Effects of placebo perceived to be caffeine on side-effects associated with caffeine supplementation

• Grant number: 24/16981-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Bryan Saunders
• Grantee: Joana Reyes Colli
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06836-0 - Placebo in sports and exercise: prevalence, conditioning and open-placebo, AP.JP2

Abstract

Recently, placebo has been used in medical and clinical contexts with the assumption of being an active substance (deceptive placebo, e.g. placebo perceived to be caffeine). In the area of sports science and sports nutrition, it has been demonstrated that deceptive placebo can induce small to moderate effects on performance and the placebo effect of caffeine is one of the most investigated. Several studies have shown improved performance in various sports modalities when the individual believed they were consuming caffeine, even when receiving a placebo. Additionally, functional Magnetic Resonance Imaging (fMRI) has been used to determine brain changes after caffeine supplementation. However, caffeine is associated with various side effects, including insomnia, nervousness, tachycardia, heart palpitations, increased urine production and others. Thus, just as placebo perceived as caffeine has an ergogenic effect, it is reasonable to hypothesize that the side effects associated with this substance may also be perceived when the individual believes they are consuming caffeine. The aim of this study is to determine the side effects after acute placebo perceived as caffeine supplementation and to compare them with caffeine perceived as caffeine. The sample will consist of 24 healthy male volunteers, aged between 18 and 40 y, who will undergo fMRI while performing cognitive tasks. There will be three main visits, and during each one, the volunteer will randomly receive supplementation: (1) caffeine perceived as caffeine (3 mg/kg/body weight); (2) placebo (flour) perceived as caffeine; and (3) placebo perceived as placebo. During an initial familiarization visit, participants will complete the "Caffeine Consumption Frequency Questionnaire," the "Habitual Caffeine Consumption-Related Symptoms Questionnaire," the "Life Orientation Test," and the "Belief in Sports Supplements Scale." During each main visit, the volunteer will complete the "Stanford Sleepiness Scale" and the "Caffeine Side Effects Questionnaire," followed by their first fMRI scan. They will then complete another "Caffeine Side Effects Questionnaire," before receiving the supplement, complete a "24-hour Dietary Recall," and 40 minutes later, another "Caffeine Side Effects Questionnaire" and a Likert scale about their expectations regarding potential performance improvements provided by the treatment. The second MRI scan will be performed 60 minutes after supplementation ingestion, and finally, the participant will complete one more questionnaire about how much they believe their performance improved with the supplementation. Between each session there will be a minimum interval of 24 h, and participants will be advised not to consume caffeine 24 h before the scan, refrain from strenuous exercise, and avoid alcohol consumption 24 h before each visit. This study will focus primarily on the side-effects experienced and reported by the volunteers during each visit. Data analysis will be performed using the R Studio program and presented as mean ± 1 standard deviation. It is expected that the side effects reported with placebo ingestion perceived as caffeine will resemble the side effects of caffeine ingestion perceived as caffeine.