Abstract
Cherries, the fruit of Prunus cerasus trees, and their juice concentrates may be clinically beneficial in various conditions, including gout, arthritis, muscle injury, diabetes and neurodegeneration.
Introduction
Cherries are the fruit of perennial trees that are closely related to plum, peach, apricot, and almond trees. Two cherry species are grown commercially in the United States: Prunus avium, the "wild" or sweet cherry, and Prunus cerasus, the tart or sour cherry. This review focuses on tart cherries, which are used primarily for cooking. In general tart cherries contain more beneficial phytochemicals. The majority of the human cherry research has been done on tart P. cerasus cherries, and unless specified otherwise all research mentioned in this review concerns Prunus cerasus.
Domesticated cherries originated in Turkey, reached Rome in 72 BC, and from there spread slowly across Europe, arriving in England during the reign of Henry VIII. Cherries were brought to North America in the 1600s. Peter Dougherty, a missionary, is credited with planting cherry trees near Traverse City, Mich., in 1852. This area became the center of American commercial cherry production. More than 75% of the US tart cherry crop is grown in Michigan,1 and the US produces about 13% of the world’s total cherries.
The average person in the United States eats about 1 pound of tart cherries each year. Most tart cherries are somehow preserved; while the majority are frozen for bakery use, about 10% are processed in juice concentrates.2 Cherry juice concentrates have become the focus of numerous recent clinical trials and show therapeutic potential.
Cherries and Gout
Ludwig Blau, MD, published the first credible report of medical benefit from cherries in the Texas Reports on Biology and Medicine in 1950. Having noticed that eating cherries reduced his own gout symptoms, Blau tested his ‘remedy’ on 12 other gout sufferers before writing his article.3
The cherry-gout cure remained anecdotal until the publication of research conducted by the US Department of Agriculture research facility in Davis, Calif., in 2003. Ten healthy women, aged 22 to 40 years, consumed about 45 sweet cherries (Prunus avium), or 280 grams, after an overnight fast. Five hours later plasma urate levels had decreased from 214 to 183 umol/L. At 3 hours after consumption, urinary urate levels had increased from 202 to 350 umol/mmol creatinine. Consumption of other fruits did not produce significant changes.4
The research moved from gout to arthritis. Three studies using rats were published, between 2004 and 2006. In each trial rats were injected with a chemical, ‘complete Freund’s adjuvant,’ which induces arthritis-like pain and inflammatory reactions. In the first paper, pain and inflammation reduction from eating cherries was compared to the benefits of indomethacin. The researchers reported that 2 ounces of tart cherries were equivalent to 50 mg of the drug. In each study, feeding the rats cherries significantly reduced signs of swelling in the targeted joints.6,7
Although this sounds like scant research to inform clinical practice, these studies proved adequate to induce a flurry of commercial promotion aimed at selling tart cherry based products. Websites selling cherry products, mostly juice concentrates, quoted these studies, especially the USDA gout paper, as proof that cherries work. In October of 2005 the Food and Drug Administration (FDA) issued cease and desist letters to 29 small orchards and cherry juice producers demanding they stop making health claims about cherries.8
In light of this apparent gout benefit, we must also consider cherries’ fructose content. Choi et al reported in their 2010 study that consuming fructose-rich beverages is associated with a higher risk of gout. This finding resulted from their analysis of data from the Nurses' Health Study, a cohort study that spanned 22 years and included data from 78,906 women. Compared to women who didn’t drink soda, those who consumed 2 fructose syrup–sweetened sodas per day increased the risk of a gout attack by nearly 2.5 times. Drinking orange juice produced a similar increased risk: One glass of orange juice per day increased the relative risk of a gout attack to 1.41 compared to women who didn’t drink juice routinely. Two glasses a day increased the relative risk to 2.42. This is why gout sufferers are now told to avoid fruit juice.9
A glass of orange juice contains about 10.5 grams of fructose. A glass of tart cherry juice made by diluting concentrate contains even more fructose, about 12.5 grams.10,11 Considering this fructose information, one could argue that cherry juice is not suitable for gout patients to drink frequently. Fructose-free cherry extracts might be more appropriate and effective for gout patients than juice concentrates.
Muscle Recovery
In recent years cherry research has focused on preventing or reducing the symptoms of muscle damage. In August 2006, researchers from the University of Vermont reported that in a placebo-controlled trial of 14 college students, drinking 12 ounces of tart cherry juice twice a day for 8 days significantly reduced the loss of strength and pain caused by bouts of eccentric elbow flexion contractions. In particular, “strength loss averaged over the 4 days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.”12
In June 2009 researchers from the Cornell College of Veterinary medicine reported that tart cherry juice protected horses from exercise-induced muscle damage. Six horses drank either 1.42 liters of cherry juice twice a day or a placebo and were put through a series of incrementally more demanding workouts. Administration of cherry juice was associated with lower serum aspartate aminotransferase (AST) compared with administration of placebo solution.13 Although we typically think of AST as a serum marker of liver disease, we should remember that it is also a marker of skeletal muscle damage, and in this situation it should be considered as such.
In May 2010, Kuehl et al from Oregon Health Sciences in Portland, Ore., reported that tart cherry juice reduced pain in distance runners. These researchers conducted a randomized, double-blind, placebo-controlled trial of 54 runners who ran the Oregon Hood to Coast relay race and covered an average of 26.3 km over a 24-hour period. Study participants drank about 12 ounces of tart cherry juice or placebo twice daily for a week before the event and on the day of the race. “While both groups reported increased pain after the race, the cherry juice group reported a significantly smaller increase in pain … compared to the placebo group.”14
Supplementation with cherry products might decrease the long-term accumulation of oxidative damage, producing benefits that amass over a period of years.
