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| Name | Class |
|---|---|
| The Cranberry Institute | OTHER |
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In this work, the investigators will assess whether cranberry (poly)phenols improve mood disorders including stress, anxiety and depression via the gut-brain axis in university students. The investigators will evaluate whether the effects observed are related to an improvement in gut microbiome diversity and function, and whether the mechanism of action may be mediated by a decrease in inflammatory markers, modulation of neurotransmitters or via an alteration of BDNF levels. The investigators will also quantify the most comprehensive panel of cranberry (poly)phenol metabolites. A double-blind, randomized placebo controlled 2-arm parallel study will be conducted in the Metabolic Research Unit (MRU, Department of Nutritional Sciences at KCL).
The study population will be final year BSc and MSc university students between 20-25 years old (n=60), who are generally healthy and not taking any medication. The study will be conducted during the period prior to their final exams (January until September). The intervention will be cranberry and placebo juice, consumed daily for 12 weeks, and will be provided free of cost by the Cranberry Institute. After a screening visit to evaluate inclusion and exclusion criteria, informed consent will be obtained, and subjects will be randomized to the treatments.
The study will consist in a total of 4 visits, one visit every 4 weeks over a total of 12 weeks intervention. Volunteers will consume a cranberry or a control drink every day for 12 weeks. The day before each visit (pre-visit), volunteers will self-collect a total of 6 saliva samples throughout the day to measure cortisol levels as a biomarker of stress. Mental health, cognitive function, diet and physical activity will also be assessed using self-reported questionnaires, an online cognitive battery test and an online 24 h dietary recall. In addition, on the day before visits 1 and 4 (baseline and 12 weeks), a stool sample will be self-collected to assess changes in gut microbiome diversity and composition. On the day of each visit, a spot urine sample will be self-collected after waking up and before breakfast. During each visit, volunteers will drop the self-collected samples, and will collect new kits for the next visit. Visits 1 and 4 will last approximately 20 min, while visits 2 and 3 will last approximately 5 minutes. In addition, during visits 1 and 4, blood samples will be taken to investigate changes in gut-brain axis and cranberry related metabolites. Blood samples will also be collected at baseline to assess general health status of participants (blood lipids, markers of liver and kidney function, urea, uric acid, creatinine, and glucose).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Cranberry flavored drink, once daily, in a 8fl oz bottle. Identical in appearance and taste compared with the treatment. |
|
| Cranberry juice | Active Comparator | 100% cranberry juice, once daily, in a 8fl oz bottle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cranberry juice | Dietary Supplement | composition: Water, cranberry juice concentrate |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in mood | Mood measured as the Total Mood Disturbance (TMD), using the Profile of Mood States (POMS) questionnaire. The POMS assessment has six scales of measure: Anger-Hostility, Confusion-Bewilderment, Depression-Dejection, Fatigue-Inertia, Tension-Anxiety, and Vigor-Activity. Scores on these items are added together to determine a Total Mood Disturbance score. Additionally, there is a measure of Friendliness which is scored separately. The POMS2 is an adjective checklist with instructions to respond "How have you been feeling over the PAST WEEK, INCLUDING TODAY" on a 5- point Likert response scale ranging from 0 = Not at all to 4 = Extremely. If one changes the instructions to "how you feel RIGHT NOW" then the instrument measures emotional states. This it is adaptable to both state and trait forms of affect. Higher scores mean a worse outcome. | Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Mental Health outcomes: stress levels | Mental Health outcomes including changes in stress levels, measured as salivary and blood cortisol and the Perceived Stress Scale (PSS) questionnaire. The questions in the PSS ask about feelings and thoughts during the last month. In each case, respondents are asked how often they felt a certain way. It consists of 10 questions, takes 5-10 minutes to complete and is for individual or group administration. Higher scores indicate higher levels of perceived stress. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in plasma metabolome | Measured via untargeted metabolomics using liquid chromatography mass spectrometry | Baseline and 12 weeks |
