The Apple Study: Two Apples a Day, Keep the Doctor Away?

Two Apples a Day, Keep the Doctor Away?

The goal of this clinical trial is to learn about the gut microbiome in healthy postmenopausal women aged 50-64. The main questions it aims to answer are:

• Investigate whether the activity of the bacterial enzyme β-glucuronidase and the abundance of β-glucuronidase-producing bacteria could be decreased by ingestion of 2 apples a day for a period of 6 weeks
• Examine changes in gut microbiota composition, diversity, and functional capacity
• Examine feasibility of eating 2 apples a day for a period of 6 weeks

Participants will eat 2 apples a day for a period of 6 weeks.

Six weeks includes the period from the start of the study and gathering of baseline characteristics/questionnaires till the finish.

Study Overview

• Status: Not yet recruiting
• Conditions: Microbial Colonization; Enzyme Overdose
• Intervention / Treatment: Other: Eating apples

Detailed Description

It is know that estrogen levels decrease after menopause. There are many different factors affecting these levels though; the gut microbiome has been identified as one of these. Not only the composition of the gut microbiota plays a role here, but also its activity is of special interest. The gut microbiota for instance produces the bacterial enzyme β-glucuronidase which has been shown to de-conjugate biliary excreted estrogens, leading to reactivation and reabsorption of estrogens into the bloodstream. It might be expected that this reabsorption results in elevated blood estrogen levels. Elevated levels of estrogen have been linked to not only development but also recurrence of breast cancer.

Apples are known for their pectin which has prebiotic properties and a potential decreasing effect on β-glucuronidase activity. In vitro studies and animal studies have already shown the β-glucuronidase decreasing impact of pectin. In humans this was never examined before.

This study aims to investigate whether it is possible to lower the activity of the bacterial enzyme β-glucuronidase and the abundance of β-glucuronidase-producing bacteria by a simple dietary intervention. This dietary intervention consists of the ingestion of two whole apples a day, one in the morning and one in the evening, during the period of 6 weeks. Thereby this study aims to examine the feasibility of this intervention.

It is hypothesized that

1. this is a feasible intervention
2. this results in a decrease in the activity of the bacterial enzyme β-glucuronidase and the abundance of β-glucuronidase-producing bacteria. Which would be in line with the findings of in vitro and animal studies and
3. an increase in microbial diversity

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marjolein Smidt, prof. dr.; Phone Number: 043 - 3877477; Email: m.smidt@mumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age 50-64
• Postmenopausal women
• Recent negative breast cancer screening (< 6 months)

Exclusion Criteria:

• The regular consumption of one ore more apples a day
• Previous gastrointestinal surgery (excl. appendix surgery)
• Any type of cancer in history, except for basal cell carcinoma (BCC)
• Inflammatory bowel disease
• Mammography older than 6 months
• Antibiotic use within three months before fecal sampling
• Physically or mentally incapable or incompetent to sign informed consent
• Known apple allergy or complaints matching with apple allergy
• Less good dental state

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apple intervention; the eating of 2 apples a day for a period of 6 weeks	Other: Eating apples; the eating of 2 apples a day for a period of 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The activity of the bacterial enzyme β-glucuronidase and the abundance of β-glucuronidase-producing bacteria	This will be measured in fecal samples by using a validated β-glucuronidase enzyme activity assay, which is based on previous studies.	6 weeks per patient
Changes in gut microbiota composition, diversity, and functional capacity	Gut microbiota composition, diversity	6 weeks per patient
Feasibility of eating 2 apples a day for a period of 6 weeks	feasibility	6 weeks per patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal levels of short-chain fatty acids (SCFA)	SCFA	6 weeks per patient
Dietary intake, medication, stool classification and frequency, blood pressure, weight, length and quality of life before and after the intervention	diet/medication etc	6 weeks per patient

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Marjolein Smidt, Prof. dr., Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): October 31, 2024

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 17, 2023
• First Posted (Estimate): February 28, 2023

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: METC22-064

Drug and device information, study documents

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