Gut-derived flavonoid compounds to support thinking and memory

MAEVE: Microbiota Mediated Flavonoid Metabolites for Cognitive Health

This trial will test whether a polyphenol supplement that boosts gut-produced flavonoid metabolites can help slow cognitive decline in people aged 50 and older who are at increased risk for Alzheimer's.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: University of Ulster (other)
• Locations: 1 site (Coleraine)
• Trial ID: NCT07226674 on ClinicalTrials.gov

What this trial studies

This interventional study randomizes adults at elevated Alzheimer's risk to receive either a polyphenol supplement or a placebo and follows cognitive tests, blood metabolites, and gut microbiome measures. The approach aims to raise circulating phenyl-γ-valerolactones (PVLs), neuroprotective compounds produced by gut bacteria from flavan-3-ols. Eligible participants are age 50+, overweight (BMI ≥25), habitually eat a Western-style diet, and have normal cognition at entry; recent antibiotic or probiotic use and existing dementia are excluded. Primary outcomes link changes in microbial composition and PVL levels with cognitive performance and related biomarkers.

Who should consider this trial

Good fit: Ideal candidates are adults aged 50 or older with BMI ≥25 who have a first-degree family history of Alzheimer's, typically eat a Western diet, and show normal cognitive testing at enrollment.

Not a fit: People with existing cognitive impairment or dementia, current dementia treatments, recent antibiotic or probiotic use, significant psychiatric history, or allergies to supplement components are unlikely to benefit.

Why it matters

Potential benefit: If successful, the supplement could delay or reduce age-related cognitive decline by increasing neuroprotective gut-derived metabolites.

How similar studies have performed: Observational studies and small trials link polyphenol-rich diets to better cognition, but interventions specifically targeting gut-derived PVLs are relatively novel and unproven.

Eligibility criteria

Inclusion Criteria:

* 50+ years
* BMI ≥ 25 kg/m2
* Enhanced risk of AD - defined as family history of AD, 1st degree family member
* Habitually consume suboptimal diets such as typical Western diet (i.e., high in animal products, refined carbohydrates and processed food).
* Subjects capable of and willing to comply with the protocol and to give their written informed consent.

Exclusion Criteria:

* Cognitive impairment at time of recruitment into the study, as measured by the Mini Mental Status Exam (MMSE, score 25-30), and Clinical Dementia Rating (CDR, score=0) or Everyday Cognition Scale-12 (ECog-12, score\<1.36 included).
* Pre-existing psychosis or psychiatric conditions.
* Currently receiving treatment for dementia.
* History of substance abuse or cerebrovascular events.
* Heavy use of tobacco (\>1/2 pack per day)
* Any intolerance or allergy documented or suspected to one of the components of the study products.
* Have taken probiotics or antibiotic therapy within the last 1 month
* Change in medication use in the last 3 months.
* Frailty, malnutrition, or food allergy/intolerance requiring special diets will also be excluded.
* Following any specific diet (vegetarian, vegan, etc.)
* Body weight at enrolment greater than 400lbs due to weight restrictions on the MRI table.
* Pregnant, breastfeeding, postpartum for less than 6 months, or unwilling to practice birth control during participation in the study.
* Unable to safely participate in the MRI (claustrophobia, presence of devices affected by MRI such as pacemakers, neurostimulators, or metallic foreign body, etc.)
* Chronic pain.
* Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
* Having a psychological or linguistic inability to sign the informed consent;
* Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision;
* Subject participating in another biomedical study or participation in another study within the 3 months before entry into this study.

Where this trial is running

Coleraine

• Ulster University, Human Intervention Studies Unit — Coleraine, United Kingdom (RECRUITING)

Study contacts

• Principal investigator: Chris Gill, PhD — Ulster University, Human Intervention Studies Unit, Coleraine, Co. Londonderry, BT52 1SA, United Kingdom.
• Study coordinator: Chris Gill, PhD

Conditions: Cognitive Decline, Cognitive Dysfunction, Polyphenols, Mediterranean Diet, Gut Microbiome, Alzheimer Disease