Cognitive Function, Mood
Conditions
Keywords
Epigallocatechin Gallate, cerebral blood flow, Near Infrared spectroscopy, Electroencephalography, cognitive function, mood, cerebro-electrical activity
Brief summary
Epigallocatechin gallate (EGCG) is the most abundant catechin (sometimes referred to as tea flavonoids) in green tea extract. A review by Nagle et al (2006) identifies that a large amount of research indicates EGCG (amongst other catechins) is responsible for most of the potential health benefits associated with green tea. EGCG is brain permeable (Nakagawa & Miyazawa, 1997), and it is considered to have neuroprotective and neurorescue effects including modulation of cell survival and cell cycle genes (Levites et al 2002). Although there have been several human studies looking at the bioavailability of EGCG when administered in varying doses, there have been no studies that have specifically investigated the cognitive effects of this catechin in humans. Therefore, the purpose of this study is to assess the cerebral blood flow (using Near Infrared Spectroscopy), cerebro-electrical activity (EEG) and behavioural effects of EGCG. A randomised, double-blind, placebo-controlled, balanced crossover study will assess the effects of 135 mg and 270 mg pure EGCG in 24 healthy, young adults (18-35). Prior to the first active study day participants will attend a screening/training visit where relevant exclusion criteria will be assessed including any food sensitivities. They will also complete a caffeine consumption questionnaire in order to control for potential caffeine withdrawal effects as a result of restrictions of the study.
Interventions
DIETARY_SUPPLEMENTEGCG
Acute oral administration of capsules containing either: 0mg, 135mg or 270mg. One dosage administered on each of three separate study days.
DIETARY_SUPPLEMENTPlacebo
Pharmaceutical grade silica was utilized as placebo
Sponsors
Northumbria University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy * aged 18-35 * either caffeine consumers (consume more than 150mg caffeine per day) or non-consumers (consume less than 44mg caffeine per day).
Exclusion criteria
* smoke or consume any tobacco products * not proficient in English language * pregnant (or seeking to become pregnant) * taking recreational, over the counter/prescription medication (including the contraceptive pill), and/or dietary/herbal supplements * have food allergies or sensitivities * have history of/current head trauma, learning difficulties , ADHD, migraines or any gastric problems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modulation of Levels of Total Haemoglobin | 42 minutes | This measure assessed changes in levels of total haemoglobin during the 42 minute post- dose task period. Levels are in μmol/L and represent change from baseline levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Significant Modulation of Cognitive Performance | 42 minutes | The cognitive performance of participants was assessed via a range of computerised, mentally demanding, executive function tasks: Serial 3s and 7s subtractions, oddball reaction time task, rapid visual information processing, stroop and simple reaction time.These tasks were completed at baseline and then again 45 minutes after treatment administration. Significant modulation was determined if participants' post dose scores were significantly higher than baseline. |
| Number of Participants With Significant Modulation of Mood. | 42 minutes | Mood was assessed via computerised visual analogue scales at baseline and post- dose time points. Mood scores were calculated as change from baseline. And significant modulation was determined if baseline scores were significantly different to post dose. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 135mg EGCG Then 0mg EGCG Then 270mg EGCG Those participants who received treatment in this order. | 7 |
| 270mg EGCG Then 135mg EGCG Then 0mg EGCG Those participants who received treatment in this order. | 4 |
| 0mg EGCG Then 135mg EGCG Then 270mg EGCG Those participants who received treatment in this order. | 6 |
| 135mg EGCG Then 270mg EGCG Then 0mg EGCG Those participants who received treatment in this order. | 4 |
| 0mg EGCG Then 270mg EGCG Then 135mg EGCG Those participants who received treatment in this order. | 4 |
| 270mg EGCG Then 0mg EGCG Then 135mg EGCG Those participants who received treatment in this order. | 7 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Day 1 | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 2 |
