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Nutritional Interventions and Athlete’s Health
Lamprecht M (ed): Acute Topics in Sport Nutrition.
Med Sport Sci. Basel, Karger, 2013, vol 59, pp 86–93
Cherry Juice Targets Antioxidant Potential
and Pain Relief
Division of Health Promotion and Sports Medicine, Department of Medicine, Oregon Health and Science University, Portland, Oreg., USA
Strenuous physical activity increases the risk of musculoskeletal injury and can induce muscle dam-
age resulting in acute inflammation and decreased performance. The human body’s natural response
to injury results in inflammation- induced pain, swelling, and erythema. Among sports medicine
physicians and athletic trainers, the mainstays of urgent treatment of soft tissue injury are rest, ice,
compression, and elevation (RICE). In order to reduce pain and inflammation, anti- inflammatory
agents such as non- steroidal anti- inflammatory drugs (NSAIDs) act on the multiple inflammatory
pathways, which, although often very effective, can have undesirable side effects such as gastric
ulceration and, infrequently, myocardial infarction and stroke. For centuries, natural anti- inflammatory
compounds have been used to mediate the inflammatory process and often with fewer side effects.
Tart cherries appear to possess similar effectiveness in treating the inflammatory reaction seen in
both acute and chronic pain syndromes encountered among athletes and non- athletes with chronic
inflammatory disease. This article reviews the antioxidant and anti- inflammatory effects of tart cher-
ries on prevention, treatment, and recovery of soft tissue injury and pain.
Epidemiological evidence suggests that a high intake of plant foods is associated with lower risk of chronic diseases, and specifically, consumption of fruit and vegetables is associated with decreased risk of cancer and heart disease [1, 2]. Research into the possible mechanism has identified numerous antioxidant and anti- inflammatory agents in plants purported to reduce illness and disease associated with inflammation and tissue damage. These disease- modifying agents include cyclooxygenase inhibitory flavonoids [3, 4] and anthocynanins with high antioxidant and anti- inflammatory activities that have been identified in foods from black tea to tart cherries to fish oil [5–8]. Most recently, there has been interest in the role of these potent natural phy-tochemicals to reduce musculoskeletal injury, inflammation and pain, and improve recovery from exercise- induced soft tissue muscle damage [9–12]. Intense physical
activity increases the risk of musculoskeletal injury and can induce acute muscle damage resulting in acute inflammation and decreased force production [13–17]. The mainstays of treatment of soft tissue injury and inflammation are rest, ice, compres-sion, elevation (RICE) and non- steroidal anti- inflammatory drugs (NSAIDs) [18, 19]. According to the US Food and Drug Administration in 2001, NSAIDs accounted for 70,000,000 prescriptions and 30 billion over- the- counter doses sold annually in the USA, making it the most used and prescribed medication in the USA. There are, how-ever, known adverse effects associated with the use of NSAIDs  and natural anti- inflammatory agents may be a beneficial and safer alternative . Consumption of cherries may be effective in prevention of oxidative damage causing disease processes and alleviating symptoms in inflammatory conditions [9, 12, 22–24]. Consumption of approximately 45 cherries per day has been shown to reduce circulating concentra-tions of inflammatory markers in healthy men and women .
Mechanism of Inflammation and Traditional Pharmacologic Therapy
Strenuous physical activity increases the risk of musculoskeletal injury and can induce acute muscle damage resulting in acute inflammation and decreased force produc-tion that can last up to 1 week post- exercise [16, 17, 26–30]. The exact mechanism by which muscle damage occurs is not completely understood, but processes involve both mechanical and metabolic pathways. Pain, heat, redness, and swelling (dolor, calor, rubor, tumor) are the classic manifestations of the inflammatory process. The acute phase of muscle damage is caused by extensive myofibril disruption triggering a localized inflammatory response including release of proinflammatory cytokines interleukin (IL)- 1α, IL- 1β, IL- 6 and tumor necrosis factor (TNF- α). Increased concen-trations of TNF- α are believed to cause the cardinal signs of inflammation to occur. In addition, these cytokines increase production of leukotrienes leading to increased vascular permeability, attracting neutrophils to the injury site, and resulting in free radical production [31, 32]. When these muscle fibers are exposed to this oxidative stress due to exercise- induced increases in reactive oxygen species (ROS) and nitric oxide (NO) derivatives that exceed the antioxidant defense capacity [13, 14, 33]. With the elucidation of the role of these inflammatory cytokines and the apparent role for ROS and NO in muscle damage, there has been considerable interest in the efficacy of antioxidant supplements in ameliorating exercise- induced muscle damage, and foods that can alleviate inflammation and relieve pain .
