Evaluation of the Impact of a Nutritional Formulation on Cognitive Performance Following Stress Exposure.

Chronic stress can have a profound impact on quality of life, including cognitive health. Nutritional interventions offer promising, non-pharmacological approaches to support brain health, with particular nutrients showing potential to modulate stress and cognitive function. Creatine, Magnesium, L-Tyrosine, L-Theanine, Rhodiola, Phosphatidylserine and Citicoline have been shown to independently offer cognitive benefits, with the greatest impact observed during episodes of physiological and psychological stress. It is currently unknown whether a combination of these nutrients could produce a synergistic effect on cognitive performance that exceeds the impact of the individual nutrients alone.

This study will follow a double-blind, placebo-controlled, randomised, acute, repeated measures cross-over study design examining cognitive performance, productivity, sleep quality, mental and physical fatigue and subjective/physiological/endocrine responses to an acute psychological and physical stressor following (i) 'nutritional formulation+caffeine' or (ii) 'placebo+caffeine' drink. This research has the potential to identify a novel nutritional intervention that can reduce the negative impacts of stress on cognition.

Participants interested in the study will first take part in an initial health screening to ensure all criteria for eligibility are met. The health screening will include questions on physical and psychological conditions, medication, menstrual cycle, dietary behaviours and supplementation use. Eligible participants will then attend the Human Behavioural Neuroscience Labs at Leeds Beckett University city campus on three occasions over a period of a maximum of 8 weeks.

Prior to all visits participants will be asked to abstain from alcohol and exercise for 24 hours and to fast one hour prior to the session. Participants will also be asked to abstain from caffeine use for a minimum of 6 hours prior to the session. The first visit will involve collection of demographic information and completion of stress, anxiety and depression scales. Daily intake of caffeine consumption and dependency, levels of sleep quality will also be measured. Height and weight will be measured and baseline blood pressure readings taken. Familiarisation with the cognitive tasks will also take place during this visit. Participants will complete the CANTAB battery cognitive tasks to reduce the impact of early practice effects during the test session assessment. Following familiarisation, baseline cognitive performance will also assessed. The CANTAB battery will include the Digit Span (assessment of working memory and attention), Intra-Extra Dimensional Set Shift ( assessment of cognitive shifting and flexibility), Stop-Signal Task (assessment of executive function and inhibitory control) and Rapid Visual Information Processing (assessment of sustained attention).

Experimental test sessions two and three will follow identical procedures. Following a 15-minute resting period, baseline cortisol saliva sample, cardiovascular measures (heart rate and blood pressure), mood state, will be taken. The intervention will then be administered (Formulation + Caffeine) or (Placebo + Caffeine) in 200ml drink and consumed within a 5-minute timeframe. Following a 30 minute absorption period, participants will then be taken to a separate stress-induction room where they will be introduced to the Trier Social Stress Test (TSST). Following completion of the TSST, participants will then complete the Socially evaluated cold pressor test (SECPT). A combination of both the TSST and SCEPT will ensure activation of the both the autonomic and glucocorticoid stress systems and reduce the level of habituation to the stress response across repeated test sessions. The stress protocol will last approximately 20 minutes.

Following stress exposure, the CANTAB battery of cognitive tests will be administered in a serial order. Cognitive assessment will take place during the 40-minute period post-stressor. Throughout the test session cortisol saliva samples, cardiovascular measures (heart rate and blood pressure), mood state, levels of fatigue and perceptions of intervention impact will be measured. Twenty-four hours post session, an online questionnaire assessing the previous night's sleep and levels of productivity since treatment consumption will be administered. Data on side effects and physical experiences following treatment/placebo consumption will also be collected at this time point.

• Salivary cortisol [Time frame: Saliva will be collected across 2 timepoints, during Visit Two (Test session 1) and Visit Three (Test session 2). During each timepoint, a total of 6 samples will be taken during the test session.]
• Blood pressure [Time frame: Blood pressure will be measured across 2 timepoints, during Visit Two (Test session 1) and Visit Three (Test session 2). During each timepoint, a total of 8 blood pressure readings will be taken across the test session.]
• Heart rate [Time frame: Heart rate will be measured across 2 timepoints, during Visit Two (Test session 1) and Visit Three (Test session 2). During each timepoint, a total of 8 heart rate epochs readings will be taken across the test session.]
• Positive and Negative Affect Scale (PANAS) [Time frame: Assessed across 2 timepoints, during Visit Two (Test session 1) and Visit Three (Test session 2). At each timepoint the measure will be completed 4 times within the test session, and once four hours post session.]
• Visual Analogue Scale (VAS) [Time frame: Assessed across 2 timepoints, during Visit Two (Test session 1) and Visit Three (Test session 2). At each timepoint the measure will be completed 7 times within the test session, and once four hours post session.]
• Felt Effect Scale [Time frame: Assessed across 2 timepoints, during Visit Two (Test session 1) and Visit Three (Test session 2). At each timepoint the measure will be completed 3 times within the test session at 30, 53, ad 95 mins post intervention, and once four hours post session.]
• Leeds Sleep Evaluation Questionnaire [Time frame: Assessed across 2 timepoints, during Visit Two (Test session 1) and Visit Three (Test session 2). At each timepoint the measure will be completed 2 times, once at the beginning of the test session, and once 24 hours post session.]
• Productivity Scale [Time frame: Assessed across 2 timepoints (once in each Arm). Assessed once 24 hours post Visit Two (Test session 1) and Visit Three (Test session 2).]
• Health Events and Physical Experiences [Time frame: Assessed across 2 timepoints (once in each Arm). Assessed 24 hours post Visit Two (Test session 1) and Visit Three (Test session 2).]