Polyphenol Supplement for Cognitive Impairment
(MAEVE Trial)
Recruiting in Palo Alto (17 mi)
Overseen byArpana Gupta, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of California, Los Angeles
Must not be taking: Psychoactive medications, Antibiotics, Probiotics
Disqualifiers: Vegan, Cognitive impairment, Psychosis, others
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you have recently changed your use of psychoactive medications or other medications that interfere with the study's outcomes, you may not be eligible to participate.
What data supports the effectiveness of the polyphenol supplement treatment for cognitive impairment?
Research suggests that diets rich in polyphenols, like those found in cocoa, may help reduce the risk of cognitive decline and Alzheimer's disease. Some studies have shown that polyphenols can improve cognitive function, especially in older adults, by potentially reducing inflammation in the brain.
12345Is the Polyphenol Supplement safe for humans?
Polyphenols, found in foods like cocoa, grapes, and blueberries, have been studied for their health benefits, including cognitive support. While research is promising, more studies are needed to fully understand their safety and effects in humans. Current evidence suggests they are generally safe, but it's important to consider individual health conditions and consult with a healthcare provider.
15678How is the polyphenol supplement treatment different from other treatments for cognitive impairment?
The polyphenol supplement is unique because it uses naturally occurring compounds found in plants, like grapes and blueberries, which may help improve cognitive function by reducing neuroinflammation and oxidative stress. Unlike some other treatments, it focuses on dietary intake and its potential benefits for cognitive health, although more research is needed to confirm its effectiveness.
12489Eligibility Criteria
This trial is for adults over 50 who are overweight or obese, speak English well, and eat a Western diet high in animal products and processed foods. They must be at higher risk of Alzheimer's due to family history but cannot participate if they have certain conditions that the provided information does not specify.Inclusion Criteria
I am 50 years old or older.
I am either male or female.
I am at high risk for Alzheimer's due to my family history.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either the Juice Plus+ intervention or placebo, with regular monitoring and assessments
12 months
4 in-clinic appointments, monthly online questionnaires
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests whether a polyphenol supplement can slow or prevent cognitive decline compared to a placebo. It involves taking pills twice daily, regular check-ins with nutritionists, brain scans, cognitive tests, stool and blood samples over one year.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Polyphenol SupplementExperimental Treatment1 Intervention
Juice Plus Essentials, Berry Blend Capsules
Group II: Placebo SupplementPlacebo Group1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California, Los AngelesLos Angeles, CA
Loading ...
Who Is Running the Clinical Trial?
University of California, Los AngelesLead Sponsor
References
Polyphenols and neuroprotection: Therapeutic implications for cognitive decline. [2022]Dietary polyphenols have been the focus of major interest for their potential benefits on human health. Several preclinical studies have been conducted to provide a rationale for their potential use as therapeutic agents in preventing or ameliorating cognitive decline. However, results from human studies are scarce and poorly documented. The aim of this review was to discuss the potential mechanisms involved in age-related cognitive decline or early stage cognitive impairment and current evidence from clinical human studies conducted on polyphenols and the aforementioned outcomes. The evidence published so far is encouraging but contrasting findings are to be taken into account. Most studies on anthocyanins showed a consistent positive effect on various cognitive aspects related to aging or early stages of cognitive impairment. Studies on cocoa flavanols, resveratrol, and isoflavones provided substantial contrasting results and further research is needed to clarify the therapeutic potential of these compounds. Results from other studies on quercetin, green tea flavanols, hydroxycinnamic acids (such as chlorogenic acid), curcumin, and olive oil tyrosol and derivatives are rather promising but still too few to provide any real conclusions. Future translational studies are needed to address issues related to dosage, optimal formulations to improve bioavailability, as well as better control for the overall diet, and correct target population.
Effect of Polyphenolic Complements on Cognitive Function in the Elderly: A Systematic Review. [2022]Polyphenols have been shown to be effective against many chronic diseases. These compounds could have a beneficial effect at the cognitive level. The exact mechanism by which they provide positive effects at the cognitive level is not well known, but it is believed that they could counteract neuroinflammation. The objective of this study is to review nutritional interventions that include foods or supplements rich in flavanols, flavonols, or stilbenes to the usual diet on cognitive deterioration in people over 50 years of age. Clinical trials published in PubMed and Web of Science from 1 March 2010 to 1 March 2020 were explored, from which 14 studies were selected. All of them showed some improvement after the intervention. In interventions with flavanols and stilbenes, relevant improvements have been observed both in healthy patients and in patients with established cognitive impairment. Most studies agree that the greatest benefits are found with high doses and longer duration treatments. The changes were fundamentally assessed through cognitive tests, and in some of the studies, through magnetic resonance imaging (fMRI). The type of cognitive test used to assess the effect of the intervention was revealed to be critical. Several studies have also shown improvements in analytical parameters and blood pressure.
Low Levels of a Urinary Biomarker of Dietary Polyphenol Are Associated with Substantial Cognitive Decline over a 3-Year Period in Older Adults: The Invecchiare in Chianti Study. [2019]To investigate the association between total urinary polyphenols (TUPs) and total dietary polyphenols (TDPs) and cognitive decline in an older population.
