Blackcurrants Modify Gut Microbiota and Reduce Osteoporosis Risk in Postmenopausal Females

Blackcurrants Mitigate Postmenopausal Bone Loss Through Gut Microbiota-Bone Axis: A Randomized Clinical Trial Coupled With a Multi-Omics Approach to Inform Precision Nutrition

The goal of this clinical trial is to evaluate the effects of blackcurrant (BC) supplementation on changes in bone density and gut microbiome composition in postmenopausal females.

Study Overview

• Status: Not yet recruiting
• Conditions: Menopause; Postmenopausal Osteoporosis; Gut Microbiome
• Intervention / Treatment: Drug: Blackcurrant (BC) extract; Drug: Blackcurrant (BC) extract; Drug: Placebo

Detailed Description

Postmenopausal osteoporosis (PMO) is a debilitating and progressive metabolic bone disorder caused by estrogen deficiency after menopause, leading to an imbalance in bone remodeling. Owing to its high morbidity and serious complications, substantial efforts have been devoted to its prevention and treatment. Emerging evidence indicates that the gut microbiome plays a pivotal role in bone health through immune and endocrine pathways, influencing bone turnover via cytokine signaling, metabolite production, and calcium balance.

Our previous 6-month trial suggested that blackcurrant (BC) may exert bone-protective effects through integrated effects on bone remodeling, gut microbiota, and metabolite signaling. Therefore, the overall goal of this study is to investigate the effects of BC supplementation on changes in gut microbiota and bone density in postmenopausal females and to elucidate the interrelationship of BC and gut microbiota with regard to bone loss mitigation. This will be accomplished using a multidisciplinary, comprehensive multi-omics approach to examine interactions among BC, gut microbiota, bacterial metabolites, and the immune and endocrine systems in relation to bone metabolism.

Investigators will conduct a randomized, placebo-controlled trial of BC supplementation for 12 months in postmenopausal females aged 45-70 years. The primary endpoint will be changes in whole-body, lumbar spine, total hip, and femoral neck bone mineral density. The secondary endpoint will be changes in biomarkers of bone remodeling. To further delineate underlying mechanisms, changes in the community structure of the gut microbiome, inflammatory-immune markers, and endocrine markers will be assessed. Additional analyses will include proteomics to identify protein biomarkers, metabolomics to identify key metabolites associated with BC supplementation and bone-related outcomes, and genotyping to evaluate genetic polymorphisms in bone-related genes.

The specific objectives of this study are to investigate the effects of BC extract on: 1) bone density and bone remodeling biomarkers; and 2) changes in gut microbiota abundance and composition, inflammatory-immune and endocrine biomarkers, protein biomarkers (proteomics), key metabolites (metabolomics), and their relationships with changes in bone density, including evaluation of genetic polymorphisms in bone-related genes (genomics).

This study will provide further insight into whether and how BC consumption may reduce the risk of postmenopausal bone and will improve understanding of the role of the gut microbiome in postmenopausal bone loss. Findings may provide novel insight into how anthocyanin-rich berries reduce PMO risk via the gut-bone axis and may support the development of future dietary recommendations and strategies for adult females approaching or experiencing menopause.

• Study Type: Interventional
• Enrollment (Estimated): 159
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ock Chun, PhD; Phone Number: 860-486-6275; Email: ock.chun@uconn.edu
• Study Contact Backup: Name: Briana Nosal, MS; Phone Number: 860-878-0679; Email: briana.nosal@uconn.edu

Study Locations

• United States
  • Connecticut
    • Storrs, Connecticut, United States, 06269
      • University of Connecticut, Department of Nutritional Sciences
      • Contact: Ock Chun, PhD; Phone Number: 860-486-6275; Email: ock.chun@uconn.edu
      • Contact: Briana Nosal, MS; Phone Number: 860-878-0679; Email: briana.nosal@uconn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• postmenopausal (defined as no more than 10 years since final menstrual cycle) females aged 45-70 years
• not on hormone replacement therapy for at least one year before initiation of the study
• maintaining normal exercise level (< 7 hours/week) and willing to avoid exercise for 24 hours prior to blood and stool sampling
• willing to ingest a dietary blackcurrant supplement or placebo (up to 1,176 mg/day, three 392mg capsules)
• willing to avoid other dietary supplements for the duration of the study
• willing to avoid intake of foods extremely rich in anthocyanins and fermented dairy products containing viable Bifidobacteria or Lactobacilli
• willing to have three blood draws, three stool collections, and three bone scans

Exclusion Criteria:

