Pilot Study of the Tart Cherry Juice for the Treatment of Insomnia and Investigation of Mechanisms

Jack N Losso, John W Finley, Namrata Karki, Ann G Liu, Alfredo Prudente, Russell Tipton, Ying Yu, Frank L Greenway, Jack N Losso, John W Finley, Namrata Karki, Ann G Liu, Alfredo Prudente, Russell Tipton, Ying Yu, Frank L Greenway

Abstract

Background: Insomnia is common in the elderly and is associated with chronic disease, but use of hypnotics increases the incidence of falls. Montmorency tart cherry juice has improved insomnia by self-report questionnaire.

Study question: Is insomnia confirmed by polysomnography and is tryptophan availability a potential mechanism for treating insomnia?

Study design: A placebo-controlled balanced crossover study with subjects older than 50 years and insomnia were randomized to placebo (2 weeks) or cherry juice (2 weeks) (240 mL 2 times/d) separated by a 2-week washout.

Measures and outcomes: Sleep was evaluated by polysomnography and 5 validated questionnaires. Serum indoleamine 2,3-dioxygenase (IDO), the kynurenine-to-tryptophan ratio, and prostaglandin E2 were measured. In vitro, Caco-2 cells were stimulated with interferon-gamma, and the ability of cherry juice procyanidin to inhibit IDO which degrades tryptophan and stimulates inflammation was measured. The content of procyanidin B-2 and other major anthocyanins in cherry juice were determined.

Results: Eleven subjects were randomized; 3 with sleep apnea were excluded and referred. The 8 completers with insomnia increased sleep time by 84 minutes on polysomnography (P = 0.0182) and sleep efficiency increased on the Pittsburgh Sleep Quality Index (P = 0.03). Other questionnaires showed no significant differences. The serum kynurenine-to-tryptophan ratio decreased, as did the level of prostaglandin E2 (both P < 0.05). In vitro, cherry juice procyanidin B-2 dose-dependently inhibited IDO.

Conclusions: Cherry juice increased sleep time and sleep efficiency. Cherry juice procyanidin B-2 inhibited IDO, increased tryptophan availability, reduced inflammation, and may be partially responsible for improvement in insomnia.

Conflict of interest statement

Conflicts of interest: none

Figures

Figure 1
Figure 1
A. Relative induction of indoleamine 2,3-dioxygenase (IDO) and COX-2 in Caco-2 cells stimulated with IFN-γ and decrease of IDO and COX-2 in cells treated with procyanidin B-2. B. Relative induction of NF-KB in Caco-2 cells stimulated with IFN-γ. 1= control, 2= IFN-γ, 3= 12.5 μM procyanidin B-2, 4= 25 μM procyanidin B-2, and 5= 50 μM procyanidin B-2
Figure 1
Figure 1
A. Relative induction of indoleamine 2,3-dioxygenase (IDO) and COX-2 in Caco-2 cells stimulated with IFN-γ and decrease of IDO and COX-2 in cells treated with procyanidin B-2. B. Relative induction of NF-KB in Caco-2 cells stimulated with IFN-γ. 1= control, 2= IFN-γ, 3= 12.5 μM procyanidin B-2, 4= 25 μM procyanidin B-2, and 5= 50 μM procyanidin B-2
Figure 2
Figure 2
Serum Kyurenine to tryptophan ratio after placebo or cherry juice treatment. *p

Figure 3

Serum PGE-2 levels after placebo…

Figure 3

Serum PGE-2 levels after placebo or cherry juice treatments. *p<0.05

Figure 3
Serum PGE-2 levels after placebo or cherry juice treatments. *p
Similar articles
Cited by
References
    1. Foley DJ, Monjan AA, Brown SL, et al. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995;18:425–432. - PubMed
    1. Suka M, Yoshida K, Sugimori H. Persistent insomnia is a predictor of hypertension in Japanese male workers. J Occup Health. 2003;45:344–350. - PubMed
    1. Vgontzas AN, Liao D, Bixler EO, et al. Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep. 2009;32:491. - PMC - PubMed
    1. Taylor DJ, Mallory LJ, Lichstein KL, et al. Comorbidity of chronic insomnia with medical problems. Sleep. 2007;30:213–218. - PubMed
    1. Cricco M, Simonsick EM, Foley DJ. The impact of insomnia on cognitive functioning in older adults. J Am Geriatr Soc. 2001;49:1185–1189. - PubMed
Show all 33 references
Publication types
MeSH terms
Full text links [x]
[x]
Cite
Copy Download .nbib .nbib
Format: AMA APA MLA NLM
Figure 3
Figure 3
Serum PGE-2 levels after placebo or cherry juice treatments. *p

