Metabolic Dysfunction-Associated Steatotic Liver DiseasePhotoGrapeNCT07886788
Study of Grape Consumption in Adaptation to Seasonal Photoperiod
A study testing Freeze-Dried Grape Powder, Plain Low-Fat Yogurt and Mediterranean-Style Dietary Guidance in people with Metabolic Dysfunction-Associated Steatotic Liver Disease and Overweight, run by University Rovira i Virgili at 1 site in Spain.
Trial summary
The goal of this randomized clinical trial is to learn whether consuming grapes during their natural season can help the body adapt to the shorter daylight hours of winter. The study includes men and women aged 30-70 years with either normal weight or overweight or obesity and metabolic dysfunction-associated… Read more about this study
- Who is it for?
- Ages 30 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Overweight, Obesity & Overweight
- What is being tested?
- Freeze-Dried Grape Powder, Plain Low-Fat Yogurt and Mediterranean-Style Dietary Guidance
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteSpain
- Study dates
- 28 Sep 2026to 6 Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women aged 30-70 years.
- Body mass index (BMI) between 18.5 and 39.9 kg/m².
- Written informed consent.
- Membership in one of the following population groups:
- Normal-weight group: BMI between 18.5 and 24.9 kg/m².
- Overweight or obesity group: BMI between 25.0 and 39.9 kg/m² and a diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD).
Who cannot join
- Alcohol consumption exceeding 10 g/day or use of other toxic substances.
- Acute or chronic liver disease of an etiology other than MASLD.
- Active inflammatory, infectious, or neoplastic disease.
- Pregnancy.
- Women receiving hormonal contraceptive treatment.
- Antibiotic treatment within the 4 weeks before enrollment.
Show all 9Show fewer
- Chronic treatment with corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs).
- Milk protein allergy.
- Grape-related food intolerances.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitari Joan XXIII - Unitat d'Investigació Clínica, IRB CatSud
Tarragona, Tarragona, 43005
About this study
The goal of this randomized clinical trial is to learn whether consuming grapes during their natural season can help the body adapt to the shorter daylight hours of winter. The study includes men and women aged 30-70 years with either normal weight or overweight or obesity and metabolic dysfunction-associated steatotic liver disease (MASLD).
The main questions it aims to answer are:
Read more
- Does seasonal grape consumption change circulating microRNAs, small molecules involved in regulating gene activity?
- Does grape consumption influence sleep, physical activity, metabolic markers, body composition, muscle function, and gut bacteria during the transition to winter?
Within each population group, researchers will compare participants consuming yogurt with freeze-dried grape powder with participants consuming the same yogurt without grape powder. Both groups will receive the same Mediterranean-style dietary guidance.
Participants will:
- Consume two yogurts daily for 3 weeks, either with or without a total daily dose of 16 grams of freeze-dried grape powder, equivalent to approximately 80 grams of fresh grapes.
- Complete a further 2 weeks of follow-up without the grape intervention.
- Attend an initial information visit and three assessment visits for blood sampling, stool sample collection, and measurements of body composition and muscle function.
- Wear a wrist device to monitor sleep and physical activity.
- Complete questionnaires, dietary records, and a sleep diary.
Read the detailed description
This study investigates the role of seasonal fruit consumption in human adaptation to changes in day length. Seasonal variations in daylight influence biological rhythms and metabolic regulation. Dietary signals may also contribute to this adaptation, although evidence from human intervention studies remains limited.
The scientific rationale is based on the xenohormesis hypothesis, which proposes that plant-derived compounds can convey information about the environmental conditions in which plants grow. Grape polyphenols may therefore act as seasonal signals that influence physiological responses in the individuals consuming them. Previous preclinical research has shown that the biological effects of grape polyphenols can depend on photoperiod and may involve biological clocks, metabolic pathways, gut microbiota, and epigenetic regulation.
This study evaluates this hypothesis in humans during the transition to the winter photoperiod. The intervention is scheduled during the local grape harvest season, with its completion aligned with the autumn clock change. Follow-up after discontinuation of grape supplementation will allow researchers to explore whether any observed responses persist during the subsequent seasonal transition.