| Changes in urinary metabolome | Measured via untargeted metabolomics using liquid chromatography mass spectrometry |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ana Rodriguez-Mateos, PhD | King's College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| King's College London | London | England | SE1 9NH | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42134099 | Derived | Kamarunzaman NNZ, Le Sayec M, Li Y, Cheok A, Wu H, Zhang Z, Xu Y, Mesnage R, Dalrymple K, Pariante CM, Borsini A, Vauzour D, Bajka B, Rodriguez-Mateos A. Effects of (poly)phenol-rich cranberry on mental health in university students: The CRANMOOD randomised controlled trial. Clin Nutr. 2026 Jul;62:106677. doi: 10.1016/j.clnu.2026.106677. Epub 2026 Apr 28. |
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Parallel assignment
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Double (Participant, Investigator)
| Placebo |
| Dietary Supplement |
composition: Water, dextrose, citric acid, malic acid, fumaric acid, colorants, xanthan gum, natural flavor, emulsion |
|
| Baseline and 12 weeks |
| Mental Health outcomes: anxiety | Mental Health outcomes including changes in anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS) questionnaire. The questionnaire comprises seven questions for anxiety and seven questions for depression, and takes 2-5min to complete. For both scales (anxiety and depression), higher scores mean a worse outcome. | Baseline and 12 weeks |
| Changes in cognitive function and performance | Measured using the Online General Cognitive Assessment Battery (CogniFit) using established procedures. The cognitive score is an aggregate measure of the current cognitive strength of different cognitive skills. The minimum cognitive score is 0 and the maximum is 800. A higher score means higher cognitive abilities. | Baseline and 12 weeks |
| Changes in plasma gut-brain-axis metabolites | Serotonin and kynurenine pathway will be measured using targeted metabolomics | Baseline and 12 weeks |
| Changes in brain-derived neurotrophic factor | Brain-derived neurotrophic factor (BDNF) will be measured using established procedures | Baseline and 12 weeks |
| Changes in inflammatory markers | Inflammatory markers, including blood cytokines (IL1β, IL2, IL4, IL6, IL8, IL10, IL12, IL13, MIF, IFN-γ, and TNF-α), will be measured using established procedures | Baseline and 12 weeks |
| Changes in plasma and faecal short chain fatty acids | Measured using gas chromatography according to established procedures | Baseline and 12 weeks |
| Changes in plasma and urinary cranberry polyphenol metabolites | Measured using a validated targeted metabolomics method | Baseline and 12 weeks |
| Assessment of habitual diet | Diet will be assessed using 7-day food diaries (from the European Prospective Investigation into Cancer and Nutrition) at baseline and after 12 weeks. | Baseline and 12 weeks |
| Assessment of physical activity | The international physical activity questionnaire (IPAQ) will also be used to assess physical activity. IPAQ assesses physical activity undertaken across a comprehensive set of domains including leisure time, domestic and gardening (yard) activities, work-related and transport-related activity. The higher the score, the higher the physical activity level. | Baseline and 12 weeks |
| Changes in gut microbiome diversity and composition. | Faecal samples will be collected at baseline and 12 weeks after consumption of cranberry or placebo drinks. Gut microbiome diversity and composition will be analysed using 16s mRNA sequencing at the Genome Centre of Queen Mary University (London, UK). | Baseline and 12 weeks |
| Baseline and 12 weeks |
| Changes in gene expression | Measured using microarray hybridization and data analyses on Affymetrix CEL files using GeneSpring GX software | Baseline and 12 weeks |
| Changes in DNA methylation | Measured using the Illumina Infinium HD Methylation Assay | Baseline and 12 weeks |
| Changes in blood pressure | Blood pressure measured as systolic and diastolic blood pressure after 12-week daily consumption of cranberry | Baseline and 12 weeks |
| Changes in sleep patterns | Measured as bedtime and sleep duration. | Baseline and 12 weeks |