Effects of Consumption of Nut Components on Cognitive Function, Intestinal Microbial Communities and Markers of Health

Study Overview
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Brief Summary
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Tree nuts (for example brazil nuts, almonds, hazelnuts, walnuts, cashew nuts etc) contain a wide variety of nutrients including fatty acids, polyphenols and micronutrients. The beneficial health effects ascribed to the consumption of tree nuts include improvements to cardiovascular outcomes and regulation of glucose levels and inflammation. Emerging evidence suggests that specific components of nuts may also contribute to brain health and function. The aim of the present study is to assess the effects of four weeks' supplementation of nut components on cognition and subjective measures. Urinary metabolites and intestinal microbial communities will also be assessed allowing biomarkers of nut exposure to be highlighted.

Detailed Description
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To date, only two small human intervention trials have evaluated the effects of nuts as a sole intervention on cognition. One study reported a benefit verbal fluency and constructional praxis following daily consumption of 6 g brazil nuts for 6 months in older adults diagnosed with mild cognitive impairment. Eight weeks' consumption of 60 g/d walnuts in healthy young adults aged 18-25 years also resulted in improved inferential verbal reasoning scores compared to placebo. The development of various 'omics' technologies has enabled researchers to investigate the influence of nutrients or dietary change on metabolic pathways at multiple levels with a view to developing biological markers of dietary intake. Metabolomic approaches have been used successfully to study nut consumption; for example putative biomarkers of nut consumption have been revealed as metabolites associated with serotonin pathways. Furthermore, certain nut biomarkers identified using metabolomics appear to be negatively associated with health parameters which is suggested to be due to gut microbiota dysbiosis and provides an important link between nut consumption, the gut microflora and metabolic pathways. This study will assess the effects of four weeks' supplementation with nut components on cognition. Metabolomic and metagenomic approaches will be utilised to analyse urinary metabolites and intestinal microbial communities allowing biomarkers of nut exposure to be highlighted. Metabolic and gut microbiota responses will then be correlated with changes in cognition in order to identify inter-individual differences in response, and further understanding of the mechanisms underpinning cognitive benefits of nut consumption.

Official Title
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Effects of Daily Tree Nut Consumption on Cognitive Function, Metabolomics and Intestinal Microbiota

Conditions
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Cognitive Function, Urinary Metabolites, Intestinal Microbiota

Intervention / Treatment
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* Other: Nut components
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Willing to abstain throughout the trial from any nutritional supplementation Willing to abstain throughout the trial from the intake of any nuts or nut containing products Exclusion Criteria: Aged under 18 or over 49 Relevant pre-existing medical condition/illness Current use of prescription medications (excluding contraception) Learning difficulties and dyslexia Visual impairment that cannot be corrected with glasses or contact lenses including colour blindness Currently suffer from migraines (> 1 per month) Smoking or use of any nicotine replacement products e.g. vaping, gum, patches History of or any current food intolerances/sensitivities, including nut/peanut allergies Never consumed nuts, or regularly consume nuts more than twice per week Irregular bowel function (less than one bowel movement per day) Body mass index (BMI) under 18.5 or over 30 Pregnancy, seeking to become pregnant, or current lactation Inability to complete all of the study assessments Current participation in other clinical or nutrition intervention studies Not proficient in English equivalent to IELTS band 6 or above Have any known active infections Blood pressure >139/89mmHg Are employed in a job that includes night shift work Have habitually used supplements within the last month (defined as more than 3 consecutive days or 4 days in total)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2 x 4 week intervention with 4 week washout
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment<br>Nut components | Other: Nut components<br>* nut components consumed daily for a period of 28 days<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Placebo consumed daily for a period of 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Logical reasoning | Cognition - executive function | At 28 days post dose, adjusted for baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Location learning | Cognition - spatial memory | At 28 days post dose, adjusted for baseline | 
| Choice reaction time | Cognition - attention | At 28 days post dose, adjusted for baseline | 
| Rapid Visual Information Processing | Cognition - working memory | At 28 days post dose, adjusted for baseline | 
| Numeric working memory | Cognition - working memory | At 28 days post dose, adjusted for baseline | 
| Stroop | Cognition - executive function | At 28 days post dose, adjusted for baseline | 
| Peg and Ball | Cognition - executive function | At 28 days post dose, adjusted for baseline | 
| Word recall | Cognition - episodic memory | At 28 days post dose, adjusted for baseline | 
| Word recognition | Cognition - episodic memory | At 28 days post dose, adjusted for baseline | 
| Picture recognition | Cognition - episodic memory | At 28 days post dose, adjusted for baseline | 
| Bond-Lader | Mood | At 28 days post dose, adjusted for baseline | 
| Profile of Mood States (POMS) | Mood | At 28 days post dose, adjusted for baseline | 
| Urinary metabolites (fingerprinting and profiling) | Liquid chromatography/mass spectrometry, combined with data mining using specific software to identify specific metabolites influenced by supplementation | At 28 days post dose, adjusted for baseline | 
| Intestinal microbial communities | Analysis of total DNA using standardised procedures targeting bacteria using the 16S rRNA gene. | At 28 days post dose, adjusted for baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognition, Metagenomics, Metabolomics