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Metabolic conditions, such as gout, can result from elevated uric acid (UA) levels. Consuming high-purine meals increases UA levels. Therefore, people with hyperuricemia typically must avoid ingesting such foods. Polyphenols have been shown to reduce uric acid levels and tart cherries (TCs) are a rich source of phenolic and anthocyanin compounds. This proof-of-concept study evaluated whether ingesting TCs with a purine-rich meal affects the uricemic response. Methods: A total of 25 adults (15 males and 10 females, 85.0 ± 17 kg, 40.6 ± 9 years, 29.1 ± 4.9 kg/m 2 ) with elevated fasting UA levels (5.8 ± 1.3 mg/dL) donated a fasting blood sample. In a randomized, double-blind, crossover, placebo-controlled, counterbalanced manner, participants ingested capsules containing 960 mg of a placebo (PLA) or concentrated TC powder containing 20.7 mg of proanthocyanins with a serving of hot soup (10 g of carbohydrate, 2 g protein, and 1 g fat) containing 3 g of purines (1 g of adenosine 5'-monophosphate, 1 g of disodium 5'-guanylate, and 1 g of disodium 5'-inosinate). Blood samples were obtained at 0, 60, 120, 180, and 240 min after ingestion to assess changes in uric acid levels and pharmacokinetic profiles. Cell blood counts, a comprehensive metabolic panel, cytokines, inflammatory markers, and subjective side effects ratings were analyzed on baseline (0 min) and post-treatment (240 min) samples. Participants continued consuming two capsules/day of the assigned treatment for one week and then repeated the experiment. Participants observed a 14-day washout and then repeated the experiment while ingesting the alternate treatment. Data were analyzed using general linear model (GLM) statistics with repeated measures, pairwise comparisons, and percentage change from baseline with 95% confidence intervals (CIs). Results: No statistically significant interaction effects or differences between treatments were seen in uric acid levels or PK profiles. Analysis of percent changes from baseline revealed that TC ingestion reduced the blood glucose levels following the ingestion of the high-purine meal (-4.2% [-7.7, -0.7], p = 0017). Additionally, there was some evidence that TC ingestion attenuated the increase from baseline in IL-1β and IL-10 and increased INF-γ. No significant differences were seen in the remaining health markers or subjective side effects ratings. Conclusions: Acute and one-week TC supplementation did not affect the uricemic response to ingesting a high-purine meal in individuals with mildly elevated UA levels. However, there was some evidence that TC supplementation may blunt the glycemic response to ingesting a meal and influence some inflammatory cytokines. Registered clinical trial NCT04837274.

Background: 2'-Fucosyllactose (2'-FL) is an oligosaccharide contained in human milk and possesses prebiotic and anti-inflammatory effects, which may alleviate skeletal muscle atrophy under caloric restriction. This study evaluated the impacts of 12 weeks of 2'-FL supplementation in conjunction with exercise (10,000 steps/day, 5 days/week) and energy-reduced (-300 kcals/day) dietary interventions on changes in body composition and health-related biomarkers., Methods: A total of 41 overweight and sedentary female and male participants (38.0 ± 13 years, 90.1 ± 15 kg, 31.6 ± 6.6 kg/m 2 , 36.9 ± 7% fat) took part in a randomized, double-blind, and placebo-controlled study. The participants underwent baseline assessments and were then assigned to ingest 3 g/day of a placebo (PLA) or Momstamin 2'-F while initiating the exercise and weight-loss program. Follow-up tests were performed after 6 and 12 weeks. Data were analyzed using general linear model statistics with repeated measures and mean changes from baseline values with 95% confidence intervals (CIs)., Results: No group × time × sex interaction effects were observed, so group × time effects are reported. Participants in both groups saw comparable reductions in weight. However, those with 2'-FL demonstrated a significantly greater reduction in the percentage of body fat and less loss of the fat-free mass. Additionally, there was evidence that 2'-FL supplementation promoted more favorable changes in resting fat oxidation, peak aerobic capacity, IL-4, and platelet aggregation, with some minimal effects on the fermentation of short-chain fatty acids and monosaccharides in fecal samples. Moreover, participants' perceptions regarding some aspects of the functional capacity and ratings of the quality of life were improved, and the supplementation protocol was well tolerated, although a small, but significant, decrease in BMC was observed., Conclusions: The results support contentions that dietary supplementation of 2'-FL (3 g/d) can promote fat loss and improve exercise- and diet-related markers of health and fitness in overweight sedentary individuals initiating an exercise and weight-loss program. Further research is needed to explore the potential health benefits of 2'-FL supplementation in both healthy and elderly individuals (Registered clinical trial #NCT06547801).

