Clinical trial NCT03500601: Effects of Consumption of Nut Components on Cognitive Function, Intestinal Microbial Communities and Markers of Health
Official title: Effects of Daily Tree Nut Consumption on Cognitive Function, Metabolomics and Intestinal Microbiota
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cognitive Function
Urinary Metabolites
Intestinal Microbiota
Keywords: Cognition
Metagenomics
Metabolomics
Lead sponsor: Northumbria University
Sponsor class: OTHER
Collaborators: name: International Nut and Dried Fruit Council
First posted: 2018-04-18
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 2 x 4 week intervention with 4 week washout
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Logical reasoning
timeFrame: At 28 days post dose, adjusted for baseline
Secondary outcomes:
measure: Location learning
timeFrame: At 28 days post dose, adjusted for baseline
measure: Choice reaction time
timeFrame: At 28 days post dose, adjusted for baseline
measure: Rapid Visual Information Processing
timeFrame: At 28 days post dose, adjusted for baseline
measure: Numeric working memory
timeFrame: At 28 days post dose, adjusted for baseline
measure: Stroop
timeFrame: At 28 days post dose, adjusted for baseline
measure: Peg and Ball
timeFrame: At 28 days post dose, adjusted for baseline
measure: Word recall
timeFrame: At 28 days post dose, adjusted for baseline
measure: Word recognition
timeFrame: At 28 days post dose, adjusted for baseline
measure: Picture recognition
timeFrame: At 28 days post dose, adjusted for baseline
measure: Bond-Lader
timeFrame: At 28 days post dose, adjusted for baseline
measure: Profile of Mood States (POMS)
timeFrame: At 28 days post dose, adjusted for baseline
measure: Urinary metabolites (fingerprinting and profiling)
timeFrame: At 28 days post dose, adjusted for baseline
measure: Intestinal microbial communities
timeFrame: At 28 days post dose, adjusted for baseline
Other outcomes:
Locations:
city: Newcastle upon Tyne
country: United Kingdom
facility: Northumbria University
state: Tyne & Wear
Study officials:
affiliation: Northumbria University
name: Crystal Haskell-Ramsay
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rita Cardoso B, Apolinario D, da Silva Bandeira V, Busse AL, Magaldi RM, Jacob-Filho W, Cozzolino SM. Effects of Brazil nut consumption on selenium status and cognitive performance in older adults with mild cognitive impairment: a randomized controlled pilot trial. Eur J Nutr. 2016 Feb;55(1):107-16. doi: 10.1007/s00394-014-0829-2. Epub 2015 Jan 8.
citation: Pribis P, Bailey RN, Russell AA, Kilsby MA, Hernandez M, Craig WJ, Grajales T, Shavlik DJ, Sabate J. Effects of walnut consumption on cognitive performance in young adults. Br J Nutr. 2012 May;107(9):1393-401. doi: 10.1017/S0007114511004302. Epub 2011 Sep 19.
citation: Tulipani S, Llorach R, Jauregui O, Lopez-Uriarte P, Garcia-Aloy M, Bullo M, Salas-Salvado J, Andres-Lacueva C. Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption. J Proteome Res. 2011 Nov 4;10(11):5047-58. doi: 10.1021/pr200514h. Epub 2011 Sep 29.
citation: Mora-Cubillos X, Tulipani S, Garcia-Aloy M, Bullo M, Tinahones FJ, Andres-Lacueva C. Plasma metabolomic biomarkers of mixed nuts exposure inversely correlate with severity of metabolic syndrome. Mol Nutr Food Res. 2015 Dec;59(12):2480-90. doi: 10.1002/mnfr.201500549. Epub 2015 Oct 21.
citation: Haskell-Ramsay CF, Dodd FL, Smith D, Cuthbertson L, Nelson A, Lodge JK, Jackson PA. Mixed Tree Nuts, Cognition, and Gut Microbiota: A 4-Week, Placebo-Controlled, Randomized Crossover Trial in Healthy Nonelderly Adults. J Nutr. 2023 Jan 14;152(12):2778-2788. doi: 10.1093/jn/nxac228.