5 vs 10-Minute Chewing of Caffeinated Gum: Plasma Caffeine Pharmacokinetics

Optimizing the Timing of Caffeinated Gum: Effects of 5- and 10-Minute Chewing on Plasma Caffeine Pharmacokinetics in Healthy Men

The goal of this study is to understand how chewing duration affects how quickly caffeine from caffeinated chewing gum appears in the blood and how long higher caffeine levels are maintained. The study compares two chewing durations (5 minutes and 10 minutes) in healthy men.

Each participant attends two study visits on separate days at least 48 hours apart and completes both chewing conditions. At each visit, participants chew caffeinated gum that provides approximately 300 mg of caffeine. Blood samples are collected before chewing and at several time points for up to 3 hours after chewing to measure plasma caffeine levels.

Researchers will compare the two chewing durations to determine whether chewing time changes peak plasma caffeine concentration, the time to reach the peak, overall exposure over 0 to 180 minutes, and the time that plasma caffeine remains near the peak level. The results may help guide practical timing of caffeinated gum use.

Study Overview

• Status: Completed
• Conditions: Caffeine
• Intervention / Treatment: Dietary supplement: Caffeine 300 MG

Detailed Description

This is a within-subject, repeated-measures, two-visit, fixed-sequence study comparing two chewing durations of caffeinated gum (5 minutes vs 10 minutes). Participants attend two visits on separate days with at least 48 hours between visits to minimize carryover effects. The order is fixed: the 5-minute chewing condition is completed at Visit 1 and the 10-minute chewing condition at Visit 2.

At each visit, participants receive approximately 300 mg of caffeine via commercially available caffeinated chewing gum (three pieces; about 100 mg per piece). Venous blood samples are collected to measure plasma caffeine concentration over time. Samples are obtained at baseline (0 minutes), during chewing (5 minutes in both conditions and 10 minutes only in the 10-minute condition), and after chewing at 30, 50, 60, 80, 90, 120, and 180 minutes. Plasma caffeine is quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

The plasma caffeine concentration-time profile is used to derive pharmacokinetic outcomes, including peak plasma caffeine concentration, time to peak concentration, exposure from 0 to 180 minutes, and the duration that plasma caffeine remains at or above 90% and 80% of the individual peak concentration.

The study was approved by the Ege University Faculty of Medicine Medical Research Ethics Committee, and written informed consent was obtained from all participants prior to participation.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Bornova
    • Izmir, Bornova, Turkey (Türkiye), 35040
      • Ege University, Faculty of Sport Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male, 18-35 years
• Good general health
• No regular use of medications or substances
• Habitual daily caffeine intake ≤300 mg/day

Exclusion Criteria:

• Habitual daily caffeine intake >300 mg/day
• Failure to participate in any study measurements
• Failure to comply with required test and measurement protocols
• Experiencing adverse effects from caffeine during the compliance period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5-Minute Chewing; Participants chew caffeinated chewing gum for 5 minutes (total caffeine approximately 300 mg).	Dietary supplement: Caffeine 300 MG; 300 mg (three pieces; ~100 mg each) administered at each visit. Participants chew for 5 minutes in one condition and 10 minutes in the other condition.
Experimental: 10-Minute Chewing; Participants chew caffeinated chewing gum for 10 minutes (total caffeine approximately 300 mg).	Dietary supplement: Caffeine 300 MG; 300 mg (three pieces; ~100 mg each) administered at each visit. Participants chew for 5 minutes in one condition and 10 minutes in the other condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Caffeine Concentration (Cpeak)	Highest observed plasma caffeine concentration over the 0-180 minute sampling period, quantified from venous blood samples analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Unit: µg/mL.	From baseline (0 minutes) up to 180 minutes post-chewing
Time to Peak Plasma Caffeine Concentration (Tpeak)	Time (minutes) from baseline (start of sampling) to the individual peak plasma caffeine concentration (Cpeak) within the 0-180 minute sampling period.	From baseline (0 minutes) up to 180 minutes post-chewing
Area Under the Plasma Caffeine Concentration-Time Curve From 0 to 180 Minutes (AUC0-180)	Total plasma caffeine exposure from 0 to 180 minutes calculated from measured plasma caffeine concentrations (trapezoidal method). Unit:mg·h/L.	0 to 180 minutes post-chewing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration Plasma Caffeine Remains at or Above 90% of Individual Peak (Sustain90)	Duration (minutes) during which plasma caffeine concentration is at or above 90% of the individual Cpeak within the 0-180 minute sampling period.	0 to 180 minutes post-chewing
Duration Plasma Caffeine Remains at or Above 80% of Individual Peak (Sustain80)	Duration (minutes) during which plasma caffeine concentration is at or above 80% of the individual Cpeak within the 0-180 minute sampling period.	0 to 180 minutes post-chewing
Plasma Caffeine Concentration-Time Profile	Plasma caffeine concentrations (µg/mL) measured at prespecified time points: 0, 5, 10 (10-minute condition only), 30, 50, 60, 80, 90, 120, and 180 minutes post-chewing, analyzed by LC-MS/MS.	Baseline (0 minutes) through 180 minutes post-chewing

Collaborators and Investigators

• Sponsor: Ege University
• Collaborators: The Scientific and Technological Research Council of Turkey
• Investigators: Principal Investigator: Hakan Arslan, Dr., Ege University; Study Chair: Gülbin Rudarlı, professor, Ege University

Publications and helpful links

General Publications

• Kamimori GH, Karyekar CS, Otterstetter R, Cox DS, Balkin TJ, Belenky GL, Eddington ND. The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. Int J Pharm. 2002 Mar 2;234(1-2):159-67. doi: 10.1016/s0378-5173(01)00958-9.

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2025
• Primary Completion (Actual): June 14, 2025
• Study Completion (Actual): June 14, 2025

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Absorption; AUC; Caffeinated chewing gum; Plasma caffeine; Chewing duration; Time to peak; Peak concentration
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Purinones; Purines; Xanthines; Caffeine
• Other Study ID Numbers: CAF-GUMPK-5v10-324S220

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No