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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: 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.

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: Ginger contains gingerols, shagaols, paradols, gingerdiones, and terpenes, which have been shown to display anti-inflammatory properties and inhibit pain receptors. For this reason, ginger has been marketed as a natural analgesic. This study examined whether a specialized ginger extract obtained through supercritical CO2 extraction and subsequent fermentation affects pain perception, functional capacity, and markers of inflammation. Methods: Thirty men and women (56.0 ± 9.0 years, 164.4 ± 14 cm, 86.5 ± 20.9 kg, 31.0 ± 7.5 kg/m2) with a history of mild to severe joint and muscle pain as well as inflammation participated in a placebo-controlled, randomized, parallel-arm study. Participants donated fasting blood, completed questionnaires, rated pain in the thighs to standardized pressure, and then completed squats/deep knee bends, while holding 30% of body mass, for 3 sets of 10 repetitions on days 0, 30, and 56 of supplementation. Participants repeated tests after 2 days of recovery following each testing session. Participants were matched by demographics and randomized to ingest 125 mg/d of a placebo or ginger (standardized to contain 10% total gingerols and no more than 3% total shogaols) for 58 days. Data were analyzed by a general linear model (GLM) analysis of variance with repeated measures, mean changes from the baseline with 95% confidence intervals, and chi-squared analysis. Results: There was evidence that ginger supplementation attenuated perceptions of muscle pain in the vastus medialis; improved ratings of pain, stiffness, and functional capacity; and affected several inflammatory markers (e.g., IL-6, INF-ϒ, TNF-α, and C-Reactive Protein concentrations), particularly following two days of recovery from resistance exercise. There was also evidence that ginger supplementation increased eosinophils and was associated with less frequent but not significantly different use of over-the-counter analgesics. Conclusions: Ginger supplementation (125 mg/d, providing 12.5 mg/d of gingerols) appears to have some favorable effects on perceptions of pain, functional capacity, and inflammatory markers in men and women experiencing mild to moderate muscle and joint pain. Registered clinical trial #ISRCTN74292348.

Intense exercise promotes fatigue and can impair cognitive function, particularly toward the end of competition when decision-making is often critical for success. For this reason, athletes often ingest caffeinated energy drinks prior to or during exercise to help them maintain focus, reaction time, and cognitive function during competition. However, caffeine habituation and genetic sensitivity to caffeine (CA) limit efficacy. Paraxanthine (PX) is a metabolite of caffeine reported to possess nootropic properties. This study examined whether ingestion of PX with and without CA affects pre- or post-exercise cognitive function. 12 trained runners were randomly assigned to consume in a double-blind, randomized, and crossover manner 400 mg of a placebo (PL); 200 mg of PL + 200 mg of CA; 200 mg of PL + 200 mg of PX (ENFINITY®, Ingenious Ingredients); or 200 mg PX + 200 mg of CA (PX+CA) with a 7-14-day washout between treatments. Participants donated fasting blood samples and completed pre-supplementation (PRE) side effects questionnaires, the Berg-Wisconsin Card Sorting Test (BCST), and the Psychomotor Vigilance Task Test (PVTT). Participants then ingested the assigned treatment and rested for 60 minutes, repeated tests (PRE-EX), performed a 10-km run on a treadmill at a competition pace, and then repeated tests (POST-EX). Data were analyzed using General Linear Model (GLM) univariate analyses with repeated measures and percent changes from baseline with 95% confidence intervals. BCST correct responses in the PX treatment increased from PRE-EX to POST-EX (6.8% [1.5, 12.1],  = 0.012). The error rate in the PL (23.5 [-2.8, 49.8] %,  = 0.078) and CA treatment (31.5 [5.2, 57.8] %,  = 0.02) increased from PRE-EX values with POST-EX errors tending to be lower with PX treatment compared to CA (-35.7 [-72.9, 1.4] %,  = 0.059). POST-EX perseverative errors with PAR rules were significantly lower with PX treatment than with CA (-26.9 [-50.5, -3.4] %,  = 0.026). Vigilance analysis revealed a significant interaction effect in Trial #2 mean reaction time values (  = 0.049, 0.134, moderate to large effect) with POST-EX reaction times tending to be faster with PX and CA treatment. POST-EX mean reaction time of all trials with PX treatment was significantly faster than PL (-23.2 [-43.4, -2.4] %,  = 0.029) and PX+CA (-29.6 [-50.3, -8.80] %,  = 0.006) treatments. There was no evidence that PX ingestion adversely affected ratings of side effects associated with stimulant intake or clinical blood markers. Results provide some evidence that pre-exercise PX ingestion improves prefrontal cortex function, attenuates attentional decline, mitigates cognitive fatigue, and improves reaction time and vigilance. Adding CA to PX did not provide additional benefits. Therefore, PX ingestion may serve as a nootropic alternative to CA.