The study includes two population cohorts representing different metabolic contexts: individuals with normal weight and individuals with overweight or obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Randomization to grape supplementation or control is performed within each cohort. A common Mediterranean-style dietary framework is used in both intervention groups.
The research combines molecular profiling with physiological and behavioral assessments to explore potential links between dietary seasonal signals and adaptation to winter. Biological samples are collected at synchronized assessment periods, while wrist-worn devices provide longitudinal information on sleep and activity under everyday living conditions.
The study is not double-blind because the control product does not contain a specifically formulated placebo. Whenever feasible, biological sample processing and analysis will be performed with researchers masked to intervention allocation.
- Conditions
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Overweight, Obesity & Overweight
- Being tested
- Freeze-Dried Grape Powder, Plain Low-Fat Yogurt, Mediterranean-Style Dietary Guidance
- Keywords
- Seasonal grape consumption, Grape polyphenols, Chrononutrition, Seasonal photoperiod, Circadian rhythms, Metabolic adaptation, Circulating microRNAs, Epigenetics, Gut microbiota, Sleep-wake patterns
- Medical subject headings
- Overweight, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Freeze-Dried Grape PowderDietary supplement
Freeze-dried Cabernet Sauvignon grape powder administered orally at a total dose of 16 g/day, equivalent to approximately 80 g of fresh grapes. The daily dose is divided into two servings, mixed with plain, low-fat yogurt without added sugar and consumed in the morning and afternoon for 3 weeks during the local grape harvest season. This is followed by 2 weeks without grape supplementation.
Plain Low-Fat YogurtOther
Two daily servings of plain, low-fat yogurt without added sugar, consumed in the morning and afternoon for 3 weeks.
Mediterranean-Style Dietary GuidanceBehavioural
Both arms receive the same dietary guidance based on a Mediterranean dietary pattern.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Freeze-Dried Grape Powder with Yogurt | Experimental | Participants consume 16 g of freeze-dried grape powder daily, equivalent to approximately 80 g of fresh grapes, divided between two servings of plain, low-fat yogurt without added sugar, taken in the morning and afternoon for 3 weeks. Participants also receive Mediterranean-style dietary guidance. The intervention is followed by 2 weeks without grape supplementation. Receives: Dietary Supplement: Freeze-Dried Grape Powder; Other: Plain Low-Fat Yogurt; Behavioral: Mediterranean-Style Dietary Guidance |
| Control: Yogurt Alone | Active comparator | Participants consume two servings of plain, low-fat yogurt without added sugar daily, taken in the morning and afternoon for 3 weeks, without freeze-dried grape powder. Participants receive the same Mediterranean-style dietary guidance as the experimental arm. The intervention is followed by a 2-week follow-up period. Receives: Other: Plain Low-Fat Yogurt; Behavioral: Mediterranean-Style Dietary Guidance |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in circulating plasma microRNA expression
Differential expression of circulating microRNAs in plasma, comparing changes from baseline between the grape supplementation and control arms at the end of the intervention and after follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Secondary outcomes (37)
Change in DNA methylation in promoter regions of selected genes
Changes in DNA methylation in the promoter regions of selected genes, measured by pyrosequencing after bisulfite treatment of DNA isolated from peripheral blood mononuclear cells (PBMCs). Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and after follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in serum metabolomic profile
Changes in the serum metabolomic profile assessed by proton nuclear magnetic resonance (1H-NMR). Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and after follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in gut microbiota diversity and composition
Changes in bacterial diversity and composition assessed by 16S ribosomal RNA gene sequencing of stool samples. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and after follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in body weight
Change in body weight, measured in kilograms, from baseline to the end of the intervention and follow-up, comparing the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in body mass index
Change in body mass index (BMI), calculated as body weight in kilograms divided by height in meters squared (kg/m²), from baseline to the end of the intervention and follow-up, comparing the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in waist circumference
Change in waist circumference, measured in centimeters, from baseline to the end of the intervention and follow-up, comparing the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in body composition assessed by bioelectrical impedance
Changes in body composition assessed using a TANITA bioelectrical impedance device, comparing changes from baseline between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in systolic and diastolic blood pressure
