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A jerte valley cherry product provides beneficial effects on sleep quality. Influence on aging



In the present work, we evaluated the effect of the intake of a Jerte Valley cherry-based product (JVCP), compared to a placebo product, on sleep quality, urinary 6-sulfatoxymelatonin (aMT6-s) levels and the serum concentration of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8).


This was a blind, placebo-controlled, randomized, crossover study.


University of Extremadura (Spain).


Ten young (20–30 years old), ten middle-aged (35–55 years old), and ten elderly (65–85 years old) participants.


A placebo (Kool-Aid®) or JVCP (patent no. ES 2342141 B1) were consumed twice a day, as lunch and dinner desserts.


Actigraphic monitoring was used to record and display the temporal patterns of the individuals’ activity and rest. Urinary aMT6-s and serum cytokines (IL-1β, TNF-α and IL-8) were also determined.


The consumption of the JVCP improved the nocturnal rest, measured by sleep efficiency, number of awakenings, total nocturnal activity, sleep latency, assumed sleep, actual sleep time and immobility. Moreover, it was detected an increase in both the levels of aMT6-s found in first-void morning urine and the concentrations of serum pro-somnogenic cytokines obtained from samples collected at the acrophase of the melatonin rhythm (1.00 am) in all experimental age groups after the JVCP consumption. Generally, better results were obtained with advancing age.


The ingestion of the JVCP may contribute to establish a high-quality sleep and be used as a potential nutraceutical tool to prevent sleep disorders with the advance of age.

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  1. 1.

    Baldwin CM, Ervin AM, Mays MZ, Robbins J, Shafazand S, Walsleben J, Weaver T (2010) Sleep disturbances, quality of life, and ethnicity: the Sleep Heart Health Study. J Clin Sleep Med 6: 176–183.

    PubMed  Google Scholar 

  2. 2.

    Krueger JM (2008) The role of cytokines in sleep regulation. Curr Pharm Des 14: 3408–3416.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Tan D, Manchester LC, Reiter RJ, Qi W, Hanes MA, Farley NJ (1999) High physiological levels of melatonin in the bile of mammals. Life Sci 65: 2523–2529.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Tamura H, Nakamura Y, Korkmaz A, Manchester LC, Tan DX, Sugino N, Reiter RJ (2009) Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril 92: 328–343.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Bittencourt LR, Santos-Silva R, de Mello MT, Andersen ML, Tufik S (2010) Chronobiological disorders: current and prevalent conditions. J Occup Rehabil 20: 21–32.

    PubMed  Article  Google Scholar 

  6. 6.

    Klerman EB, Gershengorn HB, Duffy JF, Kronauer RE (2002) Comparisons of the variability of three markers of the human circadian pacemaker. J Biol Rhythms 17: 181–193.

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, Ford I (2005) Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev 9: 41–50.

    PubMed  Article  Google Scholar 

  8. 8.

    Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Baker G, Klassen TP, Vohra S (2005) The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med 20: 1151–1158.

    PubMed  Article  Google Scholar 

  9. 9.

    Paredes SD, Terrón MP, Valero V, Barriga C, Reiter RJ, Rodríguez AB (2007) Orally administered melatonin improves nocturnal rest in young and old ringdoves (Streptopelia risoria). Basic Clin Pharmacol Toxicol 100: 258–268.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Paredes SD, Barriga C, Reiter RJ, Rodríguez AB (2009) Assessment of the potential role of tryptophan as the precursor of serotonin and melatonin for the aged sleep wake cycle and immune function: Streptopelia risoria as a model. Int J Tryptophan Res 2: 23–36.

    PubMed  CAS  Google Scholar 

  11. 11.

    Poeggeler B (2005) Melatonin, aging, and age-related diseases: perspectives for prevention, intervention, and therapy. Endocrine 27: 201–212.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Pandi-Perumal SR, Seils LK, Kayumov L, Ralph MR, Lowe A, Moller H, Swaab DF (2002) Senescence, sleep, and circadian rhythms. Ageing Res Rev 1: 559–604.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Harada T, Hirotani M, Maeda M, Nomura H, Takeuchi H (2007) Correlation between breakfast tryptophan content and morning-evening in Japanese infants and students aged 0-15 yrs. J Physiol Anthropol 26: 201–207.

