Elderberry Functional Gum and Cognitive & Oral Health in Older Adults

NCT07054645 | Not Yet Recruiting

• 1 other identifier: MAKU-AKDUMAN-1002-2025
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Globally, the aging population is increasing rapidly, leading to a dramatic rise in the prevalence of Alzheimer's disease and other types of dementia. Neurodegenerative disorders are characterized by pathological hallmarks such as β-amyloid (Aβ) plaque accumulation, tau protein aggregation, synaptic loss, and widespread neuroinflammation. These processes impair key cognitive domains including attention, memory, executive function, and orientation, hindering independent daily functioning. Beyond cognitive decline, neurodegenerative diseases are associated with a marked deterioration in oromotor functions, such as chewing and swallowing. Mastication plays a critical role not only in digestion but also in neuro-sensory stimulation. Trigeminal nerve signaling activated by chewing enhances neurotransmitter release, boosts neurotrophic factor production (e.g., BDNF), and facilitates Aβ clearance, thereby supporting synaptic plasticity and reducing inflammation. Neuroimaging studies have shown that a higher number of functional occlusal pairs is associated with increased gray and white matter volume in regions affected early in Alzheimer's disease. Systematic reviews have identified poor mastication and tooth loss as risk factors for cognitive decline and dementia. Mechanistically, loss of afferent input from the oral cavity-due to tooth loss, reduced chewing force, prosthetic use, or muscle atrophy-leads to reduced brain stimulation, diminished neurotrophic support, and impaired cerebral blood flow. Thus, geriatric-friendly chewing gum formulations with low elasticity and ease of chewing have been recommended. Chewing gum is a promising vehicle for functional compounds due to its potential for transmucosal absorption and cognitive stimulation. Randomized controlled trials have shown that both active and inactive gums improve attention and reduce error rates in cognitive tasks, highlighting the beneficial effects of mastication. Another emerging target for cognitive enhancement is the oral microbiota, a complex ecosystem of over 700 bacterial species. Dysbiosis in this ecosystem has been linked to neurological outcomes via inflammatory and neurotoxic pathways. Certain pathogens, such as Porphyromonas gingivalis, have been detected in the brains of Alzheimer's patients. Moreover, metagenomic studies have shown that reduced salivary microbial diversity correlates with poorer cognitive performance, even in young adults. Elderberry (Sambucus nigra L.) is rich in anthocyanins (e.g., cyanidin-3-glucoside, cyanidin-3-sambubioside) with strong antioxidant and anti-inflammatory properties. Literature shows that polyphenols can be absorbed via buccal and sublingual mucosa, bypassing first-pass metabolism and providing faster systemic effects. However, the impact of anthocyanin-enriched chewing gum on oral microbiota and cognitive function has not yet been systematically investigated. This study aims to develop and evaluate a geriatric-friendly functional chewing gum enriched with standardized elderberry anthocyanins. The intervention targets dual mechanisms-neurophysiological and microbial-to support cognitive health and balance oral microbiota in older adults.

Conditions

Mild Cognitive Impairment (MCI); Aging; Oral Microbiome

Keywords

Elderberry; Anthocyanins; Chewing Gum; Functional Food; Transmucosal Delivery; Oral Microbiota; Cognitive Function; MoCA; Aging; Mild Cognitive Impairment; Geriatric Nutrition; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Change in Cognitive Function Assessed by MoCA (Montreal Cognitive Assessment) Score

  The MoCA score (0-30) will be used to assess global cognitive function. A higher score indicates better cognitive performance. Measurements will be taken at baseline and at 6 weeks.

  Baseline and Week 6

Secondary Outcomes (10)

• Change in Executive Function Assessed by Stroop Test

  Baseline and Week 6

• Change in Alpha Diversity Assessed by Shannon Index

  Baseline and Week 6

• Change in Beta Diversity Assessed by UniFrac and Bray-Curtis Distances

  Baseline and Week 6

• Change in Salivary Flow Rate

  Baseline and Week 6

• Change in Salivary pH

  Baseline and Week 6

Study Arms (2)

Elderberry Chewing Gum Group

EXPERIMENTAL

Participants receive chewing gum containing standardized elderberry anthocyanins twice daily for 6 weeks

Dietary Supplement: Elderberry Anthocyanin Chewing Gum

Placebo Arm Title

PLACEBO COMPARATOR

Participants receive anthocyanin-free chewing gum matched in appearance and taste, twice daily for 6 weeks

Dietary Supplement: Placebo Chewing Gum

Interventions

Elderberry Anthocyanin Chewing Gum DIETARY_SUPPLEMENT

Participants receive a functional chewing gum containing encapsulated elderberry (Sambucus nigra L.) anthocyanins standardized for cyanidin-3-glucoside and cyanidin-3-sambubioside. The gum is formulated to be geriatric-friendly (soft, low-elasticity) and is administered twice daily for 6 weeks. It enables transmucosal polyphenol delivery through buccal absorption.

Elderberry Chewing Gum Group

Placebo Chewing Gum DIETARY_SUPPLEMENT

Participants receive a placebo chewing gum identical in appearance, taste, and texture to the active gum but containing no elderberry anthocyanins or bioactive compounds. The gum is administered twice daily for 6 weeks to match the intervention group.

Placebo Arm Title

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Individuals aged 60 and over
• Individuals with mildly reduced cognitive function using the MoCA test (MoCA score: 20-25)
• Those with stable systemic diseases (e.g. HT, controlled DM)
• Those with adequate dental health (≥20 natural teeth or no chewing problems with functional prosthesis)
• Non-smokers and those who use regular medication and do not use antibiotics or antiseptic mouthwashes that could seriously affect the oral microbiota
• Individuals who are willing to participate in the study and can give written consent

You may not qualify if:

• Moderate to severe dementia (MoCA \< 20)
• Presence of active infection or systemic inflammatory disease
• Temporomandibular joint disorders affecting gum chewing function
• Use of probiotics, prebiotics, or antibiotics within the last three months
• Known allergy to elderberry or its components

Sponsors & Collaborators

• Burdur Mehmet Akif Ersoy University: lead

Study Sites (1)

Mehmet Akif Ersoy University

Burdur, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Gül Akduman, PhD.

CONTACT

+905380458382; gakduman@mehmetakif.edu.tr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomly assigned to intervention or placebo groups using computer-generated permuted block randomization (block size = 4). Allocation sequences will be created by an independent researcher. Gums will be packaged in identical blister packs labeled with alphanumeric codes that do not reveal group assignment. Only the randomization coordinator will have access to the allocation key. Investigators and outcome assessors will be blinded throughout the study. Cognitive tests and saliva sampling will be conducted by trained staff unaware of group assignment, under standardized conditions.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Model Details: Two-arm, parallel-group design. Participants are randomly assigned to either the intervention group (elderberry-based anthocyanin chewing gum) or the placebo group. Both groups are assessed at baseline and after 6 weeks of intervention.

Study Record Dates

• First Submitted: June 19, 2025
• First Posted: July 8, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: July 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)