Changes in resting systolic and diastolic blood pressure, measured in mmHg using two readings taken one minute apart. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in resting heart rate
Change in resting heart rate, measured in beats per minute, from baseline to the end of the intervention and follow-up, comparing the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in handgrip strength
Change in handgrip strength assessed by handgrip dynamometry, comparing changes from baseline between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in gait speed over a 4-meter distance
Change in gait speed, measured in meters per second using a 4-meter walk test to assess functional performance. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in fasting blood glucose
Change in fasting blood glucose measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in fasting insulin
Change in fasting insulin measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in glycated hemoglobin (HbA1c)
Change in glycated hemoglobin (HbA1c) measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood creatinine
Change in blood creatinine measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in liver enzyme levels
Changes in blood liver enzyme levels measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood lipid profile
Changes in the blood lipid profile measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in prothrombin measurements
Changes in prothrombin measurements assessed using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood ferritin
Change in blood ferritin measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in blood albumin
Change in blood albumin measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in platelet count
Change in blood platelet count measured using standardized clinical laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood melatonin levels
Change in blood melatonin levels measured using standardized laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood cortisol levels
Change in blood cortisol levels measured using standardized laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in blood testosterone levels
Change in blood testosterone levels measured using standardized laboratory methods. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in blood triiodothyronine (T3) levels
Change in blood triiodothyronine (T3) levels from baseline to the end of the intervention and follow-up, comparing the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in blood thyroxine (T4) levels
Change in blood thyroxine (T4) levels from baseline to the end of the intervention and follow-up, comparing the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in complete blood count parameters
Changes in complete blood count parameters from baseline to the end of the intervention and follow-up, comparing the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Liver stiffness assessed by shear-wave elastography
Liver stiffness assessed by quantitative shear-wave ultrasound elastography in participants with overweight or obesity and MASLD.
Measured: Baseline (week 0).
Change in Fibrosis-4 (FIB-4) index
Changes in the Fibrosis-4 (FIB-4) index, a non-invasive liver fibrosis score calculated from age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count, in participants with overweight or obesity and MASLD. Changes from baseline will be compared between the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in AST-to-platelet ratio index (APRI)
Changes in the AST-to-platelet ratio index (APRI), a non-invasive liver fibrosis score derived from blood AST levels and platelet count, in participants with overweight or obesity and MASLD. Changes from baseline will be compared between the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Sleep-wake patterns assessed by a wrist-worn device
Sleep-wake patterns recorded longitudinally using a wrist-worn device during the intervention and follow-up periods, comparing the grape supplementation and control arms.
Measured: Throughout the 3-week intervention and the subsequent 2-week follow-up (weeks 0-5).
Sleep patterns assessed by a sleep diary
Self-reported sleep patterns recorded using the American Academy of Sleep Medicine (AASM) sleep diary during the first week of intervention and the final week of follow-up, comparing the grape supplementation and control arms.
Measured: First week of intervention (week 1) and final week of follow-up (week 5).
Sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI)
Self-reported sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI).
Measured: Baseline (week 0).
Physical activity assessed by the International Physical Activity Questionnaire-Short Form
Self-reported physical activity assessed using the short form of the International Physical Activity Questionnaire (IPAQ-short).
Measured: Baseline (week 0).
Change in Mediterranean diet adherence
Changes in adherence to the Mediterranean dietary pattern assessed using the Mediterranean diet adherence questionnaire specified in the protocol. Changes from baseline will be compared between the grape supplementation and control arms at the end of the intervention and follow-up.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Dietary intake assessed by a 48-hour dietary record
Dietary intake assessed using participant-completed 48-hour dietary records at baseline, the end of the intervention, and follow-up, comparing the grape supplementation and control arms.
