Impact of OptiCreatine on Plasma Creatine and Gastrointestinal Effects in Males and Females

The study aims to evaluate the novel OptiCreatine formulation, which combines creatine with other bioactive compounds purported to enhance absorption and reduce gastrointestinal (GI) discomfort. Using a randomized, double-blind, crossover design, the study will compare the acute and chronic effects of OptiCreatine versus Creatine monohydrate in healthy, recreationally active adults. Participants will be asked to orally consume both the OptiCreatine and the creatine monohydrate. Primary outcomes include plasma creatine concentrations, gastrointestinal symptomatology, and fluid distribution measured through bioelectrical impedance spectroscopy.

Study Overview

• Status: Completed
• Conditions: Creatine Absorption in Healthy Adults
• Intervention / Treatment: Dietary supplement: OptiCreatine; Dietary supplement: Creatine Monohydrate

Detailed Description

The study aims to evaluate the novel OptiCreatine formulation, which combines creatine with other bioactive compounds purported to enhance absorption and reduce gastrointestinal (GI) discomfort. The study objectives are as follows:

• Aim 1: To examine the acute effects of OptiCreatine compared to creatine monohydrate on plasma creatine concentrations and gastrointestinal symptoms.
• Aim 2: To example the effects of 5-days of creatine loading with OptiCreatine compared to creatine monohydrate on gastrointestinal symptoms and fluid distribution.

General Design: All data collection will be completed by the Principal Investigator and Research Assistants at the University of North Carolina. Participants will be asked to report to the Applied Physiology Laboratory and Human Performance Center for enrollment and testing sessions. Thirty-two individuals total will be enrolled into the study. Sixteen participants will be enrolled into the acute phase; Sixteen will be enrolled into the chronic phase with random assignment to OptiCreatine (n=8) or creatine monohydrate (n=8). Participants from the acute phase are eligible to enroll into the chronic phase. The acute phase will require 2 in person visits, in random order, with participants randomly assigned in a cross-over fashion to OptiCreatine vs creatine monohydrate. Blood samples will be obtained at baseline and at 0.5, 1, 1.5, 2, 3, 4, and 5 hrs. following ingestion of the assigned treatment. A minimum of 72 hrs. will take place in between acute visits. For the chronic phase, participants will complete baseline assessments for GI symptoms via questionnaires (bloating questionnaire, gastrointestinal symptom rating scale, digestion associated quality of life questionnaire) and fluid distribution from multi-frequency bioelectrical impedance analysis (MF-BIA). Following baseline testing, participants will be randomly assigned to an OptiCreatine or creatine monohydrate group. Post testing evaluation will occur within 48 hours of the 5-day loading phase.

Supplementation Phase:

• Acute: In a randomized double-blind, cross-over design study, participants will be randomly assigned using a using a computer-generated randomization scheme to consume either OptiCreatine (5 g + 6 oz water, n=8) or creatine monohydrate supplement (5 g + 6 oz water, n=8). All participants will complete both treatments, including a minimum of a 3-day washout period.
• Chronic: In a randomized double-blind design study, participants will be randomly assigned using block randomization in a 1:1 fashion using a computer generation randomization scheme to participants in a creatine loading dose (4 x 5 grams daily- 20 g per day for 5 days) of OptiCreatine or creatine monohydrate.

Participants will be asked to arrive at the laboratory for all visits after a minimum 8-hour fast from caloric foods and beverages, 48-hour abstention from vigorous exercise, and 24-hour abstention from caffeine consumption. Participants will be asked to maintain normal dietary intake along with no more than 200mg of caffeine per day for the duration of the study. Measurements of anthropometrics, GI symptoms, and fluid distribution will be obtained. For the acute phase, blood samples will be taken from the antecubital region.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-8700
      • Applied Physiology Laboratory (Fetzer Hall, Room 025)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults between the ages of 18-45 yrs
• Body mass index of <35 kg/m2
• Recreationally active [≥30 minutes of moderate-intensity physical activity per week as defined by the International Physical Activity Questionnaire (IPAQ)]
• Participant is healthy and free from disease as determined by a health history questionnaire.
• Participant agrees to abstain from caffeine (24 hrs. prior), tobacco (24 hrs. prior), and alcohol (24 hrs. prior) before testing days

