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To determine the dose-response effects of 10-day tart cherry product consumption (0, 30 ml, and 60 ml) on knee extensor isometric strength 24-h and 48-h after muscle damaging exercise and to elucidate the mechanisms of action for TC supplementation.
Montmorency cherry supplementation has been shown to exert antioxidant and anti-inflammatory effects that can be beneficial for improving recovery from exercise. However, the investigator is currently not aware of how tart cherry polyphenol supplementation produces these effects. This study aims to determine the dose-response effects of 10-day tart cherry product consumption (placebo, 30 ml, and 60 ml Montmorency tart cherry concentrate in a 500 ml beverage) on knee extensor isometric strength 24-h and 48-h after muscle damaging exercise on supplementation Day 8; on enhancing recovery of other measures of muscle function (single leg eccentric and concentric force development and single leg jump height) and muscle soreness; on reducing markers of oxidative stress and inflammation in plasma, muscle and urine; on inducing signaling in muscle via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to upregulate endogenous antioxidant enzymes in muscle; on inhibiting muscle cyclo-oxygenase (COX-1 and COX-2).
This study also aims to identify and establish the molecular mechanisms of action through which tart cherry polyphenols exert antioxidant and anti-inflammatory effects. Oxidative stress and inflammatory signaling in primary human myogenic cells will be assessed by incubating primary human myogenic cells (commercial cell line) in sera derived from 6 participants consuming 8-day placebo vs. 60 ml/day Montmorency tart cherry concentrate supplement. Subjects are permitted to participate in both the molecular mechanism of action part of the study (Part A, no exercise component) and the damaging exercise muscle recovery part of the study (Part B).
For 60 ml doses in Parts A and B, global proteomics analysis of the muscle tissue will be conducted generate more insight into the mechanisms of action. This would identify the specific pathways that are influenced by cherry supplementation and allow identification of the full range of mechanisms involved, rather than assume antioxidant/anti-inflammatory effects alone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0 ml tart cherry concentrate | Placebo Comparator | Still cherry-flavored beverage, similar in appearance, taste, aroma and calories to the 30 ml and 60 ml tart cherry concentrate beverages |
|
| 30 ml tart cherry concentrate | Experimental | "Low dose" tart cherry concentrate beverage |
|
| 60 ml tart cherry concentrate | Experimental | "High dose" tart cherry concentrate beverage |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 500 ml base solution | Other | Color, taste, aroma, and calorie matched water base |
|
| Measure | Description | Time Frame |
|---|---|---|
| Isometric knee extensor strength | Maximum voluntary contraction (MVC) as a measure of functional recovery from muscle damage. Unit of measurement is Newtons. Stronger is better. | Changes from immediately before and immediately after muscle damaging exercise on day 8 of tart cherry supplementation to 24 hours and 48 hours after muscle damaging exercise (days 9 and 10 of supplementation). |
| Measure | Description | Time Frame |
|---|---|---|
| Single leg eccentric and concentric isokinetic force production | Dynamic muscle strength measured by isokinetic contraction (IKC, 60 deg.s-1). More forceful is better. | Changes from immediately before and immediately after muscle damaging exercise on day 8 of tart cherry supplementation to 24 hours and 48 hours after muscle damaging exercise (days 9 and 10 of supplementation). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joanna Bowtell, PhD | University of Exeter, Sport and Health Sciences Department | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Exeter Sport and Health Sciences Department | Exeter | UK | EX1 2LU | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42272906 | Derived | Sabou V, O'Leary M, Jackman SR, Struszczak L, Bozbas E, Metcalf B, Tang JCY, Philo M, Kroon PA, Bowtell JL. Tart cherry supplementation causes differential regulation of skeletal muscle proteome after eccentric exercise. Front Nutr. 2026 May 26;13:1801399. doi: 10.3389/fnut.2026.1801399. eCollection 2026. |
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Repeated measures, double-blind, counter-balanced
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Taste-matched placebo
| 500 ml containing 30 ml tart cherry concentrate diluted with water and base solution | Other | Montmorency cherry concentrate |
|
| 500 ml containing 60 ml tart cherry concentrate diluted with water only | Other | Montmorency cherry concentrate |
|
| Single leg vertical jump height (SLVJ) | Dynamic muscle strength measured by jump height (cm). Higher is better. | Changes from immediately before and immediately after muscle damaging exercise on day 8 of tart cherry supplementation to 24 hours and 48 hours after muscle damaging exercise (days 9 and 10 of supplementation). |
