Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run

ABSTRACT

Rationale

Intense exercise promotes fatigue and can impair cognitive function, particularly toward the end of competition when decision-making is often critical for success. For this reason, athletes often ingest caffeinated energy drinks prior to or during exercise to help them maintain focus, reaction time, and cognitive function during competition. However, caffeine habituation and genetic sensitivity to caffeine (CA) limit efficacy. Paraxanthine (PX) is a metabolite of caffeine reported to possess nootropic properties. This study examined whether ingestion of PX with and without CA affects pre- or post-exercise cognitive function.

Methods

12 trained runners were randomly assigned to consume in a double-blind, randomized, and crossover manner 400 mg of a placebo (PL); 200 mg of PL + 200 mg of CA; 200 mg of PL + 200 mg of PX (ENFINITY®, Ingenious Ingredients); or 200 mg PX + 200 mg of CA (PX+CA) with a 7–14-day washout between treatments. Participants donated fasting blood samples and completed pre-supplementation (PRE) side effects questionnaires, the Berg-Wisconsin Card Sorting Test (BCST), and the Psychomotor Vigilance Task Test (PVTT). Participants then ingested the assigned treatment and rested for 60 minutes, repeated tests (PRE-EX), performed a 10-km run on a treadmill at a competition pace, and then repeated tests (POST-EX). Data were analyzed using General Linear Model (GLM) univariate analyses with repeated measures and percent changes from baseline with 95% confidence intervals.

Results

BCST correct responses in the PX treatment increased from PRE-EX to POST-EX (6.8% [1.5, 12.1], p = 0.012). The error rate in the PL (23.5 [−2.8, 49.8] %, p = 0.078) and CA treatment (31.5 [5.2, 57.8] %, p = 0.02) increased from PRE-EX values with POST-EX errors tending to be lower with PX treatment compared to CA (−35.7 [−72.9, 1.4] %, p = 0.059). POST-EX perseverative errors with PAR rules were significantly lower with PX treatment than with CA (−26.9 [−50.5, −3.4] %, p = 0.026). Vigilance analysis revealed a significant interaction effect in Trial #2 mean reaction time values (p = 0.049, ${\eta }_p^2$ ⁼ 0.134, moderate to large effect) with POST-EX reaction times tending to be faster with PX and CA treatment. POST-EX mean reaction time of all trials with PX treatment was significantly faster than PL (−23.2 [−43.4, −2.4] %, p = 0.029) and PX+CA (−29.6 [−50.3, −8.80] %, p = 0.006) treatments. There was no evidence that PX ingestion adversely affected ratings of side effects associated with stimulant intake or clinical blood markers.

Conclusions

Results provide some evidence that pre-exercise PX ingestion improves prefrontal cortex function, attenuates attentional decline, mitigates cognitive fatigue, and improves reaction time and vigilance. Adding CA to PX did not provide additional benefits. Therefore, PX ingestion may serve as a nootropic alternative to CA.

KEYWORDS:

• Nootropic
• caffeine alternative
• ergogenic aid
• sports nutrition

Acknowledgments

We thank the study participants, Dr. J.P. Bramhall for providing medical oversight, Dr. Peter Murano, and who served as an external safety and quality assurance monitor for this study.

Disclosure statement

R.J. M.P., and S.D.W. are researchers, scholars, and principals for the study’s sponsor. They are investors of several patent applications, including paraxanthine. However, they were not involved in data collection or analysis. R.B.K. has conducted sponsored research through grants and contracts awarded to the universities he has been affiliated with, received an honorarium for presenting research, served as an expert on cases related to exercise and nutrition, and consulted with industry on product development unrelated to the nutrient studied in the present investigation. Other authors report no conflicts.

Author contributions

Conceptualization, R.J., M.P., S.D.W., K.L., R.B.K.; project management, R.B.K., C.J.R., R.S., C.Y.; D.X., data collection C.Y., D.X., D.E.G. V.J., K.N., B.D., M.L., J.K., M.H.L.; data analysis R.B.K., R.S., M.F., W.K.; writing – original draft preparation, R.B.K.; writing – review and editing, R.B.K., R.S., M.F., W.K., R.J.; funding acquisition, R.B.K. All authors have read and approved publication of this paper.

Consent for publication

The sponsor approved the publication of this paper.

Data availability statement

Data and statistical analyses are available upon request on a case-by-case basis for noncommercial scientific inquiry and/or educational use if IRB restrictions and research agreement terms are not violated.

Institutional review board statement

This study was conducted with authorization by Texas A&M University’s Institutional Review Board (IRB2019–0928F). This study was registered with the ISRCTN registry (ISRCTN14506218).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15502783.2024.2352779.

Additional information

Funding

Ingenious Ingredients, LP (Lewisville, TX, USA) provided funding for this study through a fee-for-service contract to the Human Clinical Research Facility at Texas A&M University. The study was conducted by the Exercise & Sport Nutrition Laboratory. The sponsor did not participate in data collection or statistical analysis of data.