Measured: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Occurrence of adverse events
Occurrence of adverse events recorded during the grape supplementation or control intervention and the subsequent follow-up period.
Measured: Throughout the 3-week intervention and the subsequent 2-week follow-up (weeks 0-5).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2026
- Study start28 Sep 2026
- Primary completion6 Nov 2026 (estimated)
- Study completion6 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Metabolic Dysfunction-Associated Steatotic Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, parallel-group nutritional intervention study with two population cohorts: adults with normal weight and adults with overweight or obesity and MASLD.
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Rovira i Virgili
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paula Martínez, University Rovira i Virgili
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07886788
- Sponsor's protocol ID
- 1472026
- Other IDs
- PID2023-150028OB-I00
- Acronym
- PhotoGrape
- Status last verified
- Sep 2026
- First submitted
- 14 Oct 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Escobar-Martinez I, Arreaza-Gil V, Arola-Arnal A, Muguerza B, Mulero M, Suarez M, Torres-Fuentes C. Circannual Rhythms Affect the Bioavailability of Phenolic Compounds from Grape Seed Proanthocyanidins Extract Differently in Healthy and Obese Fischer 344 Rats. J Agric Food Chem. 2025 Oct 8;73(40):25329-25339. doi: 10.1021/acs.jafc.5c03952. Epub 2025 Sep 26.
PubMed 41002217Ribas-Latre A, Baselga-Escudero L, Casanova E, Arola-Arnal A, Salvado MJ, Blade C, Arola L. Dietary proanthocyanidins modulate BMAL1 acetylation, Nampt expression and NAD levels in rat liver. Sci Rep. 2015 Jun 8;5:10954. doi: 10.1038/srep10954.
PubMed 26051626Soliz-Rueda JR, Lopez-Fernandez-Sobrino R, Torres-Fuentes C, Bravo FI, Suarez M, Mulero M, Muguerza B. Metabolism disturbance by light/dark cycle switching depends on the rat health status: the role of grape seed flavanols. Food Funct. 2023 Jul 17;14(14):6443-6454. doi: 10.1039/d3fo00260h.
PubMed 37377055Arreaza-Gil V, Palacios-Jordan H, Romero MDM, Torres-Fuentes C, Rodriguez MA, Remesar X, Fernandez-Lopez JA, Arola-Arnal A. Administration time effect of dietary proanthocyanidins on the metabolome of Fischer 344 rats is sex- and diet-dependent. Food Funct. 2023 Jul 31;14(15):6941-6956. doi: 10.1039/d3fo01551c.
PubMed 37432474Ribas-Latre A, Baselga-Escudero L, Casanova E, Arola-Arnal A, Salvado MJ, Arola L, Blade C. Chronic consumption of dietary proanthocyanidins modulates peripheral clocks in healthy and obese rats. J Nutr Biochem. 2015 Feb;26(2):112-9. doi: 10.1016/j.jnutbio.2014.09.006. Epub 2014 Oct 13.
PubMed 25459887Ribas-Latre A, Del Bas JM, Baselga-Escudero L, Casanova E, Arola-Arnal A, Salvado MJ, Arola L, Blade C. Dietary proanthocyanidins modulate melatonin levels in plasma and the expression pattern of clock genes in the hypothalamus of rats. Mol Nutr Food Res. 2015 May;59(5):865-78. doi: 10.1002/mnfr.201400571. Epub 2015 Mar 23.
PubMed 25677201Rodriguez RM, Colom-Pellicer M, Hernandez-Baixauli J, Calvo E, Suarez M, Arola-Arnal A, Torres-Fuentes C, Aragones G, Mulero M. Grape Seed Proanthocyanidin Extract Attenuates Cafeteria-Diet-Induced Liver Metabolic Disturbances in Rats: Influence of Photoperiod. Int J Mol Sci. 2024 Jul 14;25(14):7713. doi: 10.3390/ijms25147713.
