Blackcurrants Modify Gut Microbiota and Reduce Osteoporosis and CVD Risk

Blackcurrant Modifies Gut Microbiota and Reduces the Risk of Postmenopausal Osteoporosis and Cardiovascular Disease: A Pilot Randomized Clinical Trial

Aim to evaluate the effects of blackcurrant supplementation on changes in gut microbiome, bone mass, and CVD risk factors in adult women.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Gut Microbiota; Postmenopausal Osteoporosis
• Intervention / Treatment: Drug: blackcurrant (BC) extract

Detailed Description

Postmenopausal bone loss is a primary contributor to osteoporosis and osteoporotic fractures in adult women in menopause transition. By following women over this period, studies have documented distinct patterns of a decrease in estrogen, a natural antioxidant, simultaneously with adverse alterations in body fat distribution, lipids and lipoproteins, and measures of vascular health, which can increase a woman's risk of developing CVD. Overall goal of this project is to evaluate the effects of blackcurrant (BC) supplementation on changes in gut microbiome, bone mass, and CVD risk factors in adult women. For this purpose, the investigators will conduct a pilot randomized placebo-controlled clinical trial with BC supplementation for 6 months in peri- and early postmenopausal women aged 45-60 years.

The primary endpoint will be whole-body bone mineral density (BMD); secondary endpoints will be gut microbiota composition. To delineate the underlying mechanisms of the action, changes in biomarkers for bone metabolism, bone-related immune and endocrine systemic biomarkers, and CVD risk factors by BC supplementation will be measured in plasma and peripheral blood derived mononuclear cells.

The specific objectives of the study are to investigate the effects of BC extract on: 1) bone mass and bone remodeling markers; 2) changes in the gut microbiota abundance and composition, immune and endocrine biomarkers, and CVD risk factors and their relationships with changes in bone mass.

The proposed study will provide novel insight into whether and how BC consumption reduces the risk of postmenopausal bone loss and CVD in adult women and will improve understanding of the clinical roles of gut microbiome in postmenopausal bone loss. Findings from this study will help increase awareness of the bone and heart health promoting effect of BC and motivate increased production of BC and other berry products in response to the increasing consumer demand.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Storrs, Connecticut, United States, 06269
      • University of Connecticut Department of Nutritional Sciences and Kinesiology Human Performance Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• perimenopausal or early postmenopausal women aged 45-60 years old
• not on HRT for at least one year before the initiation of the study
• maintaining normal exercise level (<7 h/wk) and willing to avoid exercise 24-h prior to blood and stool sampling and 12-h prior to bone measurements
• willing to ingest a dietary BC supplement or placebo (up to 900 mg/day, two 450 mg capsules) as well as 400 mg calcium and 500 IU vitamin D daily
• 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 3 blood draws, 2 stool collections, and 2 bone scans
• willing to take urine pregnancy test if they are perimenopausal.

Exclusion Criteria:

• those with metabolic bone disease, renal disease, cancer, cardiovascular disease, diabetes mellitus, respiratory disease, gastrointestinal disease, liver disease or other chronic diseases
• those with hypertension or on drugs that lower blood pressure
• those with planned surgery during the study period or within 2 weeks of ending the intervention
• taking medications that alter bleeding (such as antiplatelets or anticoagulants) or those with a bleeding disorder
• taking a phenothiazine drug (most commonly used for nausea or mental health conditions)
• having a sensitivity or allergy to any of ingredients for the placebo (rice powder) and calcium/D supplement (calcium citrate, polyethylene glycol, croscarmellose sodium, hydroxypropyl methylcellulose, magnesium stearate, oligofructose enriched inulin, propylene glycol dicaprylate/dicaprate, talc, titanium dioxide, vitamin D3)
• heavy smokers (>20 cigarettes/day)
• perimenopausal women with any chance or plan of pregnancy
• taking prescription medications known to alter bone and Ca metabolism such as calcitonin, bisphosphonates, raloxifene within 3 months before the start of the study
• taking anabolic agents such as parathyroid hormone, growth hormone, or steroids within 3 months before the start of the study
• planning any procedure that includes iodine, barium or nuclear medicine isotopes in next 7 months
• alcohol consumption exceeding 2 drinks/day (approximately 14 g ethanol per drink) or a total of 12/week
• UConn students and/or employees who any key personnel teach or who report to any key personnel
• study key personnel, spouses 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; consume: 1) one tablet containing 392 mg blackcurrant (BC) extract per capsule and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D	Drug: blackcurrant (BC) extract; A calcium citrate caplet (Bayer AG, Germany) will be taken by all 3 groups to avoid bone deterioration related to calcium and vitamin D deficiency; Other Names: BPE75 (392 mg and 784 mg)
Active Comparator: high-BC Group; consume: 1) two capsules containing 392 mg BC extract per tablet (total 784 mg/day) and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D	Drug: blackcurrant (BC) extract; A calcium citrate caplet (Bayer AG, Germany) will be taken by all 3 groups to avoid bone deterioration related to calcium and vitamin D deficiency; Other Names: BPE75 (392 mg and 784 mg)
Placebo Comparator: Control Group; consume: 1) one placebo capsule and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D	Drug: blackcurrant (BC) extract; A calcium citrate caplet (Bayer AG, Germany) will be taken by all 3 groups to avoid bone deterioration related to calcium and vitamin D deficiency; Other Names: BPE75 (392 mg and 784 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density (BMD)	changes in BMD of whole-body, head, arms, legs, trunk, ribs, spine, pelvis	from baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota profile	changes in the gut microbial composition	from baseline to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum bone metabolism biomarkers	changes in serum concentrations of bone metabolism (BALP, P1NP, CTX-1, OC)	from baseline to 6 months
Serum inflammation biomarker	changes in serum inflammation biomarker (hs-CRP)	from baseline to 6 months
Plasma CVD risk factors (lipids, oxidative stress, endothelial function)	changes in plasma CVD risk factors	from baseline to 6 months
Blood pressure (SBP/DBP), BMI, WC, body composition	changes in blood pressure (SBP/DBP), BMI, WC, body composition	from baseline to 6 months
Concentrations of plasma IL-1β, IL-6, TNFα, Th17 and Treg	changes in plasma concentrations of immune biomarkers	from baseline to 6 months
Concentrations of plasma IGF-1 and cGP	changes in plasma concentrations of endocrine biomarkers	from baseline to 6 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): October 3, 2022
• Study Completion (Actual): October 3, 2022

Study Registration Dates

• First Submitted: June 6, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): December 5, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: menopause; cardiovascular disease; osteoporosis; gut microbiome; women; blackcurrant; bone aging
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Cardiovascular Diseases; Osteoporosis; Osteoporosis, Postmenopausal
• Other Study ID Numbers: HR20-0035; 2020-67018-30852 (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 both to the community of scientists interested in postmenopausal osteoporosis and to those studying the biology of inflammation-induced bone resorption to avoid unintentional duplication of research.
• IPD Sharing Time Frame: Unlimited time after papers are published.

IPD Sharing Access Criteria

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

1. Presentations at national scientific meetings. From the projects, 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 the experiment data. Data used in publications will be released in a timely manner.

• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (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
• product manufactured in and exported from the U.S.: No