Exclusion Criteria:

• Has chronic kidney disease, liver disease, chronic obstructive pulmonary disease, or cancer
• Currently using medications that may directly impact the primary outcomes including: diuretics and corticosteroids)
• Currently using creatine monohydrate
• Has severely impaired hearing or speech or inability to speak English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OptiCreatine; Combines creatine with other bioactive compounds purported to enhance absorption.	Dietary supplement: OptiCreatine; OptiCreatine is a formulation, which combines creatine with other bioactive compounds purported to enhance absorption.
Active Comparator: Creatine monohydrate	Dietary supplement: Creatine Monohydrate; Creatine monohydrate (Creapure®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Outcomes: Concentration maximum (Cmax)	the maximum observed plasma concentration (Cmax)	Over a period of 5 hrs. post dose of creatine
Pharmacokinetic Outcomes: Time to concentration maximum (Tmax)	The time to reach the maximum observed plasma concentration	Over a period of 5 hrs. post dose of creatine
Pharmacokinetic Outcomes: Area Under the Curve (AUC)	The area under the concentration-time curve (AUC)	Over a period of 5 hrs. post dose of creatine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digestion-associated Quality of Life Questionnaire (DQLQ) assessment	Digestion-associated Quality of Life Questionnaire (DQLQ) will be assessed on a scale of 0% to 100% at baseline and 6 days, with 0% indicating no effect (never) on digestion-associated quality of life to 90%-100% (always effecting digestion-associated Quality of Life)	6 days
Self-perception questionnaire for assessment of bloating	Assessment of bloating using a self-perception questionnaire on a scale of None (no bloating) to very severe (severe bloating) will be conducted at the 1st study visit (baseline), at the 2nd study visit (6 days) after 5 days of creatine loading.	6 days
Gastrointestinal Symptom Rating Scale (GSRS)	Gastrointestinal Symptom Rating Scale (GSRS) will be conducted at the 1st study visit (baseline), at the 2nd study visit (6 days) after 5 days of creatine loading. The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms.	6 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluid distribution, Total Body water	A multi-frequency bioelectrical impedance spectroscopy (BIA) device will be used (InBody770) to measure fluid distribution. Device software will automatically estimate total body water (TBW), intracellular fluid (ICF), and extracellular fluid (ECF). The fluid distribution will be expressed in liters (L)	Baseline and after 6 days
Height	The height of the participants will be measured for the determination of BMI, kg/m2. Height will be measured in meters (m).	Baseline at day 6
Weight	The weight of the participants will be measured for the determination of BMI, kg/m2. Weight will be measured in kilograms (m). Weight will also be used in the body water distribution calculations.	Baseline and Day 6
Fluid distribution, Intracellular fluid	A multi-frequency bioelectrical impedance spectroscopy (BIA) device will be used (InBody770) to measure fluid distribution. Device software will automatically estimate total body water (TBW), intracellular fluid (ICF), and extracellular fluid (ECF). Water distribution will be expressed in liters (L).	Baseline and after 6 days
Fluid distribution, Extracellular fluid	A multi-frequency bioelectrical impedance spectroscopy (BIA) device will be used (InBody770) to measure fluid distribution. Device software will automatically estimate total body water (TBW), intracellular fluid (ICF), and extracellular fluid (ECF). Water distribution will be expressed in liters (L).	Baseline and 6 days

Collaborators and Investigators

• Sponsor: TSI Group LTD
• Collaborators: University of North Carolina
• Investigators: Study Director: John A Rathmacher, Ph.D., TSI Group LTD

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2025
• Primary Completion (Actual): December 19, 2025
• Study Completion (Actual): December 19, 2025

Study Registration Dates

• First Submitted: November 3, 2025
• First Submitted That Met QC Criteria: November 4, 2025
• First Posted (Actual): November 6, 2025

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Absorption; Healthy adults; creatine
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Organic Chemicals; Amino Acids; Guanidines; Amidines; Creatine
• Other Study ID Numbers: 25-2972

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