphenols.
        J Leukoc Biol. 2007; 82: 603-607
        • Graff J.C.
        • Kimmel E.M.
        • Freedman B.
        • Schepetkin I.A.
        • Holderness J.
        • Quinn M.T.
        • et al.
        Polysaccharides derived from Yamoa (Funtumia elastica) prime gammadelta T cells in vitro and enhance innate immune responses in vivo.
        Int Immunopharmacol. 2009; 9: 1313-1322
        • Percival S.S.
        • Nelson S.A.
        • Milner J.A.
        Workshop executive summary report.
        J Nutr. 2005; 135: 2898S-2920S
        • Hanson M.G.
        • Ozenci V.
        • Carlsten M.C.
        • Glimelius B.L.
        • Frodin J.E.
        • Masucci G.
        • et al.
        A short-term dietary supplementation with high doses of vitamin E increases NK cell cytolytic activity in advanced colorectal cancer patients.
        Cancer Immunol Immunother. 2007; 56: 973-984
        • Meadows G.
        • Wallendal M.
        • Kosugi A.
        • Wunderlich J.
        • Singer D.S.
        Ethanol induces marked changes in lymphocyte populations and natural killer cell activity in mice.
        Alcohol Clin Exp Res. 1992; 16: 474-479
        • Schink M.
        • Troger W.
        • Dabidian A.
        • Goyert A.
        • Scheuerecker H.
        • Meyer J.
        • et al.
        Mistletoe extract reduces the surgical suppression of natural killer cell activity in cancer patients. A randomized phase III trial.
        Forsch Komplementarmed. 2007; 14: 9-17
        • Oppenheim D.E.
        • Roberts S.J.
        • Clarke S.L.
        • Filler R.
        • Lewis J.M.
        • Tigelaar R.E.
        • et al.
        Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance.
        Nat Immunol. 2005; 6: 928-937
        • Athie-Morales V.
        • O’Connor Geraldine M.
        • Gardiner C.M.
        Activation of human NK cells by the bacterial pathogen-associated molecular pattern muramyl dipeptideTLRs mediate IFN-gamma production by human uterine NK cells in endometrium.
        J Immunol. 2008; 180: 4082-4089
        • Eriksson Mikael
        • Meadows Sarah K.
        • Basu Satarupa
        • Mselle Teddy F.
        • Wira Charles R.
        • Sentman Charles L.
        TLRs mediate IFN-gamma production by human uterine NK cells in endometrium.
        J Immunol. 2006; 176: 6219-6224
        • Ishikawa H.
        • Saeki T.
        • Otani T.
        • Suzuki T.
        • Shimozuma K.
        • Nishino H.
        • et al.
        Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer.
        J Nutr. 2006; 136: 816S-820S
        • Kandil O.M.
        • Abdullah T.H.
        • Elkadi A.
        Garlic and the immune-system in humans – its effect on natural-killer-cells.
        Fed Proc. 1987; 46 (pp. 441–441)
        • Hughes C.
        • Davoodi-Semiromi Y.
        • Colee J.C.
        • Culpepper T.
        • Dahl W.J.
        • Mai V.
        • et al.
        Galactooligosaccharide supplementation reduces stress-induced gastrointestinal dysfunction and days of cold or flu: a randomized, double-blind, controlled trial in healthy university students.
        Am J Clin Nutr. 2011; 93: 1305-1311
        • Kodera Y.
        • Suzuki A.
        • Imada O.
        • Kasuga S.
        • Sumioka I.
        • Kanezawa A.
        • et al.
        Physical, chemical, and biological properties of S-allylcysteine, an amino acid derived from garlic.
        J Agric Food Chem. 2002; 50: 622-632
      1. Bancroft TA. Topics in Intermediate Statistical Methods. 1st; 1968, pp. 7–9.

        • Bukowski J.F.
        • Percival S.S.
        L-theanine intervention enhances human gammadeltaT lymphocyte function.
        Nutr Rev. 2008; 66: 96-102
        • Percival S.S.
        • Bukowski J.F.
        • Milner J.
        Bioactive food components that enhance gamma/delta T cell function may play a role in cancer prevention.
        J Nutr. 2008; 138: 1-4
        • Turner R.B.
        Epidemiology, pathogenesis, and treatment of the common cold.
        Ann Allergy Asthma Immunol. 1997; 78: 531-539
        • Keech M.
        • Beardsworth P.
        The impact of influenza on working days lost: a review of the literature.
        Pharmacoeconomics. 2008; 26: 911-924
        • Lissiman E.
        • Bhasale A.L.
        • Cohen M.
        Garlic for the common cold.
        Cochrane Database Syst Rev. 8.07.2009; (CD006206)
        • Josling P.
        Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey.
        Adv Ther. 2001; 18: 189-193
        • Javed H.
        • Khan M.M.
        • Khan A.
        • Vaibhav K.
        • Ahmad A.
        • Khuwaja G.
        • et al.
        S-allyl cysteine attenuates oxidative stress associated cognitive impairment and neurodegeneration in mouse model of streptozotocin-induced experimental dementia of Alzheimer’s type.
        Brain Res. 2011; 1389 ([email protected] Mar 1.: 133–142): 133-142
        • Saravanan G.
        • Ponmurugan P.
        Ameliorative potential of S-allylcysteine: effect on lipid profile and changes in tissue fatty acid composition in experimental diabetes.
        Exp Toxicol Pathol. 2011;
        • Saravanan G.
        • Ponmurugan P.
        Ameliorative potential of S-allyl cysteine on oxidative stress in STZ induced diabetic rats.
        Chem Biol Interact. 1-15-2011; 189: 100-106
        • Tang F.Y.
        • Chiang E.P.
        • Pai M.H.
        Consumption of S-allylcysteine inhibits the growth of human non-small-cell lung carcinoma in a mouse xenograft model.
        J Agric Food Chem. 9-24-2010;
        • Ballatori N.
        • Krance S.M.
        • Notenboom S.
        • Shi S.
        • Tieu K.
        • Hammond C.L.
        Glutathione dysregulation and the etiology and progression of human diseases.
        Biol Chem. 2009; 390: 191-214
        • Haddad J.J.
        The involvement of L-gamma-glutamyl-L-cysteinyl-glycine (glutathione/GSH) in the mechanism of redox signaling mediating MAPK(p38)-dependent regulation of pro-inflammatory cytokine production.
        Biochem Pharmacol. 2002; 63: 305-320
        • Rahman I.
        Regulation of glutathione in inflammation and chronic lung diseases.
        Mutat Res. 2005; 579: 58-80
        • Villa P.
        • Saccani A.
        • Sica A.
        • Ghezzi P.
        Glutathione protects mice from lethal sepsis by limiting inflammation and potentiating host defense.
        J Infect Dis. 2002; 185: 1115-1120
        • Papi A.
        • Contoli M.
        • Gasparini P.
        • Bristot L.
        • Edwards M.R.
        • Chicca M.
        • et al.
        Role of xanthine oxidase activation and reduced glutathione depletion in rhinovirus induction of inflammation in respiratory epithelial cells.
        J Biol Chem. 2008; 283: 28595-28606
        • Wu D.
        • Meydani S.N.
        • Sastre J.
        • Hayek M.
        • Meydani M.
        In vitro glutathione supplementation enhances interleukin-2 production and mitogenic response of peripheral blood mononuclear cells from young and old subjects.
        J Nutr. 1994; 124: 655-663