Acute Paraxanthine Ingestion Improves Cognition and Short-Term Memory and Helps Sustain Attention in a Double-Blind, Placebo-Controlled, Crossover Trial

Abstract

This study examined the effects of acute paraxanthine (PXN) ingestion on markers of cognition, executive function, and psychomotor vigilance. In a randomized, double blind, placebo-controlled, crossover, and counterbalanced manner, 13 healthy male and female participants were randomly assigned to consume a placebo (PLA) or 200 mg of PXN (ENFINITY™, Ingenious Ingredients, L.P.). Participants completed stimulant sensitivity and side effect questionnaires and then performed the Berg Wisconsin Card Sorting Test (BCST), the Go/No-Go test (GNG), the Sternberg task test (STT), and the psychomotor vigilance task test (PVTT). Participants then ingested one capsule of PLA or PXN treatment. Participants completed side effect and cognitive function tests after 1, 2, 3, 4, 5, and 6 h after ingestion of the supplement. After 7 days, participants repeated the experiment while consuming the alternative treatment. Data were analyzed by general linear model (GLM) univariate analyses with repeated measures using body mass as a covariate, and by assessing mean and percent changes from baseline with 95% confidence intervals (CIs) expressed as means (LL, UL). PXN decreased BCST errors (PXN −4.7 [−0.2, −9.20], p = 0.04; PXN −17.5% [−36.1, 1.0], p = 0.06) and perseverative errors (PXN −2.2 [−4.2, −0.2], p = 0.03; PXN −32.8% [−64.4, 1.2], p = 0.04) at hour 6. GNG analysis revealed some evidence that PXN ingestion better maintained mean accuracy over time and Condition R Round 2 response time (e.g., PXN −25.1 [−52.2, 1.9] ms, p = 0.07 faster than PLA at 1 h), suggesting better sustained attention. PXN ingestion improved STT two-letter length absent and present reaction times over time as well as improving six-letter length absent reaction time after 2 h (PXN −86.5 ms [−165, −7.2], p = 0.03; PXN −9.0% [−18.1, 0.2], p = 0.05), suggesting that PXN enhanced the ability to store and retrieve random information of increasing complexity from short-term memory. A moderate treatment x time effect size (ηp2 = 0.08) was observed in PVTT, where PXN sustained vigilance during Trial 2 after 2 h (PXN 840 ms [103, 1576], p = 0.03) and 4 h (PXN 1466 ms [579, 2353], p = 0.002) compared to PL. As testing progressed, the response time improved during the 20 trials and over the course of the 6 h experiment in the PXN treatment, whereas it significantly increased in the PL group. The results suggest that acute PXN ingestion (200 mg) may affect some measures of short-term memory, reasoning, and response time to cognitive challenges and help sustain attention.

Dose-Response of Paraxanthine on Cognitive Function: A Double Blind, Placebo Controlled, Crossover Trial

“…The Go/No-Go test was used to assess the ability to sustain attention, control responses to visual stimulation, reaction time, and accuracy [29,30,33]. We previously reported that acute ingestion of 200 mg of PXN decreased mean response time to Go Tasks while response time increased over time with PLA treatment [25]. We observed a similar response to 100 mg and 200 mg dosages in the present study, but not 50 mg dosage.…”

“…The Sternberg Task Test assesses reaction time, accuracy, and memory of tasks of increasing complexity [34,[50][51][52]. In our initial study, we found ingestion of 200 mg of PXN improved reaction time more consistently than the PLA in shorter (2-letter) and longer (6-letter) memory challenges [25]. There was also evidence that reaction time improved more consistently over time as the number of trials progressed.…”

“…The IBM ® Version 28 SPSS ® statistical package (IBM Corp., Armonk, NY, USA) was used to analyze data. Adequate sample size was determined based on an expected improvement of 5% with a power of 85% in primary outcome cognitive function related variables observed in our prior study [25,[41][42][43]. The n-size evaluated also had sufficient power to assess clinically significant side effects consistent with similarly designed studies conducted in our lab [41][42][43][44][45].…”

“…The Psychology Experiment Building Language (PEBL) cognitive function test battery (Version 2.1, http://pebl.sourceforge.net, accessed on 10 June 2019) was used to assess changes in cognitive function [28]. This included the Berg-Wisconsin Card Sorting Task test (BCST) [28][29][30][31][32], the Go/No-Go test (GNG) test [29,30,33], the Sternberg Task Test (STT) [29,30,34], and Psychomotor Vigilance Task Test (PVTT) [28][29][30]35,36] using methods previously described in detail [25]. Participants practiced the tests three times during familiarization sessions to establish test re-test reliability.…”

“…We recently reported that one-time ingestion of 200 mg of PXN improved response time to cognitive challenges, as well as measures of memory, reasoning, and attention over a six-hour period in healthy adults [25]. Theoretically, PXN may provide an alternative to CA, particularly in individuals who are genetically less sensitive to CA and/or experience untoward side effects.…”