The Acute and Chronic Cognitive and Cerebral Blood-Flow Effects of Nepalese Pepper (Zanthoxylum armatum DC.) Extract—A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Humans
<p>Chemical structure of hydroxy α-sanshool.</p> "> Figure 2
<p>Cognitive assessments. The running order of tasks and their contribution to the cognitive factors (to the right) and global performance measures (to the left) derived from the overall battery. The selection of tasks took 60 min to complete (with the Cognitive Demand Battery comprising 30 min of this). The same assessment was completed at the pre-treatment baseline and at 1, 3 and 5 h post-dose during both Day 1 and Day 56.</p> "> Figure 3
<p>Near-infrared spectroscopy (NIRS) assessment timeline. Each NIRS assessment comprised a pre-dose resting baseline and a post-dose assessment taking place between the 60– and 180 min post-dose cognitive assessments, as shown here. The post-dose assessmentcomprised a 5 min resting period, followed by three repetitions of the Cognitive Demand Battery tasks (27 min), all of which have been shown to sensitively modulate CBF parameters in the frontal cortex previously.</p> "> Figure 4
<p>Testing session timeline on Day 1 and Day 56. Cognitive assessments were completed at 8:30 am (pre-dose) and 60-, 180- and 300 min post-dose. Cerebral blood flow measures were taken from a subset of participants at baseline and then again at post-dose between the 60- and 180 min cognitive assessments. A standardized lunch was provided at ~2:00 pm.</p> "> Figure 5
<p>Effects on Speed of Attention. Top: Acute (Day 1) effects of a single dose of ZA on the Speed of Attention factor showing the main effect (panel <b>A</b>) and the planned comparisons (panel <b>B</b>) conducted on data from each post-dose assessment (i.e., 1-, 3- and 5-h post-dose). Bottom: acute effects of ZA on the individual cognitive tasks, Delayed Word Recall errors (panel <b>C</b>) and Name to Face recall accuracy (panel <b>D</b>). Data (mean and SEM) is change from pre-dose baseline. * = <span class="html-italic">p</span> < 0.05. <span class="html-italic">n</span> = 42/35 (ZA/placebo) for panel A and B and 42/39 for panel <b>C</b> and <b>D</b>.</p> "> Figure 6
<p>Effects on the Rapid Visual Information Processing (RVIP) task. Acute (Day 1) effects of a single dose of ZA on the RVIP task from the Cognitive Demand Battery outcomes. Panel <b>A</b> shows the main effect and panel B shows the planned comparisons conducted using data from each post-dose assessment (i.e., 1-, 3- and 5-h post-dose). Data (mean and SEM) are change from pre-dose baseline. * = <span class="html-italic">p</span> < 0.05 significant difference to placebo at that time point. <span class="html-italic">n</span> = 42/35 (ZA/placebo).</p> "> Figure 7
<p>Effects on Speed of Performance. Chronic effects of 56-days administration of ZA on the global Speed of Performance measure (calculated as the average reaction time Z score for the 9 timed tasks). Panel <b>A</b> shows the main effect and panel B shows the planned comparisons conducted using data from each post-dose assessment (i.e., 1-, 3- and 5-h post-dose). Data (mean and SEM) are change from pre-dose baseline. * = <span class="html-italic">p</span> < 0.05 significant difference to placebo at that time point. <span class="html-italic">n</span> = 39/39 (ZA/placebo).</p> "> Figure 8
<p>Chronic effects of ZA on Mental Fatigue and Serial 3s subtraction performance. Panel A shows the main effect on mental fatigue and panel B shows the planned comparisons conducted on data from each post-dose assessment (i.e., 1-, 3- and 5-h post-dose). The bottom panel (C) depicts the chronic effects of ZA on the Serial 3s subtraction task. Data (mean and SEM) are change from pre-dose baseline. * = <span class="html-italic">p</span> < 0.05 significant difference to placebo. <span class="html-italic">n</span> = 39/39 (ZA/placebo).</p> "> Figure 9
