Recruiting

Polyphenols

Sponsor:

UCLA

Code:

NCT06507254

Conditions

Cognitive Decline

Cognitive Dysfunction

Eligibility Criteria

Sex: All

Age: 50+

Healthy Volunteers: Accepted

Interventions

Polyphenol Supplement

Placebo Supplement

Study Details

Brief summary:

Globally, populations are aging thereby increasing healthcare burden, overall cognitive impairment, and dementia including Alzheimers diseases (AD). The lack of effective treatments makes it essential to develop new strategies for healthy cognitive aging, including interventions to slow or prevent cognitive decline. A traditional Mediterranean diet, rich in polyphenols (PPs), may prevent or delay the onset of cognitive dysfunction in older adults, preserving healthy brain structure and function, and lowering the risk of AD. These effects, mediated in part by gut microbiome-derived PP metabolites, highlight the role alterations in the brain-gut microbiome system play in neurodegeneration. Moreover, high levels of circulating phenyl-y-valerolactones, neuroprotective compounds, exclusively produced by gut microbiota from flavan-3-ol-rich foods (e.g., cocoa, tea, berries) are associated with delaying the onset of cognitive dysfunction in older adults. Intake of such PPs can also change gut microbial composition and function, altering the physiology of the hosts secondary bile acid (BA) pool, affecting regulatory and signaling functions in the brain as well as cognitive decline and AD. The investigators hypothesize that, in older adults with enhanced AD risk, dietary intake of PPs maintains healthier brain features and cognitive function, and that this beneficial effect is mediated by gut microbiota metabolites of PPs and BAs.

In this multi-PI application by leaders in the field of brain-gut microbiome interactions, the investigators will conduct a year-long, multi-center, randomized double-blind placebo-controlled study in 300 older adults in the United States (validation sample of 100 from Northern Ireland) who are at enhanced risk of developing AD. Ultimately, the investigators will establish the protective effects of regular dietary PP intake on cognitive function and on brain-gut microbiome interactions, ideally allowing the development of effective dietary regimes to prevent of delay the onset of AD in at-risk elderly, thereby reducing cognitive decline and healthcare costs.

Participants will be asked to provide information about their diet, mood, and behaviors via food diaries, physical body measures (e.g. height, weight, etc.), and online questionnaires collected before each in-clinic appointment, as well as monthly online questionnaires. MR imaging will be collected on participants to assess neurocognitive changes as a result of the supplement. Participants will be asked to provide both stool and blood samples. Participants will be randomly assigned to either the Juice Plus+ intervention group or the placebo treatment group and then asked to take their respective supplement 4 pills twice a day. All participants will be asked to come in for 4 in-clinic appointments, including 3 brain MRI scans and 3 cognitive testing appointments, collect 3 stool samples with corresponding diet diaries, and provide 3 blood samples over the course of 12 months. Participants will also meet with a nutritionist 3 times over the 12 months to discuss diet to ensure study eligibility and any questions about the supplement.

Conditions

Cognitive Decline

Cognitive Dysfunction

Study ID

NCT06507254

Start date

Jan 9, 2025

Status verified date

Jun, 2026

Completion date

Dec 31, 2029

Anticipated

Primary completion date

Jun 30, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 50+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 50+ Years of age
  • Male or Female
  • At enhanced risk of Alzheimer's Disease (defined as family history of AD, 1st degree family member)
  • Habitually consume suboptimal diets such as typical Western Diet (i.e., high in animal products, refined carbohydrates and processed food)
  • Able to communicate well in English

Exclusion Criteria:

  • Vegan or Vegetarian
  • Presence of cognitive impairment at the time of recruitment into the study as measured by the Mini Mental Status Exam (MMSE, score 25-30) and Clinical Dementia Rating (CDR, score=0).
  • Pre-existing psychosis or psychiatric conditions
  • Currently receiving treatment for dementia
  • History of alcohol and/or substance abuse/dependence as determined by a positive endorsement on the MINI+/ If the MINI+ is positive for alcohol or drug dependence, or abuse, the participants will be excluded.
  • Heavy use of tobacco (greater than 1/2 pack per day)
  • History of cerebrovascular events
  • Existing allergies to berry fruits
  • Use of oral/IV antibiotics in the last 3 months. Use of probiotics in the last 1 month.
  • Recent Changes (last 3 months) in the use of psychoactive medications or other medications that interfere with the measured outcomes.
  • Frailty, malnutrition, or food allergy/intolerance requiring special diets.
  • Body weight at enrollment greater than 400lbs due to weight restrictions on the MRI table.
  • Women who are pregnant, lactating, or postpartum for less than 6months.
  • Women of childbearing age who are not practicing birth control or are planning to get pregnant during the study.

Unable to safely participate in the MRI (claustrophobia, presence of devices affected by MRI such as pacemakers, neurostimulators, metallic foreign body, etc.)

  • Chronic Pain

Study Design

Enrollment

300 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Polyphenol Supplement

Juice Plus Essentials, Berry Blend Capsules

placebo comparator: Placebo Supplement

Interventions

Polyphenol Supplement

Dietary supplement taken twice daily for 12 months.

Placebo Supplement

Dietary supplement taken twice daily for 12 months.

Primary outcome measure

  • Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - stool [ Time Frame: Collected three times by the participant at home, once at baseline (week 0), once at mid-study (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - blood [ Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in microbiome levels pre, mid, & post intervention - Stool [ Time Frame: Collected three times by the participant at home, once at baseline (week 0), once at mid-study (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in microbiome levels pre & post intervention - Blood [ Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in microbiome levels pre, mid, & post intervention - Stool [ Time Frame: Collected three times by the participant at home, once at baseline (week 0), once at mid-study (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in microbiome levels pre, mid, & post intervention - Blood [ Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in Cognitive Measures pre, mid, & post intervention - Executive Function [ Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in Cognitive Measures pre, mid, & post intervention - Executive Function [ Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in Cognitive Measures pre, mid, & post intervention [ Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). ]
  • Differences in Cognitive Measures pre, mid, and post intervention - Executive Functioning [ Time Frame: Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). ]

Central Contacts and Locations

Central contacts

Marika Dy, MPH

2670089ChurchLab@mednet.ucla.edu

Locations

University of California, Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Contacts

Marika Dy, MPH

3102670089ChurchLab@mednet.ucla.edu

Principal Investigator:

Arpana Church, PhD

More Information

Sponsor

University of California, Los Angeles

Last update posted

Jun 11, 2026

Last verified

Jun, 2026

Keywords

  • Polyphenols
  • Mediterranean Diet
  • Gut Microbiome
  • Alzheimers Disease

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of California, Los Angeles on 2026-06-11.