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

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], <i>p</i> = 0.04; PXN -17.5% [-36.1, 1.0], <i>p</i> = 0.06) and perseverative errors (PXN -2.2 [-4.2, -0.2], <i>p</i> = 0.03; PXN -32.8% [-64.4, 1.2], <i>p</i> = 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, <i>p</i> = 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], <i>p</i> = 0.03; PXN -9.0% [-18.1, 0.2], <i>p</i> = 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 (η_p² = 0.08) was observed in PVTT, where PXN sustained vigilance during Trial 2 after 2 h (PXN 840 ms [103, 1576], <i>p</i> = 0.03) and 4 h (PXN 1466 ms [579, 2353], <i>p</i> = 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.