    PubMed  Article  Google Scholar 

  14. 14.

    Paredes SD, Bejarano I, Terrón MP, Barriga C, Reiter RJ, Rodríguez AB (2009) Melatonin and tryptophan counteract lipid peroxidation and modulate superoxide dismutase activity in ringdove heterophils in vivo. Effect of antigen-induced activation and age. Age 31: 179–188.

    CAS  Google Scholar 

  15. 15.

    Paredes SD, Marchena AM, Bejarano I, Espino J, Barriga C, Rial RV, Reiter RJ, Rodríguez AB (2009) Melatonin and tryptophan affect the activity-rest rhythm, core and peripheral temperatures, and interleukin levels in the ringdove: changes with age. J Gerontol A Biol Sci Med Sci 64: 340–350.

    PubMed  Article  Google Scholar 

  16. 16.

    Arnulf I, Quintin P, Alvarez JC, Vigil L, Touitou Y, Lèbre AS, Bellenger A, Varoquaux O, Derenne JP, Allilaire JF, Benkelfat C, Leboyer M (2002) Mid-morning tryptophan depletion delays REM sleep onset in healthy subjects. Neuropsychopharmacology 27: 843–851.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Paredes SD, Terron MP, Cubero J, Valero V, Barriga C, Reiter RJ, Rodriguez AB (2007) Tryptophan increases nocturnal rest and affects melatonin and serotonin serum levels in old ringdove. Physiol Behav 90: 576–582.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Glass JD, DiNardo LA, Ehlen JC (2000) Dorsal raphe nuclear stimulation of SCN serotonin release and circadian phase-resetting. Brain Res 859: 224–232.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Besedovsky L, Lange T, Born J (2012) Sleep and immune function. Pflugers Arch 463: 121–137.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Opp MR (2005) Cytokines and sleep. Sleep Med Rev 9: 355–364.

    PubMed  Article  Google Scholar 

  21. 21.

    Imeri L, Bianchi S, Mancia M (1997) Muramyl dipeptide and IL-1 effects on sleep and brain temperature after inhibition of serotonin synthesis. Am J Physiol 273: R1663–R1668.

    PubMed  CAS  Google Scholar 

  22. 22.

    Imeri L, Mancia M, Opp MR (1999) Blockade of 5-hydroxytryptamine (serotonin)-2 receptors alters interleukin-1-induced changes in rat sleep. Neuroscience 92: 745–749.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    McCune LM, Kubota C, Stendell-Hollis NR, Thomson CA (2011) Cherries and health: a review. Crit Rev Food Sci Nutr 51: 1–12.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Jacob RA, Spinozzi GM, Simon VA, Kelley DS, Prior RL, Hess-Pierce B, Kader AA (2003) Consumption of cherries lowers plasma urate in healthy women. J Nutr 133: 1826–1829.

    PubMed  CAS  Google Scholar 

  25. 25.

    Connolly DA, McHugh MP, Padilla-Zakour OI, Carlson L, Sayers SP (2006) Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage. Br J Sports Med 40: 679–683.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    González-Gómez D, Lozano M, Fernández-León MF, Bernalte MJ, Ayuso MC, Rodríguez AB (2010) Sweet cherry phytochemicals: identification and characterization by HPLC-DAD/ESI-MS in six sweet-cherry cultivars grown in Valle del Jerte (Spain). J Food Compos Anal 23: 533–539.

    Article  Google Scholar 

  27. 27.

    González-Gomez D, Lozano M, Fernández-León MF, Ayuso MC, Bernalte MJ, Rodríguez AB (2009) Detection and quantification of melatonin and serotonin in eight Sweet Cherry cultivars (Prunus avium L.). Eur Food Res Technol 229: 223–229.