PubMed 39062955Arreaza-Gil V, Escobar-Martinez I, Suarez M, Bravo FI, Muguerza B, Arola-Arnal A, Torres-Fuentes C. Gut Seasons: Photoperiod Effects on Fecal Microbiota in Healthy and Cafeteria-Induced Obese Fisher 344 Rats. Nutrients. 2022 Feb 8;14(3):722. doi: 10.3390/nu14030722.
PubMed 35277081Arola-Arnal A, Cruz-Carrion A, Torres-Fuentes C, Avila-Roman J, Aragones G, Mulero M, Bravo FI, Muguerza B, Arola L, Suarez M. Chrononutrition and Polyphenols: Roles and Diseases. Nutrients. 2019 Oct 30;11(11):2602. doi: 10.3390/nu11112602.
PubMed 31671606Ibars M, Aragones G, Ardid-Ruiz A, Gibert-Ramos A, Arola-Arnal A, Suarez M, Blade C. Seasonal consumption of polyphenol-rich fruits affects the hypothalamic leptin signaling system in a photoperiod-dependent mode. Sci Rep. 2018 Sep 11;8(1):13572. doi: 10.1038/s41598-018-31855-y.
PubMed 30206280Iglesias-Carres L, Mas-Capdevila A, Bravo FI, Arola L, Muguerza B, Arola-Arnal A. Exposure of Fischer 344 rats to distinct photoperiods influences the bioavailability of red grape polyphenols. J Photochem Photobiol B. 2019 Oct;199:111623. doi: 10.1016/j.jphotobiol.2019.111623. Epub 2019 Sep 10.
PubMed 31525717Manocchio F, Soliz-Rueda JR, Ribas-Latre A, Bravo FI, Arola-Arnal A, Suarez M, Muguerza B. Grape Seed Proanthocyanidins Modulate the Hepatic Molecular Clock via MicroRNAs. Mol Nutr Food Res. 2022 Dec;66(23):e2200443. doi: 10.1002/mnfr.202200443. Epub 2022 Oct 26.
PubMed 36189890Soliz-Rueda JR, Lopez-Fernandez-Sobrino R, Bravo FI, Aragones G, Suarez M, Muguerza B. Grape Seed Proanthocyanidins Mitigate the Disturbances Caused by an Abrupt Photoperiod Change in Healthy and Obese Rats. Nutrients. 2022 Apr 27;14(9):1834. doi: 10.3390/nu14091834.
PubMed 35565801
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Grape Consumption in Adaptation to Seasonal Photoperiod
- ClinicalTrials.gov ID
- NCT07886788
- Acronym / sponsor ID
- PhotoGrape / 1472026
- Conditions
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Overweight, Obesity & Overweight
- Keywords
- Seasonal grape consumption, Grape polyphenols, Chrononutrition, Seasonal photoperiod, Circadian rhythms, Metabolic adaptation, Circulating microRNAs, Epigenetics
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University Rovira i VirgiliUniversity, hospital or other
- Study start
- 28 Sep 2026 (actual)
- Primary completion
- 6 Nov 2026 (estimated)
- Study completion
- 6 Nov 2026 (estimated)
- First posted
- 21 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this randomized clinical trial is to learn whether consuming grapes during their natural season can help the body adapt to the shorter daylight hours of winter. The study includes men and women aged 30-70 years with either normal weight or overweight or obesity and metabolic dysfunction-associated steatotic liver disease (MASLD).
The main questions it aims to answer are:
- Does seasonal grape consumption change circulating microRNAs, small molecules involved in regulating gene activity?
- Does grape consumption influence sleep, physical activity, metabolic markers, body composition, muscle function, and gut bacteria during the transition to winter?
Within each population group, researchers will compare participants consuming yogurt with freeze-dried grape powder with participants consuming the same yogurt without grape powder. Both groups will receive the same Mediterranean-style dietary guidance.
Participants will:
- Consume two yogurts daily for 3 weeks, either with or without a total daily dose of 16 grams of freeze-dried grape powder, equivalent to approximately 80 grams of fresh grapes.
- Complete a further 2 weeks of follow-up without the grape intervention.
- Attend an initial information visit and three assessment visits for blood sampling, stool sample collection, and measurements of body composition and muscle function.