Background: Previous trials have displayed augmented intracellular vitamin C concentrations in the leukocytes at 24 h after acute supplementation with 1000 mg calcium ascorbate (CA), compared to ascorbic acid (AA)., Objective: The primary objective was to evaluate comparative leukocyte vitamin C accumulation kinetics over 32 h following acute 250 mg or 500 mg doses from the two sources. Secondary objectives were to evaluate neutrophil phagocytic function and lymphocyte differentiation between the two sources of vitamin C., Methods: Ninety-three healthy females (250 mg, n = 27; 500 mg, n = 24) and males (250 mg, n = 19; 500 mg, n = 23) were assigned to ingest a single dose of CA or AA providing 250 mg or 500 mg of vitamin C in two separate double-blind, randomized crossover trials., Results: There were no significant differences in the primary or secondary outcomes between the two treatments in the 250 mg low-dose study. Conversely, there was evidence that ingestion of 500 mg of CA increased DHA in plasma, increased neutrophil functionality during the first 8 h of the PK study, promoted increased natural killer cells, and altered weight-adjusted PK profiles, suggesting greater volume distribution and clearance from the blood., Conclusions: These findings indicate that 500 mg of CA may promote some immune benefits compared to 500 mg of AA ingestion.

Phaeodactylum tricornutum ( PT ) is a microalgae extract that contains fucoxanthin and has been shown to enhance cognitive function in younger populations. The present study assessed if PT supplementation affects cognition in healthy, young-old, physically active adults with self-perceptions of cognitive and memory decline., Methods: Forty-three males and females (64.3 ± 6.0 years, 79.8 ± 16.0 kg, 27.0 ± 4.0 kg/m 2 ) with perceptions of cognitive and memory decline completed the double-blind, randomized, parallel-arm, placebo-controlled intervention clinical trial. Participants were counterbalanced by sex and BMI and randomly allocated to their respective 12-week supplementation interventions, which were either the placebo (PL) or 1100 mg/day of PT containing 8.8 mg of fucoxanthin (FX). Fasting blood samples were collected, and cognitive assessments were performed during the testing session at 0, 4, and 12 weeks of intervention. The data were analyzed by multivariate and univariate general linear model (GLM) analyses with repeated measures, pairwise comparisons, and mean changes from baseline analysis with 95% confidence intervals (CIs) to assess the clinical significance of the findings., Results: FX supplementation significantly affected ( p < 0.05) or exhibited tendencies toward significance ( p > 0.05 to p < 0.10 with effect sizes ranging from medium to large) for word recall, picture recognition reaction time, Stroop color-word test, choice reaction time, and digit vigilance test variables. Additionally, FX supplementation promoted a more consistent clinical improvement from baseline values when examining mean changes with 95% CIs, although most differences were seen over time rather than between groups., Conclusions: The results demonstrate some evidence that FX supplementation can improve working and secondary memory, vigilance, attention, accuracy, and executive function. There was also evidence that FX promoted more positive effects on insulin sensitivity and perceptions about sleep quality with no negative effects on clinical blood panels or perceived side effects. Additional research should investigate how FX may affect cognition in individuals perceiving memory and cognitive decline. Registered clinical trial #NCT05759910.

Background: Ashwagandha has been reported to reduce stress and attenuate cognitive decline associated with inflammation and neurodegeneration in clinical populations. However, the effects as a potential nootropic nutrient in younger populations are unclear. This study examined the effects of liposomal ashwagandha supplementation on cognitive function, mood, and markers of health and safety in healthy young men and women., Methods: 59 men and women (22.7 ± 7 yrs., 74.9 ± 16 kg, 26.2 ± 5 BMI) fasted for 12 h, donated a fasting blood sample, and were administered the COMPASS cognitive function test battery (Word Recall, Word recognition, Choice Reaction Time Task, Picture Recognition, Digit Vigilance Task, Corsi Block test, Stroop test) and profile of mood states (POMS). In a randomized and double-blind manner, participants were administered 225 mg of a placebo (Gum Arabic) or ashwagandha ( Withania somnifera ) root and leaf extract coated with a liposomal covering. After 60-min, participants repeated cognitive assessments. Participants continued supplementation (225 mg/d) for 30 days and then returned to the lab to repeat the experiment. Data were analyzed using a general linear model (GLM) univariate analysis with repeated measures and pairwise comparisons of mean changes from baseline with 95% confidence intervals (CI)., Results: Ashwagandha supplementation improved acute and/or 30-day measures of Word Recall (correct and recalled attempts), Choice Reaction Time (targets identified), Picture Recognition ("yes" correct responses, correct and overall reaction time), Digit Vigilance (correct reaction time), Stroop Color-Word (congruent words identified, reaction time), and POMS (tension and fatigue) from baseline more consistently with several differences observed between groups., Conclusion: Results support contentions that ashwagandha supplementation (225 mg) may improve some measures of memory, attention, vigilance, attention, and executive function while decreasing perceptions of tension and fatigue in younger healthy individuals. Retrospectively registered clinical trial ISRCTN58680760.