| Leg muscle soreness by Pressure Pain tolerance (PPT) | Pressure pain tolerance (PPT) measured by algometer. Higher tolerance is better. | Changes from immediately before and immediately after muscle damaging exercise on day 8 of tart cherry supplementation to 24 hours and 48 hours after muscle damaging exercise (days 9 and 10 of supplementation). |
| Leg muscle soreness by Visual Analogue Scale (VAS) | Measured using a visual analogue pain scale from 0 mm (no pain) to 100 mm (extremely painful). Lower score is better. | Changes from immediately before and immediately after muscle damaging exercise on day 8 of tart cherry supplementation to 24 hours and 48 hours after muscle damaging exercise (days 9 and 10 of supplementation). |
| Leg muscle biopsy for nuclear factor k-B (NFκB) | Inflammation marker expression activity of the NFκB pathway will be measured by immunoblotting. Lower is better. | Changes from pre and post exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Biopsies are done after blood samples and before muscle soreness measures. |
| Leg muscle biopsy for cyclo-oxygenase COX1 protein | Inflammation marker of cyclo-oxygenase measured by total protein carbonylation (immunoblotting). A reduction (inhibiting) is better. | Changes from pre and post exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Biopsies are done after blood samples and before muscle soreness measures. |
| Leg muscle biopsy for cyclo-oxygenase COX1 activity | Inflammation marker of cyclo-oxygenase activity measured by commercially available colorimetric assay. A reduction (inhibiting) is better. | Changes from pre and post exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Biopsies are done after blood samples and before muscle soreness measures. |
| Leg muscle biopsy for nuclear factor erythroid 2-related factor 2 (Nrf2), absolute expression, nuclear translocation | Oxidative damage marker Nrf2 pathway intended to upregulate endogenous antioxidant enzymes in muscle. Induction of signaling is better. | Changes from pre and post muscle damaging exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Biopsies are done after blood samples and before muscle soreness measures. |
| Leg muscle biopsy for global proteomics analysis of muscle tissue samples for the 60 ml dose only | Tissue analysis to identify pathways influenced by cherry supplementation and identify mechanisms of action. | Changes from pre and post muscle damaging exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Biopsies are done after blood samples and before muscle soreness measures. |
| Leg muscle biopsy for endogenous antioxidant enzyme expression | Enzymes (superoxide dismutase 1, superoxide dismutase 2, glutathione peroxidase 1 and catalase) protein expression quantified by immunoblotting. Higher values (upregulation by Nrf2) is better. | Changes from pre and post muscle damaging exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Biopsies are done after blood samples and before muscle soreness measures. |
| Leg muscle biopsy for immune cell infiltration | Inflammation marker response measured by immunohistochemistry. Less infiltration is better. | Changes from pre and post muscle damaging exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Biopsies are done after blood samples and before muscle soreness measures. |
| Plasma interleukin-6 (IL-6) | Plasma inflammatory stress response measured by ELISA. A reduction is better. | Changes from pre and post muscle damaging exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Pre exercise blood sampling is done after urine collection. Post exercise blood sampling done before biopsy. |
| Plasma protein carbonyls | Oxidative stress response and antioxidant status measured by ELISA. A reduction is better. | Changes from pre and post muscle damaging exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Pre exercise blood sampling is done after urine collection. Post exercise blood sampling done before biopsy. |
| Plasma phenolic concentration | LC-MS-MS metabolite analysis to evaluate plasma levels associated with tart cherry supplementation at 0, 30 and 60 ml/day. | Changes from pre and post muscle damaging exercise on day 8 of tart cherry supplementation to pre-exercise on days 9 and 10 of supplementation. Pre exercise blood sampling is done after urine collection. Post exercise blood sampling done before biopsy. |
| Urine oxidation-reduction potential (ORP) | Urinary oxidation-reduction potential to measure oxidative damage and antioxidant status measured by probe. Less oxidative stress/free radical production is better. | Change from pre-exercise value day 8 to days 9 and 10 of tart cherry supplementation. Collected upon arrival to the study site. |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D063806 | Myalgia |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001519 | Behavior |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D059352 | Musculoskeletal Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D014867 | Water |
| ID | Term |
|---|---|
| D006878 | Hydroxides |
| D000468 | Alkalies |
| D007287 | Inorganic Chemicals |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
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