Cognitive Dysfunction, Overweight and Obesity
Conditions
Keywords
Hesperidin, Cognitive Function, Citrus Flavonoids, Gut Microbiota, Nutritional Intervention, Middle-aged and Elderly, Randomized Controlled Trial
Brief summary
A randomized, double-blind, placebo-controlled trial was designed to test whether two doses of hesperidin (a natural flavonoid from citrus fruits) improve cognitive function in overweight and obese older adults. A total of 105 participants, aged 55-75 years with a BMI ≥24 kg/m² or elevated waist circumference, will be randomly assigned to one of three 10-week treatments: placebo, low-dose hesperidin (300 mg/day), or high-dose hesperidin (600 mg/day). The primary aim is to see if hesperidin supplementation enhances cognitive performance - specifically executive function, memory, and attention - and to explore any dose-response relationship. Secondary aims include examining changes in gut microbiota composition and related metabolites, as well as exploring potential mechanisms behind any observed effects. The findings are expected to provide scientific evidence on whether hesperidin could serve as a nutritional strategy to support cognitive health in this population.
Interventions
DIETARY_SUPPLEMENTHesperidin
Oral hesperidin supplementation or matching placebo, administered as 2 capsules per day for 10 weeks. * Placebo Comparator: corn starch 600 mg/day * Low-dose: hesperidin 300 mg + corn starch 300 mg/day (total 600 mg) * High-dose: hesperidin 600 mg/day All capsules are identical in appearance, color, smell, taste, and packaging to maintain blinding. All participants undergo scheduled assessments: physical measurements (weeks 2,4,6,8), 24h dietary recall and IPAQ (every 2 weeks), weekly urine samples, fecal samples (weeks 2,4,8,10), fasting blood samples (baseline and week 10), and bi-weekly nutrition education lectures (general health education only ,no dietary restriction).
Sponsors
Min Hou
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double-blind: Participants, investigators, and outcome assessors are blinded to group assignment.
Intervention model description
Three parallel arms: placebo, 300 mg/day hesperidin, and 600 mg/day hesperidin.
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 55-75 years * BMI ≥ 24 kg/m² or waist circumference ≥ 90 cm (men) / ≥ 85 cm (women) * Willing to participate and sign informed consent
Exclusion criteria
* MMSE score \< 20 * History of neurological diseases (Parkinson's, Alzheimer's, stroke, etc.) * Malignant tumors, severe liver/kidney/gastrointestinal diseases * Use of weight-loss drugs or antidepressants (except statins) within recent months * Strict vegetarians, binge eating disorder, heavy alcohol consumption * Participation in other intervention studies * Other conditions judged by investigators as unsuitable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cognitive Function Assessed by the Mini-Mental State Examination (MMSE) | Baseline to Week 10 | Units on a Scale (0 to 30 points).Higher scores indicate better cognitive function. Scores ≥25 are generally considered normal; scores \<24 suggest cognitive impairment. |
| Change in Cognitive Function Assessed by the Montreal Cognitive Assessment (MoCA) | Baseline to Week 10 | Units on a Scale (0 to 30 points).Higher scores indicate better cognitive function. Scores ≥26 are considered normal; scores 18-25 indicate mild cognitive impairment; scores 10-17 indicate moderate impairment; scores \<10 indicate severe impairment. |
| Change in Cognitive Function Assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) | Baseline to Week 10 | Units on a Scale (0 to 30 points). Higher scores indicate worse cognitive function (greater impairment). |
| Change in Cognitive Function Assessed by the Trail Making Test (TMT) | Baseline to Week 10 | Unit of Measure is Seconds. Shorter completion times indicate better cognitive function. Part B assesses executive function and cognitive flexibility; a higher TMT-B/TMT-A ratio may indicate greater impairment. |
| Change in Cognitive Function Assessed by the Digit Symbol Substitution Test (DSST) | Baseline to Week 10 | Unit of Measur is Number of correct responses. Higher scores indicate better processing speed, sustained attention, and working memory. |
| hange in Cognitive Function Assessed by the Wechsler Memory Scale (WMS) | Baseline to Week 10 | Raw scores for each subtest are converted to scaled scores using norm tables; scaled scores are summed to obtain the full-scale score, which is then converted to a Memory Quotient (MQ) using norm tables.Higher scores indicate better memory function. The Memory Quotient (MQ) normally ranges from 80 to 120. Scores below 80 suggest below-average memory performance; scores above 120 suggest above-average memory performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gut Microbiota Composition | Baseline to Week 10 | Changes in gut microbiota composition and diversity assessed by 16S rRNA sequencing or metagenomic analysis of fecal samples. Primary focus on alpha and beta diversity, and relative abundance of key bacterial taxa (e.g., Bifidobacterium, Lactobacillus, Akkermansia). |
| Change in Inflammatory Markers (TNF-α, IL-6, CRP) | Baseline to Week 10 | Changes in serum levels of pro-inflammatory markers including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP), measured by ELISA or multiplex assays. |
| Change in Body Weight | Baseline to Week 10 | Change in body weight measured using standard anthropometric procedures, reported in kilograms (kg); reduction indicates improvement in weight status. |
| Change in Waist Circumference | Baseline to Week 10 | Change in waist circumference measured using standard anthropometric procedures at the midpoint between the lowest rib and the iliac crest, reported in centimeters (cm); reduction indicates improvement in central adiposity. |
| Change in Body Mass Index (BMI) | Baseline to Week 10 | BMI calculated as body weight in kilograms divided by the square of height in meters (kg/m²). Height was measured at baseline only using standard anthropometric procedures. Reduction in BMI indicates improvement in overall adiposity. Per Chinese BMI classification standards: 24.0-27.9 kg/m² (overweight) and ≥28.0 kg/m² (obese); the study enrolled participants with BMI ≥ 24.0 kg/m². |
Countries
China
Contacts
CONTACTMin Hou
CONTACTShiQi Lin
Outcome results
None listed