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.

Inositol stabilized arginine silicate (ASI) ingestion has been reported to increase nitric oxide levels while inositol (I) has been reported to enhance neurotransmission. The current study examined whether acute ASI + I (Inositol-enhanced bonded arginine silicate) ingestion affects cognitive function in e-sport gamers. In a double blind, randomized, placebo controlled, and crossover trial, 26 healthy male (n = 18) and female (n = 8) experienced gamers (23 ± 5 years, 171 ± 11 cm, 71.1 ± 14 kg, 20.7 ± 3.5 kg/m2) were randomly assigned to consume 1600 mg of ASI + I (nooLVL®, Nutrition 21) or 1600 mg of a maltodextrin placebo (PLA). Prior to testing, participants recorded their diet, refrained from consuming atypical amounts of stimulants and foods high in arginine and nitrates, and fasted for 8 h. During testing sessions, participants completed stimulant sensitivity questionnaires and performed cognitive function tests (i.e., Berg-Wisconsin Card Sorting task test, Go/No-Go test, Sternberg Task Test, Psychomotor Vigilance Task Test, Cambridge Brain Sciences Reasoning and Concentration test) and a light reaction test. Participants then ingested treatments in a randomized manner. Fifteen minutes following ingestion, participants repeated tests (Pre-Game). Participants then played their favorite video game for 1-h and repeated the battery of tests (Post-Game). Participants observed a 7–14-day washout period and then replicated the study with the alternative treatment. Data were analyzed by General Linear Model (GLM) univariate analyses with repeated measures using weight as a covariate, paired t-tests (not adjusted to weight), and mean changes from baseline with 95% Confidence Intervals (CI). Pairwise comparison revealed that there was a significant improvement in Sternberg Mean Present Reaction Time (ASI + I vs. PLA; p < 0.05). In Post-Game assessments, 4-letter Absent Reaction Time (p < 0.05), 6-letter Present Reaction Time (p < 0.01), 6-letter Absent Reaction Time (p < 0.01), Mean Present Reaction Time (p < 0.02), and Mean Absent Reaction Time (p < 0.03) were improved with ASI + I vs. PLA. There was a non-significant trend in Pre-Game Sternberg 4-letter Present Reaction time in ASI + I vs. PLA (p < 0.07). ASI + I ingestion better maintained changes in Go/No-Go Mean Accuracy and Reaction Time, Psychomotor Vigilance Task Reaction Time, and Cambridge Post-Game Visio-spatial Processing and Planning. Results provide evidence that ASI + I ingestion prior to playing video games may enhance some measures of short-term and working memory, reaction time, reasoning, and concentration in experienced gamers.

Paraxanthine (PXN) is a metabolite of caffeine that has recently been reported to enhance cognition at a dose of 200 mg. Objective: To determine the acute and short-term (7-day) effects of varying doses of PXN on cognitive function and side effects. Methods: In a double blind, placebo-controlled, crossover, and counterbalanced manner, 12 healthy male and female volunteers (22.7 ± 4 years, 165 ± 7 cm, 66.5 ± 11 kg, 24.4 ± 3 kg/m2) ingested 200 mg of a placebo (PLA), 50 mg of PXN (ENFINITY™, Ingenious Ingredients, L.P.) + 150 mg PLA, 100 mg PXN + 100 mg PLA, or 200 mg of PXN. With each treatment experiment, participants completed side effect questionnaires and donated a fasting blood sample. Participants then performed a series of tests assessing cognition, executive function, memory, and reaction time. Participants then ingested one capsule of PLA or PXN treatments. Participants then completed side effects and cognitive function tests after 1, 2, 3, 4, 5, and 6 h of treatment ingestion. Participants continued ingesting one dose of the assigned treatment daily for 6-days and returned to the lab on day 7 to donate a fasting blood sample, assess side effects, and perform cognitive function tests. Participants repeated the experiment while ingesting remaining treatments in a counterbalanced manner after at least a 7-day washout period until all treatments were assessed. Results: The Sternberg Task Test (STT) 4-Letter Length Present Reaction Time tended to differ among groups (p = 0.06). Assessment of mean changes from baseline with 95% CI’s revealed several significant differences among treatments in Berg-Wisconsin Card Sorting Correct Responses, Preservative Errors (PEBL), and Preservative Errors (PAR Rules). There was also evidence of significant differences among treatments in the Go/No-Go Task tests in Mean Accuracy as well as several time points of increasing complexity among STT variables. Finally, there was evidence from Psychomotor Vigilance Task Test assessment that response time improved over the series of 20 trials assessed as well as during the 6-h experiment in the PXN treatment. Acute and short-term benefits compared to PLA were seen with each dose studied but more consistent effects appeared to be at 100 mg and 200 mg doses. No significant differences were observed among treatments in clinical chemistry panels or the frequency or severity of reported side effects. Results provide evidence that acute ingestion of 100 mg and 200 mg of PXN may affect some measures of cognition, memory, reasoning, and response time as well as help sustain attention. Additionally, that acute and daily ingestion of PXN for 7 days is not associated with any clinically significant side effects. Conclusions: PXN may serve as an effective nootropic agent at doses as low as 50 mg.

