Enhanced Absorption and Safety of MuscleBlaze CreAMP™: A Comparative Analysis With Regular Micronized Creatine Monohydrate in Healthy Male Adults

Abstract

Background Creatine monohydrate is a widely utilized dietary supplement in sports nutrition, valued for its role in enhancing muscle energy availability, power output, and performance during high-intensity, short-duration activities. Creatine monohydrate is effective but limited by absorption inefficiencies and side effects. Enhanced forms can improve uptake, reduce gastrointestinal discomfort, and optimize muscle energy utilization, meeting athletes' evolving performance needs. Methods This study involved 32 healthy male volunteers aged 18-50 years, with a BMI of 18.5-25.0 kg/m² and body weight of ≥50 kg. This study evaluated the bioavailability and safety of MuscleBlaze Creatine Monohydrate (CreAMP™) (Bright Lifecare Pvt Ltd, Gurugram, India), containing 3.0 g creatine monohydrate and 0.1 g Creabsorb™ (Indian Patent: IN202311057466), against a standard 3.0 g micronized creatine dose. In a double-blind, randomized crossover trial (CTRI/2024/08/073021), 32 healthy males (18-50 years) received both formulations under fasting conditions. The study compared two oral creatine monohydrate formulations: CreAMP™ Micronized Creatine Monohydrate (test) and Regular Micronized Creatine Monohydrate (reference) (Bright Lifecare Pvt Ltd, Gurugram, India). Blood samples were collected pre-dose and up to six hours post-dose over two periods, separated by a washout period of one week. Pharmacokinetic parameters were analyzed using Phoenix® WinNonlin® 8.5 (Certara, Radnor, PA). Results CreAMP™ has significantly higher bioavailability, absorption, and plasma retention compared to the reference formulation. With a 38.97% increase in bioavailability, an 18.10% higher C_max, a 21.37% longer half-life, 34.67% lower clearance, and a 10.13% higher mean residence time, CreAMP™ demonstrates superior pharmacokinetic properties. These findings suggest that CreAMP™ offers improved creatine uptake, sustained plasma levels, and the potential for reduced dosing frequency, making it a more effective formulation for creatine supplementation. Conclusion The study findings establish CreAMP™ as a superior creatine formulation, offering enhanced bioavailability, faster absorption, and prolonged plasma retention. These pharmacokinetic advantages indicate that CreAMP™ offers more efficient creatine uptake, improved energy availability, and optimized performance support for athletes.

Keywords: absorption; bioavailability; creamp™; muscle energy; performance; pharmacokinetics; s: : creatine monohydrate; safety; sports nutrition; supplementation.

Figure 1. Mean plasma concentration-time curve showing absorption and elimination phases

CreAMP™ (sample A-line plot with circular data points ): Mean plasma drug concentration-time curve for CreAMP™, illustrating absorption and elimination phases with peak C_max. RMCM (sample B-line plot with triangle data points): Mean plasma drug concentration-time curve for RMCM, showing its corresponding C_max. C_max: Maximum plasma concentration point for each formulation, indicating the extent of absorption. T_max: Time to reach C_max, reflecting the rate of absorption. Statistical significance: t-test was used to calculate statistical significance. The result (p-value < 0.001) indicates a significant difference between CreAMP™ and RMCM. X-axis: Time post-administration (hours). Y-axis: Plasma creatine concentration (mmol/L).

Figure 2. Peak plasma concentration (Cmax) bar graph

CreAMP™: Represents the mean plasma concentration-time profile of CreAMP™, highlighting its C_max (maximum plasma concentration) for comparison. RMCM: Depicts the mean plasma concentration-time profile of RMCM, indicating its C_max. C_max: The peak plasma concentration observed for each formulation, reflecting the rate and extent of absorption. Statistical significance: t-test was used to calculate statistical significance. The result (p-value 0.01) indicates a significant difference between CreAMP™ and RMCM. Plasma concentration (Y-axis): Measured creatine levels in plasma in (mmol/L).

Figure 3. Rate of absorption (AUC0-t ) bar graph (p-value <0.001)

CreAMP™: Represents the rate of absorption for CreAMP™, measured by the area under the curve from time zero to the last measurable concentration (AUC_₀-t). RMCM: Indicates the rate of absorption for RMCM based on its AUC_₀-t. AUC_₀-t (area under the curve): Reflects the total drug exposure over time, representing the extent of absorption. Statistical significance: t-test was used to calculate statistical significance. The result (p-value < 0.001) indicates a significant difference between CreAMP™ and RMCM. X-axis: Test formulations (CreAMP™ vs. RMCM). Y-axis: AUC_₀-t values (hr.mmol/L), representing the extent of absorption.