Background: Microalgae like Phaeodactylum tricornutum (PT) contain the carotenoid, fucoxanthin, which has been purported to promote fat loss, lower blood lipids, and improve glucose management. This study examined whether dietary supplementation with microalgae extracts from PT containing 4.4 mg/d of fucoxanthin affects changes in body composition or health markers in overweight women during an exercise and diet intervention., Materials and Methods: A total of 37 females (28.6 ± 7.9 years, 80.2 ± 14.9 kg, 29.6 ± 3.8 kg/m², 41.4 ± 4.2% fat) fasted for 12 h, donated a fasting blood sample, completed health and mood state inventories, and undertook body composition, health, and exercise assessments. In a counterbalanced, randomized, and double-blind manner, participants ingested a placebo (PL), or microalgae extract of Phaeodactylum tricornutum standardized to 4.4 mg of fucoxanthin (FX) for 12 weeks while participating in a supervised exercise program that included resistance-training and walking (3 days/week) with encouragement to accumulate 10,000 steps/day on remaining days of the week. The diet intervention involved reducing energy intake by about -300 kcal/d (i.e., ≈1400-1600 kcals/d, 55% carbohydrate, 30% fat, 15% protein) to promote a -500 kcal/d energy deficit with exercise. Follow-up testing was performed at 6 and 12 weeks. A general linear model (GLM) with repeated measures statistical analysis was used to analyze group responses and changes from baseline with 95% confidence intervals., Results: Dietary supplementation with microalgae extract from PT containing fucoxanthin for 12 weeks did not promote additional weight loss or fat loss in overweight but otherwise healthy females initiating an exercise and diet intervention designed to promote modest weight loss. However, fucoxanthin supplementation preserved bone mass, increased bone density, and saw greater improvements in walking steps/day, resting heart rate, aerobic capacity, blood lipid profiles, adherence to diet goals, functional activity tolerance, and measures of quality of life. Consequently, there appears to be some benefit to supplementing microalgae extract from PT containing fucoxanthin during a diet and exercise program. Registered clinical trial #NCT04761406.

Recent research supports previous contentions that encapsulating vitamins and minerals with liposomes help improve overall bioavailability. This study examined whether ingesting a liposomal multivitamin and mineral supplement (MVM) differentially affects the appearance and/or clearance of vitamins and minerals in the blood compared to a non-liposomal MVM supplement. In a double-blind, randomized, and counterbalanced manner, 34 healthy men and women fasted for 12 h. Then, they ingested a non-liposomal (NL) or liposomal (L) MVM supplement and a standardized snack. Venous blood samples were obtained at 0, 2, 4, and 6 h after MVM ingestion and analyzed for a panel of vitamins and minerals. Plasma levels of vitamins and minerals and mean changes from baseline with 95% confidence intervals (CIs) were analyzed using general linear model statistics with repeated measures. The observed values were also entered into pharmacokinetic analysis software and analyzed through univariate analysis of variance with repeated measure contrasts. The results revealed an overall treatment x time interaction effect among the vitamins and minerals evaluated ( p = 0.051, ηp2 = 0.054, moderate effect). Differences between treatments were also observed in volume distribution area (vitamin E, iron), median residence time (vitamin E, iron), volume distribution area (iron), volume of distribution steady state (vitamin A, E, iron), clearance rates (vitamin A, E), elimination phase half-life (vitamin E, iron), distribution/absorption phase intercept (vitamin A), and distribution/absorption phase slope and rate (vitamin C, calcium). Vitamin volume distribution was lower with liposomal MVM ingestion than non-liposomal MVM sources, suggesting greater clearance and absorption since similar amounts of vitamins and minerals were ingested. These findings indicate that coating a MVM with liposomes affects individual nutrient pharmacokinetic profiles. Additional research should evaluate how long-term supplementation of liposomal MVM supplements may affect vitamin and mineral status, nutrient function, and/or health outcomes.

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.

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/m 2 ) 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.

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 (η p 2 = 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/m 2 ) 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.