Antioxidant Capacity of Tart Cherries
Both sweet and tart cherries are rich in phenolic compounds, but tart cherries are considered to be one of the highest sources of phenolic compounds, including
Anti- Inflammatory and Antioxidant Effects of Tart Cherry Juice
cyclooxygenase inhibitory flavonoids and anthocyanins, with high levels of antioxi-dant and anti- inflammatory activity [3–5, 8]. The levels of anthocyanins and other flavonoids in the Montmorency and Balaton tart cherry were analyzed comparatively by high- performance liquid chromatography and electrospray mass spectroscopy showing the major anthocyanin compound in both of these cultivars is cyanidin- 3- glucosylrutinoside, followed by cyanidin- 3- rutinoside and peonidin- 3- glucoside . Studies on the antioxidant activities (total antioxidant status assay) of crude tart cherry extracts including juice show that these products preserve their antioxi-dant capacities after processing and storage . When the trolox equivalent antiox-idant capacity values were evaluated conceptually against the cherry phytochemical profile, cyanidin and its derivatives were found to be significant contributors to the antioxidant systems of tart cherries. One of the best known properties of anthocya-nidins is their strong antioxidant activity in metabolic reactions, due to their abil-ity to scavenge oxygen free radicals and other ROS. This biological feature makes the tart cherry a significant antioxidant food source impacting oxidative damage processes. In animal studies, tart cherry- enriched diets reduced oxidative stress and inflammation  as well as protective effects on neuronal cells  and inhibition of tumorigenesis .
Tart Cherry Flavonoids as Anti- Inflammatory Agents
The anti- inflammatory actions of flavonoids in vitro or in cellular models involve the inhibition of the synthesis and activities of different proinflammatory mediators such as eicosanoids, cytokines, adhesion molecules and CRP . Acute inflammation as stated above is an essential and complex response protecting the body against harm-ful stimuli such as pathogens, damaged cells, or other irritants, and is manifested by vascular changes, edema, and predominantly neutrophilic infiltration in a mat-ter of days. Chronic inflammation is characterized by prolonged duration (weeks or months) caused by persistent infections, immune- mediated inflammatory diseases, or prolonged exposure to toxic reagents. This results in severe tissue destruction caused predominantly by mononuclear macrophages. Macrophages are the dominant cellular player in chronic inflammation, with a lifespan of several months to years . In a study looking at the anti- inflammatory mechanism of sweet and sour cher-ries, it was demonstrated that cherries have an anti- inflammatory effect mechanism similar to traditional NSAIDs. Water extracts of Balaton and Montmorency tart cher-ries inhibited cyclooxygenase- 1 and cyclooxygenase- 2 enzyme’s effect by 84, 91, 77, and 87% respectively, at 250 μg/ml per dose .
Both sweet and tart cherries are rich in phenolic compounds, but tart cherries
are considered to be one of the highest sources of phenolic compounds, including cyclooxygenase inhibitory flavonoids and anthocyanins, with high levels of antiox-idant and anti- inflammatory activity [3–5, 8, 40]. This has led to speculation that
cherry consumption may be beneficial among patients with chronic pain and inflam-mation disease processes like arthritis, gout, and fibromyalgia. Cherry consumption relieved symptoms of arthritis in an early human trial  and more recently, a single bolus of Bing cherries administered to healthy women after a 12- hour fast showed a trend for reducing circulating concentrations of CRP and NO, and uric acid within 3 h of the bolus, but not statistically significant (p < 0.1) . In a follow- up study by Kelley et al.  in 2006, consumption of approximately 45 cherries per day was shown to reduce circulating concentrations of inflammatory markers in healthy men and women.
