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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
105
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).
Community Health Centers in Shanghai
Shanghai, Shanghai Municipality, China
RECRUITINGChange in Cognitive Function Assessed by the Mini-Mental State Examination (MMSE)
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.
Time frame: Baseline to Week 10
Change in Cognitive Function Assessed by the Montreal Cognitive Assessment (MoCA)
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.
Time frame: Baseline to Week 10
Change in Cognitive Function Assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Units on a Scale (0 to 30 points). Higher scores indicate worse cognitive function (greater impairment).
Time frame: Baseline to Week 10
Change in Cognitive Function Assessed by the Trail Making Test (TMT)
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.
Time frame: Baseline to Week 10
Change in Cognitive Function Assessed by the Digit Symbol Substitution Test (DSST)
Unit of Measur is Number of correct responses. Higher scores indicate better processing speed, sustained attention, and working memory.
Time frame: Baseline to Week 10
hange in Cognitive Function Assessed by the Wechsler Memory Scale (WMS)
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.
Time frame: Baseline to Week 10
Change in Gut Microbiota Composition
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).
Time frame: Baseline to Week 10
Change in Inflammatory Markers (TNF-α, IL-6, CRP)
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.
Time frame: Baseline to Week 10
Change in Body Weight
Change in body weight measured using standard anthropometric procedures, reported in kilograms (kg); reduction indicates improvement in weight status.
Time frame: Baseline to Week 10
Change in Waist Circumference
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.
Time frame: Baseline to Week 10
Change in Body Mass Index (BMI)
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.
Time frame: Baseline to Week 10
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