Acute Effects of Mango Leaf Extract on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study

Study Overview
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Brief Summary
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The primary aim of this randomised, double-blind, placebo-controlled, cross-over study is to assess the short-term cognitive effects of a single dose (300 mg) of Mango Leaf Extract compared to a placebo on cognitive function, including during cognitively demanding task performance. The trial will utilise the COMPASS cognitive assessment system and cognitive demand battery (CDB), and Profile of Mood States (POMS), visual analogue mood scales (VAMS), and Stress Visual Analogue Scales (S-VAS) with assessments taking place at baseline, 30 minutes, 180 minutes and 300 minutes post treatment, on two separate testing days separated by 7 days (minimum).

Official Title
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Acute Effects of Mango Leaf Extract on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study

Conditions
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Attention, Cognition, Mood

Intervention / Treatment
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* Other: Mango leaf extract capsule
* Other: Placebo capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants aged 18 to 45 years, inclusive Self-reported good health Willingness to abstain from consumption of caffeine within 12 h of testing Willing to abstain from alcohol consumption and avoid vigorous physical activity for 24 h prior to all test visits Willing to refrain from 'over the counter' medications (e.g., pain medication) and stimulant medication for 12 hours, seasonal allergy/hayfever nasal antihistamine medications for 24 hours and oral antihistamines for 48 hours prior to all test visits Understanding the study procedures and willing to provide informed consent to participate in the study and authorization to release relevant protected health information to the study investigator Exclusion Criteria: Failure to meet any one of the inclusion criteria Have any pre-existing medical condition/illness which will impact taking part in the study, interact with the active treatments or impede performance Current use of prescription medication (no antibiotics within the last 4 weeks) NOTE: the explicit exceptions to this are contraceptive treatments for female participants, and those taken 'as needed' in the treatment of asthma and hay fever. There may be other instances of medication use which, where no interaction with the active treatments is likely, and which would not be expected to have any impact on brain function, where participants may be able to progress to screening Have sleep disorders or are taking sleep aid medication Major trauma or major surgical event within 6 months of screening Extreme dietary habits, as judged by the Investigator (high fat, very high protein diets, intermittent fasting, etc.) Exposure to mango leaf extract (MLE) within 30 d prior to screening History of cancer in the prior two years, except for non-melanoma skin cancer Have a visual impairment that cannot be corrected with glasses or contact lenses (including colour blindness) Food allergies/intolerances/sensitivities to any ingredients in the study products and study meals (including related foods/beverages/products) and or unwillingness to eat or dislike for the study meals. Self-report excessive leisure time physical activity (> 7 strenuous bouts per week) Have a current or chronic gastrointestinal, sleep, or psychiatric disorders including medically diagnosed anxiety and depression Work night shifts or follow a variable work pattern that results in irregular sleep pattern Are pregnant, trying to get pregnant or lactating Smoke tobacco, vape nicotine or use nicotine replacement products (including occasional social smoking) Illegal/recreational drug use Fail to demonstrate adequate minimal performance on lab, computer-based cognitive tasks Have participated in another clinical trial within past 30 days and/or participation in another PepsiCo trial in the past 6 months 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 18.5-35 kg/m2 Have a diagnosed neurological condition, or learning/behavioural or neurodevelopmental differences (e.g. dyslexia, autism, ADHD). Excessive caffeine intake (>500 mg per day) Have taken dietary supplements e.g. Vitamins, omega 3 fish oils etc. in the last 4 weeks (Note: participation is possible following a 4-week supplement washout prior to participating and for the duration of the study on the proviso that the supplements taken are out of choice and not medically prescribed or advised) Have any health condition that would prevent fulfilment of the study requirements (this includes non-diagnosed conditions for which no medication may be taken) Has been diagnosed with/ undergoing treatment for alcohol or drug abuse in the last 12 months Have been diagnosed with/ undergoing treatment for a psychiatric disorder in the last 12 months Suffers from frequent migraines that require medication (more than or equal to 1 per month) Any known active infections Are non-compliant with regards treatment consumption Does not have a bank account (required for payment)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active capsule<br>Colored capsule containing 300 mg mango leaf extract (Zynamite®) standardized to contain ≥ 60% mangiferin. Supplied by PLT Health Solutions, Inc. | Other: Mango leaf extract capsule<br>* Single dose<br>|
| Placebo Comparator: Placebo capsule<br>Colored capsule, appearance-matched to the active experimental capsule | Other: Placebo capsule<br>* Single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of attention | Average % correct of attention tasks - choice reaction time, digit vigilance and 3 x rapid visual information processing task). Higher accuracy is better. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General mood and psychological state, including depression and anxiety: VAMS | Visual Analogue Mood Scales (VAMS). Current subjective position marked on 100 mm lines anchored at either end by 18 antonyms (e.g. 'alert-inattentive', 'lethargic-energetic'). Better mood scores are a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| General mood and psychological state, including depression and anxiety: POMS | Profile of Mood States (POMS) consisting of 65 adjectives rated on a 0-4 scale. Better mood scores are a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| General mood and psychological state, including depression and anxiety: S-VAS | Stress Visual Analogue Mood Scales (S-VAS). Four items (anxious, stressed, relaxed, calm) rated not at all to extremely on 100 mm lines. Better mood scores are a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| Cognitive domain factor scores | Composite cognitive factors (speed of attention, working memory, speed of memory and episodic memory) averaged across individual tasks. Higher scores are better. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| Global cognitive performance measures: Speed | Speed of cognitive performance comprising reaction time (msec) data averaged from all of the computerized cognitive assessment tasks that return speed data. Faster average speed is a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| Global cognitive performance measures: Accuracy | Accuracy of cognitive performance comprising % accuracy data averaged from all of the computerized cognitive assessment tasks that return accuracy data. Higher average % accuracy is a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| Cognitive performance: Episodic long term memory | A computerized series of individual cognitive tasks are presented on screen. Test components are word recall, word recognition and picture recognition. Better task performance is a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| Cognitive performance: Attention | A computerized series of individual cognitive tasks are presented on screen. Test components are choice reaction time, digit vigilance and simple reaction time. Better task performance is a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| Cognitive performance: Working memory | A computerized series of individual cognitive tasks are presented on screen. Test components are numeric working memory and corsi blocks. Better task performance is a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| Cognitive performance: Executive function | A computerized peg and ball cognitive task is presented on screen. Better task performance is a better outcome. | Change from pre-dose (baseline) to 30, 180 and 300 minutes post-treatment, comparing mango leaf to placebo | 
| Cognitive function and mental fatigue during extended performance of cognitively demanding tasks | Cognitive Demand Battery (CDB) of component tasks: Serial 3s/7s, Rapid Visual Information Processing task (RVIP), Mental Fatigue Visual Analog Scale (VAS). 30 minute test (10 minute computerized assessment run three times in succession). Higher function and lower fatigue are better outcomes. | 30, 180 and 300 minutes post-dose compared to placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mood, cognitive function, mango leaf, mango