- Wear a wrist device to monitor sleep and physical activity.
- Complete questionnaires, dietary records, and a sleep diary.
Detailed description
This study investigates the role of seasonal fruit consumption in human adaptation to changes in day length. Seasonal variations in daylight influence biological rhythms and metabolic regulation. Dietary signals may also contribute to this adaptation, although evidence from human intervention studies remains limited.
The scientific rationale is based on the xenohormesis hypothesis, which proposes that plant-derived compounds can convey information about the environmental conditions in which plants grow. Grape polyphenols may therefore act as seasonal signals that influence physiological responses in the individuals consuming them. Previous preclinical research has shown that the biological effects of grape polyphenols can depend on photoperiod and may involve biological clocks, metabolic pathways, gut microbiota, and epigenetic regulation.
This study evaluates this hypothesis in humans during the transition to the winter photoperiod. The intervention is scheduled during the local grape harvest season, with its completion aligned with the autumn clock change. Follow-up after discontinuation of grape supplementation will allow researchers to explore whether any observed responses persist during the subsequent seasonal transition.
The study includes two population cohorts representing different metabolic contexts: individuals with normal weight and individuals with overweight or obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Randomization to grape supplementation or control is performed within each cohort. A common Mediterranean-style dietary framework is used in both intervention groups.
The research combines molecular profiling with physiological and behavioral assessments to explore potential links between dietary seasonal signals and adaptation to winter. Biological samples are collected at synchronized assessment periods, while wrist-worn devices provide longitudinal information on sleep and activity under everyday living conditions.
The study is not double-blind because the control product does not contain a specifically formulated placebo. Whenever feasible, biological sample processing and analysis will be performed with researchers masked to intervention allocation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, parallel-group nutritional intervention study with two population cohorts: adults with normal weight and adults with overweight or obesity and MASLD.
| Arm | Type | Receives |
|---|---|---|
| Experimental: Freeze-Dried Grape Powder with Yogurt | Experimental | Dietary Supplement: Freeze-Dried Grape Powder, Other: Plain Low-Fat Yogurt, Behavioral: Mediterranean-Style Dietary GuidanceParticipants consume 16 g of freeze-dried grape powder daily, equivalent to approximately 80 g of fresh grapes, divided between two servings of plain, low-fat yogurt without added sugar, taken in the morning and afternoon for 3 weeks. Participants also receive Mediterranean-style dietary guidance. The intervention is followed by 2 weeks without grape supplementation. |
| Control: Yogurt Alone | Active comparator | Other: Plain Low-Fat Yogurt, Behavioral: Mediterranean-Style Dietary GuidanceParticipants consume two servings of plain, low-fat yogurt without added sugar daily, taken in the morning and afternoon for 3 weeks, without freeze-dried grape powder. Participants receive the same Mediterranean-style dietary guidance as the experimental arm. The intervention is followed by a 2-week follow-up period. |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women aged 30-70 years.
- Body mass index (BMI) between 18.5 and 39.9 kg/m².
- Written informed consent.
- Membership in one of the following population groups:
- Normal-weight group: BMI between 18.5 and 24.9 kg/m².
Key exclusion criteria (9 listed)
- Alcohol consumption exceeding 10 g/day or use of other toxic substances.
- Acute or chronic liver disease of an etiology other than MASLD.
- Active inflammatory, infectious, or neoplastic disease.
- Pregnancy.