<p>Acute effects on cerebral blood flow (CBF) parameters after the first dose of ZA. The figures show pre-dose resting baseline adjusted data (µM; mean + SEM) where placebo is compared to ZA at each 2/2.5 min epoch of pre-task rest and task performance during Serial 3s, Serial 7s and the Rapid Visual Information Processing tasks. Asterisks indicate significance on the Bonferroni adjusted planned comparisons conducted on data from each epoch. * = <span class="html-italic">p</span> < 0.05, ** = <span class="html-italic">p</span> < 0.01, *** = <span class="html-italic">p</span> < 0.001. <span class="html-italic">n</span> = 20/21 (ZA/placebo).</p> "> Figure 10
<p>Effects of ZA on hemodynamic responses to brain activation (task performance) on Day 1 and Day 56 of treatment. The figures show data (mean + SEM) from each epoch of task performance (Serial 3s, Serial 7s and the Rapid Visual Information Processing tasks) (i.e., 7–32 min), baseline adjusted to the 5 min rest period immediately before the tasks commenced. Asterisks indicate significance on the Bonferroni adjusted planned comparisons; where placebo is compared to ZA at each epoch. * = <span class="html-italic">p</span> < 0.05, ** = <span class="html-italic">p</span> < 0.01, *** = <span class="html-italic">p</span> < 0.001. <span class="html-italic">n</span> = 20/21 (ZA/placebo).</p> ">
Abstract
:1. Introduction
2. Methods
2.1. Design
2.2. Participants
Near-infrared Spectroscopy (NIRS) Cerebral Blood-Flow Participants
2.3. Treatments
- Placebo (sunflower oil)
- 2.8 g Zanthozylum armatum DC. Medium-chain triglyceride (MCT) oil extract (corresponding to 80 mg Z.armatum DC. extract)
2.4. Cognitive and Mood Measures
2.4.1. Bond-Lader Mood Scales
2.4.2. Stimuli (Picture, Name/Face, Word) Presentation
2.4.3. Immediate Word Recall
2.4.4. Numeric Working Memory
2.4.5. Corsi Blocks Task
2.4.6. Choice Reaction Time (CRT)
2.4.7. Cognitive Demand Battery
2.4.8. Peg and Ball
2.4.9. Delayed Word Recall
2.4.10. Delayed Name to Face Recall
2.4.11. Delayed Picture and Word Recognition
2.5. Cerebral Blood-Flow (via NIRS) Assessment
Near-Infrared Spectroscopy (NIRS)
2.6. Procedure
2.7. Analysis
2.7.1. Cognitive and Mood Outcomes
2.7.2. Frontal Cortex Cerebral Blood Flow analysis
3. Results
3.1. Cognitive Function and Mood
3.1.1. Baseline Differences
3.1.2. Acute Effects of ZA after a Single Dose (Day 1)
3.1.3. Chronic Effects of ZA after 56 Days Treatment
3.2. NIRS-CBF
3.2.1. Global Changes in Resting CBF Parameters
3.2.2. Acute Effects on Day 1
3.2.3. Acute (Day 1) and Chronic (Day 56) Effects on Hemodynamic Responses to Brain Activation
3.2.4. Cognitive Performance
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Clinical Trials Number
Abbreviations
References
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Placebo | ZA | |
---|---|---|
Number of Participants | 42 | 41 |
Age at Enrolment (Years) | 41.76 | 43.15 |
Sex | F30/M12 | F33/M8 |
Years in Education | 16.2 | 15.9 |
Portions of Fruit & Veg/day | 4.37 | 4.42 |
Alcohol consumption daily (units) | 0.84 | 0.72 |
Caffeine Consumption Score (mg) | 149.90 | 179.67 |
Average BP Systolic (mm Hg) | 116.92 | 116.88 |
Average BP Diastolic (mm Hg) | 78.88 | 79.21 |
Average Heart Rate (Beats per min) | 73.11 | 72.22 |
Weight (KG) | 69.51 | 73.15 |
Height (cm) | 168.51 | 167.47 |
BMI | 24.47 | 25.92 |
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Kennedy, D.; Wightman, E.; Khan, J.; Grothe, T.; Jackson, P. The Acute and Chronic Cognitive and Cerebral Blood-Flow Effects of Nepalese Pepper (Zanthoxylum armatum DC.) Extract—A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Humans. Nutrients 2019, 11, 3022. https://doi.org/10.3390/nu11123022
Kennedy D, Wightman E, Khan J, Grothe T, Jackson P. The Acute and Chronic Cognitive and Cerebral Blood-Flow Effects of Nepalese Pepper (Zanthoxylum armatum DC.) Extract—A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Humans. Nutrients. 2019; 11(12):3022. https://doi.org/10.3390/nu11123022
Chicago/Turabian StyleKennedy, David, Emma Wightman, Julie Khan, Torsten Grothe, and Philippa Jackson. 2019. "The Acute and Chronic Cognitive and Cerebral Blood-Flow Effects of Nepalese Pepper (Zanthoxylum armatum DC.) Extract—A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Humans" Nutrients 11, no. 12: 3022. https://doi.org/10.3390/nu11123022