Blackcurrants Modify Gut Microbiota and Reduce Osteoporosis and CVD Risk

Phase 1

Completed

Conditions: Postmenopausal Osteoporosis
Gut Microbiota
Cardiovascular Diseases

Interventions: Drug: blackcurrant (BC) extract

Registration Number: NCT04431960

Lead Sponsor: University of Connecticut

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 51

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
low-BC Group	blackcurrant (BC) extract	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
high-BC Group	blackcurrant (BC) extract	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
Control Group	blackcurrant (BC) extract	consume: 1) one placebo capsule and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D

Primary Outcome Measures

Name	Time	Method
Bone Mineral Density (BMD)	From baseline to 6 months	Changes in BMD of whole-body measured via dual energy x-ray absorptiometry

Secondary Outcome Measures

Name	Time	Method
Serum Marker of Bone Formation	From baseline to 6 months	Changes to serum concentrations of P1NP
Plasma Regulator of Bone Metabolism	From baseline to 6 months	Changes to plasma concentrations RANKL
Changes in Plasma Inflammatory Cytokine	From baseline to 6 months	Changes to plasma concentrations of IL-1B

Trial Locations

Locations (1): University of Connecticut Department of Nutritional Sciences and Kinesiology Human Performance Laboratory
🇺🇸
Storrs, Connecticut, United States