The Acute Effect of a Walnut Intervention on Cognitive Performance, Brain Activation, and Serum Markers of Inflammation in Young Adults (WalCog)

The Acute Effect of a Walnut Intervention on Cognitive Performance , Brain Activation, and Serum Markers of Inflammation in Young Adults

This study investigates the effect of acute walnut consumption on the cognitive behaviour, mood, brain activation, and markers of inflammation in young adults. In a within subjects design participants will receive a 50 g walnut or placebo intervention in a randomised order with a one week washout between interventions.

Study Overview

• Status: Completed
• Conditions: Cognitive Change; Inflammatory Response; Mood; Satiety; Brain Derived Neurotrophic Factor Level
• Intervention / Treatment: Other: Control; Other: 50 g Walnut

Detailed Description

Participants will attend two test session days separated by a 7 day wash out period. The procedure on each day will be identical save for the intervention breakfast which will either be a walnut rich muesli containing 50g walnut and 50g mixed cereal ingredients (active intervention), or control muesli containing 100g mixed cereal ingredients (placebo intervention). The order of intervention will be randomised such that 50% of participants receive the active intervention during visit 1 and 50% during visit 2. Participants will be required to follow a low flavonoid diet for 48 hours in advance of testing and to fast (water only) for the final 12 hours of this period. The test day will be 8hrs in total starting at 0830.

Cognitive Measures: There will be four cognitive task battery sessions taking place at baseline, then 2, 4, and 6 hours following intervention. The cognitive battery will last for 30 minutes and include:

• Auditory Verbal Learning Task (AVLT) - Participants hear and recall a list of 15 words on 8 occasions followed by a forced choice visual recognition task (10 minutes duration).
• Modified Attention Network Task (MANT) - Participants view different arrays of arrows displayed on a monitor and respond by indicating the direction of the arrow closest to a central fixation point (8 minutes duration).
• Switching Task - Participants view eight equally spaced radii of circle displayed in such a way that there are four equally spaced segments above and below a bold line. Stimulus digits selected from between 1 - 9 (excluding 5) appear in each segment in turn. Participants respond to digits above the bold line in terms of whether they are odd or even and below the bold line in terms of whether they are above or below the number 5 (10 minutes duration).
• PANAS-NOW - This measure of trait mood will be completed at the beginning and end of each task battery giving a total of 8 measurements across the day. Participants rate the extent to which they are experiencing 20 different emotions on a 5-point Likert scale ranging from 'very slightly' to 'very much' (1 minute duration).

EEG: All participants will be tested in our dedicated lab within the Reading University Centre for Integrative Neuroscience and Neurodynamics using the Brain Products EEG system with 32 channel active electrode caps. At Baseline, 2, 4 and 6 hrs waveband PSD data will be recorded during all tasks with specific attention being paid to the theta bandwidth during the AVLT and gamma bandwidth during the executive function tasks. ERP data, anchored to each trial of the executive function tasks, will also be considered with specific attention being given to latency and strength of N1 and P3 peaks.

Bloods: Participants will have bloods taken twice on each test visit with a draw being taken from each arm. The initial draw will be taken immediately prior to the baseline task battery and then immediately prior to either the 2, 4 or 6 hr session with the second draw time being randomised in such a way that 16 participants will have blood drawn at 2hrs, 16 at 4hrs, and 16 at 6hrs. Following each draw, the blood samples will be left to clot for 30-60 minutes. The serum will be separated via centrifuge and stored at at -80°C until analysis is complete. Whole blood samples will not be stored at any point during the study. Blood serum will be analysed for anti-inflammatory ability, as well as levels of BDNF, a signalling protein known to be positively related to memory function. To determine possible mechanisms of action of walnut components through which the walnut polyphenols produce their beneficial effects, microglial cells from rats will be exposed to serum from participants in both walnut and placebo conditions prior to exposure to an inflammatory challenge (LPS). Markers of inflammation will then be assessed including extracellular release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) as well as intracellular levels of inducible nitrous oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We will then determine if those subjects with the most protective serum in the cell model are those with the better cognitive performance.