- Women receiving hormonal contraceptive treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Freeze-Dried Grape PowderFreeze-dried Cabernet Sauvignon grape powder administered orally at a total dose of 16 g/day, equivalent to approximately 80 g of fresh grapes. The daily dose is divided into two servings, mixed with plain, low-fat yogurt without added sugar and consumed in the morning and afternoon for 3 weeks during the local grape harvest season. This is followed by 2 weeks without grape supplementation. | Dietary supplement | Experimental: Freeze-Dried Grape Powder with Yogurt |
| Plain Low-Fat YogurtTwo daily servings of plain, low-fat yogurt without added sugar, consumed in the morning and afternoon for 3 weeks. | Other | Control: Yogurt Alone, Experimental: Freeze-Dried Grape Powder with Yogurt |
| Mediterranean-Style Dietary GuidanceBoth arms receive the same dietary guidance based on a Mediterranean dietary pattern. | Behavioural | Control: Yogurt Alone, Experimental: Freeze-Dried Grape Powder with Yogurt |
Primary outcome
Change in circulating plasma microRNA expression
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Differential expression of circulating microRNAs in plasma, comparing changes from baseline between the grape supplementation and control arms at the end of the intervention and after follow-up.
37 secondary outcomes
Change in DNA methylation in promoter regions of selected genes
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in serum metabolomic profile
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in gut microbiota diversity and composition
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in body weight
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in body mass index
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in waist circumference
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in body composition assessed by bioelectrical impedance
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in systolic and diastolic blood pressure
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in resting heart rate
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in handgrip strength
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in gait speed over a 4-meter distance
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in fasting blood glucose
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in fasting insulin
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in glycated hemoglobin (HbA1c)
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood creatinine
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in liver enzyme levels
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood lipid profile
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in prothrombin measurements
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood ferritin
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in blood albumin
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in platelet count
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood melatonin levels
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5)
Change in blood cortisol levels
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in blood testosterone levels
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in blood triiodothyronine (T3) levels
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in blood thyroxine (T4) levels
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in complete blood count parameters
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Liver stiffness assessed by shear-wave elastography
Time frame: Baseline (week 0).
Change in Fibrosis-4 (FIB-4) index
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Change in AST-to-platelet ratio index (APRI)
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Sleep-wake patterns assessed by a wrist-worn device
Time frame: Throughout the 3-week intervention and the subsequent 2-week follow-up (weeks 0-5).
Sleep patterns assessed by a sleep diary
Time frame: First week of intervention (week 1) and final week of follow-up (week 5).
Sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI)
Time frame: Baseline (week 0).
Physical activity assessed by the International Physical Activity Questionnaire-Short Form
Time frame: Baseline (week 0).
Change in Mediterranean diet adherence
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Dietary intake assessed by a 48-hour dietary record
Time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).
Occurrence of adverse events
Time frame: Throughout the 3-week intervention and the subsequent 2-week follow-up (weeks 0-5).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Background: PubMed 41002217Escobar-Martinez I, Arreaza-Gil V, Arola-Arnal A, Muguerza B, Mulero M, Suarez M, Torres-Fuentes C. Circannual Rhythms Affect the Bioavailability of Phenolic Compounds from Grape Seed Proanthocyanidins Extract Differently in Healthy and Obese Fischer 344 Rats. J Agric Food Chem. 2025 Oct 8;73(40):25329-25339. doi: 10.1021/acs.jafc.5c03952. Epub 2025 Sep 26.
- Background: PubMed 26051626Ribas-Latre A, Baselga-Escudero L, Casanova E, Arola-Arnal A, Salvado MJ, Blade C, Arola L. Dietary proanthocyanidins modulate BMAL1 acetylation, Nampt expression and NAD levels in rat liver. Sci Rep. 2015 Jun 8;5:10954. doi: 10.1038/srep10954.
- Background: PubMed 37377055Soliz-Rueda JR, Lopez-Fernandez-Sobrino R, Torres-Fuentes C, Bravo FI, Suarez M, Mulero M, Muguerza B. Metabolism disturbance by light/dark cycle switching depends on the rat health status: the role of grape seed flavanols. Food Funct. 2023 Jul 17;14(14):6443-6454. doi: 10.1039/d3fo00260h.
- Background: PubMed 37432474Arreaza-Gil V, Palacios-Jordan H, Romero MDM, Torres-Fuentes C, Rodriguez MA, Remesar X, Fernandez-Lopez JA, Arola-Arnal A. Administration time effect of dietary proanthocyanidins on the metabolome of Fischer 344 rats is sex- and diet-dependent. Food Funct. 2023 Jul 31;14(15):6941-6956. doi: 10.1039/d3fo01551c.