Tart cherry juice is purported to benefit patients with fibromyalgia, perhaps due to
its antioxidant scavenging and anti- inflammatory properties . Fibromyalgia is a common chronic pain disorder, and physical activity is often used to manage this ill-ness . However, exercise can cause heightened discomfort following exertion, and tart cherry juice may alleviate the symptoms of delayed- onset muscle soreness associ-ated with exercise among fibromyalgia patients. To test, the efficacy of tart cherry juice to maintain strength and reduce pain undergoing arm exercise, 14 female subjects with fibromyalgia ingested tart cherry juice or placebo for 10 days in a blinded, ran-domized, crossover design . Ingestion of tart cherry juice demonstrated marginal benefits in maintaining muscle strength 24 h after strenuous exercise. In addition, a subset of participants who ingested the tart cherry juice had a significant reduction in pain after the eccentric arm exercise stress. Finding one subset of subjects who ben-efitted more than others was provocative. The response to most therapies for fibro-myalgia is variable  and unlike other studies, this study was blinded in a crossover design adding validity to the observed effects of a substantial reduction in pain in the tart cherry group as compared to placebo.
Osteoarthritis (OA) is a common syndrome affecting 65 million Americans char-
acterized by pain and disability [44, 45]. Pain relief and improvement of functional disability are the main goals of treatment. Over 40% of OA has an inflammatory component and the standardization of therapeutic criteria for inflammatory OA has stimulated much research, and understanding of the wide variety of therapeutic approaches is complicated by anecdotal and non- evidence- based basis of OA [45, 46]. Non- pharmacologic interventions are the mainstay of treatment (patient edu-cation, exercise, occupational therapy), but oral medications and nutritional sup-plements have shown positive and negative results, with acetominophen being the most common pain medication [47, 48]. A number of studies have looked at dietary factors and some have improved arthritis pain and function . A recent study looking at the effects of tart cherry on inflammatory biomarkers among inflamma-tory OA patients showed a beneficial effect on serum inflammation indices . In a double- blind, randomized placebo- controlled trial, 20 female subjects between 50 and 70 years diagnosed with Inflammatory OA consumed either placebo or Montmorency tart cherry juice (two 10- oz bottles of juice was equivalent to about 100 tart cherries per day) for 3 weeks. Among subjects consuming the tart cherry
Anti- Inflammatory and Antioxidant Effects of Tart Cherry Juice
juice as compared to the placebo beverage, a statistically significant decrease in CRP was observed. This study showed the value of looking at alternative therapies to conventional methods in the treatment and management of chronic inflamma-tory conditions. Tart cherry juice may provide beneficial anti- inflammatory activity helping OA patients manage their disease with less adverse effects than traditional arthritis medications.
Effects of Tart Cherries on Muscle Injury and Recovery
Muscle damage, inflammation, and oxidative stress typically occur in response to high intensity or prolonged physical activity [13, 14, 22, 23]. Numerous studies have examined the effect of dietary supplements that contain antioxidants on muscle func-tion, performance, and on markers of muscle damage and inflammation with mixed results. Kuehl et al.  studied the effects of tart cherry juice consumption versus placebo in a double- blinded, randomized trial design of runners participating in a 24- hour relay race in Oregon. It is well documented that running for distances in excess of typical training distances causes acute muscle injury, and that eccentric muscle actions, such as downhill running, exacerbate injury and soreness. The Hood to Coast relay requires participants to run three separate race segments over an approximately 24- hour period, including segments that ascend or descend steep terrain from Mt Hood Oregon (started at 5,500 ft elevation) to Seaside, Oregon (sea level) travers-ing the Cascade and Coastal mountain ranges. Runners drank either two 10- oz tart cherry or placebo beverage daily for 1 week prior to the race and during the race. Both groups (tart cherry and placebo) reported significantly higher pain levels based on the visual analog scale (VAS) upon completion of the race. However, participants who drank the tart cherry juice twice daily for 1 week prior to and the day of the race reported a significantly smaller increase in pain after the race (mean post- race VAS score was 12 mm in tart cherry juice as compared to a VAS score of 37 mm). The 25- mm difference in the mean VAS score is equivalent to a therapeutic pain relief dose of ibuprofen among runners consuming the tart cherry juice . These results suggest tart cherries provide a protective benefit against the acute muscle soreness caused by distance running.
