An interventional study of Elderberry Anthocyanin Chewing Gum and Placebo Chewing Gum in Mild Cognitive Impairment (MCI), Aging and Oral Microbiome, sponsored by Burdur Mehmet Akif Ersoy University. Not yet recruiting at 1 site in Turkey (Türkiye). Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2025-07-08.
Sponsored by Burdur Mehmet Akif Ersoy University · Not applicable, Interventional, and Supportive care
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.
This study is a double-blind, randomized controlled clinical trial designed to evaluate the impact of an elderberry-based functional chewing gum on cognitive function and oral microbiota in older adults.
The chewing gum intervention contains encapsulated anthocyanins derived from Sambucus nigra L., standardized for cyanidin-3-glucoside and cyanidin-3-sambubioside content, and formulated specifically for elderly individuals. The gum is designed to be soft-textured, low in elasticity, and easy to chew. It also allows transmucosal absorption through buccal and sublingual pathways, offering a rapid delivery system for polyphenols.
The study will enroll 34 participants aged 60 and above, with mild cognitive impairment (MoCA 20-25), divided equally into intervention and placebo groups. Participants will chew one gum twice daily for 6 weeks. During the intervention, participants will follow a berry-free diet to eliminate potential confounding sources of polyphenols.
Pre- and post-intervention assessments will include:
The primary hypothesis is that the anthocyanin-enriched gum will:
Anthocyanin content and release will be validated by HPLC and pH-differential spectrophotometry, and stability will be tested over a 6-month period according to ICH guidelines. Statistical analysis will be performed using ANOVA, t-tests, and linear models adjusting for education and age.
This multidisciplinary study integrates dietary polyphenols, oral delivery systems, salivary biomarkers, microbiome science, and cognitive neuroscience in a novel, geriatric-focused intervention.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's planned enrollment of 34 is below the median of 64 across 2,794 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →Burdur Mehmet Akif Ersoy University is the lead sponsor of 48 studies on the registry; 17 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive chewing gum containing standardized elderberry anthocyanins twice daily for 6 weeks
Dietary Supplement: Elderberry Anthocyanin Chewing Gum
Participants receive anthocyanin-free chewing gum matched in appearance and taste, twice daily for 6 weeks
Dietary Supplement: Placebo Chewing Gum
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.
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.
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
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
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
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
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
Change in Salivary pH
Salivary pH will be measured from unstimulated whole saliva samples collected over 5 minutes. Differences from baseline to week 6 will be analyzed.Unit of Measure: pH value (unitless)
Time frame: Baseline and Week 6
Change in Salivary Total Antioxidant Capacity (FRAP Method)
The Ferric Reducing Antioxidant Power (FRAP) assay will be used to evaluate the total antioxidant capacity of unstimulated saliva samples. Results will be expressed as micromoles of Fe²⁺ equivalents per milliliter (µmol Fe²⁺/mL).
Time frame: Baseline and Week 6
Change in Salivary Total Phenolic Content (Folin-Ciocalteu Method)
The Folin-Ciocalteu colorimetric method will be used to quantify the total phenolic content in unstimulated saliva. Results will be reported as milligrams of gallic acid equivalents per milliliter (mg GAE/mL).
Time frame: Baseline and Week 6
Change in Salivary Streptococcus mutans Count
Salivary concentration of Streptococcus mutans will be assessed using microbiological culturing on selective agar. Results will be reported as colony-forming units per milliliter (CFU/mL).
Time frame: Baseline and Week 6
Change in Salivary Lactobacillus spp. Count
Salivary concentration of Lactobacillus spp. will be assessed using microbiological culturing on selective agar. Results will be reported as colony-forming units per milliliter (CFU/mL).
Time frame: Baseline and Week 6
Product Acceptability Score (Hedonic Scale)
Participants will evaluate the taste, texture, aroma, and overall liking of the chewing gum using a 9-point hedonic scale (1 = Dislike extremely, 9 = Like extremely). Higher scores indicate greater acceptability. Unit of Measure: Score (1-9)
Time frame: Initial Exposure and Week 6
Plan to share: No — Individual participant data will not be shared due to ethical and privacy concerns. The study protocol did not include participant consent for open data sharing, and the dataset contains potentially identifiable health information.
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Burdur Mehmet Akif Ersoy University