| Day 2 | Protocol Violation | 2 | 0 | 0 | 0 | 0 | 0 |
| Day 3 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 270mg EGCG Then 135mg EGCG Then 0mg EGCG | 0mg EGCG Then 135mg EGCG Then 270mg EGCG | 135mg EGCG Then 270mg EGCG Then 0mg EGCG | 135mg EGCG Then 0mg EGCG Then 270mg EGCG | 0mg EGCG Then 270mg EGCG Then 135mg EGCG | 270mg EGCG Then 0mg EGCG Then 135mg EGCG | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 4 Participants | 7 Participants | 4 Participants | 7 Participants | 32 Participants |
| Age Continuous | 22 years STANDARD_DEVIATION 4 | 22 years STANDARD_DEVIATION 4 | 22 years STANDARD_DEVIATION 4 | 22 years STANDARD_DEVIATION 4 | 22 years STANDARD_DEVIATION 4 | 22 years STANDARD_DEVIATION 4 | 22 years STANDARD_DEVIATION 4 |
| Region of Enrollment United Kingdom | 4 participants | 6 participants | 4 participants | 7 participants | 4 participants | 7 participants | 32 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 7 | 0 / 4 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 4 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 7 |
Outcome results
Primary
Modulation of Levels of Total Haemoglobin
This measure assessed changes in levels of total haemoglobin during the 42 minute post- dose task period. Levels are in μmol/L and represent change from baseline levels.
Time frame: 42 minutes
Population: If NIRS readings were deemed not too affected by artefacts (usually caused by participants moving the headband in some way) then they were utilized in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 135mg EGCG | Modulation of Levels of Total Haemoglobin | -1.4 μmol/L | Standard Error 0.5 |
| 270mg EGCG | Modulation of Levels of Total Haemoglobin | -1.3 μmol/L | Standard Error 0.3 |
| Placebo | Modulation of Levels of Total Haemoglobin | -1.7 μmol/L | Standard Error 0.3 |
Comparison: This data was analysed by two-way repeated measures ANOVA (task \[epoch\] x treatment). In the case of those analyses that showed a significant main effect of treatment or a task/epoch x treatment interaction, planned comparisons of data from each task or epoch were then made between placebo and each of the EGCG treatment groups using t tests calculated with the Mean Squares Error from the ANOVA.p-value: <0.05ANOVA
Secondary
Number of Participants With Significant Modulation of Cognitive Performance
The cognitive performance of participants was assessed via a range of computerised, mentally demanding, executive function tasks: Serial 3s and 7s subtractions, oddball reaction time task, rapid visual information processing, stroop and simple reaction time.These tasks were completed at baseline and then again 45 minutes after treatment administration. Significant modulation was determined if participants' post dose scores were significantly higher than baseline.
Time frame: 42 minutes
Population: If participants were deemed to have completed the tasks to the best of their ability then their scores were utilized in the analysis.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| 135mg EGCG | Number of Participants With Significant Modulation of Cognitive Performance | 0 Participants | 0 |
| 270mg EGCG | Number of Participants With Significant Modulation of Cognitive Performance | 0 Participants | 0 |
| Placebo | Number of Participants With Significant Modulation of Cognitive Performance | 0 Participants | 0 |
Comparison: Task performance data were analysed by within subjects ANCOVA (treatment) with pre-treatment performance included as a co-variate for each individual task/measure.p-value: >0.05ANCOVA
Secondary
Number of Participants With Significant Modulation of Mood.
Mood was assessed via computerised visual analogue scales at baseline and post- dose time points. Mood scores were calculated as change from baseline. And significant modulation was determined if baseline scores were significantly different to post dose.
Time frame: 42 minutes
Population: As long as data for all participants was captured for all 3 sessions then that participants data was utilized in the analysis.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| 135mg EGCG | Number of Participants With Significant Modulation of Mood. | 0 Participants | 0 |
| 270mg EGCG | Number of Participants With Significant Modulation of Mood. | 0 Participants | 0 |
| Placebo | Number of Participants With Significant Modulation of Mood. | 0 Participants | 0 |
Comparison: Mood data was analysed via student t-test.p-value: >0.05t-test, 2 sided