An interventional study of Polyphenol Supplement and Placebo Supplement in Cognitive Decline and Cognitive Dysfunction, sponsored by University of California, Los Angeles. Recruiting at 1 site in United States. Open to participants aged 50 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-11.
Sponsored by University of California, Los Angeles · Not applicable, Interventional, and Prevention
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.
3,843 studies on the registry are indexed under Cognitive Dysfunction; 1,100 are open to participants now.
This study's planned enrollment of 300 is above the median of 65 across 2,808 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →University of California, Los Angeles is the lead sponsor of 1,142 studies on the registry; 192 are open to participants now.
Of its 91 completed or terminated interventional studies of FDA-regulated products, 66 (73%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Unable to safely participate in the MRI (claustrophobia, presence of devices affected by MRI such as pacemakers, neurostimulators, metallic foreign body, etc.)
Juice Plus Essentials, Berry Blend Capsules
Dietary Supplement: Polyphenol Supplement
Dietary Supplement: Placebo Supplement
Dietary supplement taken twice daily for 12 months.
Also known as: Juice Plus Essentials, Berry Blend Capsules
Dietary supplement taken twice daily for 12 months.
Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - stool
Measurement of metabolomics via stool specimen.
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
Measurement of metabolomics via blood specimen.
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
16S RNA sequencing to measure microbiome levels via stool specimen.
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
16S RNA sequencing to measure microbiome levels via blood specimen.
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
Shotgun metagenomics, sequencing to measure microbiome levels via stool specimen.
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
Shotgun metagenomics, sequencing to measure microbiome levels via blood specimen.
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
Administration of a standardized Stroop Neuro-psychological test; participants ability to correctly identify colors when words are printed in conflicting ink colors.
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
Administration of a standardized Trails A \& B; participants ability to connect dots, in order, as quickly as possible.
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
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
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
Administration of a standardized arithmetic task; participants ability to complete quick mental math.
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 tryptophan-associated metabolite profiles pre, mid, and post intervention - Stool
Measurement of tryptophan-associate metabolite profiles via stool specimen.
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 Bile Acid's (BA's) pre, mid, & post intervention - Stool
Measurement of BA's via stool specimen.
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 Inflammatory markers pre, mid, & post intervention - Blood
Measurement of inflammatory markers via blood specimen.
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 Alzheimer's Disease (AD) markers pre, mid, & post intervention - Blood
Measurement of AD markers via blood specimen.
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).
Anthropometrics - BMI
Measurement of height(in) and weight(lbs), used to calculate body mass index (BMI)
Time frame: Measured three times, once at each in-clinic appointment (week 0, month 6, month 12)
Questionnaire Data
Use of validated surveys to assess ingestive behaviors, social isolation, stress, health, physical activity, etc., self-reported by the participant at home.
Time frame: Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12.
Monthly Questionnaire Data
Use of validated surveys to assess anxiety, depression, stress, and diet, self-reported by the participant at home,
Time frame: Collected once a month for the duration of the study (12months).
Anthropometrics - waist and hip circumference
Measurement of waist and hip circumference (cm)
Time frame: Measured three times, once at each in-clinic appointment (week 0, month 6, & month 12)
Systolic and Diastolic Blood Pressure
Measurement of the pressure of circulating blood at rest
Time frame: Measured three times, once at each in-clinic appointment (week 0, month 6, month 12).
Differences in Multimodal Brain Signatures pre, mid, & post intervention
Neuroimaging of participants brain via magnetic resonance imaging (MRI) procedure.
Time frame: Measured thrice, once at baseline (week 0), mid-study (month 6), and final 12month appointment (month 12) visit.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of California, Los Angeles