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.

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/m2, 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).

: The purpose of this proof-of-concept study was to examine the effects oligosaccharide 6'-sialyllactose (6'-SL) supplementation (900 mg/d) during training on exercise performance and training adaptations in recreationally active males. : In a randomized, double-blind design, 19 healthy males (24.4 ± 6.0 yrs, 174.9 ± 5.9 cm, 82.0 ± 15.2 kg, 27.1 ± 4.7 kg/m , 26.4 ± 6.9% body fat) ingested 3 × 300 mg/d of a placebo or 6'-SL for 12 weeks while partaking in a supervised resistance-training program while following their normal diet. Body composition (DXA), body water, submaximal lactate and substrate oxidation, 5RM dynamic muscular strength, ventilatory anaerobic threshold (VANT), peak aerobic capacity (VO ), blood lactate, cycling anaerobic sprint capacity, and fasting blood samples were obtained at week 0, 6, and 12 of training and supplementation. Data were analyzed using multivariate and univariate general linear models (GLM) with repeated measures, along with assessments of mean changes from baseline and corresponding 95% confidence intervals. : Both groups observed positive training adaptations with no significant differences observed between groups in body composition, 5RM dynamic strength, or anaerobic sprint capacity. Significant interaction effects were observed VANT ( = 0.032), VO at VANT ( = 0.028), and submaximal glucose and fat oxidation ( = 0.034) while time to reach peak VO ( = 0.083), absolute ( = 0.075) and relative ( = 0.057) peak VO approached significance. At Week 6, changes in time to peak effort (196 s [-16, 409], = 0.068), absolute (0.76 L/min [-0.005, 1.53], = 0.051) and relative (10.9 mL/kg/min [0.52, 21.5], = 0.045), and fat oxidation (20.5% [3.1, 37.9], = 0.023) were significantly greater in the 6'-SL group while VANT (-9.2% [-18.3, -0.04], = 0.049), VO at VANT (-4.8% [-9.8, 0.2], = 0.06) and submaximal glucose oxidation values (-20.5% [-37.9, -3.1], = 0.024) were lower with 6'-SL. After 12 weeks of training, VANT (-9.7% [-17.7, -1.5], = 0.023) and VO at VANT (-6.4% [-11.8, -1.0], = 0.024) values were significantly lower in the 6'-SL group. No significant differences were observed in resting, submaximal, or maximal exercise blood lactate while the ratios of LDL to HDL (-0.27 [-0.53, -0.01], = 0.042) and total cholesterol to HDL (-0.32 [-0.60, -0.04], = 0.028) decreased significantly from baseline after 6 weeks of training with 6'-SL. : 6'-SL supplementation did not promote greater gains dynamic strength, fat free mass or changes in body composition. However, while there was some evidence that 6'-SL supplementation influenced training-induced changes in aerobic capacity during the first six weeks, fewer effects were observed after 12 weeks. Moreover, several differences only approached significance in this small proof-of-concept study, so results should be viewed as exploratory and hypothesis generating for additional research.

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/m2) 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: 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.