References

    1. Foley DJ, Monjan AA, Brown SL, et al. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995;18:425–432.
    1. Suka M, Yoshida K, Sugimori H. Persistent insomnia is a predictor of hypertension in Japanese male workers. J Occup Health. 2003;45:344–350.
    1. Vgontzas AN, Liao D, Bixler EO, et al. Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep. 2009;32:491.
    1. Taylor DJ, Mallory LJ, Lichstein KL, et al. Comorbidity of chronic insomnia with medical problems. Sleep. 2007;30:213–218.
    1. Cricco M, Simonsick EM, Foley DJ. The impact of insomnia on cognitive functioning in older adults. J Am Geriatr Soc. 2001;49:1185–1189.
    1. Wu TY, Chie WC, Yang RS, et al. Risk factors for single and recurrent falls: a prospective study of falls in community dwelling seniors without cognitive impairment. Prev Med. 2013;57:511–517.
    1. Pigeon WR, Carr M, Gorman C, et al. Effects of a tart cherry juice beverage on the sleep of older adults with insomnia: a pilot study. J Med Food. 2010;13:579–583.
    1. Burkhardt S, Tan DX, Manchester LC, et al. Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus) J Agric Food Chem. 2001;49:4898–4902.
    1. George CF, Millar TW, Hanly PJ, et al. The effect of L-tryptophan on daytime sleep latency in normals: correlation with blood levels. Sleep. 1989;12:345–353.
    1. Riemann D, Feige B, Hornyak M, et al. The tryptophan depletion test: impact on sleep in primary insomnia - a pilot study. Psychiatry Res. 2002;109:129–135.
    1. Arnulf I, Quintin P, Alvarez JC, et al. Mid-morning tryptophan depletion delays REM sleep onset in healthy subjects. Neuropsychopharmacology. 2002;27:843–851.
    1. Hudson C, Hudson SP, Hecht T, et al. Protein source tryptophan versus pharmaceutical grade tryptophan as an efficacious treatment for chronic insomnia. Nutr Neurosci. 2005;8:121–127.
    1. Young SN, Leyton M. The role of serotonin in human mood and social interaction. Insight from altered tryptophan levels. Pharmacol Biochem Behav. 2002;71:857–865.
    1. Dantzer R, O'Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46–56.
    1. Ou B, Bosak KN, Brickner PR, et al. Processed tart cherry products–comparative phytochemical content, in vitro antioxidant capacity and in vitro anti-inflammatory activity. J Food Sci. 2012;77:H105–112.
    1. Sano A, Yamakoshi J, Tokutake S, et al. Procyanidin B1 is detected in human serum after intake of proanthocyanidin-rich grape seed extract. Biosci Biotechnol Biochem. 2003;67:1140–1143.
    1. Roth T, Coulouvrat C, Hajak G, et al. Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, Second Edition criteria: results from the America Insomnia Survey. Biol Psychiatry. 2011;69:592–600.
    1. Gagnon C, Belanger L, Ivers H, et al. Validation of the Insomnia Severity Index in primary care. J Am Board Fam Med. 2013;26:701–710.
    1. Beaudreau SA, Spira AP, Stewart A, et al. Validation of the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale in older black and white women. Sleep Med. 2012;13:36–42.
    1. Arnau RC, Meagher MW, Norris MP, et al. Psychometric evaluation of the Beck Depression Inventory-II with primary care medical patients. Health Psychol. 2001;20:112.
    1. Quek K, Low W, Razack A, et al. Reliability and validity of the Spielberger State-Trait Anxiety Inventory (STAI) among urological patients: a Malaysian study. Med J Malaysia. 2004;59:258–267.
    1. Kleinman L, Zodet M, Hakim Z, et al. Psychometric evaluation of the fatigue severity scale for use in chronic hepatitis C. Qual Life Res. 2000;9:499–508.
    1. Vignau J, Jacquemont MC, Lefort A, et al. Simultaneous determination of tryptophan and kynurenine in serum by HPLC with UV and fluorescence detection. Biomed Chromatogr. 2004;18:872–874.
    1. Howatson G, Bell PG, Tallent J, et al. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. Eur J Nutr. 2012;51:909–916.
    1. Kennedy JA. Proanthocyanidins: Extraction, Purification, and determination of subunit composition by HPLC. John Wiley & Sons, Inc; 2002. pp. I1.4.1–I1.4.11. (Current Protocols in Food Analytical Chemistry).
    1. Kim DO, Lee CY. Extraction and isolation of polyphenolics. John Wiley & Sons, Inc; 2002. pp. I1.2.1–I1.2.12. (Current Protocols in Food Analytical Chemistry).
    1. Seymour EM, Lewis SK, Urcuyo-Llanes DE, et al. Regular tart cherry intake alters abdominal adiposity, adipose gene transcription, and inflammation in obesity-prone rats fed a high fat diet. J Med Food. 2009;12:935–942.
    1. Ciorba MA. Indoleamine 2,3 dioxygenase in intestinal disease. Curr Opin Gastroenterol. 2013;29:146–152.
    1. Mangge H, Stelzer I, Reininghaus EZ, et al. Disturbed tryptophan metabolism in cardiovascular disease. Curr Med Chem. 2014;21:1931–1937.
    1. Kosinska A, Andlauer W. Cocoa polyphenols are absorbed in Caco-2 cell model of intestinal epithelium. Food Chem. 2012;135:999–1005.
    1. Iachininoto MG, Nuzzolo ER, Bonanno G, et al. Cyclooxygenase-2 (COX-2) inhibition constrains indoleamine 2,3-dioxygenase 1 (IDO1) activity in acute myeloid leukaemia cells. Molecules. 2013;18:10132–10145.
    1. Mei J, Li MQ, Ding D, et al. Indoleamine 2,3-dioxygenase-1 (IDO1) enhances survival and invasiveness of endometrial stromal cells via the activation of JNK signaling pathway. Int J Clin Exp Pathol. 2013;6:431–444.
    1. Mei J, Jin LP, Ding D, et al. Inhibition of IDO1 suppresses cyclooxygenase-2 and matrix metalloproteinase-9 expression and decreases proliferation, adhesion and invasion of endometrial stromal cells. Mol Hum Reprod. 2012;18:467–476.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다