Tart cherry juice may prevent symptoms of muscle damage among individuals
participating in strenuous exercise. Looking at the effects of tart cherry juice on indices of recovery following a long- distance running event, Howatson et al.  evaluated marathon runners who drank cherry juice 5 days before, the day of, and after the race. Results showed those who drank cherry juice had statistically sig-nificant lower levels of inflammation markers (IL- 6 and CRP) as compared to pla-cebo. In addition to biomarkers, isometric strength recovered significantly faster in the tart cherry juice runners indicating a viable means to aid recovery following strenuous exercise. A study among healthy, exercise- naive individuals demonstrated
efficacy for tart cherry juice in decreasing muscle damage symptoms and strength loss after eccentric exercise- induced muscle damage . Fourteen male college stu-dents drank 12 fl. oz of a tart cherry juice blend or a placebo drink twice daily for 8 consecutive days. A bout of elbow flexion eccentric exercise was performed consist-ing of 2 × 20 maximum contractions at baseline to induce muscle damage. Isometric elbow flexion strength, pain, and muscle soreness were measured before and for 4 days after the muscle damage protocol. Strength loss and pain were significantly less in the cherry group versus the placebo group. For the placebo trial, strength loss was 30% at 24 h and still 12% at 96 h after eccentric exercise. By contrast, in the cherry juice trial, strength loss was only 12% at 24 h, and strength was actually 6% above baseline at 96 h. Most notably, there was a preservation of muscle function attribut-able to the cherry juice.
In the most recent study on muscle damage and recovery, Bowtell et al.  evalu-
ated the effects of Montmorency tart cherry juice on muscle damage indices after a bout of intensive exercise. Ten well- trained males completed two trials of 10 sets of 10 single- leg knee extension at baseline and 2 weeks with either 10 days of the placebo or tart cherry beverage (30 ml twice daily for 10 days). Knee extension maximum voluntary contraction force recovery was significantly faster in the subjects after con-suming cherry juice as compared to placebo. The author’s conclusion was that the improved recovery time after intensive exercise in the tart cherry juice group may be due to the attenuation of oxidative damage induced by the muscle damage protocol suggesting a myoprotective effect of tart cherries.
The human body’s natural response to injury results in inflammation- induced pain, swelling, and erythema. In order to reduce pain, anti- inflammatory agents such as NSAIDs act on the multiple inflammatory pathways, which, although often very effective, can have undesirable side effects such as gastric ulceration and, infre-quently, myocardial infarction and stroke. For centuries, natural anti- inflammatory compounds have been used to mediate the inflammatory process and often with fewer side effects. Tart cherry consumption appears to possess similar effectiveness in treating the inflammatory reaction seen in both acute inflammation injury pain syndromes encountered among athletes and chronic inflammation and pain encoun-tered in chronic inflammatory disease states.
The author has no conflicts of interest to disclose.
Anti- Inflammatory and Antioxidant Effects of Tart Cherry Juice
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Dr. Kerry S. Kuehl, MD, PHDivision of Health Promotion and Sports MedicineDepartment of Medicine, Oregon Health and Science University3181 SW Sam Jackson Park Rd, Portland, OR 97239 (USA)Tel. +1 503 494 5991, E- Mail firstname.lastname@example.org
Anti- Inflammatory and Antioxidant Effects of Tart Cherry Juice
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