    Article  Google Scholar 

  28. 28.

    Cubero J, Toribio F, Garrido M, Hernández MT, Maynar J, Barriga C, Rodríguez AB (2010) Assays of the amino acid tryptophan in cherries by HPLC-fluorescence. Food Analytical Methods. 3, 36–39.

    Article  Google Scholar 

  29. 29.

    Garrido M, Paredes SD, Cubero J, Lozano M, Toribio-Delgado AF, Muñoz JL, Reiter RJ, Barriga C, Rodríguez AB (2010) Jerte Valley cherry-enriched diets improve nocturnal rest and increase 6-sulfatoxymelatonin and total antioxidant capacity in the urine of middle-aged and elderly humans. J Gerontol A Biol Sci Med Sci 65: 909–914.

    PubMed  Article  Google Scholar 

  30. 30.

    Garrido M, González-Gómez D, Lozano M, Barriga C, Paredes SD, Rodríguez AB (2012) Characterization and trials of a Jerte Valley cherry product as a natural antioxidant-enriched supplement. Italian J Food Sci (in press).

    Google Scholar 

  31. 31.

    Delgado J, Terrón MP, Garrido M, Barriga C, Paredes SD, Espino J, Rodríguez AB (2012) Systemic inflammatory load in young and old ringdoves is modulated by consumption of a Jerte Valley cherry-based product. J Med Food 15: 707–712.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Faul F, Erdfelder E, Lang AG, Buchner A (2007) G* Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39: 175–191.

    PubMed  Article  Google Scholar 

  33. 33.

    Chauffard-Alboucq FA., Leathwood PD, Dormond CA (1991) Changes in plasma amino acid and subjective sleepiness ratings in humans after consuming Ltryptophan/maltodextrin mixes. Amino Acids 1:37–45.

    Article  CAS  Google Scholar 

  34. 34.

    Wurtman RJ, Zhdanova I (1995) Improvement of sleep quality by melatonin. Lancet 346: 1491.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Hughes RJ, Badia P (1997) Sleep-promoting and hypothermic effects of daytime melatonin administration in humans. Sleep 20:124–131.

    PubMed  CAS  Google Scholar 

  36. 36.

    Aparicio S, Garau C, Esteban S, Nicolau MC, Rivero M, Rial RV (2007) Chrononutrition: use of dissociated day/night infant milk formulas to improve the development of the wake-sleep rhythms. Effects of tryptophan. Nutr Neurosci 10: 137–143.

    Article  CAS  Google Scholar 

  37. 37.

    Silber BY, Schmitt JA (2010) Effects of tryptophan loading on human cognition, mood, and sleep. Neurosci Biobehav Rev 34: 387–407.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Chojnacki C, Poplawski T, Klupinska G, Blasiak J, Chojnacki J, Reiter RJ. Secretion of melatonin and 6-sylfatoxymelatonin urinary excretion in functional dyspepsia. World J. Gastroenterol. 2011, 17: 2646–2651.

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Oba S, Nakamura K, Sahashi Y, Hattori A, Nagata C (2008) Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration. J Pineal Res 45: 17–23.

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    González-Flores D, Velardo B, Garrido M, González-Gómez D, Lozano M, Ayuso MC, Barriga C, Paredes SD, Rodríguez AB (2011) Ingestion of Japanese plums (Prunus salicina Lindl. cv. Crimson globe) increases the urinary 6-sulfatoxymelatonin and total antioxidant capacity levels in young, middle-aged, and elderly humans: Nutritional and functional characterization of their content. J Food Nutr Res 50: 229–236.

    Google Scholar 

  41. 41.

    González-Flores D, Gamero E, Garrido M, Ramírez R, Moreno D, Delgado J, Valdés E, Barriga C, Rodríguez AB, Paredes SD (2012) Urinary 6-sulfatoxymelatonin and total antioxidant capacity increase after the intake of a grape juice cv. Tempranillo stabilized with HHP. Food Funct 3: 34–39.

    PubMed  Article  Google Scholar 

  42. 42.