Appetite Measures: Ratings of subjective appetite and fullness will be taken using visual analogue scales after baseline, breakfast, and each of the remaining test sessions. As a further measure of satiety, weighted food measurements will be taken before and after consumption of the standard low flavonoid/PUFA lunch (given immediately after task battery session 3 at 1330) to ascertain total food consumption.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG6 6AL
      • University of Reading

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy
• Normal or corrected hearing and vision

Exclusion Criteria:

• Smoker.
• Allergic to treatment contents.
• Currently on medication which may interfere with the treatment
• Anaemic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control - 50g Walnut; Control condition followed by experimental condition.	Other: Control; 100 grams breakfast cereal; Other: 50 g Walnut; 50 grams walnuts mixed with 50 gram breakfast cereal.
Experimental: 50 g Walnut - Control; Experimental condition followed by control condition.	Other: Control; 100 grams breakfast cereal; Other: 50 g Walnut; 50 grams walnuts mixed with 50 gram breakfast cereal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed Recall	AVLT - Recall of a previously presented list of words following a 25 minute delay.	2 hours following intervention.
Delayed Recall	AVLT - Recall of a previously presented list of words following a 25 minute delay.	4 hours following intervention.
Delayed Recall	AVLT - Recall of a previously presented list of words following a 25 minute delay.	6 hours following intervention.
Word Recognition	AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay.	2 hours following intervention.
Word Recognition	AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay.	4 hours following intervention.
Word Recognition	AVLT - Visual Recognition of a previously presented list of words following a 25 minute delay.	6 hours following intervention.
Response interference accuracy	Accuracy performance on the Modified Attention Network Task	2 hours following intervention.
Response interference accuracy	Accuracy performance on the Modified Attention Network Task	4 hours following intervention.
Response interference accuracy	Accuracy performance on the Modified Attention Network Task	6 hours following intervention.
Response interference reaction time	Reaction time performance on the Modified Attention Network Task	2 hours following intervention
Response interference reaction time	Reaction time performance on the Modified Attention Network Task	4 hours following intervention
Response interference reaction time	Reaction time performance on the Modified Attention Network Task	6 hours following intervention
Switching Task Accuracy	Accuracy performance on the switching task	2 hours following intervention
Switching Task Accuracy	Accuracy performance on the switching task	4 hours following intervention
Switching Task Accuracy	Accuracy performance on the switching task	6 hours following intervention
Switching Task reaction time	Reaction time performance on the switching task	2 hours following intervention
Switching Task reaction time	Reaction time performance on the switching task	4 hours following intervention
Switching Task reaction time	Reaction time performance on the switching task	6 hours following intervention
N2	Change in ERP measure of N2 latency and amplitude	2 hours following intervention
N2	Change in ERP measure of N2 latency and amplitude	4 hours following intervention
N2	Change in ERP measure of N2 latency and amplitude	6 hours following intervention
P3	Change in ERP measure of P3 latency and amplitude	2 hours following intervention
P3	Change in ERP measure of P3 latency and amplitude	4 hours following intervention
P3	Change in ERP measure of P3 latency and amplitude	6 hours following intervention
Inflammatory Measure of nitrous oxide, tumor necorsis factor-alpha, inducible nitrous oxide synthase, and tumor necrosis facor-alpha.	Change in blood serum markers of inflammation	2 hours following intervention