- Background: PubMed 25459887Ribas-Latre A, Baselga-Escudero L, Casanova E, Arola-Arnal A, Salvado MJ, Arola L, Blade C. Chronic consumption of dietary proanthocyanidins modulates peripheral clocks in healthy and obese rats. J Nutr Biochem. 2015 Feb;26(2):112-9. doi: 10.1016/j.jnutbio.2014.09.006. Epub 2014 Oct 13.
- Background: PubMed 25677201Ribas-Latre A, Del Bas JM, Baselga-Escudero L, Casanova E, Arola-Arnal A, Salvado MJ, Arola L, Blade C. Dietary proanthocyanidins modulate melatonin levels in plasma and the expression pattern of clock genes in the hypothalamus of rats. Mol Nutr Food Res. 2015 May;59(5):865-78. doi: 10.1002/mnfr.201400571. Epub 2015 Mar 23.
- Background: PubMed 39062955Rodriguez RM, Colom-Pellicer M, Hernandez-Baixauli J, Calvo E, Suarez M, Arola-Arnal A, Torres-Fuentes C, Aragones G, Mulero M. Grape Seed Proanthocyanidin Extract Attenuates Cafeteria-Diet-Induced Liver Metabolic Disturbances in Rats: Influence of Photoperiod. Int J Mol Sci. 2024 Jul 14;25(14):7713. doi: 10.3390/ijms25147713.
- Background: PubMed 35277081Arreaza-Gil V, Escobar-Martinez I, Suarez M, Bravo FI, Muguerza B, Arola-Arnal A, Torres-Fuentes C. Gut Seasons: Photoperiod Effects on Fecal Microbiota in Healthy and Cafeteria-Induced Obese Fisher 344 Rats. Nutrients. 2022 Feb 8;14(3):722. doi: 10.3390/nu14030722.
- Background: PubMed 31671606Arola-Arnal A, Cruz-Carrion A, Torres-Fuentes C, Avila-Roman J, Aragones G, Mulero M, Bravo FI, Muguerza B, Arola L, Suarez M. Chrononutrition and Polyphenols: Roles and Diseases. Nutrients. 2019 Oct 30;11(11):2602. doi: 10.3390/nu11112602.
- Background: PubMed 30206280Ibars M, Aragones G, Ardid-Ruiz A, Gibert-Ramos A, Arola-Arnal A, Suarez M, Blade C. Seasonal consumption of polyphenol-rich fruits affects the hypothalamic leptin signaling system in a photoperiod-dependent mode. Sci Rep. 2018 Sep 11;8(1):13572. doi: 10.1038/s41598-018-31855-y.
- Background: PubMed 31525717Iglesias-Carres L, Mas-Capdevila A, Bravo FI, Arola L, Muguerza B, Arola-Arnal A. Exposure of Fischer 344 rats to distinct photoperiods influences the bioavailability of red grape polyphenols. J Photochem Photobiol B. 2019 Oct;199:111623. doi: 10.1016/j.jphotobiol.2019.111623. Epub 2019 Sep 10.
- Background: PubMed 36189890Manocchio F, Soliz-Rueda JR, Ribas-Latre A, Bravo FI, Arola-Arnal A, Suarez M, Muguerza B. Grape Seed Proanthocyanidins Modulate the Hepatic Molecular Clock via MicroRNAs. Mol Nutr Food Res. 2022 Dec;66(23):e2200443. doi: 10.1002/mnfr.202200443. Epub 2022 Oct 26.
- Publications from the Nutrigenomics Research Group at Universitat Rovira i Virgili.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Freeze-Dried Grape Powder, Plain Low-Fat Yogurt and Mediterranean-Style Dietary Guidance in people with Metabolic Dysfunction-Associated Steatotic Liver Disease and Overweight, run by University Rovira i Virgili at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in circulating plasma microRNA expression (time frame: Baseline (week 0), end of intervention (week 3), and end of follow-up (week 5).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07886788, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.