4.3 Article

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

Journal

AMERICAN JOURNAL OF THERAPEUTICS
Volume 25, Issue 2, Pages E194-E201

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MJT.0000000000000584

Keywords

procyanidin; indoleamine 2; 3-dioxygenase; montmorency tart cherry juice; sleep; tryptophan; kynurenine

Funding

  1. Cherry Marketing Institute
  2. NORC Center - NIDDK [2P30DK072476]
  3. National Center for Complementary and Alternative Medicine (NCCAM) [P50AT002776]
  4. Office of Dietary Supplements (ODS) of the National Institutes of Health
  5. Department of Plant Biology and Pathology in the School of Environmental and Biological Sciences (SEBS) of Rutgers University
  6. National Institute of General Medical Sciences of the National Institutes of Health [1 U54 GM104940]

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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.

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