Figure 4. Total creatine exposure (AUC 0-inf) (p-value < 0.001)

CreAMP™: Represents the total creatine exposure for CreAMP™, measured by the area under the curve from time zero to infinity (area under the curve (AUC)_₀-∞), indicating overall creatine absorption. RMCM: Shows the total creatine exposure for RMCM, based on its AUC_₀-∞. AUC_₀-∞: Reflects the total drug exposure over time, representing both the extent and duration of absorption until complete elimination. Line bar: Indicate the absorption difference, highlighting CreAMPTM having more total creatine exposure across samples. Statistical significance: t-test was used to calculate statistical significance. The result (p-value < 0.001) indicates a significant difference between CreAMP™ and RMCM. X-axis: Test formulations (CreAMP™ vs. RMCM). Y-axis: AUC_₀-∞ values (hr.mmol/L), representing total creatine exposure.

Figure 5. Comparison of elimination half-life (T½) between CreAMP™ and RMCM (p-value 0.0983)

CreAMP™: Represents the elimination half-life (T½) of CreAMP™, indicating the time required for the plasma creatine concentration to decrease by 50%. RMCM: Shows the elimination half-life (T½) of RMCM for comparison. T½ (elimination half-life): Reflects the rate at which creatine is eliminated from the body, measured in hours. Statistical significance: t-test was used to calculate statistical significance. The result (p-value 0.0983) indicates statistically no significant difference between CreAMP™ and RMCM. X-axis: Test formulations (CreAMP™ vs. RMCM). Y-axis: Elimination half-life (T½) in hours.

Figure 6. Comparison of clearance rate (CL) and mean residence time (MRT) between CreAMP™ and RMCM (p-value 0.0000)

Statistical significance: t-test was used to calculate statistical significance. The result (p-value 0.0000) indicates a significant difference between CreAMP™ and RMCM. X-axis: Test formulations (CreAMP™ vs. RMCM) grouped by CL and MRT. Y-axis: for CL, clearance rate g/(hr*mmol/L)/kg; for MRT, mean residence time (hours)

Figure 7. Comparison of volume of distribution (Vz) between CreAMP™ and RMCM (p-value 0.0001)

CreAMP™: Represents the volume of distribution (Vz) for CreAMP™, indicating the extent to which creatine is distributed throughout body tissues. RMCM: Shows the Vz for RMCM for comparison. Vz (volume of distribution): Reflects the hypothetical volume in which creatine would need to be uniformly distributed to produce the observed plasma concentration, measured in g/(mmol/L)/kg. Statistical significance: t-test was used to calculate statistical significance. The result (p-value 0.0001) indicates a significant difference between CreAMP™ and RMCM. X-axis: Test formulations (CreAMP™ vs. RMCM). Y-axis: Volume of distribution (Vz) in g/(mmol/L)/kg. Additionally, CreAMP™ showed a 15.81% lower elimination rate constant (Kel) (Figure 8) and a 10.13% higher mean residence time (MRT) (Figure 6), prolonging its duration of action and enhancing creatine accumulation efficiency.

Figure 8. Comparison of elimination rate constant (Kel) between CreAMP™ and RMCM (p-value 0.0461)

CreAMP™: Represents the elimination rate constant (Kel) for CreAMP™, indicating the rate at which creatine is eliminated from the body. RMCM: Shows the Kel for regularized micronized creatine monohydrate for comparison. Kel (elimination rate constant): Reflects the rate of drug elimination per unit of time, measured in hr^-¹ (per hour). Statistical significance: t-test was used to calculate statistical significance. The result (p-value 0.046) indicates a significant difference between CreAMP™ and RMCM. X-axis: Test formulations (CreAMP™ vs. RMCM). Y-axis: Elimination rate constant (Kel) in hr^-¹

Figure 9. Area under the curve (AUC) (bioavailability) of creatine monohydrate and other bolus formula

Bolus formula 1 (CreaBev 1) and bolus formula 2 (CreaBev 2) refer to formulations described in the study by Antonio et al. (2022) [15]. CreaBev 1 and CreaBev 2 are investigational creatine-containing formulations evaluated for their pharmacokinetic properties.