Inflammatory Measure of nitrous oxide, tumor necorsis factor-alpha, inducible nitrous oxide synthase, and tumor necrosis facor-alpha.	Change in blood serum markers of inflammation	4 hours following intervention
Inflammatory Measure of nitrous oxide, tumor necorsis factor-alpha, inducible nitrous oxide synthase, and tumor necrosis facor-alpha.	Change in blood serum markers of inflammation	6 hours following intervention
BDNF	Change in blood serum levels of BDNF	2 hours following intervention
BDNF	Change in blood serum levels of BDNF	4 hours following intervention
BDNF	Change in blood serum levels of BDNF	6 hours following intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual analogue measure of hunger, satiety, fullness, and prospective food consumption (Flint et al., 2000).	Satiety Measure recorded on a 100 millimetre scale. Scores closer to 0 millimetres indicate less hunger - taken as a positive outcome, less satiety - taken as a negative outcome, less fullness - taken as a negative outcome, and less desire for prospective food consumption - taken as a positive.	2 hours following intervention.
Visual analogue measure of hunger, satiety, fullness, and prospective food consumption (Flint et al., 2000).	Satiety Measure recorded on a 100 millimetre scale. Scores closer to 0 millimetres indicate less hunger - taken as a positive outcome, less satiety - taken as a negative outcome, less fullness - taken as a negative outcome, and less desire for prospective food consumption - taken as a positive.	4 hours following intervention.
Visual analogue measure of hunger, satiety, fullness, and prospective food consumption (Flint et al., 2000).	Satiety Measure recorded on a 100 millimetre scale. Scores closer to 0 millimetres indicate less hunger - taken as a positive outcome, less satiety - taken as a negative outcome, less fullness - taken as a negative outcome, and less desire for prospective food consumption - taken as a positive.	6 hours following intervention.
EEG Spectral Analysis.	Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task.	2 hours following intervention.
EEG Spectral Analysis.	Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task.	4 hours following intervention.
EEG Spectral Analysis.	Changes in Power for Alpha, Beta, Gamma, Delta, and Theta bands during performance of each cognitive task.	6 hours following intervention.
Immediate Recall	AVLT - Immediate recall following first presentation of the word list	2 hours following intervention
Immediate Recall	AVLT - Immediate recall following first presentation of the word list	4 hours following intervention
Immediate Recall	AVLT - Immediate recall following first presentation of the word list	6 hours following intervention
Word Learning	AVLT - Area under the curve for first five word list recalls.	2 hours following intervention
Word Learning	AVLT - Area under the curve for first five word list recalls.	4 hours following intervention
Word Learning	AVLT - Area under the curve for first five word list recalls.	6 hours following intervention
Total Recall	AVLT - Sum of first 5 word list recalls.	2 hours following intervention.
Total Recall	AVLT - Sum of first 5 word list recalls.	4 hours following intervention.
Total Recall	AVLT - Sum of first 5 word list recalls.	6 hours following intervention.
Final Acquisition	AVLT - Immediate recall following final presentation of the word list	2 hours following intervention
Final Acquisition	AVLT - Immediate recall following final presentation of the word list	4 hours following intervention
Final Acquisition	AVLT - Immediate recall following final presentation of the word list	6 hours following intervention
Interference List Recall	AVLT - Immediate recall of second (interference) list.	2 hours following intervention.
Interference List Recall	AVLT - Immediate recall of second (interference) list.	4 hours following intervention.
Interference List Recall	AVLT - Immediate recall of second (interference) list.	6 hours following intervention.

