Elderberry Functional Gum and Cognitive & Oral Health in Older Adults

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age65+
SponsorBurdur Mehmet Akif Ersoy University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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.

Treatment groups

34 Participants
are divided into 2 treatment groups
Group A: Elderberry Chewing Gum GroupExperimental treatment 1 intervention
Group B: Placebo Arm TitlePlacebo comparator 1 intervention

Trial outcomes

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.

Time frame
Baseline and Week 6

Secondary outcomes

1

Change in Executive Function Assessed by Stroop Test

Cognitive flexibility and executive control will be assessed using the Stroop Color-Word Test (TBAG form). The interference score (difference in reaction time between incongruent and color conditions) will be used as the main outcome. Unit of Measure: milliseconds (ms)

Time frame
Baseline and Week 6
2

Change in Alpha Diversity Assessed by Shannon Index

lpha diversity of oral microbiota will be assessed using the Shannon Index, based on 16S rRNA gene sequencing. Unit of Measure: Shannon diversity index (unitless)

Time frame
Baseline and Week 6
3

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

Beta diversity of oral microbiota will be assessed using UniFrac and Bray-Curtis distances, based on 16S rRNA gene sequencing. Unit of Measure: Distance metric (unitless)

Time frame
Baseline and Week 6
4

Change in Salivary Flow Rate

Unstimulated whole saliva will be collected for 5 minutes. Flow rate will be calculated and expressed in mL/min. Differences from baseline to week 6 will be analyzed.

Time frame
Baseline and Week 6

Other outcomes

Sponsors and contacts

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