Background: Ashwagandha (Withania somnifera) has been reported to decrease perceptions of stress, enhance mood, and improve cognitive function. However, it is currently unknown whether acute ashwagandha supplementation affects memory and cognitive function. This study evaluated the effects of acute ashwagandha extract ingestion on executive function. Materials and Methods: 13 healthy volunteers were administered the Berg–Wisconsin Card Sorting (BCST), Go/No-Go (GNG), Sternberg Task (STT), and Psychomotor Vigilance Task (PVTT) tests. Participants then ingested in a double-blind, placebo-controlled, and crossover manner 400 mg of a placebo (PLA) or ashwagandha (ASH) extract (NooGandha®, Specnova Inc., Boca Raton, FL, USA). Participants then performed cognitive function tests every hour for 6 h. After a 4-day washout period, volunteers repeated the experiment while receiving the remaining supplement. Data were analyzed by repeated measures General Linear Model multivariate and univariate statistics with body weight as a covariate. Results: Acute ASH supplementation increased STT-determined working memory as demonstrated by an improvement in 6 letter length, Present Reaction Time at 3 and 6 h. PVTT analysis revealed that ASH sustained attention by helping maintain reaction times, preventing mental fatigue, and remaining vigilant. Conversely, reaction times (at task 20, hour 6; overall, hour 3) increased with PLA. In the BCST, there was evidence that ASH increased the ability to recognize and ‘shift’ to a new rule compared with baseline. However, this was not seen when evaluating changes from baseline, suggesting that differences in baseline values influence results. In the GNG test, ASH ingestion promoted faster response times to respond correctly than PLA, indicating less metal fatigue. However, ASH did not affect accuracy compared to PLA, as both treatments decreased the percentage of correct answers. Conclusions: Acute supplementation with 400 mg of ashwagandha improved selected measures of executive function, helped sustain attention, and increased short-term/working memory.

Background: Esports competitive gaming requires selective visual attention, memory, quick judgment, and an ability to sustain psychomotor performance over time. Fucoxanthin is a carotenoid, found in specific microalgae varieties such as Phaeodactylum tricornutum (PT), that has been purported to possess nootropic and neuroprotective effects through its anti-inflammatory and antioxidant properties. This study evaluated whether acute and 30-day supplementation of an extract of PT from microalgae combined with guarana (a natural source of caffeine) affects cognitive function in gamers. Materials and Methods: In a double-blind, placebo-controlled manner, 61 experienced gamers (21.7 ± 4.1 years, 73 ± 13 kg) were randomly assigned to ingest a placebo (PL), a low-dose (LD) supplement containing 440 mg of PT extract including 1% fucoxanthin +500 mg of guarana containing 40–44 mg caffeine (MicroPhyt™, Microphyt, Baillargues, FR), or a high-dose (HD) supplement containing 880 mg of PT extract +500 mg of guarana for 30 days. At baseline, cognitive function tests were administered before supplementation, 15 min post-supplementation, and after 60 min of competitive gameplay with participants’ most played video game. Participants continued supplementation for 30 days and then repeated pre-supplementation and post-gaming cognitive function tests. General linear model univariate analyses with repeated measures and changes from baseline with 95% confidence intervals were used to analyze data. Results: There was some evidence that acute and 30-day ingestion of the PT extract from microalgae with guarana improved reaction times, reasoning, learning, executive control, attention shifting (cognitive flexibility), and impulsiveness. While some effects were seen after acute ingestion, the greatest impact appeared after 30 days of supplementation, with some benefits seen in the LD and HD groups. Moreover, there was evidence that both doses of the PT extract from microalgae with guarana may support mood state after acute and 30-day supplementation. Registered clinical trial #NCT04851899.