Nepalese Pepper Extract Improves Cognition and Cerebral Blood Flow

by | Jan 21, 2020 | 2019, Botanicals, Brain Health, Cognitive Health

Written by Angeline A. De Leon, Staff Writer. Supplementation with Zanthoxylum armatum DC. ZA extract, rich in hydroxy α-sanshool, significantly improved the processing speed of cognitive tasks.

Botanical - PeppercornsTraditionally known as Nepalese or Timur pepper, Zanthoxylum armatum DC. (ZA) is a grapefruit-like spice with medicinal properties relevant to the treatment of mood disorders, digestive issues, and skin wounds 1,2. ZA contains a large number of alkamides (bioactive phytochemicals), including the compound hydroxy α-sanshool which is responsible for the numbing and tingling sensation associated with spicy foods 3. Exhibiting antimicrobial, anti-inflammatory, and immunomodulatory activity, alkamides have been shown to alleviate symptoms of anxiety and depression 1,4,5. In one rodent study, administration of an herbal medicine (Daikenchuto) containing ZA as an active component led to significant improvement in learning and memory, along with mitigation of cognitive degradation in mice 6. Researchers speculate that the cognitive benefits associated with hydroxy α-sanshool may be due to its interactions with different neurotransmission systems 7 or potential modulation of ion channel networks which influence cerebral blood flow (CBF) 8. In a 2019 study 9 published in Nutrients, researchers in the UK investigated the effects of a ZA extract on cognitive function and CBF parameters in the frontal cortex during cognitive task performance.

Using a randomized, double-blind, placebo-controlled, parallel-group study design, investigators recruited a total of 82 healthy participants (aged 30-55 years), who were randomly assigned to receive either 2.8 g ZA (containing 7.8 mg hydroxy α-sanshool) or matching placebo. To measure both the acute and chronic effects of ZA supplementation, participants were assessed at baseline and at 1, 3, and 5 hours post-ingestion of ZA on the first day, as well as after 56 days of daily ZA supplementation (at same dosage). On the first and last day of treatment, cognitive tasks and mood measures were administered using the Computerized Mental Performance Assessment System. In a subset of 41 subjects, CBF was measured in the frontal cortex using Near Infrared Spectroscopy (NIRS, proxy measure of CBF) at rest and during performance of Cognitive Demand Battery Tasks (designed to activate the frontal cortex) on Day 1 and Day 56.

Relative to placebo, acute consumption of ZA was associated with significant improvement on the Speed of Attention task at the 1-hour and 3-hour mark (p = 0.005, p < 0.001, respectively), as well as on the Rapid Visual Information Processing (RVIP) task at the 1-hour and 5-hour mark (p = 0.046, p = 0.011). After 56 days, ZA treatment also led to significant improvement on global Speed of Performance on timed tasks (p = 0.042) and a reduction in reported mental fatigue (p = 0.006). On both Day 1 and Day 56, ingestion of ZA was also linked to global reduction in CBF during RVIP task performance (driven by a decrease in oxygenated hemoglobin [treatment x task-epoch interactions: F(11, 429) = 2.21, p = 0.013]), suggesting significant modulation of hemodynamic response following both acute and chronic ZA intake.

Evidence from the study supports the relationship between ZA supplementation and enhanced cognitive function, concurrent with improved CBF parameters during task performance. Intake of ZA, both acute and chronic, was shown to bolster aspects of cognitive function, particularly those associated with processing speed and mental fatigue. Cognitive improvements were also paralleled by changes in hemodynamic response during task performance. On Day 1 and Day 56, ZA subjects exhibited reduced hemodynamic response during the RVIP, suggesting that consumption of a ZA extract containing hydroxy α-sanshool may favorably contribute to neural efficiency during executive function tasks. A primary limitation of the present study is the relatively small sample size used for NIRS analysis. In future studies, it would also be valuable to confirm the effects of ZA on CBF using more direct measures of local neural activity (e.g., event-related optical signal neuroimaging). Finally, further research is needed to elucidate the specific physiological mechanisms associated with the cognitive benefits of ZA.

Source: Kennedy D, Wightman E, Khan J, et al. 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. DOI: 10.3390/nu11123022.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Posted January 21, 2020.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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