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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04431960

Enrollment

Registered

2020-06-16

Start date

2021-07-20

Completion date

2022-10-03

Last updated

2025-08-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiovascular Diseases, Gut Microbiota, Postmenopausal Osteoporosis

Keywords

blackcurrant, gut microbiome, osteoporosis, menopause, bone aging, women, cardiovascular disease

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.

Interventions

DRUGblackcurrant (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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

The extract and placebo will have the identical shape and color and will be packaged into coded containers.

Intervention model description

The study participants will be randomly assigned to three groups and asked to consume 1 tablet containing 392 mg blackcurrant (BC) extract per capsule (low-BC Group), 2 capsules containing 392 mg BC extract per tablet (total 784 mg/day; high-BC Group), or 1 placebo capsule (Control Group) daily with breakfast meals for 6 months. To avoid bone deterioration related to calcium and vitamin D deficiency, all participants will take a calcium citrate caplet daily that includes 400 mg calcium and 500 IU vitamin D (Bayer AG, Germany) beginning 2 weeks before the study and lasting for the duration of the study.

Eligibility

Sex/Gender

FEMALE

Age

45 Years to 60 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
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

Other

Measure	Time frame	Description
Concentrations of Plasma Immune Markers	from baseline to 6 months	changes in plasma concentrations of immune biomarkers (IL-1β, IL-6, TNFα, Th17 and Treg)
Changes in Gut Microbial Composition	from baseline to 6 months	This was measured using alpha diversity by species richness and Shannon diversity and beta diversity by principal component analysis. Structural comparisons were done comparing relative abundance between groups at the genus and phylum levels
Concentrations of Plasma IGF-1 and cGP	from baseline to 6 months	changes in plasma concentrations of endocrine biomarkers
Serum Inflammation Biomarker	from baseline to 6 months	changes in serum inflammation biomarker (hs-CRP)
Fasting Blood Lipids	from baseline to 6 months	Changes in plasma CVD risk factors (total cholesterol \[TC\], high density lipoprotein \[HDL\] and triglycerides \[TG\])
Blood Pressure (SBP/DBP), BMI, WC, Body Composition	from baseline to 6 months	changes in blood pressure (SBP/DBP), BMI, WC, body composition

Countries

United States

Participant flow

Participants by arm

Arm	Count
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 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	16
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 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	11
Control Group consume: 1) one placebo capsule and 2) one calcium citrate caplet containing 400 mg calcium and 500 IU vitamin D 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	13
Total	40

Baseline characteristics

Characteristic	Control Group	Total	Low-BC Group	High-BC Group
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	13 Participants	40 Participants	16 Participants	11 Participants
Age, Continuous	54.4 years STANDARD_DEVIATION 3.8	53.1 years STANDARD_DEVIATION 4.3	53.7 years STANDARD_DEVIATION 4.5	50.9 years STANDARD_DEVIATION 4.2
Race/Ethnicity, Customized Race/ethnicity Asian-American/Pacific Islander	0 Participants	2 Participants	2 Participants	0 Participants
Race/Ethnicity, Customized Race/ethnicity Caucasian	13 Participants	37 Participants	13 Participants	11 Participants
Race/Ethnicity, Customized Race/ethnicity Hispanic	0 Participants	1 Participants	1 Participants	0 Participants
Region of Enrollment United States	13 participants	40 participants	16 participants	11 participants
Sex: Female, Male Female	13 Participants	40 Participants	16 Participants	11 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 11	0 / 13
other Total, other adverse events	0 / 16	0 / 11	0 / 13
serious Total, serious adverse events	0 / 16	0 / 11	0 / 13

Outcome results

Primary

Bone Mineral Density (BMD)

Changes in BMD of whole-body measured via dual energy x-ray absorptiometry

Time frame: From baseline to 6 months

Arm	Measure	Group	Value (MEAN)	Dispersion
Low-BC Group	Bone Mineral Density (BMD)	6 month	1.14 g/cm^2	Standard Deviation 0.12
Low-BC Group	Bone Mineral Density (BMD)	Baseline	1.14 g/cm^2	Standard Deviation 0.13
High-BC Group	Bone Mineral Density (BMD)	6 month	1.17 g/cm^2	Standard Deviation 0.08
High-BC Group	Bone Mineral Density (BMD)	Baseline	1.15 g/cm^2	Standard Deviation 0.08
Control Group	Bone Mineral Density (BMD)	6 month	1.16 g/cm^2	Standard Deviation 0.13
Control Group	Bone Mineral Density (BMD)	Baseline	1.17 g/cm^2	Standard Deviation 0.13

Secondary

Changes in Plasma Inflammatory Cytokine

Changes to plasma concentrations of IL-1B

Time frame: From baseline to 6 months

Population: Analysis was performed on 36 participants for IL-1β due to missing values.

Arm	Measure	Group	Value (MEAN)	Dispersion
Low-BC Group	Changes in Plasma Inflammatory Cytokine	Baseline	16.73 pg/mL	Standard Error 1.85
Low-BC Group	Changes in Plasma Inflammatory Cytokine	6 months	16.66 pg/mL	Standard Error 1.85
High-BC Group	Changes in Plasma Inflammatory Cytokine	Baseline	15.36 pg/mL	Standard Error 2.44
High-BC Group	Changes in Plasma Inflammatory Cytokine	6 months	15.06 pg/mL	Standard Error 2.44
Control Group	Changes in Plasma Inflammatory Cytokine	Baseline	17.95 pg/mL	Standard Error 2.09
Control Group	Changes in Plasma Inflammatory Cytokine	6 months	18.34 pg/mL	Standard Error 2.09

Secondary

Plasma Regulator of Bone Metabolism

Changes to plasma concentrations RANKL

Time frame: From baseline to 6 months

Population: Analysis was performed on 35 participants for RANKL due to missing values.

Arm	Measure	Group	Value (MEAN)	Dispersion
Low-BC Group	Plasma Regulator of Bone Metabolism	Baseline	211.12 pg/mL	Standard Error 89.94
Low-BC Group	Plasma Regulator of Bone Metabolism	6 months	210.15 pg/mL	Standard Error 90.43
High-BC Group	Plasma Regulator of Bone Metabolism	Baseline	133.99 pg/mL	Standard Error 111.89
High-BC Group	Plasma Regulator of Bone Metabolism	6 months	102.09 pg/mL	Standard Error 112.51
Control Group	Plasma Regulator of Bone Metabolism	Baseline	256.81 pg/mL	Standard Error 110.39
Control Group	Plasma Regulator of Bone Metabolism	6 months	284.47 pg/mL	Standard Error 111

Secondary

Serum Marker of Bone Formation

Changes to serum concentrations of P1NP

Time frame: From baseline to 6 months

Arm	Measure	Group	Value (MEAN)	Dispersion
Low-BC Group	Serum Marker of Bone Formation	Baseline	26.55 ng/mL	Standard Deviation 10.43
Low-BC Group	Serum Marker of Bone Formation	6 months	25.99 ng/mL	Standard Deviation 10.27
High-BC Group	Serum Marker of Bone Formation	Baseline	21.21 ng/mL	Standard Deviation 10.09
High-BC Group	Serum Marker of Bone Formation	6 months	41.79 ng/mL	Standard Deviation 39.47
Control Group	Serum Marker of Bone Formation	Baseline	32.53 ng/mL	Standard Deviation 20.93
Control Group	Serum Marker of Bone Formation	6 months	26.36 ng/mL	Standard Deviation 17.71

Other Pre-specified