Cognitive and Cerebral Blood Flow Effects of Zanthozylum Armatum Fruit Extract in Healthy Adults Aged 30 - 55

Zanthozylum armatum (Z. armatum)-otherwise known as Nepalese pepper, or timut-is an perennial shrub found in India and across Southeast Asia. Preparations of the bark, fruit and seeds of Z. armatum have been extensively used in traditional Indian medicine. Preliminary data have indicated that preparations of Z. armatum may also be beneficial to cognitive function. The study aims to investigate the effects acute and chronic consumption of Z. armatum on cognitive function and cerebral blood flow.

Zanthozylum armatum (Z. armatum) is an perennial shrub found in India and across Southeast Asia. Preparations of the bark, fruit and seeds of Z. armatum have been extensively used in traditional Indian medicine. For example, the fruits and seeds have been employed as an aromatic tonic in fever and dyspepsia and the essential oil of the fruits has exhibited antibacterial, antifungal and anthelmintic properties. Furthermore, the dried fruits are used as spice, especially in Nepalese and Sichuan cuisine with increasing popularity across Europe. With regard to physiological effects relevant to brain function, Z. armatum has also been traditionally used as a cardio-depressant; these vasodilatory properties have recently being linked to its antagonistic effect on calcium ion channel function as demonstrated in isolated rabbit aorta tissue. In addition, the observed anti-inflammatory and antioxidant effects of preparations of Z. armatum may serve to beneficially impact cognition with chronic administration.

Although direct effects of Z. armatum on brain function have yet to be assessed; Zanthozylum fruit comprises one constituent of the traditional Japanese herbal medicine Daikenchuto (DKT) where some data do exist. In a series of trials investigating the effects of DKT on learning and memory function in mice, it was established that the extract of Zanthozylum fruit contained in DKT alone that was associated with reductions in escape latency in the Morris Water Maze task. Interestingly, the authors also revealed that it was the amide hydroxy-ɑ-sanshool (HAS) isolated from the Zanthozylum fruit extract that was associated with these effects, speculating that the effect of HAS on escape latencies was due to a facilitation effect of HAS on acetylcholine release.

Given the evidence of potentially relevant mechanisms of action and initial evidence of cognitive effects of HAS in murine models, the aim of this study is to assess the acute and chronic effects of Z. armatum on cognitive function, mood, and cerebral blood flow in healthy adults aged 30 to 55 years.

Eligibility Criteria:
Inclusion Criteria:

* Participants must self-assess themselves as being in good health
* Aged 30 to 55 years at the time of giving consent
* Are proficient in English equivalent to IELTS band 6 or above

Exclusion Criteria:

* Have any pre-existing medical condition/illness which will impact taking part in the study NOTE: the explicit exceptions to this are controlled (medicated) hypertension, arthritis, asthma, hay fever, high cholesterol and reflux-related conditions. There may be other, unforeseen, exceptions and these will be considered on a case-by-case basis; i.e. participants may be allowed to progress to screening if they have a condition/illness which would not interact with the active treatments or impede performance
* Are currently taking prescription medications or dietary supplements including omega fatty acids / fish oils NOTE: the explicit exceptions to this are hormone replacement treatments for female participants where symptoms are stable, those medications used in the treatment of arthritis, high blood pressure, high cholesterol and reflux-related conditions; and those taken 'as needed' in the treatment of asthma and hay fever. As above, there may be other instances of medication use which, where no interaction with the active treatments is likely, participants may be able to progress to screening
* Have planned a surgery requiring general anaesthesia
* Have high blood pressure (systolic over 159 mm Hg or diastolic over 99 mm Hg)
* Have a Body Mass Index (BMI) outside of the range 18-35 kg/m2
* Are pregnant, seeking to become pregnant or lactating
* Have learning difficulties, dyslexia
* Have a visual impairment that cannot be corrected with glasses or contact lenses (including colour-blindness)
* Smoker or regular consumption of nicotine containing products e.g. patches, gum, vaping
* Have a history of alcohol or drug abuse
* Excessive caffeine intake (\>500 mg per day)
* Have food intolerances/sensitivities, especially against citrus fruits
* Have any health condition that would prevent fulfilment of the study requirements
* Are unable to complete all of the study assessments
* Are currently participating in other clinical or nutrition intervention studies, or have in the past 4 weeks
* Do not have a bank account (required for payment)
* Are non-compliant with regards treatment consumption