While literature surrounding caffeine’s impact on cognitive functioning can be inconsistent, it is known as the most widely used stimulant for improving focus, alertness, and concentration.1,2,3 Caffeine’s primary metabolite in humans is paraxanthine (1,7-dimethylxanthine) which might be a safer, and more effective stimulant at enhancing cognition when compared to caffeine.4,5
A recent clinical trial published in Nutrients (DOI: https://doi.org/10.3390/nu13124478) investigated paraxanthine’s impact on the primary outcome measures of cognitive and executive function in a dose-responsive manner as well as its safety.
The double blind, placebo-controlled, crossover, counterbalanced study was conducted in a university environment. Participants included faculty, staff, students, and local community members who were healthy, between 18-59 years old, and had no history of cognitive dysfunction. In total, 12 participants completed the study (3 females and 9 males) with an average age of 22.8 years, weight of 66.5 kg, and body mass index (BMI) of 24.2 kg/m2.
Supplement dosage included either 200 mg of wheat flower placebo, 50 mg of paraxanthine and 150 mg of placebo, 100 mg paraxanthine and 100mg of placebo, or 200 mg of paraxanthine. The Psychology Experiment Building Landscape (PEBL) was used for the cognitive and executive function assessment. These assessments included the Berg-Wisconsin Card Sorting Task test (BCST), the Go/No-Go test (GNG), the Sternberg Task Test (STT), and the Psychomotor Vigilance Task Test (PVTT). Before recording the test results, participants were allowed to practice three times for familiarization and re-test reliability. Participants had normal resting heart rates, systolic blood pressure, and diastolic blood pressure, averaging 74.2 bpm, 113.2 mmHg, and 70.2 mmHg respectively.
During the BCST assessment, the researchers found evidence that paraxanthine supplementation improved attention and accuracy over time when compared to placebo-supplemented responses. This was demonstrated by the decreasing number of preservative errors. The GNG test results suggested that paraxanthine supplementation improves attention and response control to visual stimuli that require positive or inhibitory decision-making skills. This was observed in 100 mg and 200 mg doses of paraxanthine which decreased mean response time during the tasks. The results of the STT test demonstrated that paraxanthine supplementation improved the ability to store and retrieve information from memory as well as sustain attention. In the test, 200 mg of paraxanthine improved 2 letter present reaction time and 100 mg of paraxanthine improved 4-letter and 6-letter present reaction times to a greater degree. In the final test, PVTT, the results showed 50 mg, 100 mg, and 200 mg of paraxanthine supplementation improved reaction times at Trial #10 compared to placebo. The results showed that paraxanthine supplementation may help sustain attention over time. No side effects were observed during the trial in relation to paraxanthine supplementation.
The researchers conclude that the “present findings confirm [their] previous results and support contentions that [paraxanthine] may have nootropic properties in doses as low as 50 mg.”
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2. Magkos F, Kavouras SA. Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Critical reviews in food science and nutrition. 2005 Oct 1;45(7-8):535-62.
3. Chester N, Wojek N. Caffeine consumption amongst British athletes following changes to the 2004 WADA prohibited list. International journal of sports medicine. 2008 Jun;29(06):524-8.
4. Stavric B. Methylxanthines: toxicity to humans. 3. Theobromine, paraxanthine and the combined effects of methylxanthines. Food and chemical toxicology. 1988 Jan 1;26(8):725-33.
5. Orrú M, Guitart X, Karcz-Kubicha M, Solinas M, Justinova Z, Barodia SK, Zanoveli J, Cortes A, Lluis C, Casado V, Moeller FG. Psychostimulant pharmacological profile of paraxanthine, the main metabolite of caffeine in humans. Neuropharmacology. 2013 Apr 1;67:476-84.