    Haimov I, Laudon M, Zisapel N, Souroujon M, Nof D, Shlitner A, Herer P, Tzischinsky O, Lavie P (1994) Sleep disorders and melatonin rhythms in elderly people. BMJ 309: 167.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Hajak G, Rodenbeck A, Adler L, Huether G, Bandelow B, Herrendorf G, Staedt J, Rüther E (1996) Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia. Pharmacopsychiatry 29: 187–192.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Rodenbeck A, Huether G, Ruther E, Hajak G (1999) Nocturnal melatonin secretion and its modification by treatment in patients with sleep disorders. Adv Exp Med Biol 467: 89–93.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Youngstedt SD, Kripke DF, Elliott JA, Klauber MR (2001) Circadian abnormalities in older adults. J Pineal Res 31: 264–272.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Mahlberg R, Tilmann A, Salewski L, Kunz D (2006) Normative data on the daily profile of urinary 6-sulfatoxymelatonin in healthy subjects between the ages of 20 and 84. Psychoneuroendocrinology 31: 634–641.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Pappenheimer JR, Koski G, Fencl V, Karnovsky ML, Krueger J (1975) Extraction of sleep-promoting factor S from cerebrospinal fluid and from brain of sleep-deprived animals. J Neurophysiol 38: 1299–1311.

    PubMed  CAS  Google Scholar 

  48. 48.

    Borbély AA, Tobler I (1989) Endogenous sleep-promoting substances and sleep regulation. Physiol Rev 69: 605–670.

    PubMed  Google Scholar 

  49. 49.

    Moldofsky H, Lue FA, Eisen J, Keystone E, Gorcynski RM (1986) The relationship of interleukin-1 and immune functions to sleep in humans. Psychosom Med 48: 309–318.

    PubMed  CAS  Google Scholar 

  50. 50.

    Alam MN, McGinty D, Bashir T, Kumar S, Imeri L, Opp MR, Szymusiak R (2004) Interleukin-1beta modulates state-dependent discharge activity of preoptic area and basal forebrain neurons: Role in sleep regulation. Eur J Neurosci 20: 207–216.

    PubMed  Article  Google Scholar 

  51. 51.

    Irwin M, Rinetti G, Redwine L, Motivala S, Dang J, Ehlers C (2004) Nocturnal proinflammatory cytokine-associated sleep disturbances in abstinent African American alcoholics. Brain Behav Immun 18: 349–360.

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Carrillo-Vico A, García-Mauriño S, Calvo JR, Guerrero JM (2003) Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its mt1 membrane receptor. FASEB J 17: 755–757.

    PubMed  CAS  Google Scholar 

  53. 53.

    Carrillo-Vico A, García-Pergañeda A, Naji L, Calvo JR, Romero MP, Guerrero JM (2003) Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system. Cell Mol Life Sci 60: 2272–2278.

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    García-Mauriño S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sánchez-Margalet V, Goberna R, Guerrero JM (1997) Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor- mediated mechanism involving T helper type 1 lymphocytes and monocytes. J Immunol 159: 574–581.

    PubMed  Google Scholar 

  55. 55.

    García-Mauriño S, Pozo D, Carrillo-Vico A, Calvo JR, Guerrero JM (1999) Melatonin activates Th1 lymphocytes by increasing IL-12 production. Life Sci 65: 2143–2150.

    PubMed  Article  Google Scholar 

  56. 56.

    Fjaerly O, Lund T, Osterud B (1999) The effect of melatonin on cellular activation processes in human blood. J Pineal Res 26: 50–55.

    Article  Google Scholar 

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Correspondence to Ana B. Rodríguez Moratinos.

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Garrido, M., Gonzalez-Gomez, D., Lozano, M. et al. A jerte valley cherry product provides beneficial effects on sleep quality. Influence on aging. J Nutr Health Aging 17, 553–560 (2013).

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Key words

  • 6-sulfatoxymelatonin
  • melatonin
  • cytokine
  • sleep
  • sweet cherry