• history of cardiovascular disease, osteoporosis, metabolic bone disease, cancer, diabetes mellitus, arthritis, or other chronic inflammatory diseases
• current smokers
• taking prescription medications known to alter bone and calcium metabolism
• taking anabolic agents such as parathyroid hormone or growth hormone, or steroid within 3 months before the start of the study
• taking medications that alter bleeding (such as antiplatelets or anticoagulants) or those with a bleeding disorder
• alcohol consumption exceeding 2 drinks/day (approximately 14g of ethanol per drink) or a total of 12/week
• those with planned surgery during the study period or within 2 weeks of ending the intervention
• those with sensitivities or allergies to any of the ingredients for the placebo (rice powder)
• planning a procedure that includes iodine, barium or nuclear medicine isotopes within the study period
• UConn students and/or employees who any key personnel teach or who report to any key personnel
• study key personnel, partners of key personnel, or dependents/relatives of any key personnel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low-BC Group; Low-dose BC extract	Drug: Blackcurrant (BC) extract; Consume three capsules per day containing 784 mg of blackcurrant (BC) extract (261.33 mg BC and 130.67 mg placebo per capsule); Drug: Blackcurrant (BC) extract; Consume three capsules containing 1,176 mg BC of extract (392 mg BC per capsule)
Active Comparator: High-BC Group; High-dose BC extract	Drug: Blackcurrant (BC) extract; Consume three capsules per day containing 784 mg of blackcurrant (BC) extract (261.33 mg BC and 130.67 mg placebo per capsule); Drug: Blackcurrant (BC) extract; Consume three capsules containing 1,176 mg BC of extract (392 mg BC per capsule)
Placebo Comparator: Control Group; Placebo (no BC extract)	Drug: Placebo; Consume three placebo capsules (392 mg placebo per capsule)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Mineral Density (BMD)	Changes from baseline in whole-body, lumbar spine, total hip and femoral neck BMD at months 6 and 12 measured via dual energy x-ray absorptiometry (DXA)	From baseline to months 6 and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum markers of bone remodeling	Changes in serum concentrations of bone remodeling markers including procollagen type I N-propeptide (P1NP), bone alkaline phosphatase (BALP), receptor activator of nuclear factor kappa-Β ligand (RANKL), and collagen Type I C-Telopeptide (CTX1)	From baseline to months 6 and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in community structure of gut microbiota	Changes in gut microbial composition will be assessed using alpha diversity (species richness and Shannon diversity) and beta diversity metrics, including Bray-Curtis dissimilarity (community abundance) and Jaccard distance (presence/absence). Taxonomic composition will be compared between groups by evaluating relative abundance at the genus and phylum levels.	from baseline to months 6 and 12
Omics outcomes	Metabolomics, proteomics, and genotyping will be performed to identify biomarkers associated with blackcurrant supplementation and bone-related outcomes.	from baseline to months 6 and 12
Plasma inflammatory-immune markers	Inflammatory biomarkers will be assessed in plasma, including IL-1beta and TNF-alpha. Additional immune response markers related to T helper cell subtypes (Th1, Th2, Th17) will be measured in plasma (e.g., interleukin (IL)-2, IL-4, IL-6, IL-10, TNF, IL-17A). CD4+ Th17 and regulatory T cell (Treg) responses will also be evaluated from peripheral blood mononuclear cells (PBMCs).	from baseline to months 6 and 12
Plasma endocrine markers	Changes in plasma concentrations of endocrine markers including insulin-like growth factor-1 (IGF-1) and cyclic glycine-proline (cGP)	from baseline to months 6 and 12

Collaborators and Investigators

• Sponsor: University of Connecticut
• Investigators: Principal Investigator: Ock Chun, PhD, University of Connecticut

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: January 16, 2026
• First Submitted That Met QC Criteria: January 16, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 25, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: menopause; osteoporosis; gut microbiome; females; blackcurrant; bone aging
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Nutritional and Metabolic Diseases; Osteoporosis; Osteoporosis, Postmenopausal
• Other Study ID Numbers: B2025-0380; 2025-67018-45103 (Other Grant/Funding Number: USDA NIFA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Once research proceedings and manuscripts are published, we will make our results available to both the community of scientists interested in postmenopausal osteoporosis and those studying the biology of inflammation-induced bone resorption and avoid unintentional duplication of research.
• IPD Sharing Time Frame: Unlimited time after papers are published.

IPD Sharing Access Criteria

Our plan for sharing of data generated by this project includes the following:

1. Presentations at national scientific meeting. From the project, it is expected that approximately two presentations at national meetings would be appropriate.
2. Publication in peer-reviewed journals. It is our explicit intention that the study findings and key data will be placed in a readily accessible public database. All efforts will be made to rapidly release data through publication of results as quickly as possible following our analysis of experiment data. Data used in publications will be released in a timely manner.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No