Cognitive Effects of Hesperidin in Overweight/Obese Older Adults

NCT07750223 | Recruiting DMC

• 1 other identifier: SJTU-PH-HESPERIDIN-2026
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Dysfunction; Overweight and Obesity

Keywords

Hesperidin; Cognitive Function; Citrus Flavonoids; Gut Microbiota; Nutritional Intervention; Middle-aged and Elderly; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (6)

• Change 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.

  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.

  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).

  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.

  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.

  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.

  Baseline to Week 10

Secondary Outcomes (5)

• Change in Gut Microbiota Composition

  Baseline to Week 10

• Change in Inflammatory Markers (TNF-α, IL-6, CRP)

  Baseline to Week 10

• Change in Body Weight

  Baseline to Week 10

• Change in Waist Circumference

  Baseline to Week 10

• Change in Body Mass Index (BMI)

  Baseline to Week 10

Study Arms (3)

Placebo Group

PLACEBO COMPARATOR

Participants receive 2 placebo capsules (corn starch 600 mg/day) daily for 10 weeks. Capsules are identical in appearance, smell, and packaging to hesperidin capsules.

Dietary Supplement: Hesperidin

Low-Dose Hesperidin Group

EXPERIMENTAL

Participants receive hesperidin 300 mg + corn starch 300 mg (total 600 mg) daily, taken as 2 capsules for 10 weeks.

Dietary Supplement: Hesperidin

High-Dose Hesperidin Group

EXPERIMENTAL

Participants receive hesperidin 600 mg daily, taken as 2 capsules for 10 weeks.

Dietary Supplement: Hesperidin

Interventions

Hesperidin DIETARY_SUPPLEMENT

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).

Also known as: Citrus Flavonoid

High-Dose Hesperidin Group; Low-Dose Hesperidin Group; Placebo Group

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55-75 years
• BMI ≥ 24 kg/m² or waist circumference ≥ 90 cm (men) / ≥ 85 cm (women)
• Willing to participate and sign informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Min Hou: lead

Study Sites (1)

Community Health Centers in Shanghai

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Related Publications (5)

• Farag S, Tsang C, Al-Dujaili EAS, Murphy PN. Effect of Polyphenol Supplementation on Memory Functioning in Overweight and Obese Adults: A Systematic Review and Meta-Analysis. Nutrients. 2024 Feb 6;16(4):474. doi: 10.3390/nu16040474.

  PMID: 38398799 BACKGROUND

• Kean RJ, Lamport DJ, Dodd GF, Freeman JE, Williams CM, Ellis JA, Butler LT, Spencer JP. Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults. Am J Clin Nutr. 2015 Mar;101(3):506-14. doi: 10.3945/ajcn.114.088518. Epub 2015 Jan 14.

  PMID: 25733635 BACKGROUND

• Hong Y, An Z. Hesperidin attenuates learning and memory deficits in APP/PS1 mice through activation of Akt/Nrf2 signaling and inhibition of RAGE/NF-kappaB signaling. Arch Pharm Res. 2018 Jun;41(6):655-663. doi: 10.1007/s12272-015-0662-z. Epub 2015 Sep 21.

  PMID: 26391026 BACKGROUND

• Wang D, Liu L, Zhu X, Wu W, Wang Y. Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimer's disease. Cell Mol Neurobiol. 2014 Nov;34(8):1209-21. doi: 10.1007/s10571-014-0098-x. Epub 2014 Aug 19.

  PMID: 25135708 BACKGROUND

• Lamport DJ, Pal D, Macready AL, Barbosa-Boucas S, Fletcher JM, Williams CM, Spencer JP, Butler LT. The effects of flavanone-rich citrus juice on cognitive function and cerebral blood flow: an acute, randomised, placebo-controlled cross-over trial in healthy, young adults. Br J Nutr. 2016 Dec;116(12):2160-2168. doi: 10.1017/S000711451600430X. Epub 2017 Jan 16.

  PMID: 28091350 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Overweight; Obesity

Interventions

Hesperidin

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Flavanones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glycosides; Carbohydrates

Central Study Contacts

Min Hou

CONTACT

13121858610; minhou@sjtu.edu.cna

ShiQi Lin

CONTACT

18616825727; olinalin@sjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind: Participants, investigators, and outcome assessors are blinded to group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor / Master's Thesis Advisor

Model Details: Three parallel arms: placebo, 300 mg/day hesperidin, and 600 mg/day hesperidin.

Study Record Dates

• First Submitted: July 17, 2026
• First Posted: August 6, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): March 30, 2027
• Last Updated: August 6, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)