Cognitive FunctionNCT03500601
Effects of Consumption of Nut Components on Cognitive Function, Intestinal Microbial Communities and Markers of Health
A study testing Nut components in people with Cognitive Function and Urinary Metabolites, run by Northumbria University at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Function, Urinary Metabolites, Intestinal Microbiota
- What is being tested?
- Nut components
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 22 Nov 2017to 19 Oct 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 19Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Northumbria University
Newcastle upon Tyne, Tyne & Wear, NE1 8ST
About this study
Official title: Effects of Daily Tree Nut Consumption on Cognitive Function, Metabolomics and Intestinal Microbiota
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.
Read the 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.
- Being tested
- Nut components, Placebo
- Keywords
- Cognition, Metagenomics, Metabolomics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nut componentsOther
nut components consumed daily for a period of 28 days
PlaceboOther
Placebo consumed daily for a period of 28 days
| Study group | Role | What they receive |
|---|---|---|
| Active treatment | Experimental | Nut components Receives: Other: Nut components |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Logical reasoning
Cognition - executive function
Measured: At 28 days post dose, adjusted for baseline
Secondary outcomes (13)
Location learning
Cognition - spatial memory
Measured: At 28 days post dose, adjusted for baseline
Choice reaction time
Cognition - attention
Measured: At 28 days post dose, adjusted for baseline
Rapid Visual Information Processing
Cognition - working memory
Measured: At 28 days post dose, adjusted for baseline
Numeric working memory
Cognition - working memory
Measured: At 28 days post dose, adjusted for baseline
Stroop
Cognition - executive function
Measured: At 28 days post dose, adjusted for baseline
Peg and Ball
Cognition - executive function
Measured: At 28 days post dose, adjusted for baseline
Word recall
Cognition - episodic memory
Measured: At 28 days post dose, adjusted for baseline
Word recognition
Cognition - episodic memory
Measured: At 28 days post dose, adjusted for baseline
Picture recognition
Cognition - episodic memory
Measured: At 28 days post dose, adjusted for baseline
Bond-Lader
Mood
Measured: At 28 days post dose, adjusted for baseline
Profile of Mood States (POMS)
Mood
Measured: 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
Measured: 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.
Measured: At 28 days post dose, adjusted for baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2018
- Study start22 Nov 2017
- Primary completion19 Oct 2018
- Study completion19 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cognitive FunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 2 x 4 week intervention with 4 week washout
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northumbria University
- Sponsor type
- University, hospital or other
- Collaborators
- International Nut and Dried Fruit Council
- Responsible party
- Sponsor
- Investigators
- Crystal Haskell-Ramsay, Principal investigator, Northumbria University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03500601
- Sponsor's protocol ID
- 51BQ1
- Status last verified
- May 2018
- First submitted
- 12 Mar 2018
- Last updated
- 13 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25567069Pribis 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.
PubMed 21923981Tulipani 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.
PubMed 21905751Mora-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.
PubMed 26412215Haskell-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.
PubMed 36202391
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Daily Tree Nut Consumption on Cognitive Function, Metabolomics and Intestinal Microbiota
- ClinicalTrials.gov ID
- NCT03500601
- Acronym / sponsor ID
- 51BQ1
- Keywords
- Cognition, Metagenomics, Metabolomics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Northumbria UniversityUniversity, hospital or other
- Collaborators
- International Nut and Dried Fruit Council
- Study start
- 22 Nov 2017 (actual)
- Primary completion
- 19 Oct 2018 (actual)
- Study completion
- 19 Oct 2018 (actual)
- First posted
- 18 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 2 x 4 week intervention with 4 week washout
| Arm | Type | Receives |
|---|---|---|
| Active treatment | Experimental | Other: Nut componentsNut components |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nut componentsnut components consumed daily for a period of 28 days | Other | Active treatment |
| PlaceboPlacebo consumed daily for a period of 28 days | Other | Placebo |
Primary outcome
Logical reasoning
Time frame: At 28 days post dose, adjusted for baseline
Cognition - executive function
13 secondary outcomes
Location learning
Time frame: At 28 days post dose, adjusted for baseline
Choice reaction time
Time frame: At 28 days post dose, adjusted for baseline
Rapid Visual Information Processing
Time frame: At 28 days post dose, adjusted for baseline
Numeric working memory
Time frame: At 28 days post dose, adjusted for baseline
Stroop
Time frame: At 28 days post dose, adjusted for baseline
Peg and Ball
Time frame: At 28 days post dose, adjusted for baseline
Word recall
Time frame: At 28 days post dose, adjusted for baseline
Word recognition
Time frame: At 28 days post dose, adjusted for baseline
Picture recognition
Time frame: At 28 days post dose, adjusted for baseline
Bond-Lader
Time frame: At 28 days post dose, adjusted for baseline
Profile of Mood States (POMS)
Time frame: At 28 days post dose, adjusted for baseline
Urinary metabolites (fingerprinting and profiling)
Time frame: At 28 days post dose, adjusted for baseline
Intestinal microbial communities
Time frame: At 28 days post dose, adjusted for baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2019.
- Background: PubMed 25567069Rita 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.
- Background: PubMed 21923981Pribis 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.
- Background: PubMed 21905751Tulipani 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.
- Background: PubMed 26412215Mora-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.
- Derived from this study: PubMed 36202391Haskell-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.
- Individual participant dataSharing planned: No
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Healthy Participants
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Crystal Haskell-Ramsay principal investigator
Northumbria University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nut components in people with Cognitive Function and Urinary Metabolites, run by Northumbria University at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Logical reasoning (time frame: At 28 days post dose, adjusted for baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03500601, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2019.