Polyphenols for the Prevention and Treatment of Cognitive Impairment. [2022]Epidemiological studies have suggested that diets rich in polyphenols/phenolic compounds are associated with reduced risk of cognitive impairment and Alzheimer's disease (AD). Experimental studies have indicated that these compounds have specific effects on AD pathogenesis as well as anti-oxidant and anti-inflammatory effects. For clinical use, several compounds have been investigated by clinical trials to establish their efficacy for prevention and treatment of AD or cognitive impairment.
The Efficacy of Cocoa Polyphenols in the Treatment of Mild Cognitive Impairment: A Retrospective Study. [2023]Background: Mild cognitive impairment (MCI) is characterized by cognition impairment that does not interfere with the usual activities of daily living. It is considered to be a transitional stage between normal aging and dementia. No treatment is available for MCI. Methods: This retrospective cohort study included 55 patients (29 males and 26 females, aged 56-75 years) with a diagnosis of amnestic MCI who attended the Center for Cognitive Disorder and Dementia of the IRCCS Centro Neurolesi Bonino Pulejo (Messina, Italy) between January and December of 2017. As we aimed to evaluate the effect of cocoa polyphenols on cognition, the study population was separated into two groups depending on the change in their Mini-Mental State Examination (MMSE) score at a one-year follow-up. Results: Compared to G2 (i.e., patients with a worsening in cognitive functions), the rate of polyphenol intake was significantly higher in patients without a worsening in cognition (i.e., G1) (χ2 = 13.79, df = 1, p-value < 0.001). By subdividing G1 patients based on whether they improved or were stable at follow-up, we found that 46.2% of those who had improved were treated with polyphenols. Conclusions: Dietary supplementation of cocoa flavonoids seems to reduce the progression of MCI to dementia. Further prospective studies with larger sample volumes are required to confirm these promising findings.
Role of phytochemicals as nutraceuticals for cognitive functions affected in ageing. [2023]Cognitive decline can occur with normal ageing and in age-related brain disorders, such as mild cognitive impairment and dementia, including Alzheimer's disease, with limited pharmacological therapies available. Other approaches to reduce cognitive decline are urgently needed, and so, the role of dietary interventions or nutraceuticals has received much attention in this respect. In this review, we examine the evidence for dietary plants and their chemical constituents as nutraceuticals, relevant to both cognitive decline in normal ageing and in dementia. Pharmacological (in vitro and in vivo), clinical and epidemiological evidence is assessed for both frequently consumed plants and their dietary forms, including tea, coffee, cocoa (chocolate), red wine, grapes, citrus and other fruits; in addition to plants used less frequently in certain diets and those that cross the blurred boundaries between foods, nutraceuticals and medicinal plants. For the latter, turmeric, saffron, sage, rosemary and lemon balm are examples of those discussed. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.
Polyphenols in dementia: From molecular basis to clinical trials. [2022]Dementia is common in the elderly, but there are currently no effective therapies available to prevent or treat this syndrome. In the last decade, polyphenols (particularly curcumin, resveratrol and tea catechins) have been under very close scrutiny as potential therapeutic agents for neurodegenerative diseases, diabetes, inflammatory diseases and aging. Data were collected from Web of Science (ISI Web of Knowledge), Pubmed and Medline (from 2000 to 2015), by searching for the keywords "dementia" AND "curcumin", "resveratrol", "EGCG", "tea catechins". The same keywords were used to investigate the current state of clinical trials recorded in the NIH clinicaltrials.gov registry. Starting from the intrinsic properties of the compounds, we explain their specific action in patients with AD and the most common types of dementia. The pharmacological actions of curcumin, resveratrol and tea catechins have mainly been attributed to their antioxidant activity, interaction with cell signaling pathways, anti-inflammatory effect, chelation of metal ions, and neuroprotection. Evidence from in vitro and in vivo studies on polyphenols have demonstrated that they may play an integral role in preventing and treating diseases associated with neurodegeneration. Furthermore, we critically analyze the clinical trials that we found, which investigate the real pharmacological actions and the possible side effects of these compounds. This review highlights the potential role of polyphenols in the prevention/treatment of dementia and describes the current limitations of research in this field.
Effects of a polyphenol-rich grape and blueberry extract (Memophenol™) on cognitive function in older adults with mild cognitive impairment: A randomized, double-blind, placebo-controlled study. [2023]Polyphenols are naturally occurring organic compounds found in plants. Research suggests that their intake reduces the risk of cognitive decline and related dementias. Grapes and blueberries are polyphenol-rich foods that have attracted attention for their potential cognitive-enhancing effects.
Prevalence of Poor Mental Health and Cognitive Status among Middle-Aged Adults and Its Predictors in Relation to Polyphenols Intake. [2022]Decline in mental health and cognitive status starts to show its sign during middle-age and is affected by dietary factors, namely the polyphenols intake. Polyphenols have received attention in improving health issues related to aging, including decline in mental health and cognitive. The aim of this study is to determine the prevalence of poor mental health and cognitive status among middle-aged adults and its predictors in relation to polyphenols intake.