Collaborators and Investigators

• Sponsor: University of Reading
• Collaborators: Tufts University; California Walnut Commission
• Investigators: Principal Investigator: Claire M Williams, PhD, University of Reading

Publications and helpful links

General Publications

• Bell L, Lamport DJ, Butler LT, Williams CM. A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action. Nutrients. 2015 Dec 9;7(12):10290-306. doi: 10.3390/nu7125538.
• Gomez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008 Jul;9(7):568-78. doi: 10.1038/nrn2421.
• Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord. 2000 Jan;24(1):38-48. doi: 10.1038/sj.ijo.0801083.
• Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Martinez-Gonzalez MA, Martinez-Lapiscina EH, Fito M, Perez-Heras A, Salas-Salvado J, Estruch R, Ros E. Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA Intern Med. 2015 Jul;175(7):1094-1103. doi: 10.1001/jamainternmed.2015.1668. Erratum In: JAMA Intern Med. 2018 Dec 1;178(12):1731-1732.
• Carey AN, Fisher DR, Joseph JA, Shukitt-Hale B. The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells. Nutr Neurosci. 2013 Jan;16(1):13-20. doi: 10.1179/1476830512Y.0000000023. Epub 2012 Dec 4.
• Fisher DR, Poulose SM, Bielinski DF, Shukitt-Hale B. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells. Nutr Neurosci. 2017 Feb;20(2):103-109. doi: 10.1179/1476830514Y.0000000150. Epub 2016 Mar 2.
• Haider S, Batool Z, Tabassum S, Perveen T, Saleem S, Naqvi F, Javed H, Haleem DJ. Effects of walnuts (Juglans regia) on learning and memory functions. Plant Foods Hum Nutr. 2011 Nov;66(4):335-40. doi: 10.1007/s11130-011-0260-2.
• Martinez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvado J, San Julian B, Sanchez-Tainta A, Ros E, Valls-Pedret C, Martinez-Gonzalez MA. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013 Dec;84(12):1318-25. doi: 10.1136/jnnp-2012-304792. Epub 2013 May 13.
• Miller MG, Thangthaeng N, Poulose SM, Shukitt-Hale B. Role of fruits, nuts, and vegetables in maintaining cognitive health. Exp Gerontol. 2017 Aug;94:24-28. doi: 10.1016/j.exger.2016.12.014. Epub 2016 Dec 21.
• Nooyens AC, Bueno-de-Mesquita HB, van Boxtel MP, van Gelder BM, Verhagen H, Verschuren WM. Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study. Br J Nutr. 2011 Sep;106(5):752-61. doi: 10.1017/S0007114511001024. Epub 2011 Apr 11.
• O'Brien J, Okereke O, Devore E, Rosner B, Breteler M, Grodstein F. Long-term intake of nuts in relation to cognitive function in older women. J Nutr Health Aging. 2014 May;18(5):496-502. doi: 10.1007/s12603-014-0014-6.
• Perez-Cano FJ, Castell M. Flavonoids, Inflammation and Immune System. Nutrients. 2016 Oct 21;8(10):659. doi: 10.3390/nu8100659.
• Poulose SM, Bielinski DF, Shukitt-Hale B. Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats. J Nutr Biochem. 2013 May;24(5):912-9. doi: 10.1016/j.jnutbio.2012.06.009. Epub 2012 Aug 20.
• 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.
• Ros E, Hu FB. Consumption of plant seeds and cardiovascular health: epidemiological and clinical trial evidence. Circulation. 2013 Jul 30;128(5):553-65. doi: 10.1161/CIRCULATIONAHA.112.001119. No abstract available.
• Sanchez-Villegas A, Galbete C, Martinez-Gonzalez MA, Martinez JA, Razquin C, Salas-Salvado J, Estruch R, Buil-Cosiales P, Marti A. The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: the PREDIMED-NAVARRA randomized trial. Nutr Neurosci. 2011 Sep;14(5):195-201. doi: 10.1179/1476830511Y.0000000011.
• Willis LM, Shukitt-Hale B, Cheng V, Joseph JA. Dose-dependent effects of walnuts on motor and cognitive function in aged rats. Br J Nutr. 2009 Apr;101(8):1140-4. doi: 10.1017/S0007114508059369.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2019
• Primary Completion (Actual): October 30, 2020
• Study Completion (Actual): October 30, 2020

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 28, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): August 20, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Flavonoid; Omega 3 Fatty Acid
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: RDG-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The full dataset will be anonymized and made available on the University of Reading Research Data Archive.
• IPD Sharing Time Frame: Data will be become available upon publication of study findings. Once published, the data will remain permanently available.
• IPD Sharing Access Criteria: The data will be Open Access and licensed as Creative Commons: Attribution 4.0
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No