Howatson et al from Northumbria, UK, published a study in December 2010 that followed 20 recreational marathon runners who drank either tart cherry juice or placebo for 5 days before, the day of, and for 2 days after a marathon run. Isometric strength recovered significantly faster in those who drank cherry juice. Markers of inflammation, including IL-6, C-reactive protein, and uric acid, were reduced in the cherry juice group. Howatson et al explain, “The cherry juice appears to provide a viable means to aid recovery following strenuous exercise by increasing total antioxidative capacity, reducing inflammation, lipid peroxidation and so aiding in the recovery of muscle function.”15
In January 2011, Bowtell et al reported the effects of tart cherry juice on oxidative damage and muscle function after intensive unilateral leg exercise. Ten trained male athletes performed sets of single leg extensions in a series with 2 weeks between each trial. They drank either cherry juice or a placebo the week prior and for 2 days after each exercise bout. As in earlier studies, the cherry juice decreased recovery time of isometric muscle strength by reducing oxidative damage induced by the exercise.16
Sleep
Cherry products may have therapeutic potential as sleep aids. Cherries—particularly the Montmorency variety of tart cherries—contain melatonin. Montmorency cherries contain about 13 ng/gm of melatonin, about 6 times more than the Balaton variety, which contain only about 2 ng/gm. These amounts do not vary much between orchard and time of harvesting.17 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 amount would seem clinically inconsequential, yet 2 recent clinical trials suggest cherry juice may nevertheless be helpful in treating insomnia.
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, they conducted a randomized, double-blind, crossover study 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.”18
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.19 It may be that the reduction in oxidative stress, rather than the melatonin, is what improves sleep.20
Cherry in Meat Products
In the late 1980s, several commercial meat products with added tart cherry pulp became the subjects of research. Although the cherry pulp had been to the meat as a novelty, researchers discovered that the fruit kept the meat fresh longer. They reported that low-fat ground beef with about 12% tart cherries added developed significantly less rancidity. Of greater interest was how the cherries reduced heterocyclic amine (HCA) formation during cooking by approximately 90%.21
Anthocyanin Content
Cherries are excellent sources of anthocyanins, which have the greatest antioxidant capacity of any of the flavonoid chemicals. Tart cherries contain substantial quantities of anthocyanin 1 and 2 that block cyclooxygenase (cox) 1 and 2. Sweet cherry anthocyanins can decrease cox 1 and cox 2 activity by almost 50%. Tart cherries contain more anthocyanins and phenols than the sweet varieties. Studies report that the anthocyanin content of tart cherries is 27% to 200% higher than in sweet cherries.23 Tart cherries yield about 90% more anthocyanin 1 and 2 than raspberries. Bilberries, blueberries, cranberries, and elderberries do not contain anthocyanin 1 and 2.24
Aspirin Equivalents
In a report written for the Cherry Marketing Institute, Russell Reiter of the University of Texas estimates “that 1 serving of tart cherries (canned) is the equivalent of 1.41 grams of aspirin. A serving of tart cherry juice contains the equivalent of 0.30 grams of aspirin; and frozen cherries equal 0.90 grams. A standard aspirin tablet is 0.325 grams.”25 This report has not been published in peer-reviewed literature, and these equivalencies, though informative, should be approached carefully.
Theories and Ideas
There are a number of areas in which cherries may eventually prove useful but which still rely on theory and animal evidence.
Cherries contain a significant amount of perillyl alcohol (POH), a chemical that may play an active role in slowing or stopping progression of certain types of cancer. POH is a naturally occurring monoterpene found in the essential oils of numerous plant species, including mints, cherries, and celery seeds.26 James Belanger in his 1998 review suggested that POH may prevent the formation or progression of a number of cancers and may be a useful adjunctive therapy in cancer treatment.27
Tart cherries may be useful in treating diabetes, particularly the anthocyanins, which are effective at increasing insulin production by pancreatic cells when exposed to sugar. Jayaprakasam reported in 2005 a 50% increase in insulin production.28 Boniface and Robert in 1996 reported a clinical trial of 12 adults with diabetes who were treated with 600 mg anthocyanosides per day for 2 months. Treatment caused a decrease in synthesis of connective tissue, especially the collagen and glycoproteins that lead to diabetic complications, including retinopathy.29
Several studies suggest that cherries may protect against brain injury. Kim et al in 2005 reported that cherry anthocyanins protect brain neurons from degeneration in a dose-dependent manner.30 In 2006, Shin et al reported that anthocyanins protect rats from cerebral ischemic injury caused by starting and stopping blood flow to their brains.31
Conclusion
There are no reports of toxicity or disease aggravation from the consumption of cherries. Instead there are tantalizing possibilities presented in these various studies. Cherries reduce oxidative damage in the muscles of athletes. Might the same effect occur after trauma or surgery? Supplementation with cherry products might decrease the long-term accumulation of oxidative damage, producing benefits that amass over a period of years. Most studies on cherries to date have been small pilot trials, seeking visible benefit over short periods, typically a week or 2 at most. Larger trials with more participants for longer periods of time are needed to substantiate these early uses and perhaps reveal other unforeseen benefits.
