Tuesday, May 01, 2012
by: Jacob Schor, ND, FABNO
Section: Abstracts & Commentary
Howatson G, et al. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. Eur J Nutr. 2011 Oct 30. [Epub ahead of print]
Randomized, double-blind, placebo-controlled, crossover design
Twenty healthy, physically active men and women (10 each gender), without disease or lifestyle that might impact results. Age range restricted to 18–40 years old.
Study Medication and Dosage
Diluted concentrates of tart Montmorency cherry juice (Prunus cerasus) were consumed 30 minutes after waking and 30 minutes before the evening meal. Each serving was made from 30 ml of juice concentrate (estimated to contain the equivalent of approximately 90–100 cherries) and diluted with approximately 200 ml of water. Each dose contained approximately 42.6 mcg melatonin, so participants received 85.2 mcg/day of exogenous melatonin during the study. The placebo group drank a commercially available fruit beverage containing less than 5% fruit and no melatonin or anthocyanins.
Measures of sleep quality recorded by actigraphy, and participants completed subjective sleep questionnaires. Sequential urine samples were collected for 48 hours before beginning the interventions and again for the 2 days after supplementation with juice or placebo. After a 14-day washout period, the groups crossed over and repeated the experiment. The melatonin metabolite, urinary 6-sulfatoxymelatonin (major metabolite of melatonin) was determined in the urine samples. In addition, total urinary melatonin content was determined over the entire sample period, before and after intervention. Trial differences were determined using a repeated measures ANOVA.
Total melatonin content was significantly elevated (P<0.05) in the cherry juice group. No differences were evident between baseline and endpoint in the placebo arm of the study. There were significant increases in time in bed, total sleep time, and sleep efficiency total (P<0.05) with cherry juice supplementation.
No difference was seen in timing of the melatonin circadian rhythm, though there was a trend to a higher mesor and amplitude.
These data expressed by Howatson et al suggest that consumption of tart cherry juice concentrate provides an increase in exogenous melatonin that is beneficial in improving sleep duration and might be of benefit in managing disturbed sleep. This is the latest in a series of studies that provide growing evidence toward this conclusion.
In June 2010 Pigeon et al from the University of Rochester in New York reported that tart cherry juice was useful in treating insomnia in older adults. Responding to anecdotal reports that cherry juice was useful, a randomized, double-blind, crossover study was conducted with each of 15 participants receiving both treatment and a placebo for a 2-week period with an intervening 2-week washout period. When compared to placebo, cherry juice produced significant reductions in insomnia severity (minutes awake after sleep onset). No improvements were observed with the placebo. The benefits were modest but were, as the authors point out, “equal to or exceeding those observed in studies of valerian and in some, but not all, studies of melatonin, the 2 most studied natural products for insomnia.”1
A second paper on cherries and sleep in older adults was published in September 2010. Garrido et al reported that consumption of Spanish sweet cherries grown in the Jerte Valley produced beneficial effects on actual sleep time, total nocturnal activity, assumed sleep, and immobility. There were significant increases in antioxidant capacity of the urine.2 It may be that the reduction in oxidative stress, rather than the melatonin, is what improves sleep.3
Cherries, in particular the Montmorency variety, contain melatonin—about 13 nanograms of melatonin per gram of cherry.4 Recall that there are a million nanograms in a milligram, so a kilogram of cherries would contain 13,000 nanograms or 0.013 mg of melatonin. Such small amounts would seem clinically inconsequential, yet those prior clinical trials do suggest cherry juice may be helpful in treating insomnia.
In the current study, the cherry juice drunk by participants provided a total of only of 85.2 mcg of melatonin per day. Typical doses of melatonin found useful in treating sleep disorders are in the range of 0.5 to 5.0 mg per day (ie, 500–5,000 mcg per day).5
The other detail that stands out on a close read of this study is the timing of when participants drank the cherry juice. They drank half of the day’s total immediately upon waking in the morning and the second dose at dinner. It is general clinical practice to administer melatonin at bedtime at doses 10 to a 100 times as high. Thus it is reasonable to question whether such small doses of melatonin given at these intervals could be adequate to have a significant effect on sleep.
Another possible explanation mentioned by Howatson et al, comes from Opp’s 2004 paper on cytokines and sleep. The anti-inflammatory properties of tart cherries may influence inflammatory cytokines involved in sleep regulation.6 Earlier studies report that the anti-inflammatory action of cherries is equivalent to a number of nonsteroidal anti-inflammatory drugs (NSAIDs).7,8 Perhaps it is the anti-inflammatory action that improves sleep. Clinical experience suggests that a number of patients are in the habit of taking a NSAID dose at bedtime. Perhaps the anti-inflammatory effects of the cherry juice have a synergistic effect with melatonin, increasing the effect.
Lacking a clear explanation should not prevent us from suggesting cherry juice to patients experiencing sleep problems. The side effect profile offers no reason not to. The best time to tell patients to drink the juice is not clear. Past clinical practice might suggest taking it at bedtime. This current study though suggests divided doses, part in the morning and the remainder with dinner.
1. Pigeon WR, Carr M, Gorman C, Perlis ML. Effects of a tart cherry juice beverage on the sleep of older adults with insomnia: a pilot study. J Med Food. 2010;13(3):579-583.
2. Garrido M, Paredes SD, Cubero J, et al. 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. 2010;65(9):909-914.
3. 20. Traustadóttir T, Davies SS, Stock AA, et al. Tart cherry juice decreases oxidative stress in healthy older men and women. J Nutr. 2009;139(10):1896-1900.
4. Burkhardt S, Tan DX, Manchester LC, Hardeland R, Reiter RJ. Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus). J Agric Food Chem. 2001;49(10):4898-4902.
5. Herxheimer A, Pertrie KJ Melatonin for the prevention of jet lag. Cochrane Database Syst Rev. 2002;9:11.24.
6. Opp MR Cytokines and sleep: the first hundred years. Brain Behav Immun. 2004; 18(4):295-297.
7. Wang H, Nair MG, Strasburg GM, et al. Antioxidant and anti-inflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries. J Nat Prod. 1999;62(2):294-296.
8. Kim D-O, Heo HJ, Kim YJ, Yang HS, Lee CY. Sweet and sour cherry phenolics and their protective effects on neuronal cells. J Agric Food Chem. 2005;53(26):9921-9927.
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